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Sample records for bioactive molecular conformational

  1. Cyndi: a multi-objective evolution algorithm based method for bioactive molecular conformational generation

    Directory of Open Access Journals (Sweden)

    Li Honglin

    2009-03-01

    Full Text Available Abstract Background Conformation generation is a ubiquitous problem in molecule modelling. Many applications require sampling the broad molecular conformational space or perceiving the bioactive conformers to ensure success. Numerous in silico methods have been proposed in an attempt to resolve the problem, ranging from deterministic to non-deterministic and systemic to stochastic ones. In this work, we described an efficient conformation sampling method named Cyndi, which is based on multi-objective evolution algorithm. Results The conformational perturbation is subjected to evolutionary operation on the genome encoded with dihedral torsions. Various objectives are designated to render the generated Pareto optimal conformers to be energy-favoured as well as evenly scattered across the conformational space. An optional objective concerning the degree of molecular extension is added to achieve geometrically extended or compact conformations which have been observed to impact the molecular bioactivity (J Comput -Aided Mol Des 2002, 16: 105–112. Testing the performance of Cyndi against a test set consisting of 329 small molecules reveals an average minimum RMSD of 0.864 Å to corresponding bioactive conformations, indicating Cyndi is highly competitive against other conformation generation methods. Meanwhile, the high-speed performance (0.49 ± 0.18 seconds per molecule renders Cyndi to be a practical toolkit for conformational database preparation and facilitates subsequent pharmacophore mapping or rigid docking. The copy of precompiled executable of Cyndi and the test set molecules in mol2 format are accessible in Additional file 1. Conclusion On the basis of MOEA algorithm, we present a new, highly efficient conformation generation method, Cyndi, and report the results of validation and performance studies comparing with other four methods. The results reveal that Cyndi is capable of generating geometrically diverse conformers and outperforms

  2. Molecular field technology applied to virtual screening and finding the bioactive conformation.

    Science.gov (United States)

    Cheeseright, Tim; Mackey Phd, Mark; Rose Phd, Sally; Vinter Phd, Andy

    2007-01-01

    Virtual screening is being applied to reduce the high-throughput screening bottleneck in many pharmaceutical companies and to reduce compound wastage. Cresset's ligand-based virtual screening technology using molecular fields can facilitate rapid identification of novel chemotypes from biologically testing only 200 - 1000 compounds. Four molecular fields calculated using the interaction of different probe atoms with the ligand are sufficient to describe how a ligand binds to its protein. Compounds with similar fields to known active ligands are predicted to have a high probability of showing similar activity. As binding is related to field similarity, this property has been exploited further to predict the bioactive conformation of small sets of structurally diverse active ligands starting from the two-dimensional structures alone without knowledge of the target site structure.

  3. Predicting bioactive conformations and binding modes of macrocycles

    Science.gov (United States)

    Anighoro, Andrew; de la Vega de León, Antonio; Bajorath, Jürgen

    2016-10-01

    Macrocyclic compounds experience increasing interest in drug discovery. It is often thought that these large and chemically complex molecules provide promising candidates to address difficult targets and interfere with protein-protein interactions. From a computational viewpoint, these molecules are difficult to treat. For example, flexible docking of macrocyclic compounds is hindered by the limited ability of current docking approaches to optimize conformations of extended ring systems for pose prediction. Herein, we report predictions of bioactive conformations of macrocycles using conformational search and binding modes using docking. Conformational ensembles generated using specialized search technique of about 70 % of the tested macrocycles contained accurate bioactive conformations. However, these conformations were difficult to identify on the basis of conformational energies. Moreover, docking calculations with limited ligand flexibility starting from individual low energy conformations rarely yielded highly accurate binding modes. In about 40 % of the test cases, binding modes were approximated with reasonable accuracy. However, when conformational ensembles were subjected to rigid body docking, an increase in meaningful binding mode predictions to more than 50 % of the test cases was observed. Electrostatic effects did not contribute to these predictions in a positive or negative manner. Rather, achieving shape complementarity at macrocycle-target interfaces was a decisive factor. In summary, a combined computational protocol using pre-computed conformational ensembles of macrocycles as a starting point for docking shows promise in modeling binding modes of macrocyclic compounds.

  4. Chain Conformation and Bioactivity of Lentinan

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The chain conformation of Lentinan, a (1→3)-(-D-glucan having (1→6) branching, from Lentinus edodes in 0.9% NaCl aqueous solution and dimethylsulfoxide (Me_2SO) was investigated by size-exclusion chromatography combined with multi-angle laser light scattering (SEC-LLS), LLS, and viscometry. The results indicated that Lentinan exists as a triple helix in 0.9% NaCl aqueous solution and as a single flexible chain in Me_2SO. Assays in vivo and in vitro against the growth of Sarcoma 180 solid tumor as well as co...

  5. Molecular mechanics conformational analysis of tylosin

    Science.gov (United States)

    Ivanov, Petko M.

    1998-01-01

    The conformations of the 16-membered macrolide antibiotic tylosin were studied with molecular mechanics (AMBER∗ force field) including modelling of the effect of the solvent on the conformational preferences (GB/SA). A Monte Carlo conformational search procedure was used for finding the most probable low-energy conformations. The present study provides complementary data to recently reported analysis of the conformations of tylosin based on NMR techniques. A search for the low-energy conformations of protynolide, a 16-membered lactone containing the same aglycone as tylosin, was also carried out, and the results were compared with the observed conformation in the crystal as well as with the most probable conformations of the macrocyclic ring of tylosin. The dependence of the results on force field was also studied by utilizing the MM3 force field. Some particular conformations were computed with the semiempirical molecular orbital methods AM1 and PM3.

  6. Molecular conformational analysis, reactivity, vibrational spectral analysis and molecular dynamics and docking studies of 6-chloro-5-isopropylpyrimidine-2,4(1H,3H)-dione, a potential precursor to bioactive agent

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    Al-Omary, Fatmah A. M.; Mary, Y. Sheena; Beegum, Shargina; Panicker, C. Yohannan; Al-Shehri, Mona M.; El-Emam, Ali A.; Armaković, Stevan; Armaković, Sanja J.; Van Alsenoy, C.

    2017-01-01

    FT-IR and FT-Raman spectra of 6-chloro-5-isopropylpyrimidine-2,4(1H,3H)-dione were recorded and analyzed. The vibrational wavenumbers were computed using DFT quantum chemical calculations and the data obtained from wavenumber calculations are used to assign the experimentally obtained bands. Potential energy distribution was done using GAR2PED software. The geometrical parameters of the title compound are in agreement with the XRD results. NBO analysis, frontier molecular orbital and first and second hyperpolarizability and molecular electrostatic potential results are also reported. The possible electrophile attacking sites of the title compound is identified using MEP surface plot study. Molecule sites prone to electrophilic attacks were identified using average local ionization energy surfaces, while further insight into the local reactivity properties of the title molecule has been gained by calculation of Fukui functions. Intra-molecular non-covalent interactions have been detected and visualized. Degradation properties based on autoxidation and hydrolysis have been investigated by calculation of bond dissociation energies and radial distribution functions, respectively. From the molecular docking study, the ligand binds at the active site of the substrate by weak non-covalent interactions and amino acids Leu89 forms alkyl interaction with the CH3 groups and Glu90 amino acid forms π-anion interaction with the pyrimidine ring and Thr369 and Ser366 amino acids form H-bond interaction with the Cdbnd O and NH group, respectively. From the conformational analysis, the calculated structures show that the C6C9C10 angle in the most stable form is about 8° smaller compared to the C8C9C10 angle, indicating a higher repulsive force between the (CH3)2HC- moiety and the chlorine atom due to the size of chlorine compared to oxygen atoms.

  7. Synthesis and bioactivity of a side chain bridged paclitaxel: A test of the T-Taxol conformation.

    Science.gov (United States)

    Hodge, Mathis; Chen, Qiao-Hong; Bane, Susan; Sharma, Shubhada; Loew, Maura; Banerjee, Abhijit; Alcaraz, Ana A; Snyder, James P; Kingston, David G I

    2009-05-15

    A knowledge of the bioactive tubulin-binding conformation of paclitaxel (Taxol()) is crucial to a full understanding of the bioactivity of this important anticancer drug, and potentially also to the design of simplified analogs. The bioactive conformation has been shown to be best approximated by the T-Taxol conformation. As a further test of this conclusion, the paclitaxel analog 4 was designed as a compound which has all the chemical functionality necessary for activity, but which cannot adopt the T-Taxol conformation. The synthesis and bioassay of 4 confirmed its lack of activity, and thus provided further support for the T-Taxol conformation as the bioactive tubulin-binding conformation.

  8. Spatial separation of molecular conformers and clusters.

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    Horke, Daniel; Trippel, Sebastian; Chang, Yuan-Pin; Stern, Stephan; Mullins, Terry; Kierspel, Thomas; Küpper, Jochen

    2014-01-09

    Gas-phase molecular physics and physical chemistry experiments commonly use supersonic expansions through pulsed valves for the production of cold molecular beams. However, these beams often contain multiple conformers and clusters, even at low rotational temperatures. We present an experimental methodology that allows the spatial separation of these constituent parts of a molecular beam expansion. Using an electric deflector the beam is separated by its mass-to-dipole moment ratio, analogous to a bender or an electric sector mass spectrometer spatially dispersing charged molecules on the basis of their mass-to-charge ratio. This deflector exploits the Stark effect in an inhomogeneous electric field and allows the separation of individual species of polar neutral molecules and clusters. It furthermore allows the selection of the coldest part of a molecular beam, as low-energy rotational quantum states generally experience the largest deflection. Different structural isomers (conformers) of a species can be separated due to the different arrangement of functional groups, which leads to distinct dipole moments. These are exploited by the electrostatic deflector for the production of a conformationally pure sample from a molecular beam. Similarly, specific cluster stoichiometries can be selected, as the mass and dipole moment of a given cluster depends on the degree of solvation around the parent molecule. This allows experiments on specific cluster sizes and structures, enabling the systematic study of solvation of neutral molecules.

  9. Patterns and conformations in molecularly thin films

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    Basnet, Prem B.

    Molecularly thin films have been a subject of great interest for the last several years because of their large variety of industrial applications ranging from micro-electronics to bio-medicine. Additionally, molecularly thin films can be used as good models for biomembrane and other systems where surfaces are critical. Many different kinds of molecules can make stable films. My research has considered three such molecules: a polymerizable phospholipid, a bent-core molecules, and a polymer. One common theme of these three molecules is chirality. The phospolipid molecules studied here are strongly chiral, which can be due to intrinsically chiral centers on the molecules and also due to chiral conformations. We find that these molecules give rise to chiral patterns. Bent-core molecules are not intrinsically chiral, but individual molecules and groups of molecules can show chiral structures, which can be changed by surface interactions. One major, unconfirmed hypothesis for the polymer conformation at surface is that it forms helices, which would be chiral. Most experiments were carried out at the air/water interface, in what are called Langmuir films. Our major tools for studying these films are Brewster Angle Microscopy (BAM) coupled with the thermodynamic information that can be deduced from surface pressure isotherms. Phospholipids are one of the important constituents of liposomes -- a spherical vesicle com-posed of a bilayer membrane, typically composed of a phospholipid and cholesterol bilayer. The application of liposomes in drug delivery is well-known. Crumpling of vesicles of polymerizable phospholipids has been observed. With BAM, on Langmuir films of such phospholipids, we see novel spiral/target patterns during compression. We have found that both the patterns and the critical pressure at which they formed depend on temperature (below the transition to a i¬‘uid layer). Bent-core liquid crystals, sometimes knows as banana liquid crystals, have drawn

  10. Conformation effects on the molecular orbitals of serine

    Institute of Scientific and Technical Information of China (English)

    Wang Ke-Dong; Ma Peng-Fei; Shan Xu

    2011-01-01

    This paper calculates the five most stable conformers of serine with Hartree-Fock theory, density functional theory (B3LYP), M0ller-Plesset perturbation theory (MP4(SDQ)) and electron propagation theory with the 6-311++G(2d,2p) basis set. The calculated vertical ionization energies for the valence molecular orbitals of each conformer are in agreement with the experimental data, indicating that a range of molecular conformations would coexist in an equilibrium sample. Information of the five outer valence molecular orbitals for each conformer is explored in coordinate and momentum spaces using dual space analysis to investigate the conformational processes, which are generated from the global minimum conformer Serl by rotation of C2-C3 (Ser4), C1-C2 (Ser5) and C1-O2 (Ser2 and Ser3). Orbitals 28a, 27a and 26a are identified as the fingerprint orbitals for all the conformational processes.

  11. Measuring the bioactivity and molecular conformation of typically globular proteins with phenothiazine-derived methylene blue in solid and in solution: A comparative study using photochemistry and computational chemistry.

    Science.gov (United States)

    Ding, Fei; Xie, Yong; Peng, Wei; Peng, Yu-Kui

    2016-05-01

    Methylene blue is a phenothiazine agent, that possesses a diversity of biomedical and biological therapeutic purpose, and it has also become the lead compound for the exploitation of other pharmaceuticals such as chlorpromazine and the tricyclic antidepressants. However, the U.S. Food and Drug Administration has acquired cases of detrimental effects of methylene blue toxicities such as hemolytic anemia, methemoglobinemia and phototoxicity. In this work, the molecular recognition of methylene blue by two globular proteins, hemoglobin and lysozyme was characterized by employing fluorescence, circular dichroism (CD) along with molecular modeling at the molecular scale. The recognition of methylene blue with proteins appears fluorescence quenching via static type, this phenomenon does cohere with time-resolved fluorescence lifetime decay that nonfluorescent protein-drug conjugate formation has a strength of 10(4)M(-1), and the primary noncovalent bonds, that is hydrogen bonds, π-conjugated effects and hydrophobic interactions were operated and remained adduct stable. Meantime, the results of far-UV CD and synchronous fluorescence suggest that the α-helix of hemoglobin/lysozyme decreases from 78.2%/34.7% (free) to 58.7%/23.8% (complex), this elucidation agrees well with the elaborate description of three-dimensional fluorescence showing the polypeptide chain of proteins partially destabilized upon conjugation with methylene blue. Furthermore, both extrinsic fluorescent indicator and molecular modeling clearly exhibit methylene blue is situated within the cavity constituted by α1, β2 and α2 subunits of hemoglobin, while it was located at the deep fissure on the lysozyme surface and Trp-62 and Trp-63 residues are nearby. With the aid of computational analyses and combining the wet experiments, it can evidently be found that the recognition ability of proteins for methylene blue is patterned upon the following sequence: lysozyme

  12. Molecular approaches to screen bioactive compounds from endophytic fungi

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    M Vasundhara

    2016-11-01

    Full Text Available Endophytic fungi are capable of producing plant associated metabolites and their analogs with therapeutic value. In order to identify the potential endophytic isolates producing bioactive compounds, one need to screen all isolated endophytes, which may run into hundreds. Isolation of endophytic fungi is relatively a simple process; but screening of the isolated fungi for required metabolite production is a cumbersome process. Endophytic fungi producing plant associated metabolites may contain genes involved in the entire biosynthetic pathway(s. Therefore, ascertaining the presence of key enzymes of a particular biosynthetic pathway could serve as a molecular marker for screening of these endophytes to produce that metabolite. In absence of entire biosynthetic pathways in endophytic fungi, plant genes associated with that metabolic pathway could serve as markers. This review focuses on the impact of molecular approaches to screen the endophytic fungi for the production of bioactive compounds. An attempt has been made on screening of anticancer compounds like taxol (paclitaxel, podophyllotoxin and camptothecin using molecular markers. The advantages of molecular approaches over conventional methods to screen endophytic fungi and also identification of endophytic fungi are also discussed.

  13. Molecular Approaches to Screen Bioactive Compounds from Endophytic Fungi.

    Science.gov (United States)

    Vasundhara, M; Kumar, Anil; Reddy, M Sudhakara

    2016-01-01

    Endophytic fungi are capable of producing plant associated metabolites and their analogs with therapeutic value. In order to identify the potential endophytic isolates producing bioactive compounds, one need to screen all isolated endophytes, which may run into hundreds. Isolation of endophytic fungi is relatively a simple process; but screening of the isolated fungi for required metabolite production is a cumbersome process. Endophytic fungi producing plant associated metabolites may contain genes involved in the entire biosynthetic pathway(s). Therefore, ascertaining the presence of key enzymes of a particular biosynthetic pathway could serve as a molecular marker for screening of these endophytes to produce that metabolite. In absence of entire biosynthetic pathways in endophytic fungi, plant genes associated with that metabolic pathway could serve as markers. This review focuses on the impact of molecular approaches to screen the endophytic fungi for the production of bioactive compounds. An attempt has been made on screening of anticancer compounds like taxol (paclitaxel), podophyllotoxin, and camptothecin using molecular markers. The advantages of molecular approaches over conventional methods to screen endophytic fungi and also identification of endophytic fungi are discussed.

  14. Conformational proofreading: the impact of conformational changes on the specificity of molecular recognition.

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    Yonatan Savir

    Full Text Available To perform recognition, molecules must locate and specifically bind their targets within a noisy biochemical environment with many look-alikes. Molecular recognition processes, especially the induced-fit mechanism, are known to involve conformational changes. This raises a basic question: Does molecular recognition gain any advantage by such conformational changes? By introducing a simple statistical-mechanics approach, we study the effect of conformation and flexibility on the quality of recognition processes. Our model relates specificity to the conformation of the participant molecules and thus suggests a possible answer: Optimal specificity is achieved when the ligand is slightly off target; that is, a conformational mismatch between the ligand and its main target improves the selectivity of the process. This indicates that deformations upon binding serve as a conformational proofreading mechanism, which may be selected for via evolution.

  15. Identification of high affinity bioactive Salbutamol conformer directed against mutated (Thr164Ile) beta 2 adrenergic receptor.

    Science.gov (United States)

    Bandaru, Srinivas; Tiwari, Geet; Akka, Jyothy; Marri, Vijaya Kumar; Alvala, Mallika; Gutlapalli, Venkata Ravi; Nayarisseri, Anuraj; Mundluru, Hema Prasad

    2015-01-01

    Salbutamol forms an important and widely administered β2 agonist prescribed in the symptomatic treatment of bronchial asthma. Unfortunately, a subset of patients show refractoriness to it owing to ADRB2 gene variant (rs 1800888). The variant substitutes Thr to Ile at the position 164 in the β2 adrenergic receptor leading to sub-optimal binding of agonists. The present study aims to associate the Salbutamol response with the variant and select the bioactive conformer of Sabutamol with optimal binding affinity against mutated receptor by in silico approaches. To assess bronchodilator response spirometry was performed before and 15 min after Salbutamol (200 mcg) inhalation. Responders to Salbutamol were categorized if percentage reversibility was greater than or equal to 12%, while those showing FEV₁ reversibility less than 12% were classified as non-responders. Among the 344 subjects screened, 238 were responders and 106 were non-responders. The frequency of mutant allele "T" was significantly higher in case of non-responders (p Salbutamol conformer ensembles supported by systematic search algorithm. 4369 conformers were generated of which only 1882 were considered bioactive conformers (threshold RMSD≤1 in reference to normalized structure of salbutamol). All the bioactive conformers were evaluated for the binding affinity against (Thr164 Ile) receptor through MolDock aided docking algorithm. One of the bioactive conformer (P.E. = -57.0038, RMSD = 0.6) demonstrated 1.54 folds greater affinity than the normal Salbutamol in the mutated receptor. The conformer identified in the present study may be put to pharmacodynamic and pharmacokinetic studies in future ahead.

  16. On the stochastic dynamics of molecular conformation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    An important functioning mechanism of biological macromolecules is the transition between different conformed states due to thermal fluctuation. In the present paper, a biological macromolecule is modeled as two strands with side chains facing each other, and its stochastic dynamics including the statistics of stationary motion and the statistics of conformational transition is studied by using the stochastic averaging method for quasi Hamiltonian systems. The theoretical results are confirmed with the results from Monte Carlo simulation.

  17. Chromatin conformation capture strategies in molecular diagnostics

    NARCIS (Netherlands)

    Vree, P.J.P. de

    2015-01-01

    In this thesis I have explored the clinical potential of the 4C-technology and worked on development of a novel chromatin conformation capture based technology, called TLA. In chapter 2 I describe how the 4C-technology can be applied as a targeted strategy to identify putative fusion-genes or chromo

  18. The Conformation and Assignment of the Proton NMR Spectrum in Water of DX600, a Bioactive Peptide with a Random Coil Conformation

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    Wayne E. Steinmetz

    2011-01-01

    Full Text Available DX600, a small peptide with 26 residues, is a potent, highly selective inhibitor of angiotensin converting enzyme 2 (ACE2. A range of NMR methods including TOCSY and ROESY yield an assignment of its proton spectrum in water and constraints on its conformation. Constrained molecular dynamics simulations of solvated DX600 show that the peptide's most abundant conformer adopts a predominantly random coil conformation. Constrained by the disulfide bond, its backbone defines an overhand knot with frayed ends.

  19. The bound conformation of microtubule-stabilizing agents: NMR insights into the bioactive 3D structure of discodermolide and dictyostatin.

    Science.gov (United States)

    Canales, Angeles; Matesanz, Ruth; Gardner, Nicola M; Andreu, José Manuel; Paterson, Ian; Díaz, J Fernando; Jiménez-Barbero, Jesús

    2008-01-01

    A protocol based on a combination of NMR experimental data with molecular mechanics calculations and docking procedures has been employed to determine the microtubule-bound conformation of two microtubule-stabilizing agents, discodermolide (DDM) and dictyostatin (DCT). The data indicate that tubulin in assembled microtubules recognizes DDM through a conformational selection process, with minor changes in the molecular skeleton between the major conformer in water solution and that bound to assembled microtubules. For DCT, the deduced bound geometry presents some key conformation differences around certain torsion angles, with respect to the major conformer in solution, and still displays mobility even when bound. The bound conformer of DCT resembles that of DDM and provides very similar contacts with the receptor. Competition experiments indicate that both molecules compete with the taxane-binding site. A model of the binding mode of DDM and DCT to tubulin is proposed.

  20. Recent advances in the investigation of the bioactive conformation of peptides active at the micro-opioid receptor. conformational analysis of endomorphins.

    Science.gov (United States)

    Gentilucci, Luca; Tolomelli, Alessandra

    2004-01-01

    Despite of the recent advances in the structural investigation of complex molecules, the comprehension of the 3D features responsible for the interaction between opioid peptides and micro-opioid receptors still remains an elusive task. This has to be attributed to the intrinsic nature of opioid peptides, which can assume a number of different conformations of similar energy, and to the flexibility of the receptorial cavity, which can modify its inner shape to host different ligands. Due to this inherent mobility of the ligand-receptor system, massive efforts devoted to the definition of a rigid bioactive conformation to be used as a template for the design of new pharmacologically active compounds might be overstressed. The future goal might be the design of peptide or nonpeptide ligands capable of maximizing specific hydrophobic interactions. This review covers the recent opinions emerged on the nature of the ligand-receptor interaction, and the development of suitable models for the determination of the bioactive conformation of peptide ligands active towards micro-opioid receptors.

  1. Employing conformational analysis in the molecular modeling of agrochemicals: insights on QSAR parameters of 2,4-D

    Directory of Open Access Journals (Sweden)

    Matheus Puggina de Freitas

    2013-12-01

    Full Text Available A common practice to compute ligand conformations of compounds with various degrees of freedom to be used in molecular modeling (QSAR and docking studies is to perform a conformational distribution based on repeated random sampling, such as Monte-Carlo methods. Further calculations are often required. This short review describes some methods used for conformational analysis and the implications of using selected conformations in QSAR. A case study is developed for 2,4-dichlorophenoxyacetic acid (2,4-D, a widely used herbicide which binds to TIR1 ubiquitin ligase enzyme. The use of such an approach and semi-empirical calculations did not achieve all possible minima for 2,4-D. In addition, the conformations and respective energies obtained by the semi-empirical AM1 method do not match the calculated trends obtained by a high level DFT method. Similar findings were obtained for the carboxylate anion, which is the bioactive form. Finally, the crystal bioactive structure of 2,4-D was not found as a minimum when using Monte-Carlo/AM1 and is similarly populated with another conformer in implicit water solution according to optimization at the B3LYP/aug-cc-pVDZ level. Therefore, quantitative structure-activity relationship (QSAR methods based on three dimensional chemical structures are not fundamental to provide predictive models for 2,4-D congeners as TIR1 ubiquitin ligase ligands, since they do not necessarily reflect the bioactive conformation of this molecule. This probably extends to other systems.

  2. Reactions driving conformational movements (molecular motors) in gels: conformational and structural chemical kinetics.

    Science.gov (United States)

    Otero, Toribio F

    2017-01-18

    In this perspective the empirical kinetics of conducting polymers exchanging anions and solvent during electrochemical reactions to get dense reactive gels is reviewed. The reaction drives conformational movements of the chains (molecular motors), exchange of ions and solvent with the electrolyte and structural (relaxation, swelling, shrinking and compaction) gel changes. Reaction-driven structural changes are identified and quantified from electrochemical responses. The empirical reaction activation energy (Ea), the reaction coefficient (k) and the reaction orders (α and β) change as a function of the conformational energy variation during the reaction. This conformational energy becomes an empirical magnitude. Ea, k, α and β include and provide quantitative conformational and structural information. The chemical kinetics becomes structural chemical kinetics (SCK) for reactions driving conformational movements of the reactants. The electrochemically stimulated conformational relaxation model describes empirical results and some results from the literature for biochemical reactions. In parallel the development of an emerging technological world of soft, wet, multifunctional and biomimetic tools and anthropomorphic robots driven by reactions of the constitutive material, as in biological organs, can be now envisaged being theoretically supported by the kinetic model.

  3. Molecular insight into conformational transmission of human P-glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Shan-Yan [Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Liu, Fu-Feng, E-mail: fufengliu@tju.edu.cn, E-mail: ysun@tju.edu.cn; Dong, Xiao-Yan; Sun, Yan, E-mail: fufengliu@tju.edu.cn, E-mail: ysun@tju.edu.cn [Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072 (China)

    2013-12-14

    P-glycoprotein (P-gp), a kind of ATP-binding cassette transporter, can export candidates through a channel at the two transmembrane domains (TMDs) across the cell membranes using the energy released from ATP hydrolysis at the two nucleotide-binding domains (NBDs). Considerable evidence has indicated that human P-gp undergoes large-scale conformational changes to export a wide variety of anti-cancer drugs out of the cancer cells. However, molecular mechanism of the conformational transmission of human P-gp from the NBDs to the TMDs is still unclear. Herein, targeted molecular dynamics simulations were performed to explore the atomic detail of the conformational transmission of human P-gp. It is confirmed that the conformational transition from the inward- to outward-facing is initiated by the movement of the NBDs. It is found that the two NBDs move both on the two directions (x and y). The movement on the x direction leads to the closure of the NBDs, while the movement on the y direction adjusts the conformations of the NBDs to form the correct ATP binding pockets. Six key segments (KSs) protruding from the TMDs to interact with the NBDs are identified. The relative movement of the KSs along the y axis driven by the NBDs can be transmitted through α-helices to the rest of the TMDs, rendering the TMDs to open towards periplasm in the outward-facing conformation. Twenty eight key residue pairs are identified to participate in the interaction network that contributes to the conformational transmission from the NBDs to the TMDs of human P-gp. In addition, 9 key residues in each NBD are also identified. The studies have thus provided clear insight into the conformational transmission from the NBDs to the TMDs in human P-gp.

  4. Molecular insight into conformational transmission of human P-glycoprotein

    Science.gov (United States)

    Chang, Shan-Yan; Liu, Fu-Feng; Dong, Xiao-Yan; Sun, Yan

    2013-12-01

    P-glycoprotein (P-gp), a kind of ATP-binding cassette transporter, can export candidates through a channel at the two transmembrane domains (TMDs) across the cell membranes using the energy released from ATP hydrolysis at the two nucleotide-binding domains (NBDs). Considerable evidence has indicated that human P-gp undergoes large-scale conformational changes to export a wide variety of anti-cancer drugs out of the cancer cells. However, molecular mechanism of the conformational transmission of human P-gp from the NBDs to the TMDs is still unclear. Herein, targeted molecular dynamics simulations were performed to explore the atomic detail of the conformational transmission of human P-gp. It is confirmed that the conformational transition from the inward- to outward-facing is initiated by the movement of the NBDs. It is found that the two NBDs move both on the two directions (x and y). The movement on the x direction leads to the closure of the NBDs, while the movement on the y direction adjusts the conformations of the NBDs to form the correct ATP binding pockets. Six key segments (KSs) protruding from the TMDs to interact with the NBDs are identified. The relative movement of the KSs along the y axis driven by the NBDs can be transmitted through α-helices to the rest of the TMDs, rendering the TMDs to open towards periplasm in the outward-facing conformation. Twenty eight key residue pairs are identified to participate in the interaction network that contributes to the conformational transmission from the NBDs to the TMDs of human P-gp. In addition, 9 key residues in each NBD are also identified. The studies have thus provided clear insight into the conformational transmission from the NBDs to the TMDs in human P-gp.

  5. Molecular motions and conformational transition between different conformational states of HIV-1 gp120 envelope glycoprotein

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The HIV-1 gp120 exterior envelope glycoprotein undergoes a series of conformational rearrangements while sequentially interacting with the receptor CD4 and coreceptor CCR5 or CXCR4 on the surface of host cells to initiate virus entry. Both the crystal structures of the HIV-1 gp120 core bound by the CD4 and antigen 17b and the SIV gp120 core prebound by CD4 are known. Despite the wealth of knowledge on these static snapshots of molecular conformations, the details of molecular motions involved in conformational transition that are crucial to intervention remain elusive. We presented comprehensive comparative analyses of the dynamics behaviors of the gp120 in its CD4-complexed, CD4-free and CD4-unliganded states based on the homology models with modeled V3 and V4 loops by means of CONCOORD computer simulation to generate ensembles of feasible protein structures that were subsequently analysed by essential dynamics analyses to identify preferred concerted motions. The revealed collective fluctuations are dominated by complex modes of combinational motions of the rotation/twisting, flexing/closure, and shortness/elongation between or within the inner, outer, and bridging-sheet domains, and these modes are related to the CD4 association and HIV neutralization avoidance. Further essential subspace overlap analyses were performed to quantitatively distinguish the preference for conformational transitions between the three states, revealing that the unliganded gp120 has a greater potential to translate its conformation into the conformational state adopted by the CD4-complexed gp120 than by the CD4-free gp120, whereas the CD4-free gp120 has a greater potential to translate its conformation into the unliganded state than the CD4-complexed gp120 does. These dy-namics data of gp120 in its different conformations are helpful in understanding the relationship be-tween the molecular motion/conformational transition and the function of gp120, and in gp120-structure-based subunit

  6. Molecularly stabilised ultrasmall gold nanoparticles: synthesis, characterization and bioactivity.

    Science.gov (United States)

    Leifert, Annika; Pan-Bartnek, Yu; Simon, Ulrich; Jahnen-Dechent, Willi

    2013-07-21

    Gold nanoparticles (AuNPs) are widely used as contrast agents in electron microscopy as well as for diagnostic tests. Due to their unique optical and electrical properties and their small size, there is also a growing field of potential applications in medical fields of imaging and therapy, for example as drug carriers or as active compounds in thermotherapy. Besides their intrinsic optical properties, facile surface decoration with (bio)functional ligands renders AuNPs ideally suited for many industrial and medical applications. However, novel AuNPs may have toxicological profiles differing from bulk and therefore a thorough analysis of the quantitative structure-activity relationship (QSAR) is required. Several mechanisms are proposed that cause adverse effects of nanoparticles in biological systems. Catalytic generation of reactive species due to the large and chemically active surface area of nanomaterials is well established. Because nanoparticles approach the size of biological molecules and subcellular structures, they may overcome natural barriers by active or passive uptake. Ultrasmall AuNPs with sizes of 2 nm or less may even behave as molecular ligands. These types of potential interactions would imply a size and ligand-dependent behaviour of any nanomaterial towards biological systems. Thus, to fully understand their QSAR, AuNPs bioactivity should be analysed in biological systems of increasing complexity ranging from cell culture to whole animal studies.

  7. Molecularly stabilised ultrasmall gold nanoparticles: synthesis, characterization and bioactivity

    Science.gov (United States)

    Leifert, Annika; Pan-Bartnek, Yu; Simon, Ulrich; Jahnen-Dechent, Willi

    2013-06-01

    Gold nanoparticles (AuNPs) are widely used as contrast agents in electron microscopy as well as for diagnostic tests. Due to their unique optical and electrical properties and their small size, there is also a growing field of potential applications in medical fields of imaging and therapy, for example as drug carriers or as active compounds in thermotherapy. Besides their intrinsic optical properties, facile surface decoration with (bio)functional ligands renders AuNPs ideally suited for many industrial and medical applications. However, novel AuNPs may have toxicological profiles differing from bulk and therefore a thorough analysis of the quantitative structure-activity relationship (QSAR) is required. Several mechanisms are proposed that cause adverse effects of nanoparticles in biological systems. Catalytic generation of reactive species due to the large and chemically active surface area of nanomaterials is well established. Because nanoparticles approach the size of biological molecules and subcellular structures, they may overcome natural barriers by active or passive uptake. Ultrasmall AuNPs with sizes of 2 nm or less may even behave as molecular ligands. These types of potential interactions would imply a size and ligand-dependent behaviour of any nanomaterial towards biological systems. Thus, to fully understand their QSAR, AuNPs bioactivity should be analysed in biological systems of increasing complexity ranging from cell culture to whole animal studies.

  8. Two different molecular conformations found in chitosan type II salts.

    Science.gov (United States)

    Lertworasirikul, Amornrat; Tsue, Shin-ichiro; Noguchi, Keiichi; Okuyama, Kenji; Ogawa, Kozo

    2003-05-23

    The type II structure of chitosan acidic salts prepared from crab tendon in solid state was studied using an X-ray fiber diffraction technique together with the linked-atom least-squares (LALS) technique. The cylindrical Patterson method was applied to confirm the molecular conformation of the chitosan. It was shown that there are two different helical conformations for type II salts. One is the relaxed twofold helix having a tetrasaccharide as an asymmetric unit as found in chitosan.HCl salt, which was previously reported as a conformation of chitosan.HCOOH salt. The other is the fourfold helix having a disaccharide as an asymmetric unit newly found in chitosan.HI salt.

  9. Conformations of terminal sialyloligosaccharide fragments--a molecular dynamics study.

    Science.gov (United States)

    Suresh, M Xavier; Veluraja, K

    2003-06-07

    Molecular dynamics simulations have been performed to understand the conformational features of the terminal sialyloligosaccharide fragments NeuNAc alpha(2-3)Gal, NeuNAc alpha(2-6)Gal, NeuNAc alpha(2-8)NeuNAc and NeuNAc alpha(2-9)NeuNAc. The conformational regions A(i), B(i) and C(i) were identified in the Ramachandran plot. Analysis of the 1000 ps trajectories collected through simulation (2000 ps in the case of NeuNAc alpha (2-9)NeuNAc) revealed that these molecules have conformational propensity in region B(i). The occurrence of these molecules in the common conformational space leads to a structural similarity between them. This structural similarity may be an essential requirement for the neuraminidase activity towards sialyloligosaccharides. The local change in the conformation of the active site residues of neuraminidases may contribute for the specificity differences between different linkages of sialyloligosaccharides. A highly conserved water-mediated hydrogen bond observed in these structures between the sugar residues, acts as an additional stabilizing force.

  10. Probing the bioactive conformation of an archetypal natural product HDAC inhibitor with conformationally homogeneous triazole-modified cyclic tetrapeptides.

    Science.gov (United States)

    Horne, W Seth; Olsen, Christian A; Beierle, John M; Montero, Ana; Ghadiri, M Reza

    2009-01-01

    Fooling enzymes with mock amides: Analogues of apicidin, a cyclic-tetrapeptide inhibitor of histone deacetylase (HDAC), were designed with a 1,4- or 1,5-disubstituted 1,2,3-triazole in place of a backbone amide bond to fix the bond in question in either a trans-like or a cis-like configuration. Thus, the binding affinity of distinct peptide conformations (see picture) could be probed. One analogue proved in some cases to be superior to apicidin as an HDAC inhibitor.

  11. Molecular mechanics study on conformation of perylene-quinonoid photosensitizers

    Institute of Scientific and Technical Information of China (English)

    张红雨; 张志义

    1997-01-01

    Using molecular mechanics method,values of the heat of formation (HF) of different conformations,of perylenequinonoid photosensitizes hypocrellin A (HA) and hypocrellin B (HB) were calculated and the variance of HF after phenolic protons’ dissociation were calculated as well The following was found:(i) The HF values of lour conformational isomers of HA and HB are similar to each other,so the four isomcrs can transform to each other room temperature,(ii) There exists the difference between the ability of dissociation of phenolic protons of HA and that of HB,the former is higher than the latter (iii) There exist two intramolecular hydrogen bonds in HA and HB The bond energy is approximately 8 kJ/mol and the energy of conformation Ⅰ is lower than that of conformationⅡ The bond energy of HA is lower than that of HB.(iv) There exists a low energy snot when phenolic hydroxyl bond twists 180° from the position where hydrogen bond is formed,which suggests that this kind of conformation probably exists,(v) Th

  12. Conformations of cyclopentasilane stereoisomers control molecular junction conductance

    DEFF Research Database (Denmark)

    Li, Haixing; Garner, Marc Hamilton; Shangguan, Zhichun;

    2016-01-01

    Here we examine the impact of ring conformation on the charge transport characteristics of cyclic pentasilane structures bound to gold electrodes in single molecule junctions. We investigate the conductance properties of alkylated cyclopentasilane cis and trans stereoisomers substituted in the 1......,3-position with methylthiomethyl electrode binding groups using both the scanning tunneling microscope-based break junction technique and density functional theory based ab initio calculations. In contrast with the linear ones, these cyclic silanes yield lower conductance values; calculations reveal...... that the constrained dihedral geometries occurring within the ring are suboptimal for σ-orbital delocalization, and therefore, conductance. Theoretical calculations reproduce the measured conductance trends for both cis and trans isomers and find several distinct conformations that are likely to form stable molecular...

  13. Optimization of a genetic algorithm for searching molecular conformer space

    Science.gov (United States)

    Brain, Zoe E.; Addicoat, Matthew A.

    2011-11-01

    We present two sets of tunings that are broadly applicable to conformer searches of isolated molecules using a genetic algorithm (GA). In order to find the most efficient tunings for the GA, a second GA - a meta-genetic algorithm - was used to tune the first genetic algorithm to reliably find the already known a priori correct answer with minimum computational resources. It is shown that these tunings are appropriate for a variety of molecules with different characteristics, and most importantly that the tunings are independent of the underlying model chemistry but that the tunings for rigid and relaxed surfaces differ slightly. It is shown that for the problem of molecular conformational search, the most efficient GA actually reduces to an evolutionary algorithm.

  14. Sampling Molecular Conformers in Solution with Quantum Mechanical Accuracy at a Nearly Molecular-Mechanics Cost.

    Science.gov (United States)

    Rosa, Marta; Micciarelli, Marco; Laio, Alessandro; Baroni, Stefano

    2016-09-13

    We introduce a method to evaluate the relative populations of different conformers of molecular species in solution, aiming at quantum mechanical accuracy, while keeping the computational cost at a nearly molecular-mechanics level. This goal is achieved by combining long classical molecular-dynamics simulations to sample the free-energy landscape of the system, advanced clustering techniques to identify the most relevant conformers, and thermodynamic perturbation theory to correct the resulting populations, using quantum-mechanical energies from density functional theory. A quantitative criterion for assessing the accuracy thus achieved is proposed. The resulting methodology is demonstrated in the specific case of cyanin (cyanidin-3-glucoside) in water solution.

  15. Molecular Approaches to Screen Bioactive Compounds from Endophytic Fungi

    OpenAIRE

    Vasundhara, M.; Anil Kumar; M. Sudhakara Reddy

    2016-01-01

    Endophytic fungi are capable of producing plant associated metabolites and their analogs with therapeutic value. In order to identify the potential endophytic isolates producing bioactive compounds, one need to screen all isolated endophytes, which may run into hundreds. Isolation of endophytic fungi is relatively a simple process; but screening of the isolated fungi for required metabolite production is a cumbersome process. Endophytic fungi producing plant associated metabolites may contain...

  16. Influence of conformational molecular dynamics on matter wave interferometry

    CERN Document Server

    Gring, Michael; Eibenberger, Sandra; Nimmrichter, Stefan; Berrada, Tarik; Arndt, Markus; Ulbricht, Hendrik; Hornberger, Klaus; Müri, Marcel; Mayor, Marcel; Böckmann, Marcus; Doltsinis, Nikos

    2014-01-01

    We investigate the influence of thermally activated internal molecular dynamics on the phase shifts of matter waves inside a molecule interferometer. While de Broglie physics generally describes only the center-of-mass motion of a quantum object, our experiment demonstrates that the translational quantum phase is sensitive to dynamic conformational state changes inside the diffracted molecules. The structural flexibility of tailor-made hot organic particles is sufficient to admit a mixture of strongly fluctuating dipole moments. These modify the electric susceptibility and through this the quantum interference pattern in the presence of an external electric field. Detailed molecular dynamics simulations combined with density functional theory allow us to quantify the time-dependent structural reconfigurations and to predict the ensemble-averaged square of the dipole moment which is found to be in good agreement with the interferometric result. The experiment thus opens a new perspective on matter wave interfe...

  17. Syntheses and Bioactivities of Targeted and Conformationally Restrained Paclitaxel and Discodermolide Analogs

    OpenAIRE

    Yang, Chao

    2008-01-01

    Paclitaxel was isolated from the bark of Taxus brevifolia in the late 1960s. It exerts its biological effect by promoting tubulin polymerization and stabilizing the resulting microtubules. Paclitaxel has become one of the most important current drugs for the treatment of breast and ovarian cancers. Studies aimed at understanding the biologically active conformation of paclitaxel bound on ï ¢â tubulin are described. In this work, the synthesis of isotopically labeled taxol analogs is desc...

  18. Mechanical, Rheological, and Bioactivity Properties of Ultra High-Molecular-Weight Polyethylene Bioactive Composites Containing Polyethylene Glycol and Hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Mazatusziha Ahmad

    2012-01-01

    Full Text Available Ultrahigh-molecular-weight polyethylene/high-density polyethylene (UHMWPE/HDPE blends prepared using polyethylene glycol PEG as the processing aid and hydroxyapatite (HA as the reinforcing filler were found to be highly processable using conventional melt blending technique. It was demonstrated that PEG reduced the melt viscosity of UHMWPE/HDPE blend significantly, thus improving the extrudability. The mechanical and bioactive properties were improved with incorporation of HA. Inclusion of HA from 10 to 50 phr resulted in a progressive increase in flexural strength and modulus of the composites. The strength increment is due to the improvement on surface contact between the irregular shape of HA and polymer matrix by formation of mechanical interlock. The HA particles were homogenously distributed even at higher percentage showed improvement in wetting ability between the polymer matrix and HA. The inclusion of HA enhanced the bioactivity properties of the composite by the formation of calcium phosphate (Ca-P precipitates on the composite surface as proven from SEM and XRD analysis.

  19. Mechanical, rheological, and bioactivity properties of ultra high-molecular-weight polyethylene bioactive composites containing polyethylene glycol and hydroxyapatite.

    Science.gov (United States)

    Ahmad, Mazatusziha; Uzir Wahit, Mat; Abdul Kadir, Mohammed Rafiq; Mohd Dahlan, Khairul Zaman

    2012-01-01

    Ultrahigh-molecular-weight polyethylene/high-density polyethylene (UHMWPE/HDPE) blends prepared using polyethylene glycol PEG as the processing aid and hydroxyapatite (HA) as the reinforcing filler were found to be highly processable using conventional melt blending technique. It was demonstrated that PEG reduced the melt viscosity of UHMWPE/HDPE blend significantly, thus improving the extrudability. The mechanical and bioactive properties were improved with incorporation of HA. Inclusion of HA from 10 to 50 phr resulted in a progressive increase in flexural strength and modulus of the composites. The strength increment is due to the improvement on surface contact between the irregular shape of HA and polymer matrix by formation of mechanical interlock. The HA particles were homogenously distributed even at higher percentage showed improvement in wetting ability between the polymer matrix and HA. The inclusion of HA enhanced the bioactivity properties of the composite by the formation of calcium phosphate (Ca-P) precipitates on the composite surface as proven from SEM and XRD analysis.

  20. Sphingoid esters from the molecular distillation of squid oil: A preliminary bioactivity determination.

    Science.gov (United States)

    Saliu, Francesco; Longhin, Eleonora; Salanti, Anika; Degano, Ilaria; Della Pergola, Roberto

    2016-06-15

    A mixture of sphingoid esters was isolated (1.4% w/w) from the molecular distillation of crude squid visceral oil. A preliminary investigation on the bioactivity profile and toxic potential of this residue was carried out by in vitro experiments. No cytotoxicity and a moderate lipase inhibition activity were highlighted.

  1. Physicochemical analyses of a bioactive 4-aminoantipyrine analogue - synthesis, crystal structure, solid state interactions, antibacterial, conformational and docking studies

    Science.gov (United States)

    Alam, Mohammad Sayed; Lee, Dong-Ung

    2016-01-01

    , and positions involved in ligand-receptor interactions. Finally, the torsion energies of crystal structure and optimized and bioactive conformers of MBA-dMPP were compared to predict its bioactive conformation. PMID:28096791

  2. Physicochemical analyses of a bioactive 4-aminoantipyrine analogue - synthesis, crystal structure, solid state interactions, antibacterial, conformational and docking studies.

    Science.gov (United States)

    Alam, Mohammad Sayed; Lee, Dong-Ung

    2016-01-01

    potentials, and positions involved in ligand-receptor interactions. Finally, the torsion energies of crystal structure and optimized and bioactive conformers of MBA-dMPP were compared to predict its bioactive conformation.

  3. Enhanced molecular dynamics sampling of drug target conformations.

    Science.gov (United States)

    Rodriguez-Bussey, Isela G; Doshi, Urmi; Hamelberg, Donald

    2016-01-01

    Computational docking and virtual screening are two main important methods employed in structure-based drug design. Unlike the traditional approach that allows docking of a flexible ligand against a handful of receptor structures, receptor flexibility has now been appreciated and increasingly incorporated in computer-aided docking. Using a diverse set of receptor conformations increases the chances of finding potential drugs and inhibitors. Molecular dynamics (MD) is greatly useful to generate various receptor conformations. However, the diversity of the structures of the receptor, which is usually much larger than the ligand, depends on the sampling efficiency of MD. Enhanced sampling methods based on accelerated molecular dynamics (aMD) can alleviate the sampling limitation of conventional MD and aid in representation of the phase space to a much greater extent. RaMD-db, a variant of aMD that applies boost potential to the rotatable dihedrals and non-bonded diffusive degrees of freedom has been proven to reproduce the equilibrium properties more accurately and efficiently than aMD. Here, we discuss recent advances in the aMD methodology and review the applicability of RaMD-db as an enhanced sampling method. RaMD-db is shown to be able to generate a broad distribution of structures of a drug target, Cyclophilin A. These structures that have never been observed previously in very long conventional MD can be further used for structure-based computer-aided drug discovery, and docking, and thus, in the identification and design of potential novel inhibitors.

  4. Molecular dynamics simulation study on zwitterionic structure to maintain the normal conformations of Glutathione

    Institute of Scientific and Technical Information of China (English)

    YAN; Han; ZHU; HaoMiao; SHEN; Jian

    2007-01-01

    Molecular dynamics simulations were applied to normal conformational Glutathione (GSH) and GSH over zwitterionic and hydrophobic surfaces respectively. Conformational analysis of GSH during the simulation time on RMSD, conformational flexibility and dihedral distribution were performed. The results showed that zwitterionic structure maintains the normal conformations of GSH to a better extent, which should be a first good proof of the hypothesis of "maintain of normal structure".

  5. Conformational analysis of methylphenidate: comparison of molecular orbital and molecular mechanics methods

    Science.gov (United States)

    Gilbert, Kathleen M.; Skawinski, William J.; Misra, Milind; Paris, Kristina A.; Naik, Neelam H.; Buono, Ronald A.; Deutsch, Howard M.; Venanzi, Carol A.

    2004-11-01

    Methylphenidate (MP) binds to the cocaine binding site on the dopamine transporter and inhibits reuptake of dopamine, but does not appear to have the same abuse potential as cocaine. This study, part of a comprehensive effort to identify a drug treatment for cocaine abuse, investigates the effect of choice of calculation technique and of solvent model on the conformational potential energy surface (PES) of MP and a rigid methylphenidate (RMP) analogue which exhibits the same dopamine transporter binding affinity as MP. Conformational analysis was carried out by the AM1 and AM1/SM5.4 semiempirical molecular orbital methods, a molecular mechanics method (Tripos force field with the dielectric set equal to that of vacuum or water) and the HF/6-31G* molecular orbital method in vacuum phase. Although all three methods differ somewhat in the local details of the PES, the general trends are the same for neutral and protonated MP. In vacuum phase, protonation has a distinctive effect in decreasing the regions of space available to the local conformational minima. Solvent has little effect on the PES of the neutral molecule and tends to stabilize the protonated species. The random search (RS) conformational analysis technique using the Tripos force field was found to be capable of locating the minima found by the molecular orbital methods using systematic grid search. This suggests that the RS/Tripos force field/vacuum phase protocol is a reasonable choice for locating the local minima of MP. However, the Tripos force field gave significantly larger phenyl ring rotational barriers than the molecular orbital methods for MP and RMP. For both the neutral and protonated cases, all three methods found the phenyl ring rotational barriers for the RMP conformers/invertamers (denoted as cte, tte, and cta) to be: cte, tte> MP > cta. Solvation has negligible effect on the phenyl ring rotational barrier of RMP. The B3LYP/6-31G* density functional method was used to calculate the phenyl

  6. Molecular cloning, in vitro expression and bioactivity of quail BAFF.

    Science.gov (United States)

    Chen, Chuan-mei; Ren, Wen-hua; Yang, Guang; Zhang, Chuan-song; Zhang, Shuang-quan

    2009-07-15

    B cell activating factor (BAFF), belonging to the TNF (tumor necrosis factor) family, is critical for B cell survival and maturation. In the present study, a quail BAFF cDNA, named qBAFF, was amplified from quail spleen by RT-PCR and RACE (rapid amplification of cDNA ends) strategies. The open reading frame (ORF) of qBAFF cDNA encodes a protein consisting of 288-amino acid. The deduced amino acid sequence contains a predicted transmembrane domain and a putative furin protease cleavage site like other identified BAFF homologues. The qBAFF shows 96, 93, 93, 53 and 51% amino acid sequence identity with chicken (cBAFF), goose (gBAFF), duck (dBAFF), human (hBAFF) and mouse BAFF (mBAFF), respectively, with the functional soluble parts of qBAFF is 98, 99, 98, 78 and 71%, respectively. RT-PCR showed that BAFF is expressed in many tissues in the quail, including bursa, spleen, liver, brain, heart, intestine, kidney, thymus and muscle. Recombinant soluble qBAFF (qsBAFF) fused with His(6) tag was efficiently expressed in Escherichia coli BL21 (DE3) and its molecular weight of approximately 19kDa was identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. In vitro, purified qsBAFF was able to promote the survival of quail bursa B cells. Our results suggest that qBAFF plays an important role in survival of quail B cells cultured in vitro.

  7. Electrospinning of gelatin for tissue engineering--molecular conformation as one of the overlooked problems.

    Science.gov (United States)

    Sajkiewicz, P; Kołbuk, D

    2014-01-01

    Gelatin is one of the most promising materials in tissue engineering as a scaffold component. This biopolymer indicates biocompatibility and bioactivity caused by the existence of specific amino acid sequences, being preferred sites for interactions with cells, with high similarity to natural extracellular matrix. The present paper does not aspire to be a full review of electrospinning of gelatin and gelatin containing nanofibers as scaffolds in tissue engineering. It is focused on the still open question of the role of the higher order structures of gelatin in scaffold's bioactivity/functionality. Gelatin molecules can adopt various conformations depending on temperature, solvent, pH, etc. Our review indicates the potential ways for formation of α-helix conformation during electrospinning and the methods of further structure stabilization. It is intuitively expected that the native α-helix conformation appearing as a result of partial renaturation of gelatin can be beneficial from the viewpoint of bioactivity of scaffolds, providing thus a much cheaper alternative approach as opposed to expensive electrospinning of native collagen.

  8. Systematic Assessment of Molecular Selectivity at the Level of Targets, Bioactive Compounds, and Structural Analogues.

    Science.gov (United States)

    Hu, Ye; Bajorath, Jürgen

    2016-06-20

    Through systematic mining of compound activity data, the target selectivity of bioactive compounds was systematically explored. The analysis was facilitated by applying, extending, and combining the concepts of target cliffs, selectivity cliffs, and matched molecular pairs. Selectivity relationships were explored at different levels including targets, individual bioactive compounds, and pairs of structural analogues. A variety of targets were identified for which active compounds were consistently nonselective or, by contrast, exclusively selective, making it possible to prioritize, or de-prioritize, targets for compound development. Furthermore, many chemical modifications were detected that altered compound selectivity in a well-defined manner including small structural changes that converted nonselective into target-selective compounds or inverted the target selectivity of active compounds. A large knowledge base of selectivity relationships across pharmaceutical targets and chemical modifications that alter selectivity was generated; this has been made freely available to the scientific community as a part of this investigation.

  9. Various conformations of carbon nanocoils prepared by supported Ni-Fe/molecular sieve catalyst.

    Science.gov (United States)

    Yang, Shaoming; Chen, Xiuqin; Takeuchi, K; Motojima, Seiji

    2006-01-01

    The carbon nanocoils with various kinds of conformations were prepared by the catalytic pyrolysis of acetylene using the Ni metal catalyst supported on molecular Sieves which was prepared using Fe-containing kaolin as the raw material. There are four kinds of carbon nanocoils conformations produced by this catalyst. The influences of reaction temperature and gas conditions on the conformations of the nanocoils were investigated and the reasons of forming nano-size coils were discussed by comparison with pure Ni metal catalyst.

  10. Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations.

    Science.gov (United States)

    Koldsø, Heidi; Autzen, Henriette Elisabeth; Grouleff, Julie; Schiøtt, Birgit

    2013-01-01

    The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design.

  11. Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Heidi Koldsø

    Full Text Available The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design.

  12. [Conformation motion equation and primitive molecular machines for electron (ion) transport in biological systems].

    Science.gov (United States)

    Shaĭtan, K V; Rubin, A B

    1982-01-01

    A general theory of electron-conformation interactions and correlation between electron transfer rates and conformational mobility are discussed on the basis of a stochastic model of protein dynamics. A set of equations is developed and solved for primitive molecular "machines". Estimation of structural parameters for the reduction of the secondary acceptor in bacterial photosynthesis is given.

  13. First steps towards conformationally selective artificial lectins: the chair-boat discrimination by molecularly imprinted polymers.

    Science.gov (United States)

    de Talancé, Vincent Lemau; Massinon, Olivier; Baati, Rachid; Wagner, Alain; Vincent, Stéphane P

    2012-11-07

    A series of molecularly imprinted polymers (MIPs) were prepared in the presence of a synthetic galactoside locked in a (1,4)B boat conformation. This study demonstrates that, depending on the polymerisation technique, an organic material can selectively bind a carbohydrate in a biologically relevant boat conformation.

  14. Milk proteins-derived bioactive peptides in dairy products: molecular, biological and methodological aspects

    Directory of Open Access Journals (Sweden)

    Bartłomiej Dziuba

    2014-03-01

    Full Text Available Proteins are one of the primary components of the food, both in terms of nutrition and function. They are main source of amino acids, essential for synthesis of proteins, and also source of energy. Additionally, many proteins exhibit specifi c biological activities, which may have effect on functional or pro-health properties of food products. These proteins and their hydrolysis products, peptides, may infl uence the properties of food and human organism. The number of commercially available food products containing bioactive peptides is very low, apart from that milk proteins are their rich source. It could be supposed that number of available products with declared activity will rise in near future because of observed strong uptrend on interest in such products. Molecular and biological properties of milk proteins, as precursors of bioactive peptides was characterised in the work. Therefore, the strategy of research and obtaining of such peptides both in laboratory and industrial scale, as well as the range of their commercial application, was presented. Several examples of research efforts presenting high potential to develop new products containing bioactive peptides from milk proteins and predetermined as nutraceuticals was described.

  15. Milk proteins-derived bioactive peptides in dairy products: molecular, biological and methodological aspects.

    Science.gov (United States)

    Dziuba, Bartłomiej; Dziuba, Marta

    2014-01-01

    Proteins are one of the primary components of the food, both in terms of nutrition and function. They are main source of amino acids, essential for synthesis of proteins, and also source of energy. Additionally, many proteins exhibit specific biological activities, which may have effect on functional or pro-health properties of food products. These proteins and their hydrolysis products, peptides, may influence the properties of food and human organism. The number of commercially available food products containing bioactive peptides is very low, apart from that milk proteins are their rich source. It could be supposed that number of available products with declared activity will rise in near future because of observed strong uptrend on interest in such products. Molecular and biological properties of milk proteins, as precursors of bioactive peptides was characterised in the work. Therefore, the strategy of research and obtaining of such peptides both in laboratory and industrial scale, as well as the range of their commercial application, was presented. Several examples of research efforts presenting high potential to develop new products containing bioactive peptides from milk proteins and predetermined as nutraceuticals was described.

  16. Low molecular weight phenols from the bioactive aqueous fraction of Cestrum parqui.

    Science.gov (United States)

    D'Abrosca, Brigida; DellaGreca, Marina; Fiorentino, Antonio; Monaco, Pietro; Zarrelli, Armando

    2004-06-30

    The aqueous fraction of fresh leaves of Cestrum parqui and its organic fractions have been assayed for their phytotoxicity on Lactuca sativa, Lycopersicon esculentum, and Allium cepa. The tests showed that the bioactivity was retained in the organic fractions. Chromatographic processes led to isolation and characterization of the N-(p-carboxymethylphenyl)-p-hydroxybenzamide together with 17 low molecular weight phenols and 2 flavones. The phytotoxicity tests showed a good activity of these compounds on the target species. Comparison of some metabolites with commercial herbicides revealed a major activity of the natural compounds at lower concentrations.

  17. A phenomenological relationship between molecular geometry change and conformational energy change

    Science.gov (United States)

    Bodi, Andras; Bjornsson, Ragnar; Arnason, Ingvar

    2010-08-01

    A linear correlation is established between the change in the axial/equatorial conformational energy difference and the change in the molecular geometry transformation during conformational inversion in substituted six-membered ring systems, namely in the 1-substituted cyclohexane/silacyclohexane, cyclohexane/ N-substituted piperidine and 1-substituted silacyclohexane/ P-substituted phosphorinane compound families, and for the analogous gauche/anti conformational isomerism in 1-substituted propanes/1-silapropanes. The nuclear repulsion energy parameterizes the molecular geometry, and changes in the conformational energy between the related compound families are linearly correlated with the changes in the nuclear repulsion energy difference based on DFT (B3LYP, M06-2X), G3B3, and CBS-QB3 calculations. This correlation reproduces the sometimes remarkable contrast between the conformational behavior of analogous compounds, e.g., the lack of a general equatorial preference in silacyclohexanes.

  18. Stereoelectronic effects dictate molecular conformation and biological function of heterocyclic amides.

    Science.gov (United States)

    Reid, Robert C; Yau, Mei-Kwan; Singh, Ranee; Lim, Junxian; Fairlie, David P

    2014-08-27

    Heterocycles adjacent to amides can have important influences on molecular conformation due to stereoelectronic effects exerted by the heteroatom. This was shown for imidazole- and thiazole-amides by comparing low energy conformations (ab initio MP2 and DFT calculations), charge distribution, dipole moments, and known crystal structures which support a general principle. Switching a heteroatom from nitrogen to sulfur altered the amide conformation, producing different three-dimensional electrostatic surfaces. Differences were attributed to different dipole and orbital alignments and spectacularly translated into opposing agonist vs antagonist functions in modulating a G-protein coupled receptor for inflammatory protein complement C3a on human macrophages. Influences of the heteroatom were confirmed by locking the amide conformation using fused bicyclic rings. These findings show that stereoelectronic effects of heterocycles modulate molecular conformation and can impart strikingly different biological properties.

  19. De novo designed coiled-coil proteins with variable conformations as components of molecular electronic devices.

    Science.gov (United States)

    Shlizerman, Clara; Atanassov, Alexander; Berkovich, Inbal; Ashkenasy, Gonen; Ashkenasy, Nurit

    2010-04-14

    Conformational changes of proteins are widely used in nature for controlling cellular functions, including ligand binding, oligomerization, and catalysis. Despite the fact that different proteins and artificial peptides have been utilized as electron-transfer mediators in electronic devices, the unique propensity of proteins to switch between different conformations has not been used as a mechanism to control device properties and performance. Toward this aim, we have designed and prepared new dimeric coiled-coil proteins that adopt different conformations due to parallel or antiparallel relative orientations of their monomers. We show here that controlling the conformation of these proteins attached as monolayers to gold, which dictates the direction and magnitude of the molecular dipole relative to the surface, results in quantitative modulation of the gold work function. Furthermore, charge transport through the proteins as molecular bridges is controlled by the different protein conformations, producing either rectifying or ohmic-like behavior.

  20. Structural determination of molecular stereochemistry using VCD spectroscopy and a conformational code: absolute configuration and solution conformation of a chiral liquid pesticide, (R)-(+)-malathion.

    Science.gov (United States)

    Izumi, Hiroshi; Ogata, Atsushi; Nafie, Laurence A; Dukor, Rina K

    2009-01-01

    The absolute configuration and solution conformation of (R)-(+)-malathion were determined by using vibrational circular dichroism spectroscopy and a fragment-conformational search with a recently published conformational code. The determination of molecular stereochemistry was carried out without a conformational search using molecular mechanics calculations. Density functional theory calculations of the fragments of (R)-malathion, ethyl propionate, (R)-ethyl 2-(methylthio)propanoate, (R)-diethyl 2-(methylthio)succinate, and O,O,S-trimethyl phosphorodithioate were carried out, and the principal conformational features of the fragments were profiled. This fragment-conformational search reduces the time needed for the selection of the predominant conformations for (R)-malathion and significantly improves the accuracy of the determination of absolute configuration.

  1. Molecular, chemical and biological screening of soil actinomycete isolates in seeking bioactive peptide metabolites

    Directory of Open Access Journals (Sweden)

    Javad Hamedi

    2015-10-01

    Full Text Available Background and Objective: Due to the evolution of multidrug-resistant strains, screening of natural resources, especially actinomycetes, for new therapeutic agents discovery has become the interests of researchers. In this study, molecular, chemical and biological screening of soil actinomycetes was carried out in order to search for peptide-producing actinomycetes.Materials and Methods: 60 actinomycetes were isolated from soils of Iran. The isolates were subjected to molecular screening for detection NRPS (non-ribosomal peptide synthetases gene. Phylogenic identification of NRPS containing isolates was performed. Chemical screening of the crude extracts was performed using chlorine o-dianisidine as peptide detector reagent and bioactivity of peptide producing strains was determined by antimicrobial bioassay. High pressure liquid chromatography- mass spectrometry (HPLC-MS with UV-visible spectroscopy was performed for detection of the metabolite diversity in selected strain.Results: Amplified NRPS adenylation gene (700 bp was detected among 30 strains. Phylogenic identification of these isolates showed presence of rare actinomycetes genera among the isolates and 10 out of 30 strains were subjected to chemical screening. Nocardia sp. UTMC 751 showed antimicrobial activity against bacterial and fungal test pathogens. HPLC-MSand UV-visible spectroscopy results from the crude extract showed that this strain has probably the ability to produce new metabolites.Conclusion: By application of a combined approach, including molecular, chemical and bioactivity analysis, a promising strain of Nocardia sp. UTMC 751 was obtained. This strain had significant activity against Staphylococcus aureus and Pseudomonas aeruginosa. Strain Nocardia sp. UTMC 751 produce five unknown and most probably new metabolites with molecular weights of 274.2, 390.3, 415.3, 598.4 and 772.5. This strain had showed 99% similarity to Nocardia ignorata DSM 44496 T.

  2. Probing flexible conformations in molecular junctions by inelastic electron tunneling spectroscopy

    Directory of Open Access Journals (Sweden)

    Mingsen Deng

    2015-01-01

    Full Text Available The probe of flexible molecular conformation is crucial for the electric application of molecular systems. We have developed a theoretical procedure to analyze the couplings of molecular local vibrations with the electron transportation process, which enables us to evaluate the structural fingerprints of some vibrational modes in the inelastic electron tunneling spectroscopy (IETS. Based on a model molecule of Bis-(4-mercaptophenyl-ether with a flexible center angle, we have revealed and validated a simple mathematical relationship between IETS signals and molecular angles. Our results might open a route to quantitatively measure key geometrical parameters of molecular junctions, which helps to achieve precise control of molecular devices.

  3. Influence of Molecular Solvation on the Conformation of Star Polymers

    CERN Document Server

    Li, Xin; Sánchez-Diáz, Luis E; Do, Changwoo; Liu, Yun; Kim, Tae-Hwan; Smith, Gregory S; Hamilton, William A; Hong, Kunlun; Chen, Wei-Ren

    2014-01-01

    We have used neutron scattering to investigate the influence of concentration on the conformation of a star polymer. By varying the contrast between the solvent and isotopically labeled stars, we obtain the distributions of polymer and solvent within a star polymer from analysis of scattering data. A correlation between the local desolvation and the inward folding of star branches is discovered. From the perspective of thermodynamics, we find an analogy between the mechanism of polymer localization driven by solvent depletion and that of the hydrophobic collapse of polymers in solutions.

  4. Modeling and analysis of Schistosoma Argonaute protein molecular spatial conformation

    Institute of Scientific and Technical Information of China (English)

    Jianhua Zhang; Zhigang Shang; Xiaohui Zhang; Yuntao Zhang

    2011-01-01

    Objective: To analyze the amino acid sequence composition, secondary structure, the spatial conformation of its domain and other characteristics of Argonaute protein. Methods:Bioinformatics tools and the internet server were used. Firstly, the amino acid sequence composition features of the Argonaute protein were analyzed, and the phylogenetic tree was constructed. Secondly, Argonaute protein’s distribution of secondary structure and its physicochemical properties were predicted. Lastly, the protein functional expression form of the domain group was established through the Phyre-based analysis on the spatial conformation of Argonaute protein domains. Results: 593 amino acids were encoded by Argonaute protein, the phylogenetic tree was constructed, and Argonaute protein’s distribution of secondary structure and its physicochemical properties were obtained through analysis. In addition, the functional expression form which comprised the N-terminal PAZ domain and C-terminal Piwi domain for the Argonaute protein was obtained with Phyre. Conclusions: The information relationship between the structure and function of the Argonaute protein can be initially established with bioinformatics tools and the internet server, and this provides the theoretical basis for further clarifying the function of Schistosoma Argonaute protein.

  5. Isolation and molecular characterization of bioactive secondary metabolites fromCallyspongia spp. associated fungi

    Institute of Scientific and Technical Information of China (English)

    Meenupriya J; Thangaraj M

    2010-01-01

    Objective:To isolate and characterize the bioactive secondary metabolite fromCallyspongia spp. associated fungi.Methods:In vitro antibacterial screening of fungi associated with Callyspongia species, collected from south east coast of India, against selected clinical isolates of bacteria were conducted in this study. The extracts showing good antimicrobial activity were subjected to further analysis to identify the active constituents sponge associated fungi (both biomass and filtrate) with five different solvents. The compound responsible for bioactivity was characterized using Fouvier-transform infrared (FT-IR) and gas chromatography-mass spectrometry(GC-MS) instrumental analysis to identify the functional group and compound. The molecular characterization of the elite fungal strains were done by isolating their genomicDNA and amplify the internal transcribed spacer(ITS) region of5.8srRNA using specific ITS primer. The novelty of the strain was proved by BlastN analysis against non-redundant(NR) database and hence was submitted to GenBank.Results: Active compound was Desmethylnomifensine confirmed byGC-MS and the potent fungi wasAspergillus flavusGU815344.Conclusions:The isolate exhibits a marked antagonistic activity against potential bacterial pathogens thus illuminating the advanced researches in this decade to focus on clinical pharmacology to identify novel therapeutic targets. The present study depicts a promising scenario to focus onAspergillus flavus derived compounds which can be easily scaled up for large biomass production and stable formulation as a drug.

  6. Extracting Conformational Ensembles of Small Molecules from Molecular Dynamics Simulations: Ampicillin as a Test Case

    Directory of Open Access Journals (Sweden)

    Giuliano Malloci

    2016-01-01

    Full Text Available The accurate and exhaustive description of the conformational ensemble sampled by small molecules in solution, possibly at different physiological conditions, is of primary interest in many fields of medicinal chemistry and computational biology. Recently, we have built an on-line database of compounds with antimicrobial properties, where we provide all-atom force-field parameters and a set of molecular properties, including representative structures extracted from cluster analysis over μs-long molecular dynamics (MD trajectories. In the present work, we used a medium-sized antibiotic from our sample, namely ampicillin, to assess the quality of the conformational ensemble. To this aim, we compared the conformational landscape extracted from previous unbiased MD simulations to those obtained by means of Replica Exchange MD (REMD and those originating from three freely-available conformer generation tools widely adopted in computer-aided drug-design. In addition, for different charge/protonation states of ampicillin, we made available force-field parameters and static/dynamic properties derived from both Density Functional Theory and MD calculations. For the specific system investigated here, we found that: (i the conformational statistics extracted from plain MD simulations is consistent with that obtained from REMD simulations; (ii overall, our MD-based approach performs slightly better than any of the conformer generator tools if one takes into account both the diversity of the generated conformational set and the ability to reproduce experimentally-determined structures.

  7. Molecular conformation and structural correlations of liquid D-1-propanol through neutron diffraction

    Indian Academy of Sciences (India)

    A Sahoo; S Sarkar; P S R Krishna; V Bhagat; R N Joarder

    2008-07-01

    An analysis of neutron diffraction data of liquid deuterated 1-propanol at room temperature to extract its molecular conformation is presented. Being a big molecule with twelve atomic sites, the analysis is tricky and needs careful consideration. The resulting molecular parameters are compared with electron diffraction (gas phase), X-ray diffraction (liquid phase) and MD simulation results. Information about the hydrogen-bonded intermolecular structure in liquid is extracted and nature of the probable molecular association suggested.

  8. Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

    Science.gov (United States)

    Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian

    2016-07-01

    The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of peptide conformations. These findings are consistent with experimental results, and give a molecular level interpretation for the reduced cytotoxicity of Vpr13-33 to some extent upon graphene exposure. Meanwhile, this study provides some significant insights into the detailed mechanism of graphene-induced protein conformation transition.

  9. Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules

    Directory of Open Access Journals (Sweden)

    Dorothy Moseti

    2016-01-01

    Full Text Available Adipogenesis is the process by which precursor stem cells differentiate into lipid laden adipocytes. Adipogenesis is regulated by a complex and highly orchestrated gene expression program. In mammalian cells, the peroxisome proliferator-activated receptor γ (PPARγ, and the CCAAT/enhancer binding proteins (C/EBPs such as C/EBPα, β and δ are considered the key early regulators of adipogenesis, while fatty acid binding protein 4 (FABP4, adiponectin, and fatty acid synthase (FAS are responsible for the formation of mature adipocytes. Excess accumulation of lipids in the adipose tissue leads to obesity, which is associated with cardiovascular diseases, type II diabetes and other pathologies. Thus, investigating adipose tissue development and the underlying molecular mechanisms is vital to develop therapeutic agents capable of curbing the increasing incidence of obesity and related pathologies. In this review, we address the process of adipogenic differentiation, key transcription factors and proteins involved, adipogenic regulators and potential anti-adipogenic bioactive molecules.

  10. Molecular Clustering Interrelationships and Carbohydrate Conformation in Hull and Seeds Among Barley Cultivars

    Energy Technology Data Exchange (ETDEWEB)

    N Liu; P Yu

    2011-12-31

    The objective of this study was to use molecular spectral analyses with the diffuse reflectance Fourier transform infrared spectroscopy (DRIFT) bioanlytical technique to study carbohydrate conformation features, molecular clustering and interrelationships in hull and seed among six barley cultivars (AC Metcalfe, CDC Dolly, McLeod, CDC Helgason, CDC Trey, CDC Cowboy), which had different degradation kinetics in rumen. The molecular structure spectral analyses in both hull and seed involved the fingerprint regions of ca. 1536-1484 cm{sup -1} (attributed mainly to aromatic lignin semicircle ring stretch), ca. 1293-1212 cm{sup -1} (attributed mainly to cellulosic compounds in the hull), ca. 1269-1217 cm{sup -1} (attributed mainly to cellulosic compound in the seeds), and ca. 1180-800 cm{sup -1} (attributed mainly to total CHO C-O stretching vibrations) together with an agglomerative hierarchical cluster (AHCA) and principal component spectral analyses (PCA). The results showed that the DRIFT technique plus AHCA and PCA molecular analyses were able to reveal carbohydrate conformation features and identify carbohydrate molecular structure differences in both hull and seeds among the barley varieties. The carbohydrate molecular spectral analyses at the region of ca. 1185-800 cm{sup -1} together with the AHCA and PCA were able to show that the barley seed inherent structures exhibited distinguishable differences among the barley varieties. CDC Helgason had differences from AC Metcalfe, MeLeod, CDC Cowboy and CDC Dolly in carbohydrate conformation in the seed. Clear molecular cluster classes could be distinguished and identified in AHCA analysis and the separate ellipses could be grouped in PCA analysis. But CDC Helgason had no distinguished differences from CDC Trey in carbohydrate conformation. These carbohydrate conformation/structure difference could partially explain why the varieties were different in digestive behaviors in animals. The molecular spectroscopy

  11. Conformational and functional analysis of molecular dynamics trajectories by Self-Organising Maps

    Directory of Open Access Journals (Sweden)

    Stella Fabio

    2011-05-01

    Full Text Available Abstract Background Molecular dynamics (MD simulations are powerful tools to investigate the conformational dynamics of proteins that is often a critical element of their function. Identification of functionally relevant conformations is generally done clustering the large ensemble of structures that are generated. Recently, Self-Organising Maps (SOMs were reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data mining problems. We present a novel strategy to analyse and compare conformational ensembles of protein domains using a two-level approach that combines SOMs and hierarchical clustering. Results The conformational dynamics of the α-spectrin SH3 protein domain and six single mutants were analysed by MD simulations. The Cα's Cartesian coordinates of conformations sampled in the essential space were used as input data vectors for SOM training, then complete linkage clustering was performed on the SOM prototype vectors. A specific protocol to optimize a SOM for structural ensembles was proposed: the optimal SOM was selected by means of a Taguchi experimental design plan applied to different data sets, and the optimal sampling rate of the MD trajectory was selected. The proposed two-level approach was applied to single trajectories of the SH3 domain independently as well as to groups of them at the same time. The results demonstrated the potential of this approach in the analysis of large ensembles of molecular structures: the possibility of producing a topological mapping of the conformational space in a simple 2D visualisation, as well as of effectively highlighting differences in the conformational dynamics directly related to biological functions. Conclusions The use of a two-level approach combining SOMs and hierarchical clustering for conformational analysis of structural ensembles of proteins was proposed. It can easily be extended to other study cases and to

  12. Molecular conformation and liquid structure of 2-propanol through neutron diffraction

    Indian Academy of Sciences (India)

    A Sahoo; S Sarkar; P S R Krishna; R N Joarder

    2010-05-01

    The neutron diffraction data analysis of deuterated liquid 2-propanol at room temperature to define its molecular conformation is presented. 2-Propanol being a large molecule with twelve atomic sites, the conformation analysis is tricky and an improved method of data analysis is given. The intermolecular structural correlations, i.e., hydrogen-bonded liquid structure, can be modelled accurately to extract the nature of the average hydrogen-bonded molecular association in liquid state at room temperature. Like other alcohols these are mostly hexamer ring chain (HRC) clusters. The cluster analysis of recent X-ray data available in the literature also support the same liquid structure.

  13. Conformational study of acyclic alcohols by NMR spectroscopic analysis, molecular force field and Ab initio calculations

    Energy Technology Data Exchange (ETDEWEB)

    Abe, K.; Ito, K.; Suezawa, H.; Hirota, M.; Nishio, M.

    1986-10-01

    Conformations of a series of acyclic alcohols (CH/sub 3/CH(R)CH(OH)CH/sub 3/, CH/sub 3/CH(R)CH(OH)CH(R')CH/sub 3/, and CH/sub 3/CH(R)CH(OH)Bu/sup t/) were studied (1) by measuring vicinal H-H coupling constants (/sup 3/JH-H), (2) by lanthanoid-induced shift (LIS) analysis, (3) by molecular mechanics calculations (MM2), and (4) by ab initio (STO-3G, 4-31G geometry optimization) calculations. In the case of conformationally flexible alcohols as exemplified by 2-butanol and 3-pentanol, population of conformers determined by the LIS method do not agree with those determined by the /sup 3/JH-H, MM2, and ab initio methods. The discrepancy comes from the fact that the LIS measurement gives the most stable conformation of the alcohol in the LSR-alcohol complex and not of the free alcohol. In some flexible molecules, the most stable conformer in the complex can be different from that of the free molecule. In general, the conformational equilibrium is shifted by coordination of the shift reagent to the conformer whose alkyl chain stretches opposite to the direction of the coordination site of the shift reagent. 21 references, 1 figure, 6 tables.

  14. Conformational analysis of 2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) by NMR and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Marcelle de S.; Figueroa-Villar, Jose D., E-mail: jdfv2009@gmail.com [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Dept. de Quimica. Grupo de Medicina Quimica

    2014-05-15

    2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-ones) with para and ortho-R groups on the benzene ring were prepared and studied by nuclear magnetic resonance (NMR) and molecular modeling to determine their conformational exchanges. Experimental and calculated results indicated conformational interconversions in these compounds by rotation of benzene ring and slow movement of dimedone rings, leading to intramolecular hydrogen bond length variation. The presence of one R group at the ortho position on the benzene ring modifies conformational exchange, leading to disappearance of one intramolecular hydrogen bond and superposition of diverse NMR signals. The correlation of σ{sub p} values with chemical shifts, angles and atomic charges confirms that para-R groups electronic properties are involved in conformational exchange and chemical shift variance. These results will be used to study the interaction of these compounds with bio-molecules and their use as starting materials for design and synthesis of new bioactive agents. (author)

  15. Conformational space of clindamycin studied by ab initio and full-atom molecular dynamics.

    Science.gov (United States)

    Kulczycka-Mierzejewska, Katarzyna; Trylska, Joanna; Sadlej, Joanna

    2016-01-01

    Molecular dynamics (MD) simulations allow determining internal flexibility of molecules at atomic level. Using ab initio Born-Oppenheimer molecular dynamics (BOMD), one can simulate in a reasonable time frame small systems with hundreds of atoms, usually in vacuum. With quantum mechanics/molecular mechanics (QM/MM) or full-atom molecular dynamics (FAMD), the influence of the environment can also be simulated. Here, we compare three types of MD calculations: ab initio BOMD, hybrid QM/MM, and classical FAMD. As a model system, we use a small antibiotic molecule, clindamycin, which is one of the lincosamide antibiotics. Clindamycin acquires two energetically stable forms and we investigated the transition between these two experimentally known conformers. We performed 60-ps BOMD simulations in vacuum, 50-ps QM/MM, and 100-ns FAMD in explicit water. The transition between two antibiotic conformers was observed using both BOMD and FAMD methods but was not noted in the QM/MM simulations.

  16. Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms.

    Science.gov (United States)

    Mori, Takaharu; Miyashita, Naoyuki; Im, Wonpil; Feig, Michael; Sugita, Yuji

    2016-07-01

    This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.

  17. Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian, E-mail: jianzhou@scut.edu.cn

    2016-07-30

    Graphical abstract: Preferential adsorption of Vpr13-33 on graphene accompanied by early conformational change from α-helix to β-sheet structures was observed by molecular simulations. This work presents the molecular mechanism of graphene-induced peptide conformational alteration and sheds light on developing graphene-based materials to inhibit HIV. - Highlights: • Graphene induced early structural transition of Vpr13-33 is studied by MD simulations. • Both π-π stacking and hydrophobic interactions orchestrate the peptide adsorption. • Vpr has an increased propensity of β-sheet content on graphene surface. • To develop graphene-based materials to inhibit HIV is possible. - Abstract: The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of

  18. Parallel Cascade Selection Molecular Dynamics (PaCS-MD) to generate conformational transition pathway.

    Science.gov (United States)

    Harada, Ryuhei; Kitao, Akio

    2013-07-21

    Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of "reactant" and "product" structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways.

  19. Coupling between internal dynamics and rotational diffusion in the presence of exchange between discrete molecular conformations.

    Science.gov (United States)

    Ryabov, Yaroslav; Clore, G Marius; Schwieters, Charles D

    2012-01-21

    We present a general formalism for the computation of orientation correlation functions involving a molecular system undergoing rotational diffusion in the presence of transitions between discrete conformational states. In this formalism, there are no proscriptions on the time scales of conformational rearrangement relative to that for rotational diffusion, and the rotational diffusion tensors of the different states can be completely arbitrary. Although closed-form results are limited to the frequency domain, this is generally useful for many spectroscopic observables as the result allows the computation of the spectral density function. We specialize the results for the computation of the frequency-domain correlation function associated with the NMR relaxation.

  20. DFT molecular modeling and NMR conformational analysis of a new longipinenetriolone diester

    Science.gov (United States)

    Cerda-García-Rojas, Carlos M.; Guerra-Ramírez, Diana; Román-Marín, Luisa U.; Hernández-Hernández, Juan D.; Joseph-Nathan, Pedro

    2006-05-01

    The structure and conformational behavior of the new natural compound (4 R,5 S,7 S,8 R,9 S,10 R,11 R)-longipin-2-en-7,8,9-triol-1-one 7-angelate-9-isovalerate (1) isolated from Stevia eupatoria, were studied by molecular modeling and NMR spectroscopy. A Monte Carlo search followed by DFT calculations at the B3LYP/6-31G* level provided the theoretical conformations of the sesquiterpene framework, which were in full agreement with results derived from the 1H- 1H coupling constant analysis.

  1. Theoretical studies on the molecular structure, conformational preferences, topological and vibrational analysis of allicin

    Science.gov (United States)

    Durlak, Piotr; Berski, Sławomir; Latajka, Zdzisław

    2016-01-01

    The molecular structure, conformational preferences, topological and vibrational analysis of allicin has been investigated at two different approaches. Calculations have been carried out on static (DFT and MP2) levels with an assortment of Dunning's basis sets and dynamic CPMD simulations. In this both case within the isolated molecule approximation. The results point out that at least twenty different conformers coexist on the PES as confirmed by the flexible character of this molecule. The topological analysis of ELF showed very similar nature of the Ssbnd S and Ssbnd O bonds. The infrared spectrum has been calculated, and a comparative vibrational analysis has been performed.

  2. Study of Two Bioactive Peptides in Vacuum and Solvent by Molecular Modeling

    Science.gov (United States)

    Yaşar, F.; Demir, K.

    The thermodynamic and structural properties of Tyrosine-Glycine-Leusine-Phenylalanine (YGLF, in a one letter code) and Lysine-Valine-Leusine-Proline-Valine-Proline-Glutamine (KVLPVPQ) peptide sequences were studied by three-dimensional molecular modeling in vacuum and solution. All the three-dimensional conformations of each peptide sequences were obtained by multicanonical simulations with using ECEPP/2 force field and each simulation started from completely random initial conformation. Solvation contributions are included by a term that is proportional to solvent-accessible surface areas of peptides. In the present study, we calculated the average values of total energy, specific heat, fourth-order cumulant and end-to-end distance for two peptide sequences of milk protein as a function of temperature. With using major advantage of this simulation technique, Ramachandran plots were prepared and analysed to predict the relative occurrence probabilities of β-turn, γ-turn and helical structures. Although structural predictions of these sequences indicate both the presence of high level of γ-turns and low level of β-turns in vacuum and solvent, it was observed that these probabilities in vacuum were higher than the ones in solvent model.

  3. A molecular simulation study of the protection of insulin bioactive structure by trehalose.

    Science.gov (United States)

    Li, Daixi; Liu, Li; Yu, Huaxing; Zhai, Zhen; Zhang, Yan; Guo, Baisong; Yang, Chunsheng; Liu, Baolin

    2014-11-01

    Biopharmaceuticals are proteins with a crucial role in the treatment of many diseases. However, these protein medicines are often thermally labile and therefore unsuitable for long-term application and storage, as they tend to lose their activity under ambient conditions. Desiccation is one approach to improving protein stability, but the drying process itself can cause irreversible damage. In the current study, insulin was chosen as an example of a thermally sensitive biopharmaceutical to investigate whether the disaccharide, trehalose, can prevent loss of structural integrity due to drying. The experiment was performed using replica exchange molecular simulation and Gromacs software with a Gromos96 (53a6) force field. The results indicate that trehalose preserves the bioactive structure of insulin during drying, consistent with the use of trehalose as a protectant for thermally sensitive biopharmaceuticals. For instance, at the water content of 1.77%, insulin without any protectants yields the highest RMSD value as 0.451 nm, then the RMSD of insulin in presence of trehalose only ca. 0.100 nm.

  4. Impact of molecular weight on the formation of electrosprayed chitosan microcapsules as delivery vehicles for bioactive compounds.

    Science.gov (United States)

    Gómez-Mascaraque, Laura G; Sanchez, Gloria; López-Rubio, Amparo

    2016-10-01

    The molecular weight of chitosan is one of its most determinant characteristics, which affects its processability and its performance as a biomaterial. However, information about the effect of this parameter on the formation of electrosprayed chitosan microcapsules is scarce. In this work, the impact of chitosan molecular weight on its electrosprayability was studied and correlated with its effect on the viscosity, surface tension and electrical conductivity of solutions. A Discriminant Function Analysis revealed that the morphology of the electrosprayed chitosan materials could be correctly predicted using these three parameters for almost 85% of the samples. The suitability of using electrosprayed chitosan capsules as carriers for bioactive agents was also assessed by loading them with a model active compound, (-)-epigallocatechin gallate (EGCG). This encapsulation, with an estimated efficiency of around 80% in terms of preserved antioxidant activity, showed the potential to prolong the antiviral activity of EGCG against murine norovirus via gradual bioactive release combined with its protection against degradation in simulated physiological conditions.

  5. Finding Stable Graphene Conformations from Pull and Release Experiments with Molecular Dynamics

    Science.gov (United States)

    Yamaletdinov, Ruslan D.; Pershin, Yuriy V.

    2017-01-01

    Here, we demonstrate that stable conformations of graphene nanoribbons can be identified using pull and release experiments, when the stretching force applied to a single-layer graphene nanoribbon is suddenly removed. As it is follows from our numerical experiments performed by means of molecular dynamics simulations, in such experiments, favorable conditions for the creation of folded structures exist. Importantly, at finite temperatures, the process of folding is probabilistic. We have calculated the transition probabilities to folded conformations for a graphene nanoribbon of a selected size. Moreover, the ground state conformation has been identified and it is shown that its type is dependent on the nanoribbon length. We anticipate that the suggested pull and release approach to graphene folding may find applications in the theoretical studies and fabrication of emergent materials and their structures. PMID:28195156

  6. Molecular modeling of the conformational dynamics of the cellular prion protein

    Science.gov (United States)

    Nguyen, Charles; Colling, Ian; Bartz, Jason; Soto, Patricia

    2014-03-01

    Prions are infectious agents responsible for transmissible spongiform encephalopathies (TSEs), a type of fatal neurodegenerative disease in mammals. Prions propagate biological information by conversion of the non-pathological version of the prion protein to the infectious conformation, PrPSc. A wealth of knowledge has shed light on the nature and mechanism of prion protein conversion. In spite of the significance of this problem, we are far from fully understanding the conformational dynamics of the cellular isoform. To remedy this situation we employ multiple biomolecular modeling techniques such as docking and molecular dynamics simulations to map the free energy landscape and determine what specific regions of the prion protein are most conductive to binding. The overall goal is to characterize the conformational dynamics of the cell form of the prion protein, PrPc, to gain insight into inhibition pathways against misfolding. NE EPSCoR FIRST Award to Patricia Soto.

  7. Molecular mechanics approach for design and conformational studies of macrocyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Rohini,; Akbar, Rifat; Kanungo, B. K., E-mail: b.kanungo@gmail.com [Department of Chemistry, Sant Longowal Institute of Engineering & Technology, Longowal-148106 (India)

    2015-08-28

    Computational Chemistry has revolutionized way of viewing molecules at the quantum mechanical scale by allowing simulating various chemical scenarios that are not possible to study in a laboratory. The remarkable applications of computational chemistry have promoted to design and test of the effectiveness of various methods for searching the conformational space of highly flexible molecules. In this context, we conducted a series of optimization and conformational searches on macrocyclic based ligands, 9N3Me5Ox, (1,4,7-tris(5-methyl-8-hydroxyquinoline)-1,4,7-triazacyclononane) and 12N3Me5Ox, (1,5,9-tris(5-methyl-8-hydroxyquinoline)-1,5,9-triazacyclododecane) and studied their selectivity and coordination behavior with some lanthanide metal ions in molecular mechanics and semiempirical methods. The methods include both systematic and random conformational searches for dihedral angles, torsion angles and Cartesian coordinates. Structural studies were carried out by using geometry optimization, coordination scans and electronic properties were evaluated. The results clearly show that chair-boat conformational isomer of 9N3Me5Ox ligand is more stable due to lower eclipsing ethane interaction and form stronger adduct complexes with lanthanide metal ion. This is because of the fact that, in a central unit of 9N3 of the ligand form six endo type bonds out of nine. The rest of bonds have trans conformation. In contrast, for the adduct of 12N3Me5Ox, two C-C bonds have on eclipsed conformation, and others have synclinal and antiperiplanar confirmations. The distortion of the two eclipsed conformations may affect the yields and the stability of the complexes.

  8. Conformational preferences of proline derivatives incorporated into vasopressin analogues: NMR and molecular modelling studies.

    Science.gov (United States)

    Sikorska, Emilia; Sobolewski, Dariusz; Kwiatkowska, Anna

    2012-04-01

    In this study, arginine vasopressin analogues modified with proline derivatives - indoline-2-carboxylic acid (Ica), (2S,4R)-4-(naphthalene-2-ylmethyl)pyrrolidine-2-carboxylic acid (Nmp), (2S,4S)-4-aminopyroglutamic acid (APy) and (2R,4S)-4-aminopyroglutamic acid, (Apy) - were examined using NMR spectroscopy and molecular modelling methods. The results have shown that Ica is involved in the formation of the cis peptide bond. Moreover, it reduces to a great extent the conformational flexibility of the peptide. In turn, incorporation of (2S,4R)-Nmp stabilizes the backbone conformation, which is heavily influenced by the pyrrolidine ring. However, the aromatic part of the Nmp side chain exhibits a high degree of conformational freedom. With analogues IV and V, introduction of the 4-aminopyroglumatic acid reduces locally conformational space of the peptides, but it also results in weaker interactions with the dodecylphosphocholine/sodium dodecyl sulphate micelle. Admittedly, both analogues are adsorbed on the micelle's surface but they do not penetrate into its core. With analogue V, the interactions between the peptide and the micelle seem to be so weak that conformational equilibrium is established between different bound states.

  9. Molecular Dynamics Simulations of Insulin: Elucidating the Conformational Changes that Enable Its Binding.

    Directory of Open Access Journals (Sweden)

    Anastasios Papaioannou

    Full Text Available A sequence of complex conformational changes is required for insulin to bind to the insulin receptor. Recent experimental evidence points to the B chain C-terminal (BC-CT as the location of these changes in insulin. Here, we present molecular dynamics simulations of insulin that reveal new insights into the structural changes occurring in the BC-CT. We find three key results: 1 The opening of the BC-CT is inherently stochastic and progresses through an open and then a "wide-open" conformation--the wide-open conformation is essential for receptor binding, but occurs only rarely. 2 The BC-CT opens with a zipper-like mechanism, with a hinge at the Phe24 residue, and is maintained in the dominant closed/inactive state by hydrophobic interactions of the neighboring Tyr26, the critical residue where opening of the BC-CT (activation of insulin is initiated. 3 The mutation Y26N is a potential candidate as a therapeutic insulin analogue. Overall, our results suggest that the binding of insulin to its receptor is a highly dynamic and stochastic process, where initial docking occurs in an open conformation and full binding is facilitated through interactions of insulin receptor residues with insulin in its wide-open conformation.

  10. Parallel cascade selection molecular dynamics for efficient conformational sampling and free energy calculation of proteins

    Science.gov (United States)

    Kitao, Akio; Harada, Ryuhei; Nishihara, Yasutaka; Tran, Duy Phuoc

    2016-12-01

    Parallel Cascade Selection Molecular Dynamics (PaCS-MD) was proposed as an efficient conformational sampling method to investigate conformational transition pathway of proteins. In PaCS-MD, cycles of (i) selection of initial structures for multiple independent MD simulations and (ii) conformational sampling by independent MD simulations are repeated until the convergence of the sampling. The selection is conducted so that protein conformation gradually approaches a target. The selection of snapshots is a key to enhance conformational changes by increasing the probability of rare event occurrence. Since the procedure of PaCS-MD is simple, no modification of MD programs is required; the selections of initial structures and the restart of the next cycle in the MD simulations can be handled with relatively simple scripts with straightforward implementation. Trajectories generated by PaCS-MD were further analyzed by the Markov state model (MSM), which enables calculation of free energy landscape. The combination of PaCS-MD and MSM is reported in this work.

  11. Conformational studies of immunodominant myelin basic protein 1-11 analogues using NMR and molecular modeling.

    Science.gov (United States)

    Laimou, Despina; Lazoura, Eliada; Troganis, Anastassios N; Matsoukas, Minos-Timotheos; Deraos, Spyros N; Katsara, Maria; Matsoukas, John; Apostolopoulos, Vasso; Tselios, Theodore V

    2011-11-01

    Τwo dimensional nuclear magnetic resonance studies complimented by molecular dynamics simulations were conducted to investigate the conformation of the immunodominant epitope of acetylated myelin basic protein residues 1-11 (Ac-MBP(1-11)) and its altered peptide ligands, mutated at position 4 to an alanine (Ac-MBP(1-11)[4A]) or a tyrosine residue (Ac-MBP(1-11)[4Y]). Conformational analysis of the three analogues indicated that they adopt an extended conformation in DMSO solution as no long distance NOE connectivities were observed and seem to have a similar conformation when bound to the active site of the major histocompatibility complex (MHC II). The interaction of each peptide with MHC class II I-A(u) was further investigated in order to explore the molecular mechanism of experimental autoimmune encephalomyelitis induction/inhibition in mice. The present findings indicate that the Gln(3) residue, which serves as a T-cell receptor (TCR) contact site in the TCR/peptide/I-A(u) complex, has a different orientation in the mutated analogues especially in the Ac-MBP(1-11)[4A] peptide. In particular the side chain of Gln(3) is not solvent exposed as for the native Ac-MBP(1-11) and it is not available for interaction with the TCR.

  12. Exploring Ramachandran and chi space: conformationally constrained amino acids and peptides in the design of bioactive polypeptide ligands.

    Science.gov (United States)

    Cowell, S M; Lee, Y S; Cain, J P; Hruby, V J

    2004-11-01

    Ligand binding and concomitant changes in receptor structure provide the means to target signal transduction pathways. With appropriate refinement of the ligand's interaction with the "receptor," one in theory could produce ligands that have greater therapeutic benefits. This review will discuss how, when these ligands are amino acids and peptides, the introduction of appropriate conformational constraints provides a powerful strategy for improved drug design. This review will discuss how various constraints on amino acids can provide a powerful tool for ligand design, determination of the three dimensional pharmacophore and new insights into receptor systems and information transduction. Through the use of constrained ligands, new information regarding their interaction with their "receptor" systems, and further refinement of the use of constraints, scientists can produce more beneficial drugs for mankind.

  13. Determining molecular structures and conformations directly from electron diffraction using a genetic algorithm.

    Science.gov (United States)

    Habershon, Scott; Zewail, Ahmed H

    2006-02-13

    A global optimization strategy, based upon application of a genetic algorithm (GA), is demonstrated as an approach for determining the structures of molecules possessing significant conformational flexibility directly from gas-phase electron diffraction data. In contrast to the common approach to molecular structure determination, based on trial-and-error assessment of structures available from quantum chemical calculations, the GA approach described here does not require expensive quantum mechanical calculations or manual searching of the potential energy surface of the sample molecule, relying instead upon simple comparison between the experimental and calculated diffraction pattern derived from a proposed trial molecular structure. Structures as complex as all-trans retinal and p-coumaric acid, both important chromophores in photosensing processes, may be determined by this approach. In the examples presented here, we find that the GA approach can determine the correct conformation of a flexible molecule described by 11 independent torsion angles. We also demonstrate applications to samples comprising a mixture of two distinct molecular conformations. With these results we conclude that applications of this approach are very promising in elucidating the structures of large molecules directly from electron diffraction data.

  14. Conformational stability, spectroscopic and computational studies, HOMO-LUMO, NBO, ESP analysis, thermodynamic parameters of natural bioactive compound with anticancer potential of 2-(hydroxymethyl)anthraquinone.

    Science.gov (United States)

    Balachandran, V; Karpagam, V; Revathi, B; Kavimani, M; Ilango, G

    2015-11-05

    Natural product drugs play a dominant role in pharmaceutical care. Nature is an attractive source of new therapeutic candidate compounds as a tremendous chemical diversity is found in millions of species of plants, animals, marine organism and micro-organism. A antifungal activity against important opportunist micro-organism and against those involved in superficial mycosis, all from nosocomial origin. The acute in vitro cytotoxicity evaluation of each anthraquinone (AQ) isolated from these bioactive extracts, on a mammalian eukaryotic cell line (Vero cells), allowed us to establish the non-cytotoxic concentration range, which was used to evaluate the anti-microbial effect. A comprehensive ab initio calculation using the DFT/6-31+G(d) level theory showed that 2-(hydroxymethyl)anthraquinone can exist in four possible conformations, which can interchange through the OH group on the five-membered ring. Density functional theory calculations were used to predict the vibrational frequencies and to help in normal mode, assignments. Furthermore, a natural bond orbital analysis was performed describing each hydrogen bond as donor accepter interaction. The Fourier transform infrared spectra (4000-400 cm(-1)) and the Fourier transform Raman spectra (3500-100 cm(-1)) of the HMA in the solid space have been recorded. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecule. The calculated ESP contour map shows the electrophilic and nucleophilic region of the molecule.

  15. Investigation of the molecular conformations of ethanol using electron momentum spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Ning, C G; Luo, Z H; Huang, Y R; Liu, K; Zhang, S F; Deng, J K [Department of Physics and Key Laboratory of Atomic and Molecular NanoSciences of MOE, Tsinghua University, Beijing 100084 (China); Hajgato, B; Morini, F; Deleuze, M S [Research Group of Theoretical Chemistry, Department SBG, Hasselt University, Agoralaan Gebouw D, B-3590 Diepenbeek (Belgium)], E-mail: ningcg@tsinghua.edu.cn, E-mail: djk-dmp@tsinghua.edu.cn, E-mail: michael.deleuze@uhasselt.be

    2008-09-14

    The valence electronic structure and momentum-space electron density distributions of ethanol have been investigated with our newly constructed high-resolution electron momentum spectrometer. The measurements are compared to thermally averaged simulations based on Kohn-Sham (B3LYP) orbital densities as well as one-particle Green's function calculations of ionization spectra and Dyson orbital densities, assuming Boltzmann's statistical distribution of the molecular structure over the two energy minima defining the anti and gauche conformers. One-electron ionization energies and momentum distributions in the outer-valence region were found to be highly dependent upon the molecular conformation. Calculated momentum distributions indeed very sensitively reflect the distortions and topological changes that molecular orbitals undergo due to the internal rotation of the hydroxyl group, and thereby exhibit variations which can be traced experimentally. The B3LYP model Kohn-Sham orbital densities are overall in good agreement with the experimental distributions, and closely resemble benchmark ADC(3) Dyson orbital densities. Both approaches fail to quantitatively reproduce the experimental momentum distributions characterizing the highest occupied molecular orbital. Since electron momentum spectroscopy measurements at various electron impact energies indicate that the plane wave impulse approximation is valid, this discrepancy between theory and experiment is tentatively ascribed to thermal disorder, i.e. large-amplitude and thermally induced dynamical distortions of the molecular structure in the gas phase.

  16. Probing molecular conformations in momentum space: The case of n-pentane

    Science.gov (United States)

    Knippenberg, S.; Huang, Y. R.; Hajgató, B.; François, J.-P.; Deng, J. K.; Deleuze, M. S.

    2007-11-01

    A comprehensive study, throughout the valence region, of the electronic structure and electron momentum density distributions of the four conformational isomers of n-pentane is presented. Theoretical (e,2e) valence ionization spectra at high electron impact energies (1200eV+electron binding energy) and at azimuthal angles ranging from 0° to 10° in a noncoplanar symmetric kinematical setup are generated according to the results of large scale one-particle Green's function calculations of Dyson orbitals and related electron binding energies, using the third-order algebraic-diagrammatic construction [ADC(3)] scheme. The results of a focal point analysis (FPA) of relative conformer energies [A. Salam and M. S. Deleuze, J. Chem. Phys. 116, 1296 (2002)] and improved thermodynamical calculations accounting for hindered rotations are also employed in order to quantitatively evaluate the abundance of each conformer in the gas phase at room temperature and reliably predict the outcome of experiments on n-pentane employing high resolution electron momentum spectroscopy. Comparison with available photoelectron measurements confirms the suggestion that, due to entropy effects, the trans-gauche (tg) conformer strongly dominates the conformational mixture characterizing n-pentane at room temperature. Our simulations demonstrate therefore that experimental measurements of (e,2e) valence ionization spectra and electron momentum distributions would very consistently and straightforwardly image the topological changes and energy variations that molecular orbitals undergo due to torsion of the carbon backbone. The strongest fingerprints for the most stable conformer (tt) are found for the electron momentum distributions associated with ionization channels at the top of the inner-valence region, which sensitively image the development of methylenic hyperconjugation in all-staggered n-alkane chains.

  17. Molecular dynamics simulation and conformational analysis of some catalytically active peptides.

    Science.gov (United States)

    Honarparvar, Bahareh; Skelton, Adam A

    2015-04-01

    The design of stable and inexpensive artificial enzymes with potent catalytic activity is a growing field in peptide science. The first step in this design process is to understand the key factors that can affect the conformational preference of an enzyme and correlate them with its catalytic activity. In this work, molecular dynamics simulations in explicit water of two catalytically active peptides (peptide 1: Fmoc-Phe1-Phe2-His-CONH2; peptide 2: Fmoc-Phe1-Phe2-Arg-CONH2) were performed at temperatures of 300, 400, and 500 K. Conformational analysis of these peptides using Ramachandran plots identified the secondary structures of the amino acid residues involved (Phe1, Phe2, His, Arg) and confirmed their conformational flexibility in solution. Furthermore, Ramachandran maps revealed the intrinsic preference of the constituent residues of these compounds for a helical conformation. Long-range interaction distances and radius of gyration (R g) values obtained during 20 ns MD simulations confirmed their tendency to form folded conformations. Results showed a decrease in side-chain (Phe1, Phe2, His ring, and Arg) contacts as the temperature was raised from 300 to 400 K and then to 500 K. Finally, the radial distribution functions (RDF) of the water molecules around the nitrogen atoms in the catalytically active His and Arg residues of peptide 1 and peptide 2 revealed that the strongest water-peptide interaction occurred with the arginine nitrogen atoms in peptide 2. Our results highlight differences in the secondary structures of the two peptides that can be explained by the different arrangement of water molecules around the nitrogen atoms of Arg in peptide 2 as compared to the arrangement of water molecules around the nitrogen atoms of His in peptide 1. The results of this work thus provide detailed insight into peptide conformations which can be exploited in the future design of peptide analogs.

  18. Conformational polymorphism of the PrP106-126 peptide in different environments : A molecular dynamics study

    NARCIS (Netherlands)

    Villa, Alessandra; Mark, AE; Saracino, GAA; Cosentino, U; Pitea, D; Moro, G; Salmona, M

    2006-01-01

    Extensive molecular dynamic simulations (similar to 240 ns) have been used to investigate the conformational behavior of PrP106-126 prion peptide in four different environments (water, dimethyl sulfoxide, hexane, and trifluoroethanol) and under both neutral and acidic conditions. The conformational

  19. The molecular mechanism of toxin-induced conformational changes in a potassium channel : relation to C-type inactivation

    NARCIS (Netherlands)

    Zachariae, U.; Schneider, R.; Velisetty, P.; Lange, A.; Seeliger, D.; Wacker, S.J.; Karimi-Nejad, Y.; Vriend, G.; Becker, S.; Pongs, O.; Baldus, M.; Groot, B.L. de

    2008-01-01

    Recently, a solid-state NMR study revealed that scorpion toxin binding leads to conformational changes in the selectivity filter of potassium channels. The exact nature of the conformational changes, however, remained elusive. We carried out all-atom molecular dynamics simulations that enabled us to

  20. Elucidating molecular motion through structural and dynamic filters of energy-minimized conformer ensembles.

    Science.gov (United States)

    Emani, Prashant S; Bardaro, Michael F; Huang, Wei; Aragon, Sergio; Varani, Gabriele; Drobny, Gary P

    2014-02-20

    Complex RNA structures are constructed from helical segments connected by flexible loops that move spontaneously and in response to binding of small molecule ligands and proteins. Understanding the conformational variability of RNA requires the characterization of the coupled time evolution of interconnected flexible domains. To elucidate the collective molecular motions and explore the conformational landscape of the HIV-1 TAR RNA, we describe a new methodology that utilizes energy-minimized structures generated by the program "Fragment Assembly of RNA with Full-Atom Refinement (FARFAR)". We apply structural filters in the form of experimental residual dipolar couplings (RDCs) to select a subset of discrete energy-minimized conformers and carry out principal component analyses (PCA) to corroborate the choice of the filtered subset. We use this subset of structures to calculate solution T1 and T(1ρ) relaxation times for (13)C spins in multiple residues in different domains of the molecule using two simulation protocols that we previously published. We match the experimental T1 times to within 2% and the T(1ρ) times to within less than 10% for helical residues. These results introduce a protocol to construct viable dynamic trajectories for RNA molecules that accord well with experimental NMR data and support the notion that the motions of the helical portions of this small RNA can be described by a relatively small number of discrete conformations exchanging over time scales longer than 1 μs.

  1. Major Ampullate Spider Silk with Indistinguishable Spidroin Dope Conformations Leads to Different Fiber Molecular Structures

    Directory of Open Access Journals (Sweden)

    Justine Dionne

    2016-08-01

    Full Text Available To plentifully benefit from its properties (mechanical, optical, biological and its potential to manufacture green materials, the structure of spider silk has to be known accurately. To this aim, the major ampullate (MA silk of Araneus diadematus (AD and Nephila clavipes (NC has been compared quantitatively in the liquid and fiber states using Raman spectromicroscopy. The data show that the spidroin conformations of the two dopes are indistinguishable despite their specific amino acid composition. This result suggests that GlyGlyX and GlyProGlyXX amino acid motifs (X = Leu, Glu, Tyr, Ser, etc. are conformationally equivalent due to the chain flexibility in the aqueous environment. Species-related sequence specificity is expressed more extensively in the fiber: the β-sheet content is lower and width of the orientation distribution of the carbonyl groups is broader for AD (29% and 58°, respectively as compared to NC (37% and 51°, respectively. β-Sheet content values are close to the proportion of polyalanine segments, suggesting that β-sheet formation is mainly dictated by the spidroin sequence. The extent of molecular alignment seems to be related to the presence of proline (Pro that may decrease conformational flexibility and inhibit chain extension and alignment upon drawing. It appears that besides the presence of Pro, secondary structure and molecular orientation contribute to the different mechanical properties of MA threads.

  2. Major Ampullate Spider Silk with Indistinguishable Spidroin Dope Conformations Leads to Different Fiber Molecular Structures

    Science.gov (United States)

    Dionne, Justine; Lefèvre, Thierry; Auger, Michèle

    2016-01-01

    To plentifully benefit from its properties (mechanical, optical, biological) and its potential to manufacture green materials, the structure of spider silk has to be known accurately. To this aim, the major ampullate (MA) silk of Araneus diadematus (AD) and Nephila clavipes (NC) has been compared quantitatively in the liquid and fiber states using Raman spectromicroscopy. The data show that the spidroin conformations of the two dopes are indistinguishable despite their specific amino acid composition. This result suggests that GlyGlyX and GlyProGlyXX amino acid motifs (X = Leu, Glu, Tyr, Ser, etc.) are conformationally equivalent due to the chain flexibility in the aqueous environment. Species-related sequence specificity is expressed more extensively in the fiber: the β-sheet content is lower and width of the orientation distribution of the carbonyl groups is broader for AD (29% and 58°, respectively) as compared to NC (37% and 51°, respectively). β-Sheet content values are close to the proportion of polyalanine segments, suggesting that β-sheet formation is mainly dictated by the spidroin sequence. The extent of molecular alignment seems to be related to the presence of proline (Pro) that may decrease conformational flexibility and inhibit chain extension and alignment upon drawing. It appears that besides the presence of Pro, secondary structure and molecular orientation contribute to the different mechanical properties of MA threads. PMID:27548146

  3. Studies on the Conformational Features of Neomycin-B and its Molecular Recognition by RNA and Bacterial Defense Proteins

    Science.gov (United States)

    Asensio, Juan Luis; Bastida, Agatha; Jiménez-Barbero, Jesús

    According to NMR and molecular dynamics simulations, the conformational behavior of natural aminoglycosides is characterized by a remarkable flexibility, with different conformations, even non-exo-anomeric ones, in fast exchange. Very probably, this feature allows the adaptation of these ligands to the spatial and electronic requirements of different receptors. The large diversity of structures adopted by aminoglycosides in the binding pocket of the different RNA receptors and the distinct enzymes involved in bacterial resistance are consistent with this view. This conformational diversity can, in certain favorable cases, be exploited in the design of new antibiotic derivatives not susceptible to enzymatic inactivation, by designing tailor-made conformationally locked aminoglycosides.

  4. Conformation of Randomly Sulfonated Pentablock Ionomers in Dilute Solution: Molecular Dynamic Simulation Study

    Science.gov (United States)

    Aryal, Dipak; Perahia, Dvora; Grest, Gary S.

    2011-03-01

    As part of our efforts to define the factors that control the structure and dynamics of structures ionic polymers, the conformation of a pentablock copolymer that consists of randomly sulfonated polystyrene, an ionomeric block, bound to poly-ethylene-r-propylene end caped by poly-t-butylstyrene has been studied in dilute solutions using molecular dynamic simulations. Multi-block copolymers offer a means to tailor several properties into one molecule, taking advantage of their rich phase diagram together with unique properties of specific blocks. We varied the solvent quality for the different blocks and followed the changes in conformation. The spatial configuration of the pentablock as well as the dynamics of the polymer was studied. We find that, independent on the solvent, the higher the sulfonation level, the lower Rg . The static and dynamic structure factors were calculated and compared in an implicit poor solvent, water and a common solvent. These data are compared with results obtained from neutron scattering.

  5. Conformational Solvation Studies of LIGNOLs with Molecular Dynamics and Conductor-Like Screening Model

    Directory of Open Access Journals (Sweden)

    Thomas Sandberg

    2012-08-01

    Full Text Available Molecular dynamics (MD simulations were performed on sterically hindered -conidendrin-based chiral 1,4-diols (LIGNOLs from the naturally occurring lignan hydroxymatairesinol (HMR using the GROMACS software. The aim of this study was to explore the conformational behaviour of the LIGNOLs in aqueous solution adopting the TIP4P model. The topologies of the LIGNOLs were constructed manually and they were modeled with the OPLS-AA force field implemented in GROMACS. The four most relevant torsional angles in the LIGNOLs were properly analyzed during the simulations. The determining property for the conformation preferred in aqueous solution was found to be the lowest energy in gas phase. The solvation effects on the LIGNOLs were also studied by quantum chemical calculations applying the COnductor-like Screening MOdel (COSMO. The hydration studies of the MD simulations showed that several of these LIGNOLs, produced from a renewable source, have a great potential of acting as chiral catalysts.

  6. Designing molecular dynamics simulations to shift populations of the conformational states of calmodulin.

    Directory of Open Access Journals (Sweden)

    Ayse Ozlem Aykut

    Full Text Available We elucidate the mechanisms that lead to population shifts in the conformational states of calcium-loaded calmodulin (Ca(2+-CaM. We design extensive molecular dynamics simulations to classify the effects that are responsible for adopting occupied conformations available in the ensemble of NMR structures. Electrostatic interactions amongst the different regions of the protein and with its vicinal water are herein mediated by lowering the ionic strength or the pH. Amino acid E31, which is one of the few charged residues whose ionization state is highly sensitive to pH differences in the physiological range, proves to be distinctive in its control of population shifts. E31A mutation at low ionic strength results in a distinct change from an extended to a compact Ca(2+-CaM conformation within tens of nanoseconds, that otherwise occur on the time scales of microseconds. The kinked linker found in this particular compact form is observed in many of the target-bound forms of Ca(2+-CaM, increasing the binding affinity. This mutation is unique in controlling C-lobe dynamics by affecting the fluctuations between the EF-hand motif helices. We also monitor the effect of the ionic strength on the conformational multiplicity of Ca(2+-CaM. By lowering the ionic strength, the tendency of nonspecific anions in water to accumulate near the protein surface increases, especially in the vicinity of the linker. The change in the distribution of ions in the vicinal layer of water allows N- and C- lobes to span a wide variety of relative orientations that are otherwise not observed at physiological ionic strength. E31 protonation restores the conformations associated with physiological environmental conditions even at low ionic strength.

  7. DNA Conformational Variations Induced by Stretching 3'5'-Termini Studied by Molecular Dynamics Simulations

    Institute of Scientific and Technical Information of China (English)

    QI Wen-Peng; LEI Xiao-Ling

    2011-01-01

    @@ Investigating the interaction between protein and stretched DNA molecules has become a new way to study the protein DNA interaction.The conformations from different stretching methods give us a further understanding of the interaction between protein and DNA.We study the conformational variations of a 22-mer DNA caused by stretching both 3'-and 5'-termini by molecular dynamics simulations.It requires 250kJ/mol to stretch the DNA molecule by 3'5'-termini for 3.5 run and the force plateau is at 123.8 pN.The stretching 3'5'-termini leads to large values of the angle opening and the dihedral propeller between bases in one base pair, the double helix untwists from 34°to 20°and the successive base pairs rolls to the side of the DNA major groove.The distances between successive base pairs increases from 3.2.(A) to 5.6(A).%Investigating the interaction between protein and stretched DNA molecules has become a new way to study the protein DNA interaction. The conformations from different stretching methods give us a further understanding of the interaction between protein and DNA. We study the conformational variations of a 22-met DNA caused by stretching both 3'- and 5'-termini by molecular dynamics simulations. It requires 250k J/mol to stretch the DNA molecule by 3'5'-termini for 3.5nm and the force plateau is at 123.8pN. The stretching 3'5'-termini leads to large values of the angle opening and the dihedral propeller between bases in one base pair, the double helix untwists from 34° to 20° and the successive base pairs rolls to the side of the DNA major groove. The distances between successive base pairs increases from 3.2 (A) to 5.6 (A).

  8. Accelerated molecular dynamics and protein conformational change: a theoretical and practical guide using a membrane embedded model neurotransmitter transporter.

    Science.gov (United States)

    Gedeon, Patrick C; Thomas, James R; Madura, Jeffry D

    2015-01-01

    Molecular dynamics simulation provides a powerful and accurate method to model protein conformational change, yet timescale limitations often prevent direct assessment of the kinetic properties of interest. A large number of molecular dynamic steps are necessary for rare events to occur, which allow a system to overcome energy barriers and conformationally transition from one potential energy minimum to another. For many proteins, the energy landscape is further complicated by a multitude of potential energy wells, each separated by high free-energy barriers and each potentially representative of a functionally important protein conformation. To overcome these obstacles, accelerated molecular dynamics utilizes a robust bias potential function to simulate the transition between different potential energy minima. This straightforward approach more efficiently samples conformational space in comparison to classical molecular dynamics simulation, does not require advanced knowledge of the potential energy landscape and converges to the proper canonical distribution. Here, we review the theory behind accelerated molecular dynamics and discuss the approach in the context of modeling protein conformational change. As a practical example, we provide a detailed, step-by-step explanation of how to perform an accelerated molecular dynamics simulation using a model neurotransmitter transporter embedded in a lipid cell membrane. Changes in protein conformation of relevance to the substrate transport cycle are then examined using principle component analysis.

  9. Adsorption mechanisms of microcystin variant conformations at water-mineral interfaces: A molecular modeling investigation.

    Science.gov (United States)

    Pochodylo, Amy L; Aoki, Thalia G; Aristilde, Ludmilla

    2016-10-15

    Microcystins (MCs) are potent toxins released during cyanobacterial blooms. Clay minerals are implicated in trapping MCs within soil particles in surface waters and sediments. In the absence of molecular characterization, the relevance of previously proposed adsorption mechanisms is lacking. Towards obtaining this characterization, we conducted Monte Carlo simulations combined with molecular dynamics relaxation of two MC variants, MC-leucine-arginine (MC-LR) and MC-leucine-alanine (MC-LA), adsorbed on hydrated montmorillonite with different electrolytes. The resulting adsorbate structures revealed how MC conformations and aqueous conditions dictate binding interactions at the mineral surface. Electrostatic coupling between the arginine residue and a carboxylate in MC-LR excluded the participation of arginine in mediating adsorption on montmorillonite in a NaCl solution. However, in a CaCl2 solution, the complexation of Ca by two carboxylate moieties in MC-LR changed the MC conformation, which allowed arginine to mediate electrostatic interaction with the mineral. By contrast, due to the lack of arginine in MC-LA, complexation of Ca by only one carboxylate in MC-LA was required to favor Ca-bridging interaction with the mineral. Multiple water-bridged H-bonding interactions were also important in anchoring MCs at the mineral surface. Our modeling results offer molecular insights into the structural and chemical factors that can control the fate of MCs at water-mineral interfaces.

  10. Enhanced conformational sampling of nucleic acids by a new Hamiltonian replica exchange molecular dynamics approach.

    Science.gov (United States)

    Curuksu, Jeremy; Zacharias, Martin

    2009-03-14

    Although molecular dynamics (MD) simulations have been applied frequently to study flexible molecules, the sampling of conformational states separated by barriers is limited due to currently possible simulation time scales. Replica-exchange (Rex)MD simulations that allow for exchanges between simulations performed at different temperatures (T-RexMD) can achieve improved conformational sampling. However, in the case of T-RexMD the computational demand grows rapidly with system size. A Hamiltonian RexMD method that specifically enhances coupled dihedral angle transitions has been developed. The method employs added biasing potentials as replica parameters that destabilize available dihedral substates and was applied to study coupled dihedral transitions in nucleic acid molecules. The biasing potentials can be either fixed at the beginning of the simulation or optimized during an equilibration phase. The method was extensively tested and compared to conventional MD simulations and T-RexMD simulations on an adenine dinucleotide system and on a DNA abasic site. The biasing potential RexMD method showed improved sampling of conformational substates compared to conventional MD simulations similar to T-RexMD simulations but at a fraction of the computational demand. It is well suited to study systematically the fine structure and dynamics of large nucleic acids under realistic conditions including explicit solvent and ions and can be easily extended to other types of molecules.

  11. New binding site conformations of the dengue virus NS3 protease accessed by molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Hugo de Almeida

    Full Text Available Dengue fever is caused by four distinct serotypes of the dengue virus (DENV1-4, and is estimated to affect over 500 million people every year. Presently, there are no vaccines or antiviral treatments for this disease. Among the possible targets to fight dengue fever is the viral NS3 protease (NS3PRO, which is in part responsible for viral processing and replication. It is now widely recognized that virtual screening campaigns should consider the flexibility of target protein by using multiple active conformational states. The flexibility of the DENV NS3PRO could explain the relatively low success of previous virtual screening studies. In this first work, we explore the DENV NS3PRO conformational states obtained from molecular dynamics (MD simulations to take into account protease flexibility during the virtual screening/docking process. To do so, we built a full NS3PRO model by multiple template homology modeling. The model comprised the NS2B cofactor (essential to the NS3PRO activation, a glycine flexible link and the proteolytic domain. MD simulations had the purpose to sample, as closely as possible, the ligand binding site conformational landscape prior to inhibitor binding. The obtained conformational MD sample was clustered into four families that, together with principal component analysis of the trajectory, demonstrated protein flexibility. These results allowed the description of multiple binding modes for the Bz-Nle-Lys-Arg-Arg-H inhibitor, as verified by binding plots and pair interaction analysis. This study allowed us to tackle protein flexibility in our virtual screening campaign against the dengue virus NS3 protease.

  12. Single-strand conformation polymorphism for molecular variability studies of six viroid species.

    Science.gov (United States)

    Elleuch, Amine; Hamdi, Imen; Bessaies, Nabiha; Fakhfakh, Hatem

    2013-01-01

    Molecular diversity within six viroid species and different molecular variants, in each species infecting fruit trees was first estimated by the single-strand conformation polymorphism (SSCP) technique and then by direct sequencing analysis. The different variants studied are to three Australian grapevine viroids(AGVd), four citrus dwarfing viroids (CDVd), eleven grapevine yellow speckle viroids type-1 (GYSVd-1), four hop stunt viroids (HSVd), seven peach latent mosaic viroids (PLMVd), and eight pear blister canker viroids (PBCVd). Polyacrylamide gel electrophoresis (PAGE) conditions were compared and optimized to improve the sensitivity of the existing SSCP parameters. The relationships among the various SSCP profiles observed and the variation in nucleotide sequences was studied. The results indicate that the variations of some parameters of electrophoresis for each species allowed higher resolution and hence detection of single nucleotide variations among clones initially clustered into the same group.

  13. Peptoid conformational free energy landscapes from implicit-solvent molecular simulations in AMBER.

    Science.gov (United States)

    Voelz, Vincent A; Dill, Ken A; Chorny, Ilya

    2011-01-01

    To test the accuracy of existing AMBER force field models in predicting peptoid conformation and dynamics, we simulated a set of model peptoid molecules recently examined by Butterfoss et al. (JACS 2009, 131, 16798-16807) using QM methods as well as three peptoid sequences with experimentally determined structures. We found that AMBER force fields, when used with a Generalized Born/Surface Area (GBSA) implicit solvation model, could accurately reproduce the peptoid torsional landscape as well as the major conformers of known peptoid structures. Enhanced sampling by replica exchange molecular dynamics (REMD) using temperatures from 300 to 800 K was used to sample over cis-trans isomerization barriers. Compared to (Nrch)5 and cyclo-octasarcosyl, the free energy of N-(2-nitro-3-hydroxyl phenyl)glycine-N-(phenyl)glycine has the most "foldable" free energy landscape, due to deep trans-amide minima dictated by N-aryl sidechains. For peptoids with (S)-N (1-phenylethyl) (Nspe) side chains, we observe a discrepancy in backbone dihedral propensities between molecular simulations and QM calculations, which may be due to force field effects or the inability to capture n --> n* interactions. For these residues, an empirical phi-angle biasing potential can "rescue" the backbone propensities seen in QM. This approach can serve as a general strategy for addressing force fields without resorting to a complete reparameterization. Overall, this study demonstrates the utility of implicit-solvent REMD simulations for efficient sampling to predict peptoid conformational landscapes, providing a potential tool for first-principles design of sequences with specific folding properties.

  14. Conformational flexibility of β-secretase:molecular dynamics simulation and essential dynamics analysis

    Institute of Scientific and Technical Information of China (English)

    Bing XIONG; Xiao-qin HUANG; Ling-ling SHEN; Jian-hua SHEN; Xiao-min LUO; Xu SHEN; Hua-liang JIANG; Kai-xian CHEN

    2004-01-01

    AIM: Based on the structural analysis to reveal the mechanism of ligand binding to β-secretase and the specificity of each binding sub-site. METHODS: Molecular dynamics was used to simulate on the ligand free β-secretase and ligand bound β-secretase. The trajectories were analyzed using the essential dynamics, and the significant conformational change was illustrated employing the DynDom program. RESULTS: The essential dynamics and DynDom analyses clearly showed that the β-secretase experienced a large conformational change upon the substrate or inhibitor binding. The flap structure adopted a swing motion, gradually covering the active site to facilitate the ligand binding process. Residues Ser86 and Ile87 served as the hinge point. Inhibitor-enzyme interaction analysis revealed that residues at P2, Pl, and P1' positions of the inhibitor were very important for the binding, and residues at P2' and P3' positions may be modified to improve the binding specificity. S3 subsite of the enzyme still had space to modify the inhibitors in increasing the binding affinity. CONCLUSION: The information presented here is valuable and could be used to identify small molecular inhibitors of β-secretase.

  15. Structural and molecular conformation of myosin in intact muscle fibers by second harmonic generation

    Science.gov (United States)

    Nucciotti, V.; Stringari, C.; Sacconi, L.; Vanzi, F.; Linari, M.; Piazzesi, G.; Lombardi, V.; Pavone, F. S.

    2009-02-01

    Recently, the use of Second Harmonic Generation (SHG) for imaging biological samples has been explored with regard to intrinsic SHG in highly ordered biological samples. As shown by fractional extraction of proteins, myosin is the source of SHG signal in skeletal muscle. SHG is highly dependent on symmetries and provides selective information on the structural order and orientation of the emitting proteins and the dynamics of myosin molecules responsible for the mechano-chemical transduction during contraction. We characterise the polarization-dependence of SHG intensity in three different physiological states: resting, rigor and isometric tetanic contraction in a sarcomere length range between 2.0 μm and 4.0 μm. The orientation of motor domains of the myosin molecules is dependent on their physiological states and modulate the SHG signal. We can discriminate the orientation of the emitting dipoles in four different molecular conformations of myosin heads in intact fibers during isometric contraction, in resting and rigor. We estimate the contribution of the myosin motor domain to the total second order bulk susceptibility from its molecular structure and its functional conformation. We demonstrate that SHG is sensitive to the fraction of ordered myosin heads by disrupting the order of myosin heads in rigor with an ATP analog. We estimate the fraction of myosin motors generating the isometric force in the active muscle fiber from the dependence of the SHG modulation on the degree of overlap between actin and myosin filaments during an isometric contraction.

  16. Isolation of Ion-Driven Conformations in Diphenylacetylene Molecular Switches Using Cryogenic Infrared Spectroscopy

    Science.gov (United States)

    Wolk, Arron B.; Garand, Etienne; Jones, Ian M.; Kamrath, Michael Z.; Hamilton, Rew; Johnson, Mark A.

    2012-06-01

    We report the infrared predissociation spectra of a family of ionic diphenylacetylene molecular switch complexes. The electrosprayed complexes were trapped and cooled in a cryogenic (10K) quadrupole ion trap and tagged with molecular deuterium. The infrared spectra of the vibrationally cold species reveal sharp transitions over a wide energy range (800 - 3800 cm-1), facilitating comparison to harmonic spectra. The evolution of the band pattern upon derivatization of the complexes exposes the signatures of the amide, urea, and carbonyl functionalities, enabling unambiguous identification of the non-covalent interactions that control the secondary structure of the molecule. Complexation with the tetramethylammonium cation reveals a conformation analogous to that of the neutral molecule, while halide ion attachment induces a conformational change similar to that observed earlier in solution. In several cases, both the donor and acceptor groups involved in the multidentate H-bonds are observed, providing a microscopic mechanical picture of the interactions at play. I. Jones, and A. Hamilton, Angew. Chem. Intl. Edit. 50, 4597 (2011).

  17. Predicting the glass transition temperature of bioactive glasses from their molecular chemical composition.

    Science.gov (United States)

    Hill, Robert G; Brauer, Delia S

    2011-10-01

    A recently published paper (M.D. O'Donnell, Acta Biomaterialia 7 (2011) 2264-2269) suggests that it is possible to correlate the glass transition temperature (T(g)) of bioactive glasses with their molar composition, based on iterative least-squares fitting of published T(g) data. However, we show that the glass structure is an important parameter in determining T(g). Phase separation, local structural effects and components (intermediate oxides) which can switch their structural role in the glass network need to be taken into consideration, as they are likely to influence the glass transition temperature of bioactive glasses. Although the model suggested by O'Donnell works reasonably well for glasses within the composition range presented, it is oversimplified and fails for glasses outside certain compositional boundaries.

  18. Earle K. Plyler Prize for Molecular Spectroscopy and Dynamics Lecture: 2D IR Spectroscopy of Peptide Conformation

    Science.gov (United States)

    Tokmakoff, Andrei

    2012-02-01

    Descriptions of protein and peptide conformation are colored by the methods we use to study them. Protein x-ray and NMR structures often lead to impressions of rigid or well-defined conformations, even though these are dynamic molecules. The conformational fluctuations and disorder of proteins and peptides is more difficult to quantify. This presentation will describe an approach toward characterizing and quantifying structural heterogeneity and disorder in peptides using 2D IR spectroscopy. Using amide I vibrational spectroscopy, isotope labeling strategies, and computational modeling based on molecular dynamics simulations and Markov state models allows us to characterize distinct peptide conformers and conformational variation. The examples illustrated include the beta-hairpin tripzip2 and elastin-like peptides.

  19. NMR and molecular dynamics studies of the conformational epitope of the type III group B Streptococcus capsular polysaccharide and derivatives.

    Science.gov (United States)

    Brisson, J R; Uhrinova, S; Woods, R J; van der Zwan, M; Jarrell, H C; Paoletti, L C; Kasper, D L; Jennings, H J

    1997-03-18

    The conformational epitope of the type III group B Streptococcus capsular polysaccharide (GBSP III) exhibits unique properties which can be ascribed to the presence of sialic acid in its structure and the requirement for an extended binding site. By means of NMR and molecular dynamics studies on GBSP III and its fragments, the extended epitope of GBSP III was further defined. The influence of sialic acid on the conformational properties of GBSP III was examined by performing conformational analysis on desialylated GBSP III, which is identical to the polysaccharide of Streptococcus pneumoniae type 14, and also on oxidized and reduced GBSP III. Conformational changes were gauged by 1H and 13C chemical shift analysis, NOE, 1D selective TOCSY-NOESY experiments, J(HH) and J(CH) variations, and NOE of OH resonances. Changes in mobility were examined by 13C T1 and T2 measurements. Unrestrained molecular dynamics simulations with explicit water using the AMBER force field and the GLYCAM parameter set were used to assess static and dynamic conformational models, simulate the observable NMR parameters and calculate helical parameters. GBSP III was found to be capable of forming extended helices. Hence, the length dependence of the conformational epitope could be explained by its location on extended helices within the random coil structure of GBSP III. The interaction of sialic acid with the backbone of the PS was also found to be important in defining the conformational epitope of GBSP III.

  20. Bioactivation of particles

    Energy Technology Data Exchange (ETDEWEB)

    Pinaud, Fabien (Berkeley, CA); King, David (San Francisco, CA); Weiss, Shimon (Los Angeles, CA)

    2011-08-16

    Particles are bioactivated by attaching bioactivation peptides to the particle surface. The bioactivation peptides are peptide-based compounds that impart one or more biologically important functions to the particles. Each bioactivation peptide includes a molecular or surface recognition part that binds with the surface of the particle and one or more functional parts. The surface recognition part includes an amino-end and a carboxy-end and is composed of one or more hydrophobic spacers and one or more binding clusters. The functional part(s) is attached to the surface recognition part at the amino-end and/or said carboxy-end.

  1. Molecular modeling of sigma 1 receptor ligands: a model of binding conformational and electrostatic considerations.

    Science.gov (United States)

    Gund, Tamara M; Floyd, Jie; Jung, Dawoon

    2004-01-01

    We have performed molecular modeling studies on several sigma 1 specific ligands, including PD144418, spipethiane, haloperidol, pentazocine, and others to develop a pharmacophore for sigma 1 receptor-ligand binding, under the assumption that all the compounds interact at the same receptor binding site. The modeling studies have investigated the conformational and electrostatic properties of the ligands. Superposition of active molecules gave the coordinates of the hypothetical 5-point sigma 1 pharmacophore, as follows: R1 (0.85, 7.26, 0.30); R2 (5.47, 2.40, -1.51); R3 (-2.57, 4.82, -7.10); N (-0.71, 3.29, -6.40); carbon centroid (3.16, 4.83, -0.60), where R1, R2 were constructed onto the aromatic ring of each compound to represent hydrophobic interactions with the receptor; and R3 represents a hydrogen bond between the nitrogen atom and the receptor. Additional analyses were used to describe secondary binding sites to electronegative groups such as oxygen or sulfur atom. Those coordinates are (2.34, 5.08, -4.18). The model was verified by fitting other sigma 1 receptor ligands. This model may be used to search conformational databases for other possibly active ligands. In conjunction with rational drug design techniques the model may be useful in design and synthesis of novel sigma 1 ligands of high selectivity and potency. Calculations were performed using Sybyl 6.5.

  2. Synthesis, structural investigations, hydrogen-deuterium exchange studies, and molecular modeling of conformationally stablilized aromatic oligoamides.

    Science.gov (United States)

    Yan, Yan; Qin, Bo; Ren, Changliang; Chen, Xiuying; Yip, Yeow Kwan; Ye, Ruijuan; Zhang, Dawei; Su, Haibin; Zeng, Huaqiang

    2010-04-28

    Biasing the conformational preferences of aromatic oligoamides by internally placing intramolecular hydrogen bonds has led to a series of stably folded molecular strands. This article presents the results from extensive solid-state, solution, and computational studies on these folding oligomers. Depending on its backbone length, an oligoamide adopts a crescent or helical conformation. Surprisingly, despite the highly repetitive nature of the backbone, the internally placed, otherwise very similar intramolecular hydrogen bonds showed significantly different stabilities as demonstrated by hydrogen-deuterium exchange data. It was also observed that the hydrogen-bonding strength can be tuned by adjusting the substituents attached to the exterior of the aromatic backbones. Examining the amide hydrogen-deuterium exchange rates of trimers revealed that a six-membered hydrogen bond nearing the ester end is the weakest among all the four intramolecular hydrogen bonds of a molecule. This observation was verified by ab initio quantum mechanical calculations at the level of B3LYP/6-31G*. Such a "weak point" creates the "battle of the bulge" where backbone twisting is centered, which is consistently observed in the solid-state structures of the four trimer molecules studied. In the solid state, the oligomers assemble into interesting one-dimensional structures. A pronounced columnar packing of short oligomers (i.e., dimers, trimers, and tetramer) and channel-like, potentially ion-conducting stacks of longer oligomers (i.e., tetramer, pentamer, and hexamer) were observed.

  3. CONFORMATION AND CHAIN PACKING STRUCTURES OF POLY(p-PHENYLENE BENZOBISTHIAZOLE) BY MOLECULAR SIMULATION

    Institute of Scientific and Technical Information of China (English)

    YANG Xiaozheng; LIU Yue; HSU Shaw Ling

    1997-01-01

    The conformation, the chain packing stabilization and the unit cell modeling of poly(p-phenylene benzobisthiazole) have been investigated by using molecular simulation technique in the prese nt work. A coupling behaviour of σ-bond rotations at either side of the phenylene ring or the heterocyclic ring was found surely to exceed a length of the repeat unit of the polymer chain. For a single chain model, the stable torsion angle of the repeat resulted at 14°. In the crystalline cell minimization, the dihedral angle along the polymer chain could even be stabilized in various values. It therefore indicates that the intermolecular interaction does play a considerable role for this polymer forming the conformation. According to cohesive energies calculated for these unit cell models, the torsion angle in the most stable crystalline cell is 0°. When the chains packing together, there exist so many energy stable wells along the chain axis 0.35-0.36nm apart from neighbouring chains.Most of the unit cells have quite closed cohesive energies. These factors thus cause the difficulty of forming an unique perfect crystalline structure of the polymer. The present study suggested a number of reasonable unit cells, and the most stable crystalline structure for this polymer that is monoclinic, non-primitive unit cell.

  4. Conformational Search on the Lewis X Structure by Molecular Dynamic: Study of Tri- and Pentasaccharide

    Directory of Open Access Journals (Sweden)

    N. Khebichat

    2012-01-01

    Full Text Available Carbohydrates play vital roles in many biological processes, such as recognition, adhesion, and signalling between cells. The Lewis X determinant is a trisaccharide fragment implicated as a specific differentiation antigen, tumor antigen, and key component of the ligand for the endothelial leukocyte adhesion molecule, so it is necessary or essential to determine and to know their conformational and structural properties. In this work, conformational analysis was performed using molecular dynamics (MD simulation with the AMBER10 program package in order to study the dynamic behavior of of the Lewis X trisaccharide (β-D-Gal-(1,4-[α-L-Fuc-(1,3]-β-D-GlcNAc-OMe and the Lewis X pentasaccharide (β-D-Gal-(1,4-[α-L-Fuc-(1,3]-β-D-GlcNAc-(1,3-β-D-Gal-(1,4-β-D-Glu-OMe in explicit water model at 300 K for 10 ns using the GLYCAM 06 force field.

  5. Assessing polyglutamine conformation in the nucleating event by molecular dynamics simulations.

    Science.gov (United States)

    Miettinen, Markus S; Knecht, Volker; Monticelli, Luca; Ignatova, Zoya

    2012-08-30

    Polyglutamine (polyQ) diseases comprise a group of dominantly inherited pathology caused by an expansion of an unstable polyQ stretch which is presumed to form β-sheets. Similar to other amyloid pathologies, polyQ amyloidogenesis occurs via a nucleated polymerization mechanism, and proceeds through energetically unfavorable nucleus whose existence and structure are difficult to detect. Here, we use atomistic molecular dynamics simulations in explicit solvent to assess the conformation of the polyQ stretch in the nucleus that initiates polyQ fibrillization. Comparison of the kinetic stability of various structures of polyQ peptide with a Q-length in the pathological range (Q40) revealed that steric zipper or nanotube-like structures (β-nanotube or β-pseudohelix) are not kinetically stable enough to serve as a template to initiate polyQ fibrillization as opposed to β-hairpin-based (β-sheet and β-sheetstack) or α-helical conformations. The selection of different structures of the polyQ stretch in the aggregation-initiating event may provide an alternative explanation for polyQ aggregate polymorphism.

  6. Molecular identification of Amazonian stingless bees using polymerase chain reaction single-strand conformation polymorphism.

    Science.gov (United States)

    Souza, M T; Carvalho-Zilse, G A

    2014-07-25

    In countries containing a mega diversity of wildlife, such as Brazil, identifying and characterizing biological diversity is a continuous process for the scientific community, even in face of technological and scientific advances. This activity demands initiatives for the taxonomic identification of highly diverse groups, such as stingless bees, including molecular analysis strategies. This type of bee is distributed in all of the Brazilian states, with the highest species diversity being found in the State of Amazônia. However, the estimated number of species diverges among taxonomists. These bees are considered the main pollinators in the Amazon rainforest, in which they obtain food and shelter; however, their persistence is constantly threatened by deforestation pressure. Hence, it is important to classify the number and abundance of bee specie, to measure their decline and implement meaningful, priority conservation strategies. This study aims to maximize the implementation of more direct, economic and successful techniques for the taxonomic identification of stingless bees. Specifically, the genes 16S rRNA and COI from mitochondrial DNA were used as molecular markers to differentiate 9 species of Amazonian stingless bees based on DNA polymorphism, using the polymerase chain reaction-single-strand conformation polymorphism technique. We registered different, exclusive SSCP haplotypes for both genes in all species analyzed. These results demonstrate that SSCP is a simple and cost-effective technique that is applicable to the molecular identification of stingless bee species.

  7. Influence of Molecular Conformations and Microstructure on the Optoelectronic Properties of Conjugated Polymers

    KAUST Repository

    Botiz, Ioan

    2014-03-19

    It is increasingly obvious that the molecular conformations and the long-range arrangement that conjugated polymers can adopt under various experimental conditions in bulk, solutions or thin films, significantly impact their resulting optoelectronic properties. As a consequence, the functionalities and efficiencies of resulting organic devices, such as field-effect transistors, light-emitting diodes, or photovoltaic cells, also dramatically change due to the close structure/property relationship. A range of structure/optoelectronic properties relationships have been investigated over the last few years using various experimental and theoretical methods, and, further, interesting correlations are continuously revealed by the scientific community. In this review, we discuss the latest findings related to the structure/optoelectronic properties interrelationships that exist in organic devices fabricated with conjugated polymers in terms of charge mobility, absorption, photoluminescence, as well as photovoltaic properties. © 2014 by the authors.

  8. Water-mediated conformational transitions in nicotinic receptor M2 helix bundles: a molecular dynamics study.

    Science.gov (United States)

    Sankararamakrishnan, R; Sansom, M S

    1995-12-27

    The ion channel of the nicotinic acetylcholine receptor is a water-filled pore formed by five M2 helix segments, one from each subunit. Molecular dynamics simulations on bundles of five M2 alpha 7 helices surrounding a central column of water and with caps of water molecules at either end of the pore have been used to explore the effects of intrapore water on helix packing. Interactions of water molecules with the N-terminal polar sidechains lead to a conformational transition from right- to left-handed supercoils during these stimulations. These studies reveal that the pore formed by the bundle of M2 helices is flexible. A structural role is proposed for water molecules in determining the geometry of bundles of isolated pore-forming helices.

  9. Conformation, molecular packing and field effect mobility of regioregular beta,beta'-dihexylsexithiophiophene

    DEFF Research Database (Denmark)

    Kiriy, N.; Kiriy, A.; Bocharova, V.

    2004-01-01

    by the pulse-radiolysis time-resolved microwave conductivity (PR-TRMC) technique was found to be Sigmamu(min) = 3.9 x 10(-3) cm(2) V-1 s(-1), which is comparable with the PR-TRMC mobility found for alpha,omega-DH6T. The field-effect mobility (FEM) of beta,beta'-DH6T was found to be on the order of 10(-5) cm(2......) V-1 s(-1), which is considerably less than the FEM of alpha,omega-DH6T. To understand the reason for such poor macroscopic electrical properties, the conformation and the molecular packing of beta,beta'-DH6T were systematically studied by means of UV-vis spectroscopy, scanning electron microscopy...

  10. Influence of Molecular Conformations and Microstructure on the Optoelectronic Properties of Conjugated Polymers

    Directory of Open Access Journals (Sweden)

    Ioan Botiz

    2014-03-01

    Full Text Available It is increasingly obvious that the molecular conformations and the long-range arrangement that conjugated polymers can adopt under various experimental conditions in bulk, solutions or thin films, significantly impact their resulting optoelectronic properties. As a consequence, the functionalities and efficiencies of resulting organic devices, such as field-effect transistors, light-emitting diodes, or photovoltaic cells, also dramatically change due to the close structure/property relationship. A range of structure/optoelectronic properties relationships have been investigated over the last few years using various experimental and theoretical methods, and, further, interesting correlations are continuously revealed by the scientific community. In this review, we discuss the latest findings related to the structure/optoelectronic properties interrelationships that exist in organic devices fabricated with conjugated polymers in terms of charge mobility, absorption, photoluminescence, as well as photovoltaic properties.

  11. Predicting bioactive glass properties from the molecular chemical composition: glass transition temperature.

    Science.gov (United States)

    O'Donnell, Matthew D

    2011-05-01

    The glass transition temperature (T(g)) of inorganic glasses is an important parameter than can be used to correlate with other glass properties, such as dissolution rate, which governs in vitro and in vivo bioactivity. Seven bioactive glass compositional series reported in the literature (77 in total) were analysed here with T(g) values obtained by a number of different methods: differential thermal analysis, differential scanning calorimetry and dilatometry. An iterative least-squares fitting method was used to correlate T(g) from thermal analysis of these compositions with the levels of individual oxide and fluoride components in the glasses. When all seven series were fitted a reasonable correlation was found between calculated and experimental values (R(2)=0.89). When the two compositional series that were designed in weight percentages (the remaining five were designed in molar percentage) were removed from the model an improved fit was achieved (R(2)=0.97). This study shows that T(g) for a wide range in compositions (e.g. SiO(2) content of 37.3-68.4 mol.%) can be predicted to reasonable accuracy enabling processing parameters to be predicted such as annealing, fibre-drawing and sintering temperatures.

  12. Conformational gel analysis and graphics: Measurement of side chain rotational isomer populations by NMR and molecular mechanics

    CERN Document Server

    Haydock, Christopher

    2007-01-01

    Conformational gel analysis and graphics systematically identifies and evaluates plausible alternatives to the side chain conformations found by conventional peptide or protein structure determination methods. The proposed analysis determines the populations of side chain rotational isomers and the probability distribution of these populations. The following steps are repeated for each side chain of a peptide or protein: first, extract the local molecular mechanics of side chain rotational isomerization from a single representative global conformation; second, expand the predominant set of rotational isomers to include all probable rotational isomers down to those that constitute just a small percentage of the population; and third, evaluate the constraints vicinal coupling constants and NOESY cross relaxation rates place on rotational isomer populations. In this article we apply conformational gel analysis to the cobalt glycyl-leucine dipeptide and detail the steps necessary to generalize the analysis to oth...

  13. Molecular characteristics of humic acids isolated from vermicomposts and their relationship to bioactivity.

    Science.gov (United States)

    Martinez-Balmori, Dariellys; Spaccini, Riccardo; Aguiar, Natália Oliveira; Novotny, Etelvino Henrique; Olivares, Fábio Lopes; Canellas, Luciano Pasqualoto

    2014-11-26

    Vermitechnology is an effective composting method, which transforms biomass into nutrient-rich organic fertilizer. Mature vermicompost is a renewable organic product containing humic substances with high biological activity. The aim of this study was to assess the chemical characteristics and the bioactivity of humic acids isolated from different vermicomposts produced with either cattle manure, sugar cane bagasse, sunflower cake from seed oil extraction, or filter cake from a sugar cane factory. More than 200 different molecules were found, and it was possible to identify chemical markers on humic acids according to the nature of the organic source. The large hydrophobic character of humic extracts and the preservation of altered lignin derivatives confer to humic acids the ability to induce lateral root emergence in maize seedlings. Humic acid-like substances extracted from plant biomass residues represent an additional valuable product of vermicomposting that can be used as a plant growth promoter.

  14. Mussel adhesion is dictated by time-regulated secretion and molecular conformation of mussel adhesive proteins

    Science.gov (United States)

    Petrone, Luigi; Kumar, Akshita; Sutanto, Clarinda N.; Patil, Navinkumar J.; Kannan, Srinivasaraghavan; Palaniappan, Alagappan; Amini, Shahrouz; Zappone, Bruno; Verma, Chandra; Miserez, Ali

    2015-10-01

    Interfacial water constitutes a formidable barrier to strong surface bonding, hampering the development of water-resistant synthetic adhesives. Notwithstanding this obstacle, the Asian green mussel Perna viridis attaches firmly to underwater surfaces via a proteinaceous secretion (byssus). Extending beyond the currently known design principles of mussel adhesion, here we elucidate the precise time-regulated secretion of P. viridis mussel adhesive proteins. The vanguard 3,4-dihydroxy-L-phenylalanine (Dopa)-rich protein Pvfp-5 acts as an adhesive primer, overcoming repulsive hydration forces by displacing surface-bound water and generating strong surface adhesion. Using homology modelling and molecular dynamics simulations, we find that all mussel adhesive proteins are largely unordered, with Pvfp-5 adopting a disordered structure and elongated conformation whereby all Dopa residues reside on the protein surface. Time-regulated secretion and structural disorder of mussel adhesive proteins appear essential for optimizing extended nonspecific surface interactions and byssus' assembly. Our findings reveal molecular-scale principles to help the development of wet-resistant adhesives.

  15. Molecular effects of bioactive fraction of Curcuma mangga (DLBS4847) as a downregulator of 5α-reductase activity pathways in prostatic epithelial cells

    OpenAIRE

    TJANDRAWINATA, Raymond; Karsono, Agung Heru; Tandrasasmita,Olivia

    2014-01-01

    Agung Heru Karsono, Olivia Mayasari Tandrasasmita, Raymond R TjandrawinataSection of Molecular Pharmacology, Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, Dexa Medica, Cikarang, IndonesiaAbstract: DLBS4847 is a standardized bioactive fraction of Curcuma mangga. In this study, we used prostate cancer (PC)-3 as the cell line to study the effects of DLBS4847 on prostatic cell viability, as well as related molecular changes associated with the decreased cell numbe...

  16. Conformations of some lower-size large-ring cyclodextrins derived from conformational search with molecular dynamics and principal component analysis

    Science.gov (United States)

    Ivanov, Petko

    2012-02-01

    Computational studies were conducted on the conformations of some lower-size large-ring cyclodextrins, CDn (n = 11, 12, 13, 15, 16, 17). Principal component analysis (PCA) was applied for post-processing of trajectories from conformational search based on 100.0 ns molecular dynamics (MD) simulations. The dominant PCA modes for concerted motions of the macroring atoms were monitored in a lower-dimensions subspace. The first six lowest indexed principal components contribute more than 90% of the total atomic motions in all cases, with about 70% (CD12) to 90% (CD17) contribution coming from the three highest-eigenvalue principal components. Representative average geometries of the cyclodextrin macrorings were also obtained for the whole simulation and for the ten 10.0 ns time intervals of the simulation. We concluded that the whole set of structures could be sorted into two clearly distinguished groups, separated by the figure-eight conformation of CD14: (i) open bent boat-like macrorings (CD11 to CD13), and (ii) two winded single helical strands (an anti-parallel double helix with foldbacks at each end), CD15 to CD17, shaped as number eight for the odd-number-residues cases, CD15 and CD17. CD13 and CD14 mark the borderline between lower and higher flexibilities of the lower-size LR-CDs macrorings.

  17. DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening

    Directory of Open Access Journals (Sweden)

    Villoutreix Bruno O

    2009-11-01

    Full Text Available Abstract Background Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. Results Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. Conclusion DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.

  18. Quantitatively integrating molecular structure and bioactivity profile evidence into drug-target relationship analysis

    Directory of Open Access Journals (Sweden)

    Xu Tianlei

    2012-05-01

    Full Text Available Abstract Background Public resources of chemical compound are in a rapid growth both in quantity and the types of data-representation. To comprehensively understand the relationship between the intrinsic features of chemical compounds and protein targets is an essential task to evaluate potential protein-binding function for virtual drug screening. In previous studies, correlations were proposed between bioactivity profiles and target networks, especially when chemical structures were similar. With the lack of effective quantitative methods to uncover such correlation, it is demanding and necessary for us to integrate the information from multiple data sources to produce an comprehensive assessment of the similarity between small molecules, as well as quantitatively uncover the relationship between compounds and their targets by such integrated schema. Results In this study a multi-view based clustering algorithm was introduced to quantitatively integrate compound similarity from both bioactivity profiles and structural fingerprints. Firstly, a hierarchy clustering was performed with the fused similarity on 37 compounds curated from PubChem. Compared to clustering in a single view, the overall common target number within fused classes has been improved by using the integrated similarity, which indicated that the present multi-view based clustering is more efficient by successfully identifying clusters with its members sharing more number of common targets. Analysis in certain classes reveals that mutual complement of the two views for compound description helps to discover missing similar compound when only single view was applied. Then, a large-scale drug virtual screen was performed on 1267 compounds curated from Connectivity Map (CMap dataset based on the fused similarity, which obtained a better ranking result compared to that of single-view. These comprehensive tests indicated that by combining different data representations; an improved

  19. Temperature-accelerated molecular dynamics gives insights into globular conformations sampled in the free state of the AC catalytic domain.

    Science.gov (United States)

    Selwa, Edithe; Huynh, Tru; Ciccotti, Giovanni; Maragliano, Luca; Malliavin, Thérèse E

    2014-10-01

    The catalytic domain of the adenyl cyclase (AC) toxin from Bordetella pertussis is activated by interaction with calmodulin (CaM), resulting in cAMP overproduction in the infected cell. In the X-ray crystallographic structure of the complex between AC and the C terminal lobe of CaM, the toxin displays a markedly elongated shape. As for the structure of the isolated protein, experimental results support the hypothesis that more globular conformations are sampled, but information at atomic resolution is still lacking. Here, we use temperature-accelerated molecular dynamics (TAMD) simulations to generate putative all-atom models of globular conformations sampled by CaM-free AC. As collective variables, we use centers of mass coordinates of groups of residues selected from the analysis of standard molecular dynamics (MD) simulations. Results show that TAMD allows extended conformational sampling and generates AC conformations that are more globular than in the complexed state. These structures are then refined via energy minimization and further unrestrained MD simulations to optimize inter-domain packing interactions, thus resulting in the identification of a set of hydrogen bonds present in the globular conformations.

  20. Molecular dynamics analysis of conformational change of paramyxovirus F protein during the initial steps of membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Garcia, Fernando; Mendieta-Moreno, Jesus Ignacio; Mendieta, Jesus [Centro de Biologia Molecular ' Severo Ochoa' (CSIC/UAM), C/ Nicolas Cabrera, 1, Cantoblanco, 28049 Madrid (Spain); Biomol-Informatics SL, Parque Cientifico de Madrid, C/ Faraday, 7, Cantoblanco, 28049 Madrid (Spain); Gomez-Puertas, Paulino, E-mail: pagomez@cbm.uam.es [Centro de Biologia Molecular ' Severo Ochoa' (CSIC/UAM), C/ Nicolas Cabrera, 1, Cantoblanco, 28049 Madrid (Spain)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Initial conformational change of paramyxovirus F protein is caused only by mechanical forces. Black-Right-Pointing-Pointer HRA region undergoes a structural change from a beta + alpha conformation to an extended coil and then to an all-alpha conformation. Black-Right-Pointing-Pointer HRS domains of F protein form three single {alpha}-helices prior to generation of the coiled coil. -- Abstract: The fusion of paramyxovirus to the cell membrane is mediated by fusion protein (F protein) present in the virus envelope, which undergoes a dramatic conformational change during the process. Unlike hemagglutinin in orthomyxovirus, this change is not mediated by an alteration of environmental pH, and its cause remains unknown. Steered molecular dynamics analysis leads us to suggest that the conformational modification is mediated only by stretching mechanical forces once the transmembrane fusion peptide of the protein is anchored to the cell membrane. Such elongating forces will generate major secondary structure rearrangement in the heptad repeat A region of the F protein; from {beta}-sheet conformation to an elongated coil and then spontaneously to an {alpha}-helix. In addition, it is proposed that the heptad repeat A region adopts a final three-helix coiled coil and that this structure appears after the formation of individual helices in each monomer.

  1. Molecular Docking Study of Bioactive Compound of Andrographolide against Ebola Virus

    Directory of Open Access Journals (Sweden)

    R.Sharmila

    2016-05-01

    Full Text Available Ebola virus is a single-stranded, negative-sense RNA virus that causes severe hemorrhagic fever in humans and nonhuman primates. This virus is resistance to many antibiotics also there is no proper treatment for EBOLA viral infection. In worldwide,thus many people affected by this virus and there is no drug available for treatment of Ebola virus infection. Therefore new drugs are need for therapy and prevention for this life threatening infection. Hence the current study deals with the evaluation of the potent bioactive compound Andrographolide against the three receptors of Ebola virus receptor proteins. The protein receptors VP40, VP35 and VP24 were docked with the Andrographolide and evaluated on the basis of total energy and binding affinity scores byAutoDock. Andrographolide showed a high docking score against the VP40, VP35 and VP24. Theestimated binding free energy of VP40 is −3.57 kcal/mol, the VP35 binding free energy is −7.18 kcal/mol. The VP24 binding free energy is −8.5 kcal/mol. This study showed that Andrographolide have high binding affinity and exhibit better interactions with all the Ebola Virus Protein receptors. This study will help to identify the new drug development for the EBOLA virus.

  2. On the connection between nonmonotonic taste behavior and molecular conformation in solution: The case of rebaudioside-A

    Energy Technology Data Exchange (ETDEWEB)

    Chopade, Prashant D.; Sarma, Bipul; Santiso, Erik E.; Chen, Jie; Trout, Bernhardt L.; Myerson, Allan S., E-mail: myerson@mit.edu [Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 66-568, Cambridge, Massachusetts 02139 (United States); Simpson, Jeffrey [Department of Chemistry Instrumentation Facility, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 18-0090, Cambridge, Massachusetts 02139 (United States); Fry, John C.; Biermann, Kari L. [Connect Consulting, 6 Hollands Field, Horsham RH123HQ (United Kingdom); Yurttas, Nese [Cargill, Inc., Global Food Technology, 2301 Crosby Road, Wayzata, Minnesota 55391 (United States)

    2015-12-28

    The diterpene steviol glycoside, rebaudioside A, is a natural high potency non-caloric sweetener extracted from the leaves of Stevia rebaudiana. This compound shows a parabolic change in sweet taste intensity with temperature which contrasts with the general finding for other synthetic or natural sweeteners whose sweet taste increases with temperature. The nonmonotonic taste behavior was determined by sensory analysis using large taste panels. The conformational landscape of rebaudioside A was established at a range of temperatures by means of nuclear magnetic resonance and molecular dynamics simulation. The relationship between various conformations and the observed sweetness of rebaudioside A is described.

  3. On the connection between nonmonotonic taste behavior and molecular conformation in solution: The case of rebaudioside-A

    Science.gov (United States)

    Chopade, Prashant D.; Sarma, Bipul; Santiso, Erik E.; Simpson, Jeffrey; Fry, John C.; Yurttas, Nese; Biermann, Kari L.; Chen, Jie; Trout, Bernhardt L.; Myerson, Allan S.

    2015-12-01

    The diterpene steviol glycoside, rebaudioside A, is a natural high potency non-caloric sweetener extracted from the leaves of Stevia rebaudiana. This compound shows a parabolic change in sweet taste intensity with temperature which contrasts with the general finding for other synthetic or natural sweeteners whose sweet taste increases with temperature. The nonmonotonic taste behavior was determined by sensory analysis using large taste panels. The conformational landscape of rebaudioside A was established at a range of temperatures by means of nuclear magnetic resonance and molecular dynamics simulation. The relationship between various conformations and the observed sweetness of rebaudioside A is described.

  4. Molecular detection of plant pathogenic bacteria using polymerase chain reaction single-strand conformation polymorphism.

    Science.gov (United States)

    Srinivasa, Chandrashekar; Sharanaiah, Umesha; Shivamallu, Chandan

    2012-03-01

    The application of polymerase chain reaction (PCR) technology to molecular diagnostics holds great promise for the early identification of agriculturally important plant pathogens. Ralstonia solanacearum, Xanthomoans axonopodis pv. vesicatoria, and Xanthomonas oryzae pv. oryzae are phytopathogenic bacteria, which can infect vegetables, cause severe yield loss. PCR-single-strand conformation polymorphism (PCR-SSCP) is a simple and powerful technique for identifying sequence changes in amplified DNA. The technique of PCR-SSCP is being exploited so far, only to detect and diagnose human bacterial pathogens in addition to plant pathogenic fungi. Selective media and serology are the commonly used methods for the detection of plant pathogens in infected plant materials. In this study, we developed PCR-SSCP technique to identify phytopathogenic bacteria. The PCR product was denatured and separated on a non-denaturing polyacrylamide gel. SSCP banding patterns were detected by silver staining of nucleic acids. We tested over 56 isolates of R. solanacearum, 44 isolates of X. axonopodis pv. vesicatoria, and 20 isolates of X. oryzae pv. oryzae. With the use of universal primer 16S rRNA, we could discriminate such species at the genus and species levels. Species-specific patterns were obtained for bacteria R. solanacearum, X. axonopodis pv. vesicatoria, and X. oryzae pv. oryzae. The potential use of PCR-SSCP technique for the detection and diagnosis of phytobacterial pathogens is discussed in the present paper.

  5. Molecular detection of plant pathogenic bacteria using polymerase chain reaction single-strand conformation polymorphism

    Institute of Scientific and Technical Information of China (English)

    Chandrashekar Srinivasa; Umesha Sharanaiah; Chandan Shivamallu

    2012-01-01

    The application of polymerase chain reaction (PCR) technology to molecular diagnostics holds great promise for the early identification of agriculturally important plant pathogens.Ralstonia solanacearum,Xanthomoans axonopodis pv.vesicatoria,and Xanthomonas oryzae pv.oryzae are phytopathogenic bacteria,which can infect vegetables,cause severe yield loss.PCR-single-strand conformation polymorphism (PCR-SSCP) is a simple and powerful technique for identifying sequence changes in amplified DNA.The technique of PCR-SSCP is being exploited so far,only to detect and diagnose human bacterial pathogens in addition to plant pathogenic fungi.Selective media and serology are the commonly used methods for the detection of plant pathogens in infected plant materials.In this study,we developed PCR-SSCP technique to identify phytopathogenic bacteria.The PCR product was denatured and separated on a non-denaturing polyacrylamide gel.SSCP banding patterns were detected by silver staining of nucleic acids.We tested over 56 isolates of R. solanacearum,44 isolates of X. axonopodis pv.vesicatoria,and 20 isolates of X.oryzae pv.oryzae.With the use of universal primer 16S rRNA,we could discriminate such species at the genus and species levels.Speciesspecific patterns were obtained for bacteria R.solanacearum,X.axonopodis pv.vesicatoria,and X.oryzae pv.oryzae.The potential use of PCR-SSCP technique for the detection and diagnosis of phytobacterial pathogens is discussed in the present paper.

  6. Role of molecular conformations in rubrene polycrystalline films growth from vacuum deposition at various substrate temperatures

    Science.gov (United States)

    Lin, Ku-Yen; Wang, Yan-Jun; Chen, Ko-Lun; Ho, Ching-Yuan; Yang, Chun-Chuen; Shen, Ji-Lin; Chiu, Kuan-Cheng

    2017-01-01

    We report on the optical and structural characterization of rubrene polycrystalline films fabricated from vacuum deposition with various substrate temperatures (Tsub). Depending on Tsub, the role of twisted and planar rubrene conformational isomers on the properties of rubrene films is focused. The temperature (T)-dependent inverse optical transmission (IOT) and photoluminescence (PL) spectra were performed on these rubrene films. The origins of these IOT and PL peaks are explained in terms of the features from twisted and planar rubrene molecules and of the band characteristics from rubrene molecular solid films. Here, two rarely reported weak-peaks at 2.431 and 2.605 eV were observed from IOT spectra, which are associated with planar rubrene. Besides, the T-dependence of optical bandgap deduced from IOT spectra is discussed with respect to Tsub. Together with IOT and PL spectra, for Tsub > 170 °C, the changes in surface morphology and unit cell volume were observed for the first time, and are attributed to the isomeric transformation from twisted to planar rubrenes during the deposition processes. Furthermore, a unified schematic diagram in terms of Frenkel exciton recombination is suggested to explain the origins of the dominant PL peaks performed on these rubrene films at 15 K.

  7. Bioactivity of Variant Molecular Weight Chitosan Against Drug-Resistant Bacteria Isolated from Human Wounds.

    Science.gov (United States)

    Bano, Ijaz; Arshad, Muhammad; Ghauri, Muhammad Afzal; Yasin, Tariq; Younus, Muhammad

    2017-03-30

    Chitosan available from crab shells is usually of high molecular weight which may result in reduced efficiency for its antibacterial activity. One of the techniques for improving chitosan antibacterial efficiency is reducing its molecular weight. The irradiation of chitosan by gamma radiations is considered to be one of the most effective and widely used methods for improving its antibacterial activity. Chitosan obtained from crab shells was irradiated with gamma radiations at different doses, and effects on chitosan were analyzed by molecular weight determination and Fourier Transform Infrared spectroscopy. Unirradiated and irradiated chitosans were studied for their antibacterial properties against bacterial pathogens, that is, Pseudomonas aeruginosa (SS29), Escherichia coli (SS2, SS9), Proteus mirabilis (SS77), and Staphylococcus aureus (LM15). Studies have shown that irradiation has significantly developed and improved the antibacterial activity of crab shell chitosan. A correlation was found between bacterial metabolites and antibacterial activity by the analysis for 4-hydroxy-2-alkylquinolines and related metabolites of P. aeruginosa (SS29) in the absence and presence of chitosan by liquid chromatography mass spectrometer, exhibiting the suppression of these virulence factors due to chitosan. Antibacterial efficiency of chitosan was found to be molecular weight dependent and applied concentration of the chitosan. The findings suggest on the use of low-molecular weight chitosan as antibacterial agent in pharmaceutical preparations.

  8. Charge-dependent conformations and dynamics of pamam dendrimers revealed by neutron scattering and molecular dynamics

    Science.gov (United States)

    Wu, Bin

    Neutron scattering and fully atomistic molecular dynamics (MD) are employed to investigate the structural and dynamical properties of polyamidoamine (PAMAM) dendrimers with ethylenediamine (EDA) core under various charge conditions. Regarding to the conformational characteristics, we focus on scrutinizing density profile evolution of PAMAM dendrimers as the molecular charge of dendrimer increases from neutral state to highly charged condition. It should be noted that within the context of small angle neutron scattering (SANS), the dendrimers are composed of hydrocarbon component (dry part) and the penetrating water molecules. Though there have been SANS experiments that studied the charge-dependent structural change of PAMAM dendrimers, their results were limited to the collective behavior of the aforementioned two parts. This study is devoted to deepen the understanding towards the structural responsiveness of intra-molecular polymeric and hydration parts separately through advanced contrast variation SANS data analysis scheme available recently and unravel the governing principles through coupling with MD simulations. Two kinds of acids, namely hydrochloric and sulfuric acids, are utilized to tune the pH condition and hence the molecular charge. As far as the dynamical properties, we target at understanding the underlying mechanism that leads to segmental dynamic enhancement observed from quasielstic neutron scattering (QENS) experiment previously. PAMAM dendrimers have a wealth of potential applications, such as drug delivery agency, energy harvesting medium, and light emitting diodes. More importantly, it is regarded as an ideal system to test many theoretical predictions since dendrimers conjugate both colloid-like globular shape and polymer-like flexible chains. This Ph.D. research addresses two main challenges in studying PAMAM dendrimers. Even though neutron scattering is an ideal tool to study this PAMAM dendrimer solution due to its matching temporal and

  9. Characteristics and bioactivities of different molecular weight polysaccharides from camellia seed cake.

    Science.gov (United States)

    Xu, Zhou; Li, Xu; Feng, Shiling; Liu, Jing; Zhou, Lijun; Yuan, Ming; Ding, Chunbang

    2016-10-01

    Four polysaccharides, namely COP-1, COP-2, COP-3 and COP-4, were ultrafiltrated from crud Camellia oleifera seed cake polysaccharides (COP-c), purified, and characterized, including the determination of antioxidant and antiproliferative activities. Their molecular weights were 7.9, 36, 83 and 225kDa, respectively. All COPs showed the similar FT-IR spectrums, but significant differentials in monosaccharide components. COP-2 exhibited the highest radical scavenging abilities. COP-1 has the strongest metal chelating capabilities. Although with higher molecular weight, COP-4 showed the poorest antioxidant abilities. These results suggested appreciate molecular weight COP possessed a better antioxidant activities. Additionally, all COPs had non-significant antiproliferative abilities in HaLa and HepG2 cells.

  10. Encapsulation of bioactive whey peptides in soy lecithin-derived nanoliposomes: Influence of peptide molecular weight.

    Science.gov (United States)

    Mohan, Aishwarya; McClements, David Julian; Udenigwe, Chibuike C

    2016-12-15

    Encapsulation of peptides can be used to enhance their stability, delivery and bioavailability. This study focused on the effect of the molecular weight range of whey peptides on their encapsulation within soy lecithin-derived nanoliposomes. Peptide molecular weight did not have a major impact on encapsulation efficiency or liposome size. However, it influenced peptide distribution amongst the surface, core, and bilayer regions of the liposomes, as determined by electrical charge (ζ-potential) and FTIR analysis. The liposome ζ-potential depended on peptide molecular weight, suggesting that the peptide charged groups were in different locations relative to the liposome surfaces. FTIR analysis indicated that the least hydrophobic peptide fractions interacted more strongly with choline on the liposome surfaces. The results suggested that the peptides were unequally distributed within the liposomes, even at the same encapsulation efficiency. These findings are important for designing delivery systems for commercial production of encapsulated peptides with improved functional attributes.

  11. Conformational analysis of phloroglucinols from hypericum Brasiliense by using x-ray diffraction and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Katia Z.; Lindgren, Eric B.; Correa, Arthur L., E-mail: kzleal@uol.com.b [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Inst. de Quimica. Dept. de Fisico-Quimica; Yoneda, Julliane D. [Universidade Federal Fluminense (UFF), Volta Redonda, RJ (Brazil). Polo Universitario de Volta Redonda; Pinheiro, Carlos B. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Fisica; Franca, Hildegardo S. [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Faculdade de Farmacia. Dept. de Tecnologia Farmaceutica

    2010-07-01

    In this work we intend to verify the applicability of a computational methodology to predict structural features of organic compounds with biological activity. We selected three phloroglucinols and compared their calculated conformational data with their X-ray crystallographic structure. The results showed that conformations obtained by conformational analysis with the AM1 method followed by geometry optimization by using the DFT B3LYP/6-31 G(d,p) basis set are in very good agreement with X-ray data, indicating that the methodology employed here seems to be a very useful tool in order to predict the conformational preference for this class of compounds. (author)

  12. Combined experimental powder X-ray diffraction and DFT data to obtain the lowest energy molecular conformation of friedelin

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Djalma Menezes de; Mussel, Wagner da Nova; Duarte, Lucienir Pains; Silva, Gracia Divina de Fatima; Duarte, Helio Anderson; Gomes, Elionai Cassiana de Lima [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Quimica; Guimaraes, Luciana [Universidade Federal de Sao Joao Del-Rei (UFSJ), MG (Brazil). Dept. de Ciencias Naturais; Vieira Filho, Sidney A., E-mail: bibo@ef.ufop.br [Universidade Federal de Ouro Preto (UFOP), MG (Brazil). Dept. de Farmacia

    2012-07-01

    Friedelin molecular conformers were obtained by Density Functional Theory (DFT) and by ab initio structure determination from powder X-ray diffraction. Their conformers with the five rings in chair-chair-chair-boat-boat, and with all rings in chair, are energy degenerated in gas-phase according to DFT results. The powder diffraction data reveals that rings A, B and C of friedelin are in chair, and rings D and E in boat-boat, conformation. The high correlation values among powder diffraction data, DFT and reported single crystal data indicate that the use of conventional X-ray diffractometer can be applied in routine laboratory analysis in the absence of a single-crystal diffractometer. (author)

  13. Comparison of Chain Conformation of Poly(vinyl alcohol) in Solutions and Melts from Quantum Chemistry Based Molecular Dynamics Simulations

    Science.gov (United States)

    Jaffe, Richard; Han, Jie; Matsuda, Tsunetoshi; Yoon, Do; Langhoff, Stephen R. (Technical Monitor)

    1997-01-01

    Confirmations of 2,4-dihydroxypentane (DHP), a model molecule for poly(vinyl alcohol), have been studied by quantum chemistry (QC) calculations and molecular dynamics (MD) simulations. QC calculations at the 6-311G MP2 level show the meso tt conformer to be lowest in energy followed by the racemic tg, due to intramolecular hydrogen bond between the hydroxy groups. The Dreiding force field has been modified to reproduce the QC conformer energies for DHP. MD simulations using this force field have been carried out for DHP molecules in the gas phase, melt, and CHCl3 and water solutions. Extensive intramolecular hydrogen bonding is observed for the gas phase and CHCl3 solution, but not for the melt or aqueous solution, Such a condensed phase effect due to intermolecular interactions results in a drastic change in chain conformations, in agreement with experiments.

  14. Combined experimental powder X-ray diffraction and DFT data to obtain the lowest energy molecular conformation of friedelin

    Directory of Open Access Journals (Sweden)

    Djalma Menezes de Oliveira

    2012-01-01

    Full Text Available Friedelin molecular conformers were obtained by Density Functional Theory (DFT and by ab initio structure determination from powder X-ray diffraction. Their conformers with the five rings in chair-chair-chair-boat-boat, and with all rings in chair, are energy degenerated in gas-phase according to DFT results. The powder diffraction data reveals that rings A, B and C of friedelin are in chair, and rings D and E in boat-boat, conformation. The high correlation values among powder diffraction data, DFT and reported single-crystal data indicate that the use of conventional X-ray diffractometer can be applied in routine laboratory analysis in the absence of a single-crystal diffractometer.

  15. Bioactive substances

    Digital Repository Service at National Institute of Oceanography (India)

    Wahidullah, S.

    Chemistry related to certain bioactive molecules, from Indian Ocean Region, developed into drugs or which served as models for the synthesis of more effective bioactive substances or in use in fundamental studies of physiological and biochemical...

  16. Characterizing the conformational dynamics of metal-free PsaA using molecular dynamics simulations and electron paramagnetic resonance spectroscopy.

    Science.gov (United States)

    Deplazes, Evelyne; Begg, Stephanie L; van Wonderen, Jessica H; Campbell, Rebecca; Kobe, Bostjan; Paton, James C; MacMillan, Fraser; McDevitt, Christopher A; O'Mara, Megan L

    2015-12-01

    Prokaryotic metal-ion receptor proteins, or solute-binding proteins, facilitate the acquisition of metal ions from the extracellular environment. Pneumococcal surface antigen A (PsaA) is the primary Mn(2+)-recruiting protein of the human pathogen Streptococcus pneumoniae and is essential for its in vivo colonization and virulence. The recently reported high-resolution structures of metal-free and metal-bound PsaA have provided the first insights into the mechanism of PsaA-facilitated metal binding. However, the conformational dynamics of metal-free PsaA in solution remain unknown. Here, we use continuous wave electron paramagnetic resonance (EPR) spectroscopy and molecular dynamics (MD) simulations to study the relative flexibility of the structural domains in metal-free PsaA and its distribution of conformations in solution. The results show that the crystal structure of metal-free PsaA is a good representation of the dominant conformation in solution, but the protein also samples structurally distinct conformations that are not captured by the crystal structure. Further, these results suggest that the metal binding site is both larger and more solvent exposed than indicated by the metal-free crystal structure. Collectively, this study provides atomic-resolution insight into the conformational dynamics of PsaA prior to metal binding and lays the groundwork for future EPR and MD based studies of PsaA in solution.

  17. Applications of single-strand conformation polymorphism (SSCP) to taxonomy, diagnosis, population genetics and molecular evolution of parasitic nematodes.

    Science.gov (United States)

    Gasser, R B; Chilton, N B

    2001-11-22

    The analysis of genetic variation in parasitic nematodes has important implications for studying aspects of taxonomy, diagnosis, population genetics, drug resistance and molecular evolution. This article highlights some applications of PCR-based single-strand conformation polymorphism (SSCP) for the analysis of sequence variation in individual parasites (and their populations) to address some of these areas. It also describes the principles and advantages of SSCP, and provides some examples for future applications in parasitology.

  18. [Analysis of Conformational Features of Watson-Crick Duplex Fragments by Molecular Mechanics and Quantum Mechanics Methods].

    Science.gov (United States)

    Poltev, V I; Anisimov, V M; Sanchez, C; Deriabina, A; Gonzalez, E; Garcia, D; Rivas, F; Polteva, N A

    2016-01-01

    It is generally accepted that the important characteristic features of the Watson-Crick duplex originate from the molecular structure of its subunits. However, it still remains to elucidate what properties of each subunit are responsible for the significant characteristic features of the DNA structure. The computations of desoxydinucleoside monophosphates complexes with Na-ions using density functional theory revealed a pivotal role of DNA conformational properties of single-chain minimal fragments in the development of unique features of the Watson-Crick duplex. We found that directionality of the sugar-phosphate backbone and the preferable ranges of its torsion angles, combined with the difference between purines and pyrimidines. in ring bases, define the dependence of three-dimensional structure of the Watson-Crick duplex on nucleotide base sequence. In this work, we extended these density functional theory computations to the minimal' fragments of DNA duplex, complementary desoxydinucleoside monophosphates complexes with Na-ions. Using several computational methods and various functionals, we performed a search for energy minima of BI-conformation for complementary desoxydinucleoside monophosphates complexes with different nucleoside sequences. Two sequences are optimized using ab initio method at the MP2/6-31++G** level of theory. The analysis of torsion angles, sugar ring puckering and mutual base positions of optimized structures demonstrates that the conformational characteristic features of complementary desoxydinucleoside monophosphates complexes with Na-ions remain within BI ranges and become closer to the corresponding characteristic features of the Watson-Crick duplex crystals. Qualitatively, the main characteristic features of each studied complementary desoxydinucleoside monophosphates complex remain invariant when different computational methods are used, although the quantitative values of some conformational parameters could vary lying within the

  19. Conformations of Carnosine in Aqueous Solutions by All-Atom Molecular Dynamics Simulations and 2D-NOSEY Spectrum

    Institute of Scientific and Technical Information of China (English)

    Rong Zhang; Dan Wang; Wen-juan Wu

    2013-01-01

    All-atom molecular simulations and two-dimensional nuclear overhauser effect spectrum have been used to study the conformations of carnosine in aqueous solution.Intramolecular distances,root-mean-square deviation,radius of gyration,and solvent-accessible surface are used to characterize the properties of the carnosine.Carnosine can shift between extended and folded states,but exists mostly in extended state in water.Its preference for extension in pure water has been proven by the 2D nuclear magnetic resonance (NMR) experiment.The NMR experimental results are consistent with the molecular dynamics simulations.

  20. Modeling signal propagation mechanisms and ligand-based conformational dynamics of the Hsp90 molecular chaperone full-length dimer.

    Directory of Open Access Journals (Sweden)

    Giulia Morra

    2009-03-01

    Full Text Available Hsp90 is a molecular chaperone essential for protein folding and activation in normal homeostasis and stress response. ATP binding and hydrolysis facilitate Hsp90 conformational changes required for client activation. Hsp90 plays an important role in disease states, particularly in cancer, where chaperoning of the mutated and overexpressed oncoproteins is important for function. Recent studies have illuminated mechanisms related to the chaperone function. However, an atomic resolution view of Hsp90 conformational dynamics, determined by the presence of different binding partners, is critical to define communication pathways between remote residues in different domains intimately affecting the chaperone cycle. Here, we present a computational analysis of signal propagation and long-range communication pathways in Hsp90. We carried out molecular dynamics simulations of the full-length Hsp90 dimer, combined with essential dynamics, correlation analysis, and a signal propagation model. All-atom MD simulations with timescales of 70 ns have been performed for complexes with the natural substrates ATP and ADP and for the unliganded dimer. We elucidate the mechanisms of signal propagation and determine "hot spots" involved in interdomain communication pathways from the nucleotide-binding site to the C-terminal domain interface. A comprehensive computational analysis of the Hsp90 communication pathways and dynamics at atomic resolution has revealed the role of the nucleotide in effecting conformational changes, elucidating the mechanisms of signal propagation. Functionally important residues and secondary structure elements emerge as effective mediators of communication between the nucleotide-binding site and the C-terminal interface. Furthermore, we show that specific interdomain signal propagation pathways may be activated as a function of the ligand. Our results support a "conformational selection model" of the Hsp90 mechanism, whereby the protein may

  1. Systems Chemo-Biology and Transcriptomic Meta-Analysis Reveal the Molecular Roles of Bioactive Lipids in Cardiomyocyte Differentiation.

    Science.gov (United States)

    de Faria Poloni, Joice; Bonatto, Diego

    2015-09-01

    Lipids, which are essential constituents of biological membranes, play structural and functional roles in the cell. In recent years, certain lipids have been identified as regulatory signaling molecules and have been termed "bioactive lipids". Subsequently, the importance of bioactive lipids in stem cell differentiation and cardiogenesis has gained increasing recognition. Therefore, the aim of this study was to identify the biological processes underlying murine cardiac differentiation and the mechanisms by which bioactive lipids affect these processes. For this purpose, a transcriptomic meta-analysis of microarray and RNA-seq data from murine stem cells undergoing cardiogenic differentiation was performed. The differentially expressed genes identified via this meta-analysis, as well as bioactive lipids, were evaluated using systems chemo-biology tools. These data indicated that bioactive lipids are associated with the regulation of cell motility, cell adhesion, cytoskeletal rearrangement, and gene expression. Moreover, bioactive lipids integrate the signaling pathways involved in cell migration, the secretion and remodeling of extracellular matrix components, and the establishment of the cardiac phenotype. In conclusion, this study provides new insights into the contribution of bioactive lipids to the induction of cellular responses to various stimuli, which may originate from the extracellular environment and morphogens, and the manner in which this contribution directly affects murine heart morphogenesis.

  2. Lysozyme-magnesium aluminum silicate microparticles: Molecular interaction, bioactivity and release studies

    DEFF Research Database (Denmark)

    Kanjanakawinkul, Watchara; Medlicott, Natalie J.; Rades, Thomas;

    2015-01-01

    The objectives of this study were to investigate the adsorption behavior of lysozyme (LSZ) onto magnesium aluminum silicate (MAS) at various pHs and to characterize the LSZ–MAS microparticles obtained from the molecular interaction between LSZ and MAS. The results showed that LSZ could be bound...... onto the MAS layers at different pHs, leading to the formation of LSZ–MAS microparticles. The higher preparation pH permitted greater adsorption affinity but a lower adsorption capacity of LSZ onto MAS. LSZ could interact with MAS via hydrogen bonds and electrostatic forces, resulting in the formation......, the LSZ extracted from microparticles prepared at pH 4 showed an obvious change in the tertiary structure, leading to a decrease in the biological activity of the LSZ released. These findings suggested that LSZ can strongly interact with MAS to form microparticles that may potentially be used as delivery...

  3. From Chemistry to Behavior. Molecular Structure and Bioactivity of Repellents against Ixodes ricinus Ticks.

    Directory of Open Access Journals (Sweden)

    Simone Del Fabbro

    Full Text Available Tick-borne zoonoses are considered as emerging diseases. Tick repellents represent an effective tool for reducing the risk of tick bite and pathogens transmission. Previous work demonstrated the repellent activity of the phenylpropanoid eugenol against Ixodes ricinus; here we investigate the relationship between molecular structure and repellency in a group of substances related to that compound. We report the biological activity of 18 compounds varying for the presence/number of several moieties, including hydroxyl and methoxy groups and carbon side-chain. Each compound was tested at different doses with a bioassay designed to measure repellency against individual tick nymphs. Both vapor pressure and chemical features of the tested compounds appeared to be related to repellency. In particular, the hydroxyl and methoxy groups as well as the side-chain on the benzene ring seem to play a role. These results are discussed in light of available data on chemical perception in ticks. In the course of the study new repellent compounds were identified; the biological activity of some of them (at least as effective as the "gold standard" repellent DEET appears to be very promising from a practical point of view.

  4. Bioactive compounds from culinary herbs inhibit a molecular target for type 2 diabetes management, dipeptidyl peptidase IV

    Science.gov (United States)

    Greek oregano (Origanum vulgare), marjoram (Origanum majorana), rosemary (Rosmarinus officinalis) and Mexican oregano (Lippia graveolens) are concentrated sources of bioactive compounds. The aims of this study were to characterize extracts from greenhouse grown or commercially purchased herbs for th...

  5. Chiral lactic hydrazone derivatives as potential bioactive antibacterial agents: Synthesis, spectroscopic, structural and molecular docking studies

    Science.gov (United States)

    Noshiranzadeh, Nader; Heidari, Azam; Haghi, Fakhri; Bikas, Rahman; Lis, Tadeusz

    2017-01-01

    A series of novel chiral lactic-hydrazone derivatives were synthesized by condensation of (S)-lactic acid hydrazide with salicylaldehyde derivatives and characterized by elemental analysis and spectroscopic studies (FT-IR, 1H NMR and 13C NMR spectroscopy). The structure of one compound was determined by single crystal X-ray analysis. Antibacterial activity of the synthesized compounds was studied against Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli and Pseudomonas aeruginosa as bacterial cultures by broth microdilution method. All of the synthesized compounds showed good antibacterial activity with MIC range of 64-512 μg/mL. Compounds (S,E)-2-hydroxy-N-(2-hydroxy-5-nitrobenzylidene)propanehydrazide (5) and (S,E)-2-hydroxy-N-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)propanehydrazide (7) were the most effective antibacterial derivatives against S. aureus and E. coli respectively with a MIC value of 64 μg/mL. Bacterial biofilm formation assay showed that these compounds significantly inhibited biofilm formation of P. aeruginosa. Also, in silico molecular docking studies were performed to show lipoteichoic acid synthase (LtaS) inhibitory effect of lactic hydrazone derivatives. The association between electronic and structural effects of some substituents on the benzylidene moiety and the biological activity of these chiral compounds were studied. Structural studies show that compound with higher hydrogen bonding interactions show higher antibacterial activity. The results show chiral hydrazone derivatives based on lactic acid hydrazide could be used as potential lead compounds for developing novel antibacterial agents.

  6. Acyclic forms of aldohexoses and ketohexoses in aqueous and DMSO solutions: conformational features studied using molecular dynamics simulations.

    Science.gov (United States)

    Plazinski, Wojciech; Plazinska, Anita; Drach, Mateusz

    2016-04-14

    The molecular properties of aldohexoses and ketohexoses are usually studied in the context of their cyclic, furanose or pyranose structures which is due to the abundance of related tautomeric forms in aqueous solution. We studied the conformational features of a complete series of D-aldohexoses (D-allose, D-altrose, D-glucose, D-mannose, D-gulose, d-idose, D-galactose and D-talose) and D-ketohexoses (D-psicose, D-fructose, D-sorbose and D-tagatose) as well as of L-psicose by using microsecond-timescale molecular dynamics in explicit water and DMSO with the use of enhanced sampling methods. In each of the studied cases the preferred conformation corresponded to an extended chain structure; the less populated conformers included the quasi-cyclic structures, close to furanose rings and common for both aldo- and ketohexoses. The orientational preferences of the aldehyde or ketone groups are correlated with the relative populations of anomers characteristic of cyclic aldo- and ketohexoses, respectively, thus indicating that basic features of anomeric equilibria are preserved even if hexose molecules are not in their cyclic forms. No analogous relationship is observed in the case of other structural characteristics, such as the preferences of acyclic molecules to form either the furanose-or pyranose-like structures or maintaining the chair-like geometry of pseudo-pyranose rings.

  7. Setting the anomeric effect against steric effects in simple acyclic acetals. Non-anomeric non-classical conformations. An n.m.r. and molecular mechanics investigation

    DEFF Research Database (Denmark)

    Anderson, J. Edgar; Heki, Katsuhiko; Hirota, Minoru

    1987-01-01

    N.m.r. parameters for a series of simple aliphatic acetals indicate that the preferred conformation changes from the anomeric one found in formaldehyde dimethyl acetal (formal), to a new one whose structure is suggested by molecular mechanics calculations.......N.m.r. parameters for a series of simple aliphatic acetals indicate that the preferred conformation changes from the anomeric one found in formaldehyde dimethyl acetal (formal), to a new one whose structure is suggested by molecular mechanics calculations....

  8. Role of the Subunits Interactions in the Conformational Transitions in Adult Human Hemoglobin: an Explicit Solvent Molecular Dynamics Study

    CERN Document Server

    Yusuff, Olaniyi K; Bussi, Giovanni; Raugei, Simone

    2012-01-01

    Hemoglobin exhibits allosteric structural changes upon ligand binding due to the dynamic interactions between the ligand binding sites, the amino acids residues and some other solutes present under physiological conditions. In the present study, the dynamical and quaternary structural changes occurring in two unligated (deoxy-) T structures, and two fully ligated (oxy-) R, R2 structures of adult human hemoglobin were investigated with molecular dynamics. It is shown that, in the sub-microsecond time scale, there is no marked difference in the global dynamics of the amino acids residues in both the oxy- and the deoxy- forms of the individual structures. In addition, the R, R2 are relatively stable and do not present quaternary conformational changes within the time scale of our simulations while the T structure is dynamically more flexible and exhibited the T\\rightarrow R quaternary conformational transition, which is propagated by the relative rotation of the residues at the {\\alpha}1{\\beta}2 and {\\alpha}2{\\b...

  9. Effect of low molecular weight additives on immobilization strength, activity, and conformation of protein immobilized on PVC and UHMWPE.

    Science.gov (United States)

    Kondyurin, Alexey; Nosworthy, Neil J; Bilek, Marcela M M

    2011-05-17

    Horseradish peroxidase (HRP) was immobilized onto both plasticized and unplasticized polyvinylchloride (PVC) and ultrahigh molecular weight polyethylene (UHMWPE). Plasma immersion ion implantation (PIII) in a nitrogen plasma with 20 kV bias was used to facilitate covalent immobilization and to improve the wettability of the surfaces. The surfaces and immobilized protein were studied using attenuated total reflection infrared (ATR-IR) spectroscopy and water contact angle measurements. Protein elution on exposure to repeated sodium dodecyl sulfate (SDS) washing was used to assess the strength of HRP immobilization. The presence of low molecular weight components (plasticizer, additives in solvent, unreacted monomers, adsorbed molecules on surface) was found to have a major influence on the strength of immobilization and the conformation of the protein on the samples not exposed to the PIII treatment. A phenomenological model considering interactions between the low molecular weight components, the protein molecule, and the surface is developed to explain these observations.

  10. Molecular Mechanism and Energy Basis of Conformational Diversity of Antibody SPE7 Revealed by Molecular Dynamics Simulation and Principal Component Analysis

    Science.gov (United States)

    Chen, Jianzhong; Wang, Jinan; Zhu, Weiliang

    2016-11-01

    More and more researchers are interested in and focused on how a limited repertoire of antibodies can bind and correspondingly protect against an almost limitless diversity of invading antigens. In this work, a series of 200-ns molecular dynamics (MD) simulations followed by principal component (PC) analysis and free energy calculations were performed to probe potential mechanism of conformational diversity of antibody SPE7. The results show that the motion direction of loops H3 and L3 is different relative to each other, implying that a big structural difference exists between these two loops. The calculated energy landscapes suggest that the changes in the backbone angles ψ and φ of H-Y101 and H-Y105 provide significant contributions to the conformational diversity of SPE7. The dihedral angle analyses based on MD trajectories show that the side-chain conformational changes of several key residues H-W33, H-Y105, L-Y34 and L-W93 around binding site of SPE7 play a key role in the conformational diversity of SPE7, which gives a reasonable explanation for potential mechanism of cross-reactivity of single antibody toward multiple antigens.

  11. Applications of the Local Mode Model to CH Bond Length Changes, Molecular Conformations and Vibrational Dynamics

    OpenAIRE

    Henry, Bryan R.; Gough, Kathleen M.

    1983-01-01

    The theoretical basis for the local mode model is reviewed. The model is applied to gas phase overtone spectra of aromatic molecules to investigate both substituent induced CH bond length changes and conformationally inequivalent hydrogens. The dynamic implications of the local mode model are discussed.

  12. From flexibility to function: Molecular dynamics simulations of conformational changes in chaperones and photoreceptors

    NARCIS (Netherlands)

    Singhal, K.

    2016-01-01

    Proteins are uniquely-shaped macromolecules that function as biological machines, and regulate a living cell’s behavior. Crucial to protein function is the folding of the polypeptide chain into a unique well-defined three-dimensional conformation. In complex cell environments, the spontaneous unassi

  13. Molecular Fluorescence Lifetime Fluctuations: On the Possible Role of Conformational Effects

    NARCIS (Netherlands)

    Vallée, R.A.L.; Vancso, G.J.; Hulst, van N.F.; Calbert, J.-P.; Cornil, J.; Brédas, J.L.

    2003-01-01

    The radiative lifetime of single 1,1'-dioctadecyl-3,3,3',3'- etramethylindodicarbocyanine molecules, embedded in a polymer thin film, has been characterized. At room temperature the chemically identical molecules exhibit strong fluctuations in their fluorescence lifetime. The possible conformational

  14. Relationship between Oversulfation and Conformation of Low and High Molecular Weight Fucoidans and Evaluation of Their in Vitro Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Myoung Lae Cho

    2010-12-01

    Full Text Available Low and high molecular weight fucoidans (F5-30K and F>30K were chemically modified through the addition of sulfate groups, and the effect of oversulfation on the in vitro anticancer activity was investigated. After the addition of sulfate groups, a considerable increase of 35.5 to 56.8% was observed in the sulfate content of the F5-30K fraction, while the sulfate content of the F>30K fraction increased to a lesser extent (from 31.7 to 41.2%. Significant differences in anticancer activity were observed between the oversulfated F5–30K and F>30K fractions, with activities of 37.3–68.0% and 20.6–35.8%, respectively. This variation in the anticancer activity of oversulfated fucoidan derivatives was likely due to differences in their sulfate content. The results suggest that the molecular conformation of these molecules is closely related to the extent of sulfation in the fucan backbones and that the sulfates are preferably substituted when the fucoidan polymers are in a loose molecular conformation.

  15. Stabilization of Human Serum Albumin by the Binding of Phycocyanobilin, a Bioactive Chromophore of Blue-Green Alga Spirulina: Molecular Dynamics and Experimental Study.

    Science.gov (United States)

    Radibratovic, Milica; Minic, Simeon; Stanic-Vucinic, Dragana; Nikolic, Milan; Milcic, Milos; Cirkovic Velickovic, Tanja

    2016-01-01

    Phycocyanobilin (PCB) binds with high affinity (2.2 x 106 M-1 at 25°C) to human serum albumin (HSA) at sites located in IB and IIA subdomains. The aim of this study was to examine effects of PCB binding on protein conformation and stability. Using 300 ns molecular dynamics (MD) simulations, UV-VIS spectrophotometry, CD, FT-IR, spectrofluorimetry, thermal denaturation and susceptibility to trypsin digestion, we studied the effects of PCB binding on the stability and rigidity of HSA, as well as the conformational changes in PCB itself upon binding to the protein. MD simulation results demonstrated that HSA with PCB bound at any of the two sites showed greater rigidity and lower overall and individual domain flexibility compared to free HSA. Experimental data demonstrated an increase in the α-helical content of the protein and thermal and proteolytic stability upon ligand binding. PCB bound to HSA undergoes a conformational change to a more elongated conformation in the binding pockets of HSA. PCB binding to HSA stabilizes the structure of this flexible transport protein, making it more thermostable and resistant to proteolysis. The results from this work explain at molecular level, conformational changes and stabilization of HSA structure upon ligand binding. The resultant increased thermal and proteolytic stability of HSA may provide greater longevity to HSA in plasma.

  16. Multiple conformational states and gate opening of outer membrane protein TolC revealed by molecular dynamics simulations.

    Science.gov (United States)

    Wang, Beibei; Weng, Jingwei; Wang, Wenning

    2014-09-01

    Outer membrane protein TolC serves as an exit duct for exporting substances out of cell. The occluded periplasmic entrance of TolC is required to open for substrate transport, although the opening mechanism remains elusive. In this study, systematic molecular dynamics (MD) simulations for wild type TolC and six mutants were performed to explore the conformational dynamics of TolC. The periplasmic gate was shown to sample multiple conformational states with various degrees of gating opening. The gate opening was facilitated by all mutations except Y362F, which adopts an even more closed state than wild type TolC. The interprotomer salt-bridge R367-D153 is turned out to be crucial for periplasmic gate opening. The mutations that disrupt the interactions at the periplasmic tip may affect the stability of the trimeric assembly of TolC. Structural asymmetry of the periplasmic gate was observed to be opening size dependent. Asymmetric conformations are found in moderately opening states, while the most and the least opening states are often more symmetric. Finally, it is shown that lowering pH can remarkably stabilize the closed state of the periplasmic gate.

  17. Molecular simulations of conformation change and aggregation of HIV-1 Vpr13-33 on graphene oxide

    Science.gov (United States)

    Zeng, Songwei; Zhou, Guoquan; Guo, Jianzhong; Zhou, Feng; Chen, Junlang

    2016-04-01

    Recent experiments have reported that the fragment of viral protein R (Vpr), Vpr13-33, can assemble and change its conformation after adsorbed on graphene oxide (GO) and then reduce its cytotoxicity. This discovery is of great importance, since the mutation of Vpr13-33 can decrease the viral replication, viral load and delay the disease progression. However, the interactions between Vpr13-33 and GO at atomic level are still unclear. In this study, we performed molecular dynamics simulation to investigate the dynamic process of the adsorption of Vpr13-33 onto GO and the conformation change after aggregating on GO surface. We found that Vpr13-33 was adsorbed on GO surface very quickly and lost its secondary structure. The conformation of peptides-GO complex was highly stable because of π-π stacking and electrostatic interactions. When two peptides aggregated on GO, they did not dimerize, since the interactions between the two peptides were much weaker than those between each peptide and GO.

  18. Study on the Application of the Combination of TMD Simulation and Umbrella Sampling in PMF Calculation for Molecular Conformational Transitions

    Directory of Open Access Journals (Sweden)

    Qing Wang

    2016-05-01

    Full Text Available Free energy calculations of the potential of mean force (PMF based on the combination of targeted molecular dynamics (TMD simulations and umbrella samplings as a function of physical coordinates have been applied to explore the detailed pathways and the corresponding free energy profiles for the conformational transition processes of the butane molecule and the 35-residue villin headpiece subdomain (HP35. The accurate PMF profiles for describing the dihedral rotation of butane under both coordinates of dihedral rotation and root mean square deviation (RMSD variation were obtained based on the different umbrella samplings from the same TMD simulations. The initial structures for the umbrella samplings can be conveniently selected from the TMD trajectories. For the application of this computational method in the unfolding process of the HP35 protein, the PMF calculation along with the coordinate of the radius of gyration (Rg presents the gradual increase of free energies by about 1 kcal/mol with the energy fluctuations. The feature of conformational transition for the unfolding process of the HP35 protein shows that the spherical structure extends and the middle α-helix unfolds firstly, followed by the unfolding of other α-helices. The computational method for the PMF calculations based on the combination of TMD simulations and umbrella samplings provided a valuable strategy in investigating detailed conformational transition pathways for other allosteric processes.

  19. Continuum molecular simulation of large conformational changes during ion-channel gating.

    Directory of Open Access Journals (Sweden)

    Ali Nekouzadeh

    Full Text Available A modeling framework was developed to simulate large and gradual conformational changes within a macromolecule (protein when its low amplitude high frequency vibrations are not concerned. Governing equations were derived as alternative to Langevin and Smoluchowski equations and used to simulate gating conformational changes of the Kv7.1 ion-channel over the time scale of its gating process (tens of milliseconds. The alternative equations predict the statistical properties of the motion trajectories with good accuracy and do not require the force field to be constant over the diffusion length, as assumed in Langevin equation. The open probability of the ion-channel was determined considering cooperativity of four subunits and solving their concerted transition to the open state analytically. The simulated open probabilities for a series of voltage clamp tests produced current traces that were similar to experimentally recorded currents.

  20. Stereoselective synthesis of conformationally constrained cyclohexanediols: a set of molecular scaffolds for the synthesis of glycomimetics.

    Science.gov (United States)

    Bernardi, A; Arosio, D; Manzoni, L; Micheli, F; Pasquarello, A; Seneci, P

    2001-09-21

    The practical, stereoselective synthesis of the three diastereoisomeric 1,2-trans-dicarboxy-4,5-cyclohexanediols 1-3 (DCCHDs) is described, starting from a common precursor, easily available in both enantiomeric forms. The regioselective derivatization of all functional groups of 1 is also reported. The three DCCHDs are locked in a single chair conformation and thus can be used to mimic vicinally disubstituted monosaccharides of any relative configuration.

  1. Molecular Docking Study of Conformational Polymorph: Building Block of Crystal Chemistry

    Directory of Open Access Journals (Sweden)

    Rashmi Dubey

    2013-01-01

    Full Text Available Two conformational polymorphs of novel 2-[2-(3-cyano-4,6-dimethyl-2-oxo-2H-pyridin-1-yl-ethoxy]-4,6-dimethyl nicotinonitrile have been developed. The crystal structure of both polymorphs (1a and 1b seems to be stabilized by weak interactions. A difference was observed in the packing of both polymorphs. Polymorph 1b has a better binding affinity with the cyclooxygenase (COX-2 receptor than the standard (Nimesulide.

  2. Molecular Docking Study of Conformational Polymorph: Building Block of Crystal Chemistry

    Science.gov (United States)

    Dubey, Rashmi; Tewari, Ashish Kumar; Singh, Ved Prakash; Singh, Praveen; Dangi, Jawahar Singh; Puerta, Carmen; Valerga, Pedro; Kant, Rajni

    2013-01-01

    Two conformational polymorphs of novel 2-[2-(3-cyano-4,6-dimethyl-2-oxo-2H-pyridin-1-yl)-ethoxy]-4,6-dimethyl nicotinonitrile have been developed. The crystal structure of both polymorphs (1a and 1b) seems to be stabilized by weak interactions. A difference was observed in the packing of both polymorphs. Polymorph 1b has a better binding affinity with the cyclooxygenase (COX-2) receptor than the standard (Nimesulide). PMID:24250264

  3. β-Glucans: Relationships between Modification, Conformation and Functional Activities

    Directory of Open Access Journals (Sweden)

    Qiang Wang

    2017-02-01

    Full Text Available β-glucan is a type of polysaccharide which widely exists in bacteria, fungi, algae, and plants, and has been well known for its biological activities such as enhancing immunity, antitumor, antibacterial, antiviral, and wound healing activities. The conformation of β-glucan plays a crucial role on its biological activities. Therefore, β-glucans obtained from different sources, while sharing the same basic structures, often show different bioactivities. The basic structure and inter-molecular forces of polysaccharides can be changed by modification, which leads to the conformational transformation in solution that can directly affect bioactivity. In this review, we will first determine different ways to modify β-glucan molecules including physical methods, chemical methods, and biological methods, and then reveal the relationship of the flexible helix form of the molecule chain and the helix conformation to their bioactivities. Last, we summarize the scientific challenges to modifying β-glucan’s conformation and functional activity, and discuss its potential future development.

  4. Conformational Dynamics in FKBP Domains: Relevance to Molecular Signaling and Drug Design.

    Science.gov (United States)

    LeMaster, David M; Hernandez, Griselda

    2015-01-01

    Among the 22 FKBP domains in the human genome, FKBP12.6 and the first FKBP domains (FK1) of FKBP51 and FKBP52 are evolutionarily and structurally most similar to the archetypical FKBP12. As such, the development of inhibitors with selectivity among these four FKBP domains poses a significant challenge for structure-based design. The pleiotropic effects of these FKBP domains in a range of signaling processes such as the regulation of ryanodine receptor calcium channels by FKBP12 and FKBP12.6 and steroid receptor regulation by the FK1 domains of FKBP51 and FKBP52 amply justify the efforts to develop selective therapies. In contrast to their close structural similarities, these four FKBP domains exhibit a substantial diversity in their conformational flexibility. A number of distinct conformational transitions have been characterized for FKBP12 spanning timeframes from 20 s to 10 ns and in each case these dynamics have been shown to markedly differ from the conformational behavior for one or more of the other three FKBP domains. Protein flexibilitybased inhibitor design could draw upon the transitions that are significantly populated in only one of the targeted proteins. Both the similarities and differences among these four proteins valuably inform the understanding of how dynamical effects propagate across the FKBP domains as well as potentially how such intramolecular transitions might couple to the larger scale transitions that are central to the signaling complexes in which these FKBP domains function.

  5. Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) for Conformational Space Search of Peptide and Miniprotein.

    Science.gov (United States)

    Hao, Ge-Fei; Xu, Wei-Fang; Yang, Sheng-Gang; Yang, Guang-Fu

    2015-10-23

    Protein and peptide structure predictions are of paramount importance for understanding their functions, as well as the interactions with other molecules. However, the use of molecular simulation techniques to directly predict the peptide structure from the primary amino acid sequence is always hindered by the rough topology of the conformational space and the limited simulation time scale. We developed here a new strategy, named Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) to identify the native states of a peptide and miniprotein. A cluster of near native structures could be obtained by using the MSA-MD method, which turned out to be significantly more efficient in reaching the native structure compared to continuous MD and conventional SA-MD simulation.

  6. Molecular dynamics simulation of phosphorylation-induced conformational transitions in the mycobacterium tuberculosis response regulator PrrA

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Guo [Los Alamos National Laboratory; Mcmahon, Benjamin H [Los Alamos National Laboratory; Tung, Chang - Shung [Los Alamos National Laboratory

    2008-01-01

    Phosphorylation-activated modulation of response regulators (RR) is predominantly used by bacteria as a strategy in regulating their two-component signaling (TCS) systems, the underlying molecular mechanisms are however far from fully understood. In this work we have conducted a molecular dynamics (MD) simulation of the phosphorylation-induced conformational transitions of RRs with the Mycobacterium Tuberculosis PrrA as a particular example. Starting from the full-length inactive structure of PrrA we introduced a local disturbance by phosphorylating the conserved aspartic acid residue, Asp-58, in the regulatory domain. A Go-model-type algorithm packaged with AMBER force fields was then applied to simulate the dynamics upon phosphorylation. The MD simulation shows that the phosphorylation of Asp-58 facilitates PrrA, whose inactive state has a compact conformation with a closed interdomain interface, to open up with its interdomain separation being increased by an average of about 1.5 {angstrom} for a simulation of 20 ns. The trans-activation loop, which is completely buried within the interdomain interface in the inactive PrrA, is found to become more exposed with the phosphorylated structure as well. These results provide more structural details of how the phosphorylation of a local aspartate activates PrrA to undergo a global conformational rearrangement toward its extended active state. This work also indicates that MD simulations can serve as a fast tool to unravel the regulation mechanisms of all RRs, which is especially valuable when the structures of full-length active RRs are currently unavailable.

  7. Impact of Interfacial Molecular Conformation and Aggregation State on the Energetic Landscape and Performance in Organic Photovoltaics

    KAUST Repository

    Ngongang Ndjawa, Guy Olivier

    2016-11-25

    In organic photovoltaics (OPVs) the key processes relevant to device operation such as exciton dissociation and free carriers recombination occur at the donor-acceptor (D-A) interface. OPV devices require the bulk heterojunction (BHJ) architecture to function efficiently. In these BHJs, D-A interfaces are arranged in three dimensions, which makes molecular arrangements at these interfaces ill defined and hard to characterize. In addition, molecular materials used in OPVs are inherently disordered and may exhibit variable degrees of structural order in the same BHJ. Yet, D-A molecular arrangements and structure are crucial because they shape the energy landscape and photovoltaic (PV) performance in OPVs. Studies that use well-defined model systems to look in details at the interfacial molecular structure in OPVs and link it to interfacial energy landscape and device operation are critically lacking. We have used in situ photoelectron spectroscopy and ex situ x-ray scattering to study D-A interfaces in tailored bilayers and BHJs based on small molecule donors. We show preferential miscibility at the D-A interface depending on molecular conformation in zinc phthalocyanine (ZnPc)/ C60 bilayers and we derive implications for exciton dissociation. Using sexithiophene (6T), a crystalline donor, we show that the energy landscape at the D-A interface varies markedly depending on the molecular composition of the BHJ. Both the ionization energies of sexithiophene and C60 shift by over ~0.4 eV while the energy of the charge transfer state shifts by ~0.5 eV depending on composition. Such shifts create a downward energy landscape that helps interfacial excitons to overcome their binding energies. Finally, we demonstrate that when both disordered and ordered phases of D coexist at the interface, low-lying energy states form in ordered phases and significantly limit the Voc in devices. Overall our work underlines the importance of the aggregation and conformation states of

  8. Identification of a Novel Parallel beta-Strand Conformation within Molecular Monolayer of Amyloid Peptide

    DEFF Research Database (Denmark)

    Liu, Lei; Li, Qiang; Zhang, Shuai;

    2016-01-01

    technique with force controlled in pico-Newton range, combining with molecular dynamic simulation. The identified parallel beta-strand-like structure of molecular monolayer is distinct from the antiparallel beta-strand structure of A beta(33-42) amyloid fibril. This finding enriches the molecular structures....... In this work, the early A beta(33-42) aggregates forming the molecular monolayer at hydrophobic interface are investigated. The molecular monolayer of amyloid peptide A beta(33-42) consisting of novel parallel beta-strand-like structure is further revealed by means of a quantitative nanomechanical spectroscopy......The differentiation of protein properties and biological functions arises from the variation in the primary and secondary structure. Specifically, in abnormal assemblies of protein, such as amyloid peptide, the secondary structure is closely correlated with the stable ensemble and the cytotoxicity...

  9. Quantum/molecular mechanics study of firefly bioluminescence on luciferase oxidative conformation

    Science.gov (United States)

    Pinto da Silva, Luís; Esteves da Silva, Joaquim C. G.

    2014-07-01

    This is the first report of a computational study of the color tuning mechanism of firefly bioluminescence, using the oxidative conformation of luciferase. The results of these calculations demonstrated that the electrostatic field generated by luciferase is fundamental both for the emission shift and efficiency. Further calculations indicated that a shift in emission is achieved by modulating the energy, at different degrees, of the emissive and ground states. These differences in energy modulation will then lead to changes in the energy gap between the states.

  10. Direct observation of bis(dicarbollyl)nickel conformers in solution by fluorescence spectroscopy: an approach to redox-controlled metallacarborane molecular motors.

    Science.gov (United States)

    Safronov, Alexander V; Shlyakhtina, Natalia I; Everett, Thomas A; VanGordon, Monika R; Sevryugina, Yulia V; Jalisatgi, Satish S; Hawthorne, M Frederick

    2014-10-06

    As a continuation of work on metallacarborane-based molecular motors, the structures of substituted bis(dicarbollyl)nickel complexes in Ni(III) and Ni(IV) oxidation states were investigated in solution by fluorescence spectroscopy. Symmetrically positioned cage-linked pyrene molecules served as fluorescent probes to enable the observation of mixed meso-trans/dl-gauche (pyrene monomer fluorescence) and dl-cis/dl-gauche (intramolecular pyrene excimer fluorescence with residual monomer fluorescence) cage conformations of the nickelacarboranes in the Ni(III) and Ni(IV) oxidation states, respectively. The absence of energetically disfavored conformers in solution--dl-cis in the case of nickel(III) complexes and meso-trans in the case of nickel(IV)--was demonstrated based on spectroscopic data and conformer energy calculations in solution. The conformational persistence observed in solution indicates that bis(dicarbollyl)nickel complexes may provide attractive templates for building electrically driven and/or photodriven molecular motors.

  11. Exploring transition pathway and free-energy profile of large-scale protein conformational change by combining normal mode analysis and umbrella sampling molecular dynamics.

    Science.gov (United States)

    Wang, Jinan; Shao, Qiang; Xu, Zhijian; Liu, Yingtao; Yang, Zhuo; Cossins, Benjamin P; Jiang, Hualiang; Chen, Kaixian; Shi, Jiye; Zhu, Weiliang

    2014-01-09

    Large-scale conformational changes of proteins are usually associated with the binding of ligands. Because the conformational changes are often related to the biological functions of proteins, understanding the molecular mechanisms of these motions and the effects of ligand binding becomes very necessary. In the present study, we use the combination of normal-mode analysis and umbrella sampling molecular dynamics simulation to delineate the atomically detailed conformational transition pathways and the associated free-energy landscapes for three well-known protein systems, viz., adenylate kinase (AdK), calmodulin (CaM), and p38α kinase in the absence and presence of respective ligands. For each protein under study, the transient conformations along the conformational transition pathway and thermodynamic observables are in agreement with experimentally and computationally determined ones. The calculated free-energy profiles reveal that AdK and CaM are intrinsically flexible in structures without obvious energy barrier, and their ligand binding shifts the equilibrium from the ligand-free to ligand-bound conformation (population shift mechanism). In contrast, the ligand binding to p38α leads to a large change in free-energy barrier (ΔΔG ≈ 7 kcal/mol), promoting the transition from DFG-in to DFG-out conformation (induced fit mechanism). Moreover, the effect of the protonation of D168 on the conformational change of p38α is also studied, which reduces the free-energy difference between the two functional states of p38α and thus further facilitates the conformational interconversion. Therefore, the present study suggests that the detailed mechanism of ligand binding and the associated conformational transition is not uniform for all kinds of proteins but correlated to their respective biological functions.

  12. Optimized Solid Phase-Assisted Synthesis of Dendrons Applicable as Scaffolds for Radiolabeled Bioactive Multivalent Compounds Intended for Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Gabriel Fischer

    2014-05-01

    Full Text Available Dendritic structures, being highly homogeneous and symmetric, represent ideal scaffolds for the multimerization of bioactive molecules and thus enable the synthesis of compounds of high valency which are e.g., applicable in radiolabeled form as multivalent radiotracers for in vivo imaging. As the commonly applied solution phase synthesis of dendritic scaffolds is cumbersome and time-consuming, a synthesis strategy was developed that allows for the efficient assembly of acid amide bond-based highly modular dendrons on solid support via standard Fmoc solid phase peptide synthesis protocols. The obtained dendritic structures comprised up to 16 maleimide functionalities and were derivatized on solid support with the chelating agent DOTA. The functionalized dendrons furthermore could be efficiently reacted with structurally variable model thiol-bearing bioactive molecules via click chemistry and finally radiolabeled with 68Ga. Thus, this solid phase-assisted dendron synthesis approach enables the fast and straightforward assembly of bioactive multivalent constructs for example applicable as radiotracers for in vivo imaging with Positron Emission Tomography (PET.

  13. Steered molecular dynamics simulations of a type IV pilus probe initial stages of a force-induced conformational transition.

    Directory of Open Access Journals (Sweden)

    Joseph L Baker

    2013-04-01

    Full Text Available Type IV pili are long, protein filaments built from a repeating subunit that protrudes from the surface of a wide variety of infectious bacteria. They are implicated in a vast array of functions, ranging from bacterial motility to microcolony formation to infection. One of the most well-studied type IV filaments is the gonococcal type IV pilus (GC-T4P from Neisseria gonorrhoeae, the causative agent of gonorrhea. Cryo-electron microscopy has been used to construct a model of this filament, offering insights into the structure of type IV pili. In addition, experiments have demonstrated that GC-T4P can withstand very large tension forces, and transition to a force-induced conformation. However, the details of force-generation, and the atomic-level characteristics of the force-induced conformation, are unknown. Here, steered molecular dynamics (SMD simulation was used to exert a force in silico on an 18 subunit segment of GC-T4P to address questions regarding the nature of the interactions that lead to the extraordinary strength of bacterial pili. SMD simulations revealed that the buried pilin α1 domains maintain hydrophobic contacts with one another within the core of the filament, leading to GC-T4P's structural stability. At the filament surface, gaps between pilin globular head domains in both the native and pulled states provide water accessible routes between the external environment and the interior of the filament, allowing water to access the pilin α1 domains as reported for VC-T4P in deuterium exchange experiments. Results were also compared to the experimentally observed force-induced conformation. In particular, an exposed amino acid sequence in the experimentally stretched filament was also found to become exposed during the SMD simulations, suggesting that initial stages of the force induced transition are well captured. Furthermore, a second sequence was shown to be initially hidden in the native filament and became exposed upon

  14. Intramolecular interactions stabilizing compact conformations of the intrinsically disordered kinase-inhibitor domain of Sic1: a molecular dynamics investigation.

    Directory of Open Access Journals (Sweden)

    Matteo eLambrughi

    2012-11-01

    Full Text Available Cyclin-dependent kinase inhibitors (CKIs are key regulatory proteins of the eukaryotic cell cycle, which modulate cyclin-dependent kinase (Cdk activity. CKIs perform their inhibitory effect by the formation of ternary complexes with a target kinase and its cognate cyclin. These regulators generally belong to the class of intrinsically disordered proteins (IDPs, which lack a well-defined and organized three-dimensional structure in their free state, undergoing folding upon binding to specific partners. Unbound IDPs are not merely random-coil structures, but can present intrinsically folded structural units (IFSUs and collapsed conformations. These structural features can be relevant to protein function in vivo.The yeast CKI Sic1 is a 284-amino acid IDP that binds to Cdk1 in complex with the Clb5,6 cyclins, preventing phosphorylation of G1 substrates and, therefore, entrance to the S phase. Sic1 degradation, triggered by multiple phosphorylation events, promotes cell-cycle progression. Previous experimental studies pointed out a propensity of Sic1 and its isolated domains to populate both extended and compact conformations. The present contribution provides models of the compact conformations of the Sic1 kinase-inhibitory domain (KID by all-atom molecular-dynamics simulations in explicit solvent and in the absence of interactors. The results are integrated by spectroscopic and spectrometric data. Helical IFSUs are identified, along with networks of intramolecular interactions. The results identify a group of hub residues and electrostatic interactions which are likely to be involved in the stabilization of globular states.

  15. Variety of molecular conformation of plasmid pUC18 DNA and solenoidally supercoiled DNA

    Institute of Scientific and Technical Information of China (English)

    黄熙泰; 王照清; 吴永文; 樊廷玉; 王树荣; 王勖焜

    1996-01-01

    The plasmid pUC18 DNA isolated from Escherichia coli HB101 were analyzed by two-dimensional agarose gel electrophoresis and hybridization. The results show that the DNA sample can be separated into six groups of different structural components. The plectonemically and solenoidally supercoiled pUC18 DNA coexist in it. These two different conformations of supercoiled DNA are interchangeable with the circumstances (ionic strength and type, etc.). The amount of solenoidally supercoiled pUC18 DNA in the samples can be changed by treatment of DNA topoisome rases. Under an electron microscope, the solenoidal supercoiling DNA has a round shape with an average diameter of 45 nm. The facts suggest that solenoidaUy supercoiled DNA be a structural entity independent of histones. The polymorphism of DNA structure may be important to packing of DNA in vivo.

  16. Molecular architecture with carbohydrate functionalized β-peptides adopting 314-helical conformation

    Directory of Open Access Journals (Sweden)

    Nitin J. Pawar

    2014-04-01

    Full Text Available Carbohydrate recognition is essential in cellular interactions and biological processes. It is characterized by structural diversity, multivalency and cooperative effects. To evaluate carbohydrate interaction and recognition, the structurally defined attachment of sugar units to a rigid template is highly desired. β-Peptide helices offer conformationally stable templates for the linear presentation of sugar units in defined distances. The synthesis and β-peptide incorporation of sugar-β-amino acids are described providing the saccharide units as amino acid side chain. The respective sugar-β-amino acids are accessible by Michael addition of ammonia to sugar units derivatized as α,β-unsaturated esters. Three sugar units were incorporated in β-peptide oligomers varying the sugar (glucose, galactose, xylose and sugar protecting groups. The influence of sugar units and the configuration of sugar-β-amino acids on β-peptide secondary structure were investigated by CD spectroscopy.

  17. Stochastic structure determination for conformationally flexible heterogenous molecular clusters: application to ionic liquids.

    Science.gov (United States)

    Addicoat, Matthew A; Fukuoka, Syou; Page, Alister J; Irle, Stephan

    2013-11-15

    We present a novel method that enables accurate and efficient computational determination of conformationally flexible clusters, "Kick(3)" This method uses stochastically generated structures in combination with fast quantum mechanical methods. We demonstrate the power of this method by elucidating the structure of ionic liquid (IL) ([xMIM(+)][NO3(-)])n clusters (x = E, B, D, n = 1-10,15). Dispersion-corrected, third-order self-consistent-charge density-functional tight-binding (DFTB3) is shown to be a computationally efficient, yet reliable approximation to density functional theory for predicting and understanding IL structure and stability. The presented approach, therefore, enables the accurate and efficient screening of ILs with high potential toward practical applications, without recourse to more expensive quantum chemical methods.

  18. Inter-helical conformational preferences of HIV-1 TAR-RNA from maximum occurrence analysis of NMR data and molecular dynamics simulations.

    Science.gov (United States)

    Andrałojć, Witold; Ravera, Enrico; Salmon, Loïc; Parigi, Giacomo; Al-Hashimi, Hashim M; Luchinat, Claudio

    2016-02-17

    Detecting conformational heterogeneity in biological macromolecules is a key for the understanding of their biological function. We here provide a comparison between two independent approaches to assess conformational heterogeneity: molecular dynamics simulations, performed without inclusion of any experimental data, and maximum occurrence (MaxOcc) distribution over the topologically available conformational space. The latter only reflects the extent of the averaging and identifies regions which are most compliant with the experimentally measured NMR Residual Dipolar Couplings (RDCs). The analysis was performed for the HIV-1 TAR RNA, consisting of two helical domains connected by a flexible bulge junction, for which four sets of RDCs were available as well as an 8.2 μs all-atom molecular dynamics simulation. A sample and select approach was previously applied to extract from the molecular dynamics trajectory conformational ensembles in agreement with the four sets of RDCs. The MaxOcc analysis performed here identifies the most likely sampled region in the conformational space of the system which, strikingly, overlaps well with the structures independently sampled in the molecular dynamics calculations and even better with the RDC selected ensemble.

  19. Molecular Dynamics Simulation of Tau Peptides for the Investigation of Conformational Changes Induced by Specific Phosphorylation Patterns.

    Science.gov (United States)

    Gandhi, Neha S; Kukic, Predrag; Lippens, Guy; Mancera, Ricardo L

    2017-01-01

    The Tau protein plays an important role due to its biomolecular interactions in neurodegenerative diseases. The lack of stable structure and various posttranslational modifications such as phosphorylation at various sites in the Tau protein pose a challenge for many experimental methods that are traditionally used to study protein folding and aggregation. Atomistic molecular dynamics (MD) simulations can help around deciphering relationship between phosphorylation and various intermediate and stable conformations of the Tau protein which occur on longer timescales. This chapter outlines protocols for the preparation, execution, and analysis of all-atom MD simulations of a 21-amino acid-long phosphorylated Tau peptide with the aim of generating biologically relevant structural and dynamic information. The simulations are done in explicit solvent and starting from nearly extended configurations of the peptide. The scaled MD method implemented in AMBER14 was chosen to achieve enhanced conformational sampling in addition to a conventional MD approach, thereby allowing the characterization of folding for such an intrinsically disordered peptide at 293 K. Emphasis is placed on the analysis of the simulation trajectories to establish correlations with NMR data (i.e., chemical shifts and NOEs). Finally, in-depth discussions are provided for commonly encountered problems.

  20. Effect of graphene oxide on the conformational transitions of amyloid beta peptide: A molecular dynamics simulation study.

    Science.gov (United States)

    Baweja, Lokesh; Balamurugan, Kanagasabai; Subramanian, Venkatesan; Dhawan, Alok

    2015-09-01

    The interactions between nanomaterials (NMs) and amyloid proteins are central to the nanotechnology-based diagnostics and therapy in neurodegenerative disorders such as Alzheimer's and Parkinson's. Graphene oxide (GO) and its derivatives have shown to modulate the aggregation pattern of disease causing amyloid beta (Aβ) peptide. However, the mechanism is still not well understood. Using molecular dynamics simulations, the effect of graphene oxide (GO) and reduced graphene oxide (rGO) having carbon:oxygen ratio of 4:1 and 10:1, respectively, on the conformational transitions (alpha-helix to beta-sheet) and the dynamics of the peptide was investigated. GO and rGO decreased the beta-strand propensity of amino acid residues in Aβ. The peptide displayed different modes of adsorption on GO and rGO. The adsorption on GO was dominated by electrostatic interactions, whereas on rGO, both van der Waals and electrostatic interactions contributed in the adsorption of the peptide. Our study revealed that the slight increase in the hydrophobic patches on rGO made it more effective inhibitor of conformational transitions in the peptide. Alpha helix-beta sheet transition in Aβ peptide could be one of the plausible mechanism by which graphene oxide may inhibit amyloid fibrillation.

  1. Molecular Dynamics Simulation on the Conformational Transition of the Mad2 Protein from the Open to the Closed State

    Directory of Open Access Journals (Sweden)

    Chaoqun Li

    2014-03-01

    Full Text Available The Mad2 protein, with two distinct conformations of open- and closed-states, is a key player in the spindle checkpoint. The closed Mad2 state is more active than the open one. We carried out conventional and targeted molecular dynamics simulations for the two stable Mad2 states and their conformational transition to address the dynamical transition mechanism from the open to the closed state. The intermediate structure in the transition process shows exposure of the β6 strand and an increase of space around the binding sites of β6 strand due to the unfolding of the β7/8 sheet and movement of the β6/4/5 sheet close to the αC helix. Therefore, Mad2 binding to the Cdc20 protein in the spindle checkpoint is made possible. The interconversion between these two states might facilitate the functional activity of the Mad2 protein. Motion correlation analysis revealed the allosteric network between the β1 strand and β7/8 sheet via communication of the β5-αC loop and the β6/4/5 sheet in this transition process.

  2. Conformational studies of vasopressin and mesotocin using NMR spectroscopy and molecular modelling methods. Part I: Studies in water.

    Science.gov (United States)

    Sikorska, Emilia; Rodziewicz-Motowidło, Sylwia

    2008-01-01

    Arginine vasopressin (AVP) and mesotocin (MT) belong to the neurohypophyseal hormone family. The former plays a very important role in the control of urine concentration and the blood pressure in mammals, whereas the latter stimulates uterine concentration and initiates birth in amphibians, marsupials, wallabies, birds, and fishes. Analysis of their 3D structure could be helpful for understanding the evolutionary relationship between all vasopressin- and oxytocin-like hormones. In addition, it allows design of new analogs with appropriate biological activity for humans and animals. In this paper, we present the conformational studies of AVP and MT, under the aqueous conditions. In our investigations, we used 2D NMR spectroscopy and time-averaged molecular dynamics calculations in explicit water. Our studies have shown that both peptides, despite displaying a high sequence homology, differ from each other with regard to the three-dimensional structure. They are in conformational equilibrium as a result of the cis/trans isomerization across the Cys(6)-Pro(7) peptide bond. Both peptides form beta-turns in their cyclic part, wherein the C-terminal fragment of MT is bent, whereas that of AVP is extended.

  3. Low molecular weight oligomers of amyloid peptides display β-barrel conformations: A replica exchange molecular dynamics study in explicit solvent

    Science.gov (United States)

    De Simone, Alfonso; Derreumaux, Philippe

    2010-04-01

    The self-assembly of proteins and peptides into amyloid fibrils is connected to over 40 pathological conditions including neurodegenerative diseases and systemic amyloidosis. Diffusible, low molecular weight protein and peptide oligomers that form in the early steps of aggregation appear to be the harmful cytotoxic species in the molecular etiology of these diseases. So far, the structural characterization of these oligomers has remained elusive owing to their transient and dynamic features. We here address, by means of full atomistic replica exchange molecular dynamics simulations, the energy landscape of heptamers of the amyloidogenic peptide NHVTLSQ from the beta-2 microglobulin protein. The simulations totaling 5 μs show that low molecular weight oligomers in explicit solvent consist of β-barrels in equilibrium with amorphous states and fibril-like assemblies. The results, also accounting for the influence of the pH on the conformational properties, provide a strong evidence of the formation of transient β-barrel assemblies in the early aggregation steps of amyloid-forming systems. Our findings are discussed in terms of oligomers cytotoxicity.

  4. Chemical structure-optical property understanding in bisphenyls and substituted polycarbonates by molecular simulations: Role of polarizabilities and conformations

    Science.gov (United States)

    Natarajan, Upendra; Sulatha, M. S.

    2005-03-01

    We present calculations of polarizability tensors, optical anisotropy of organic molecules, repeating units and polymer chains of several bisphenyls, bisphenol carbonates and polycarbonates with a variety of chemical substitutions.^1,2 Theoretical calculations of polarizabilities and optical birefringence of several newer structures having specific side-group substitutions which render low birefringence, not previously reported, is also shown here. Our method combines VOSRIS scheme^3, molecular geometry and conformations from force-field simulations and accurate anisotropic polarizability tensors. Aliphatic, aliphatic aromatic and cycloaliphatic substitutions reduce optical anisotropy in relation to bisphenol A polycarbonate. Calculated /x of these structurally modified polycarbonates^2 follows linear behavior with respect to experimentally observed melt stress-optical coefficient (Cm). *J. Phys. Chem. A, 107, 97 (2003) *Macromolecules, 36, 2944 (2003) *P.J. Flory, Statistical Mechanics of Chain Molecules, Wiley Interscience, New York (1969)

  5. Ab initio molecular orbital and infrared spectroscopic study of the conformation of secondary amides: derivatives of formanilide, acetanilide and benzylamides

    Science.gov (United States)

    Ilieva, S.; Hadjieva, B.; Galabov, B.

    1999-09-01

    Ab initio molecular orbital calculations at HF/4-31G level and infrared spectroscopic data for the frequencies are applied to analyse the grouping in a series model aromatic secondary amides: formanilide; acetanilide; o-methylacetanilide; 2,6-dimethylformanilide, 2,6-dimethylacetanilide; N-benzylacetamide and N-benzylformamide. The theoretical and experimental data obtained show that the conformational state of the molecules studied is determined by the fine balance of several intramolecular factors: resonance effect between the amide group and the aromatic ring, steric interaction between various substituents around the -NH-CO- grouping in the aromatic ring, conjugation between the carbonyl bond and the nitrogen lone pair as well as direct field influences inside the amide group.

  6. Structural analysis of prolyl oligopeptidases using molecular docking and dynamics: insights into conformational changes and ligand binding.

    Directory of Open Access Journals (Sweden)

    Swati Kaushik

    Full Text Available Prolyl oligopeptidase (POP is considered as an important pharmaceutical target for the treatment of numerous diseases. Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, human and A. thaliana. Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, human POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in human context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of molecular dynamics (MD simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in β-propeller pore size, which was found to be hidden by five lysine residues present on blades one and seven. During simulation, β-propeller pore size was increased by ∼2 Å in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in human and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several neurodegenerative diseases.

  7. Efficient Conformational Sampling in Explicit Solvent Using a Hybrid Replica Exchange Molecular Dynamics Method

    Science.gov (United States)

    2011-12-01

    and Biochemistry , U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland §Computational Sciences and Engineering Branch...of motion of a system with constraints: molecular dynamics of n- alkanes . J. Comput. Phys. 1977, 23, 327–341. (29) Feig, M.; Karanicolas, J.; Brooks, C

  8. Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Eibl, Clarissa; Hessenberger, Manuel; Wenger, Julia; Brandstetter, Hans, E-mail: hans.brandstetter@sbg.ac.at [University of Salzburg, Billrothstrasse 11, 5020 Salzburg (Austria)

    2014-07-01

    Pyrin domains (PYDs) recruit downstream effector molecules in NLR signalling. A specific charge-relay system suggests a the formation of a signalling complex involving a PYD dimer. The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed.

  9. Using attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) to study the molecular conformation of parchment artifacts in different macroscopic states.

    Science.gov (United States)

    Gonzalez, Lee; Wade, Matthew; Bell, Nancy; Thomas, Kate; Wess, Tim

    2013-02-01

    Maintaining appropriate temperatures and relative humidity is considered essential to extending the useful life of parchment artifacts. Although the relationship between environmental factors and changes to the physical state of artifacts is reasonably understood, an improved understanding of the relationship between the molecular conformation and changes to the macroscopic condition of parchment is needed to optimize environmental conditions. Using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR FT-IR) analysis, the conformation of the molecular structure in selected parchment samples with specific macroscopic conditions, typically discoloration and planar deformations (e.g., cockling and tearing), have been made. The results of this investigation showed that the Fourier transform infrared signal differs for parchment samples exhibiting different macroscopic conditions. In areas exhibiting planar deformation, a change in the Fourier Transform Infrared signal was observed that indicates unfolding of the molecular conformation. In comparison, the discolored samples showed a change in molecular conformation that indicates a chemical change within the collagen molecular structure. This paper discusses the possible causal associations and implications of these findings for the conservation and preservation of parchment artifacts.

  10. Effect of trifluoroethylene monomers on molecular conformation of poly (vinylidene fluoride-trifluoroethylene) copolymer

    Institute of Scientific and Technical Information of China (English)

    Li Ji-Chao; Wang Chun-Lei; Zhong Wei-Lie

    2004-01-01

    Hartree-Fock and density functional theory (DFT) methods were employed to study poly (vinylidene fluoridetrifluoroethylene) [P(VDF-TrFE)] molecular chains with different VDF contents. The dependence of dipole moment of P(VDF-TrFE) chains on VDF content obtained from our calculation is in good agreement with the experiment. The TrFE monomer plays an important role in introducing the gauche bond into copolymer chains. A possible mechanism was interpreted.

  11. Optimization of capillary array electrophoresis single-strand conformation polymorphism analysis for routine molecular diagnostics.

    Science.gov (United States)

    Jespersgaard, Cathrine; Larsen, Lars Allan; Baba, Shingo; Kukita, Yoji; Tahira, Tomoko; Christiansen, Michael; Vuust, Jens; Hayashi, Kenshi; Andersen, Paal Skytt

    2006-10-01

    Mutation screening is widely used for molecular diagnostics of inherited disorders. Furthermore, it is anticipated that the present and future identification of genetic risk factors for complex disorders will increase the need for high-throughput mutation screening technologies. Capillary array electrophoresis (CAE) SSCP analysis is a low-cost, automated method with a high throughput and high reproducibility. Thus, the method fulfills many of the demands to be met for application in routine molecular diagnostics. However, the need for performing the electrophoresis at three temperatures between 18 degrees C and 35 degrees C for achievement of high sensitivity is a disadvantage of the method. Using a panel of 185 mutant samples, we have analyzed the effect of sample purification, sample medium and separation matrix on the sensitivity of CAE-SSCP analysis to optimize the method for molecular diagnostic use. We observed different effects from sample purification and sample medium at different electrophoresis temperatures, probably reflecting the complex interplay between sequence composition, electrophoresis conditions and sensitivity in SSCP analysis. The effect on assay sensitivity from three different polymers was tested using a single electrophoresis temperature of 27 degrees C. The data suggest that a sensitivity of 98-99% can be obtained using a 10% long chain poly-N,N-dimethylacrylamide polymer.

  12. Co-conformational Exchange Triggered by Molecular Recognition in a Di(acylamino)pyridine-Based Molecular Shuttle Containing Two Pyridine Rings at the Macrocycle.

    Science.gov (United States)

    Martinez-Cuezva, Alberto; Carro-Guillen, Fernando; Pastor, Aurelia; Marin-Luna, Marta; Orenes, Raul-Angel; Alajarin, Mateo; Berna, Jose

    2016-06-17

    We describe the incorporation of endo-pyridine units into the tetralactam ring of di(acylamino)pyridine-based rotaxanes. This macrocycle strongly associates with the linear interlocked component as confirmed by X-ray diffraction studies of rotaxane 2 b. Dynamic NMR studies of 2 b in solution revealed a rotational energy barrier that was higher than that of the related rotaxane 2 a, which lacks of pyridine rings in the macrocycle. The macrocycle distribution of the molecular shuttle 4 b, containing two endo-pyridine rings, shows that the major co-conformer is that with the cyclic component sitting over the di(acylamino)pyridine station. DFT calculations also support the marked preference of the ring for occupying the heterocyclic binding site. The association of N-hexylthymine with the di(acylamino)pyridine binding site of 4 b led to the formation of a rare 'S'-shaped co-conformer in which the tetralactam ring interacts simultaneously with both stations of the thread.

  13. Viscoelasticity Enhancement of Surfactant Solutions Depends on Molecular Conformation: Influence of Surfactant Headgroup Structure and Its Counterion.

    Science.gov (United States)

    Lutz-Bueno, Viviane; Pasquino, Rossana; Liebi, Marianne; Kohlbrecher, Joachim; Fischer, Peter

    2016-05-03

    During the anisotropic growth from globular to wormlike micelles, the basic interactions among distinct parts of the surfactant monomer, its counterion, and additives are fundamental to tune molecular self-assembly. We investigate the addition of sodium salicylate (NaSal) to hexadecyltrimethylammonium chloride and bromide (CTAC and CTAB), 1-hexadecylpyridinium chloride and bromide (CPyCl and CPyBr), and benzyldimethylhexadecylammonium chloride (BDMC), which have the same hydrophobic tail. Their potential to enhance viscoelasticity by anisotropic micellar growth upon salt addition was compared in terms of (i) the influence of the headgroup structure, and (ii) the influence of surfactant counterion type. Employing proton nuclear magnetic resonance ((1)H NMR), we focused on the molecular conformation of surfactant monomers in the core and polar shell regions of the micelles and their interactions with increasing concentration of NaSal. The viscoelastic response was investigated by rotational and oscillatory rheology. We show that micellar growth rates can be tuned by varying the flexibility and size of the surfactant headgroup as well as the dissociation degree of the surfactant counterion, which directly influences the strength of headgroup-counterion pairing. As a consequence, the morphological transitions depend directly on charge neutralization by electrostatic screening. For example, the amount of salt necessary to start the rodlike-to-wormlike micelle growth depends directly on the number of dissociated counterions in the polar shell.

  14. An in silico study of the molecular basis of B-RAF activation and conformational stability

    DEFF Research Database (Denmark)

    Fratev, Filip Filipov; Jonsdottir, Svava Osk

    2009-01-01

    B-RAF kinase plays an important role both in tumour induction and maintenance in several cancers and it is an attractive new drug target. However, the structural basis of the B-RAF activation is still not well understood. RESULTS: In this study we suggest a novel molecular basis of B-RAF activation....... It was found that several mutations, which directly or indirectly destabilized the interactions between these residues within this network, contributed to the changes in B-RAF activity. CONCLUSION: Our results showed that the above mechanisms lead to the disruption of the electrostatic interactions between...

  15. Spectroscopy of the conformational disorder in molecular films: Tetracosane and squalane on Pt(111)

    Science.gov (United States)

    Fuhrmann, D.; Graham, A. P.

    2004-02-01

    The spectroscopic investigation of the molecular vibrations of adsorbed branched and unbranched alkane molecules using helium atom scattering (HAS) provides evidence for the thermal formation of gauche defects in tetracosane (C24H50) monolayers above 200 K. HAS results for the vibration of tetracosane molecules perpendicular to the Pt(111) surface reveal a strong frequency decrease and peak broadening above the transition temperature which can be related to a reduction of the force holding the molecules to the surface. This reduction of the force is interpreted as being due to the thermal formation of gauche defects within the tetracosane molecules.

  16. Assignment of Side-Chain Conformation Using Adiabatic Energy Mapping, Free Energy Perturbation, and Molecular Dynamic Simulations

    DEFF Research Database (Denmark)

    Frimurer, Thomas M.; Günther, Peter H.; Sørensen, Morten Dahl;

    1999-01-01

    adiabatic mapping, conformational change, essentialdynamics, free energy simulations, Kunitz type inhibitor *ga3(VI)......adiabatic mapping, conformational change, essentialdynamics, free energy simulations, Kunitz type inhibitor *ga3(VI)...

  17. An in silico study of the molecular basis of B-RAF activation and conformational stability

    Directory of Open Access Journals (Sweden)

    Jónsdóttir Svava

    2009-07-01

    Full Text Available Abstract Background B-RAF kinase plays an important role both in tumour induction and maintenance in several cancers and it is an attractive new drug target. However, the structural basis of the B-RAF activation is still not well understood. Results In this study we suggest a novel molecular basis of B-RAF activation based on molecular dynamics (MD simulations of B-RAFWT and the B-RAFV600E, B-RAFK601E and B-RAFD594V mutants. A strong hydrogen bond network was identified in B-RAFWT in which the interactions between Lys601 and the well known catalytic residues Lys483, Glu501 and Asp594 play an important role. It was found that several mutations, which directly or indirectly destabilized the interactions between these residues within this network, contributed to the changes in B-RAF activity. Conclusion Our results showed that the above mechanisms lead to the disruption of the electrostatic interactions between the A-loop and the αC-helix in the activating mutants, which presumably contribute to the flipping of the activation segment to an active form. Conversely, in the B-RAFD594V mutant that has impaired kinase activity, and in B-RAFWT these interactions were strong and stabilized the kinase inactive form.

  18. UFSRAT: Ultra-fast Shape Recognition with Atom Types--the discovery of novel bioactive small molecular scaffolds for FKBP12 and 11βHSD1.

    Directory of Open Access Journals (Sweden)

    Steven Shave

    Full Text Available Using molecular similarity to discover bioactive small molecules with novel chemical scaffolds can be computationally demanding. We describe Ultra-fast Shape Recognition with Atom Types (UFSRAT, an efficient algorithm that considers both the 3D distribution (shape and electrostatics of atoms to score and retrieve molecules capable of making similar interactions to those of the supplied query.Computational optimization and pre-calculation of molecular descriptors enables a query molecule to be run against a database containing 3.8 million molecules and results returned in under 10 seconds on modest hardware. UFSRAT has been used in pipelines to identify bioactive molecules for two clinically relevant drug targets; FK506-Binding Protein 12 and 11β-hydroxysteroid dehydrogenase type 1. In the case of FK506-Binding Protein 12, UFSRAT was used as the first step in a structure-based virtual screening pipeline, yielding many actives, of which the most active shows a KD, app of 281 µM and contains a substructure present in the query compound. Success was also achieved running solely the UFSRAT technique to identify new actives for 11β-hydroxysteroid dehydrogenase type 1, for which the most active displays an IC50 of 67 nM in a cell based assay and contains a substructure radically different to the query. This demonstrates the valuable ability of the UFSRAT algorithm to perform scaffold hops.A web-based implementation of the algorithm is freely available at http://opus.bch.ed.ac.uk/ufsrat/.

  19. Detection of conformational changes in immunoglobulin G using isothermal titration calorimetry with low-molecular-weight probes.

    Science.gov (United States)

    Rispens, Theo; Lakemond, Catriona M M; Derksen, Ninotska I L; Aalberse, Rob C

    2008-09-15

    Proteins for therapeutic use may contain small amounts of partially misfolded monomeric precursors to postproduction aggregation. To detect these misfolded proteins in the presence of an excess of properly folded protein, fluorescent probes such as 8-anilino-1-naphthalene sulfonate (ANS) are commonly used. We investigated the possibility of using isothermal titration calorimetry (ITC) to improve the detection of this type of conformational change using hydrophobic probes. As a case study, conformational changes in human polyclonal immunoglobulin G (IgG) were monitored by measuring the enthalpies of binding of ANS using ITC. Results were compared with those using fluorescence spectroscopy. IgG heated at 63 degrees C was used as a model system for "damaged" IgG. Heat-treated IgG can be detected already at levels below 5% with both ITC and fluorescence. However, ITC allows a much wider molar probe-to-protein ratio to be sampled. In particular, using reverse titration experiments (allowing high probe-to-protein ratios not available to fluorescence spectroscopy), an increase in the number of binding sites with a K(d)>10 mM was observed for heat-treated IgG, reflecting subtle changes in structure. Both ITC and fluorescence spectroscopy showed low background signals for native IgG. The nature of the background signals was not clear from the fluorescence measurements. However, further analysis of the ITC background signals shows that a fraction (8%) binds ANS with a dissociation constant of approximately 0.2 mM. Measurements were also carried out at pH 4.5. Precipitation of IgG was induced by ANS at concentrations above 0.5 mM, interfering with the ITC measurements. Instead, with the nonfluorescent probes 4-amino-1-naphthalene sulfonate and 1-naphthalene sulfonate, no precipitation is observed. These probes yield differences in the enthalpies of binding to heated and nonheated IgG similar to ANS. The data illustrate that ITC with low-molecular-weight probes is a versatile

  20. Conformational and Molecular Structures of α,β-Unsaturated Acrylonitrile Derivatives: Photophysical Properties and Their Frontier Orbitals

    Directory of Open Access Journals (Sweden)

    María Judith Percino

    2016-03-01

    Full Text Available We report single crystal X-ray diffraction (hereafter, SCXRD analyses of derivatives featuring the electron-donor N-ethylcarbazole or the (4-diphenylaminophenyl moieties associated with a -CN group attached to a double bond. The compounds are (2Z-3-(4-(diphenylamino-phenyl-2-(pyridin-3-ylprop-2-enenitrile (I, (2Z-3-(4-(diphenylaminophenyl-2-(pyridin-4-yl-prop-2-enenitrile (II and (2Z-3-(9-ethyl-9H-carbazol-3-yl-2-(pyridin-2-ylenenitrile (III. SCXRD analyses reveal that I and III crystallize in the monoclinic space groups P2/c with Z’ = 2 and C2/c with Z’ = 1, respectively. Compound II crystallized in the orthorhombic space group Pbcn with Z’ = 1. The molecular packing analysis was conducted to examine the pyridine core effect, depending on the ortho, meta- and para-positions of the nitrogen atom, with respect to the optical properties and number of independent molecules (Z’. It is found that the double bond bearing a diphenylamino moiety introduced properties to exhibit a strong π-π-interaction in the solid state. The compounds were examined to evaluate the effects of solvent polarity, the role of the molecular structure, and the molecular interactions on their self-assembly behaviors. Compound I crystallized with a cell with two conformers, anti and syn, due to interaction with solvent. DFT calculations indicated the anti and syn structures of I are energetically stable (less than 1 eV. Also electrochemical and photophysical properties of the compounds were investigated, as well as the determination of optimization calculations in gas and different solvent (chloroform, cyclohexane, methanol, ethanol, tetrahydrofuran, dichloromethane and dimethyl sulfoxide in the Gaussian09 program. The effect of solvent by PCM method was also investigated. The frontier HOMO and LUMO energies and gap energies are reported.

  1. Conformational and Molecular Structures of α,β-Unsaturated Acrylonitrile Derivatives: Photophysical Properties and Their Frontier Orbitals.

    Science.gov (United States)

    Percino, María Judith; Cerón, Margarita; Rodríguez, Oscar; Soriano-Moro, Guillermo; Castro, María Eugenia; Chapela, Víctor M; Siegler, Maxime A; Pérez-Gutiérrez, Enrique

    2016-03-28

    We report single crystal X-ray diffraction (hereafter, SCXRD) analyses of derivatives featuring the electron-donor N-ethylcarbazole or the (4-diphenylamino)phenyl moieties associated with a -CN group attached to a double bond. The compounds are (2Z)-3-(4-(diphenylamino)-phenyl)-2-(pyridin-3-yl)prop-2-enenitrile (I), (2Z)-3-(4-(diphenylamino)phenyl)-2-(pyridin-4-yl)-prop-2-enenitrile (II) and (2Z)-3-(9-ethyl-9H-carbazol-3-yl)-2-(pyridin-2-yl)enenitrile (III). SCXRD analyses reveal that I and III crystallize in the monoclinic space groups P2/c with Z' = 2 and C2/c with Z' = 1, respectively. Compound II crystallized in the orthorhombic space group Pbcn with Z' = 1. The molecular packing analysis was conducted to examine the pyridine core effect, depending on the ortho, meta- and para-positions of the nitrogen atom, with respect to the optical properties and number of independent molecules (Z'). It is found that the double bond bearing a diphenylamino moiety introduced properties to exhibit a strong π-π-interaction in the solid state. The compounds were examined to evaluate the effects of solvent polarity, the role of the molecular structure, and the molecular interactions on their self-assembly behaviors. Compound I crystallized with a cell with two conformers, anti and syn, due to interaction with solvent. DFT calculations indicated the anti and syn structures of I are energetically stable (less than 1 eV). Also electrochemical and photophysical properties of the compounds were investigated, as well as the determination of optimization calculations in gas and different solvent (chloroform, cyclohexane, methanol, ethanol, tetrahydrofuran, dichloromethane and dimethyl sulfoxide) in the Gaussian09 program. The effect of solvent by PCM method was also investigated. The frontier HOMO and LUMO energies and gap energies are reported.

  2. Hydrocarbons depending on the chain length and head group adopt different conformations within a water-soluble nanocapsule: 1H NMR and molecular dynamics studies.

    Science.gov (United States)

    Choudhury, Rajib; Barman, Arghya; Prabhakar, Rajeev; Ramamurthy, V

    2013-01-10

    In this study we have examined the conformational preference of phenyl-substituted hydrocarbons (alkanes, alkenes, and alkynes) of different chain lengths included within a confined space provided by a molecular capsule made of two host cavitands known by the trivial name "octa acid" (OA). One- and two-dimensional (1)H NMR experiments and molecular dynamics (MD) simulations were employed to probe the location and conformation of hydrocarbons within the OA capsule. In general, small hydrocarbons adopted a linear conformation while longer ones preferred a folded conformation. In addition, the extent of folding and the location of the end groups (methyl and phenyl) were dependent on the group (H(2)C-CH(2), HC═CH, and C≡C) adjacent to the phenyl group. In addition, the rotational mobility of the hydrocarbons within the capsule varied; for example, while phenylated alkanes tumbled freely, phenylated alkenes and alkynes resisted such a motion at room temperature. Combined NMR and MD simulation studies have confirmed that molecules could adopt conformations within confined spaces different from that in solution, opening opportunities to modulate chemical behavior of guest molecules.

  3. Hamming distance geometry of a protein conformational space. Application to the clustering of a 4 ns molecular dynamics trajectory of the HIV-1 integrase catalytic core

    CERN Document Server

    Laboulais, C; Le Bret, M; Gabarro-Arpa, J; Laboulais, Cyril; Ouali, Mohammed; Bret, Marc Le; Gabarro-Arpa, Jacques

    2001-01-01

    Protein structures can be encoded into binary sequences, these are used to define a Hamming distance in conformational space: the distance between two different molecular conformations is the number of different bits in their sequences. Each bit in the sequence arises from a partition of conformational space in two halves. Thus, the information encoded in the binary sequences is also used to characterize the regions of conformational space visited by the system. We apply this distance and their associated geometric structures, to the clustering and analysis of conformations sampled during a 4 ns molecular dynamics simulation of the HIV-1 integrase catalytic core. The cluster analysis of the simulation shows a division of the trajectory into two segments of 2.6 and 1.4 ns length, which are qualitatively different: the data points to the fact that equilibration is only reached at the end of the first segment. Some length of the paper is devoted to compare the Hamming distance to the r.m.s. deviation measure. Th...

  4. Conformational sampling enhancement of replica exchange molecular dynamics simulations using swarm particle intelligence

    Energy Technology Data Exchange (ETDEWEB)

    Kamberaj, Hiqmet, E-mail: hkamberaj@ibu.edu.mk [Department of Computer Engineering, International Balkan University, Tashko Karadza 11A, Skopje (Macedonia, The Former Yugoslav Republic of)

    2015-09-28

    In this paper, we present a new method based on swarm particle social intelligence for use in replica exchange molecular dynamics simulations. In this method, the replicas (representing the different system configurations) are allowed communicating with each other through the individual and social knowledge, in additional to considering them as a collection of real particles interacting through the Newtonian forces. The new method is based on the modification of the equations of motion in such way that the replicas are driven towards the global energy minimum. The method was tested for the Lennard-Jones clusters of N = 4,  5, and 6 atoms. Our results showed that the new method is more efficient than the conventional replica exchange method under the same practical conditions. In particular, the new method performed better on optimizing the distribution of the replicas among the thermostats with time and, in addition, ergodic convergence is observed to be faster. We also introduce a weighted histogram analysis method allowing analyzing the data from simulations by combining data from all of the replicas and rigorously removing the inserted bias.

  5. Conformational Transitions

    Science.gov (United States)

    Czerminski, Ryszard; Roitberg, Adrian; Choi, Chyung; Ulitsky, Alexander; Elber, Ron

    1991-10-01

    Two computational approaches to study plausible conformations of biological molecules and the transitions between them are presented and discussed. The first approach is a new search algorithm which enhances the sampling of alternative conformers using a mean field approximation. It is argued and demonstrated that the mean field approximation has a small effect on the location of the minima. The method is a combination of the LES protocol (Locally Enhanced Sampling) and simulated annealing. The LES method was used in the past to study the diffusion pathways of ligands from buried active sites in myoglobin and leghemoglobin to the exterior of the protein. The present formulation of LES and its implementation in a Molecular Dynamics program is described. An application for side chain placement in a tetrapeptide is presented. The computational effort associated with conformational searches using LES grows only linearly with the number of degrees of freedom, whereas in the exact case the computational effort grows exponentially. Such saving is of course associated with a mean field approximation. The second branch of studies pertains to the calculation of reaction paths in large and flexible biological systems. An extensive mapping of minima and barriers for two different tetrapeptides is calculated from the known minima and barriers of alanine tetrapeptide which we calculated recently.1 The tetrapeptides are useful models for the formation of secondary structure elements since they are the shortest possible polymers of this type which can still form a complete helical turn. The tetrapeptides are isobutyryl-val(χ1=60)-ala-ala and isobutyryl-val(χ1=-60)-ala-ala. Properties of the hundreds of minima and of the hundreds intervening barriers are discussed. Estimates for thermal transition times between the many conformers (and times to explore the complete phase space) are calculated and compared. It is suggested that the most significant effect of the side chain size is

  6. Molecular design and prediction of bioactivity of chimeric calcitonin%嵌合降钙素的分子设计与生物学活性预测

    Institute of Scientific and Technical Information of China (English)

    王玉梅; 周一江; 张学成

    2009-01-01

    Objective:To design one new type of calcitonin(CT)analogue with higher bioactivity but lower sideeffects.Methods:According to the principle of bioactive peptide drug design and previous work experience,an assumption was raised that bioactivity of new type of calcitonin call be improved by increasing isoelectric point(pI),N-terminal hydrophobicity and C-terminal hydrophilicity of calcitonin molecules.Based on human and salmon calcitonin,a large number of calcitonin analogues were designed and then analyzed in sequence with the help of protein analysis software.The contradictions between activities and side-effects were taken into account and a new type of calcitonin analogue to meet the requirements was determined.Results:Calcitonin analogue meeting bioactivity requirements was chimeric calcitonin of human and salmon calcitonin.Structure prediction showed that the molecular conflonnation of new calcitonin analogue was similar to salmon calcitonin(sCT).The isoelectric point of chimeric calcitonin analogue was between human and salmon calcitonin.The N-terminal hydrophobicity of new calcitonin analogue Was increased more than that of human calcitonin(hCT)and as same as that of salmon calcitonin.Its C-terminal hydrophilicity was as same as that of salmon calcitonin and increased with a high degree compared with human calcitonin.Conclusion:The activity of new calcitonin analogue was predicted to have higher bioactivity than that of human calcitonin,while the side-effects was lower than that of salmon calcitonin.%目的:设计一种高活性、低副作用的降钙素类似物.方法:根据生物活件肽药物设计原理,结合前人的工作经验,提出提高降钙素分子等电点(pI)、增加N-末端疏水性和C-末端亲水性可以提高新型降钙素活件的假设.以人和鲑鱼降钙素为先导物,设计了大量的降钙素类似物,然后利用蛋白质分析计算软件,逐一分析,综合考虑到副作用与活性的矛盾,确定符合要求的新型

  7. Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering.

    Science.gov (United States)

    Wall, Michael E; Van Benschoten, Andrew H; Sauter, Nicholas K; Adams, Paul D; Fraser, James S; Terwilliger, Thomas C

    2014-12-16

    X-ray diffraction from protein crystals includes both sharply peaked Bragg reflections and diffuse intensity between the peaks. The information in Bragg scattering is limited to what is available in the mean electron density. The diffuse scattering arises from correlations in the electron density variations and therefore contains information about collective motions in proteins. Previous studies using molecular-dynamics (MD) simulations to model diffuse scattering have been hindered by insufficient sampling of the conformational ensemble. To overcome this issue, we have performed a 1.1-μs MD simulation of crystalline staphylococcal nuclease, providing 100-fold more sampling than previous studies. This simulation enables reproducible calculations of the diffuse intensity and predicts functionally important motions, including transitions among at least eight metastable states with different active-site geometries. The total diffuse intensity calculated using the MD model is highly correlated with the experimental data. In particular, there is excellent agreement for the isotropic component of the diffuse intensity, and substantial but weaker agreement for the anisotropic component. Decomposition of the MD model into protein and solvent components indicates that protein-solvent interactions contribute substantially to the overall diffuse intensity. We conclude that diffuse scattering can be used to validate predictions from MD simulations and can provide information to improve MD models of protein motions.

  8. Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction

    Science.gov (United States)

    Ciemny, Maciej Pawel; Debinski, Aleksander; Paczkowska, Marta; Kolinski, Andrzej; Kurcinski, Mateusz; Kmiecik, Sebastian

    2016-12-01

    Protein-peptide interactions are often associated with large-scale conformational changes that are difficult to study either by classical molecular modeling or by experiment. Recently, we have developed the CABS-dock method for flexible protein-peptide docking that enables large-scale rearrangements of the protein chain. In this study, we use CABS-dock to investigate the binding of the p53-MDM2 complex, an element of the cell cycle regulation system crucial for anti-cancer drug design. Experimental data suggest that p53-MDM2 binding is affected by significant rearrangements of a lid region - the N-terminal highly flexible MDM2 fragment; however, the details are not clear. The large size of the highly flexible MDM2 fragments makes p53-MDM2 intractable for exhaustive binding dynamics studies using atomistic models. We performed extensive dynamics simulations using the CABS-dock method, including large-scale structural rearrangements of MDM2 flexible regions. Without a priori knowledge of the p53 peptide structure or its binding site, we obtained near-native models of the p53-MDM2 complex. The simulation results match well the experimental data and provide new insights into the possible role of the lid fragment in p53 binding. The presented case study demonstrates that CABS-dock methodology opens up new opportunities for protein-peptide docking with large-scale changes of the protein receptor structure.

  9. Structural insights for designed alanine-rich helices: Comparing NMR helicity measures and conformational ensembles from molecular dynamics simulation

    Science.gov (United States)

    Song, Kun; Stewart, James M.; Fesinmeyer, R. Matthew

    2013-01-01

    The temperature dependence of helical propensities for the peptides Ac-ZGG-(KAAAA)3X-NH2 (Z = Y or G, X = A, K, and d-Arg) were studied both experimentally and by molecular dynamics simulations. Good agreement is observed in both the absolute helical propensities as well as relative helical content along the sequence; the global minimum on the calculated free energy landscape corresponds to a single α-helical conformation running from K4 – A18 with some terminal fraying, particularly at the C-terminus. Energy component analysis shows that the single helix state has favorable intramolecular electrostatic energy due to hydrogen bonds, and that less-favorable two-helix globular states have favorable solvation energy. The central lysine residues do not appear to increase helicity; however, both experimental and simulation studies show increasing helicity in the series X = Ala → Lys → d-Arg. This C-capping preference was also experimentally confirmed in Ac-(KAAAA)3X-GY-NH2 and (KAAAA)3X-GY-NH2 sequences. The roles of the C-capping groups, and of lysines throughout the sequence, in the MD-derived ensembles are analyzed in detail. PMID:18428207

  10. Conformal organic-inorganic hybrid network polymer thin films by molecular layer deposition using trimethylaluminum and glycidol.

    Science.gov (United States)

    Gong, Bo; Peng, Qing; Parsons, Gregory N

    2011-05-19

    Growing interest in nanoscale organic-inorganic hybrid network polymer materials is driving exploration of new bulk and thin film synthesis reaction mechanisms. Molecular layer deposition (MLD) is a vapor-phase deposition process, based on atomic layer deposition (ALD) which proceeds by exposing a surface to an alternating sequence of two or more reactant species, where each surface half-reaction goes to completion before the next reactant exposure. This work describes film growth using trimethyl aluminum and heterobifunctional glycidol at moderate temperatures (90-150 °C), producing a relatively stable organic-inorganic network polymer of the form (-Al-O-(C(4)H(8))-O-)(n). Film growth rate and in situ reaction analysis indicate that film growth does not initially follow a steady-state rate, but increases rapidly during early film growth. The mechanism is consistent with subsurface species transport and trapping, previously documented during MLD and ALD on polymers. A water exposure step after the TMA produces a more linear growth rate, likely by blocking TMA subsurface diffusion. Uniform and conformal films are formed on complex nonplanar substrates. Upon postdeposition annealing, films transform into microporous metal oxides with ∼5 Å pore size and surface area as high as ∼327 m(2)/g, and the resulting structures duplicate the shape of the original substrate. These hybrid films and porous materials could find uses in several research fields including gas separations and diffusion barriers, biomedical scaffolds, high surface area coatings, and others.

  11. Ground and excited state proton transfer of the bioactive plant flavonol robinetin in a protein environment: spectroscopic and molecular modeling studies.

    Science.gov (United States)

    Pahari, Biswa Pathik; Chaudhuri, Sudip; Chakraborty, Sandipan; Sengupta, Pradeep K

    2015-02-12

    We performed spectroscopic and molecular modeling studies to explore the interaction of the bioactive plant flavonol robinetin (3,7,3',4',5'-OH flavone), with the carrier protein human serum albumin (HSA). Multiparametric fluorescence sensing, exploiting the intrinsic "two color" fluorescence of robinetin (comprising excited state intramolecular proton transfer (ESIPT) and charge transfer (CT) emissions) reveals that binding to HSA significantly affects the emission and excitation profiles, with strongly blue-shifted (∼29 nm) normal fluorescence and remarkable increase in the ESIPT fluorescence anisotropy (r) and lifetime (τ). Flavonol-induced HSA (tryptophan) fluorescence quenching data yield the dynamic quenching constant (KD) as 5.42 × 10(3) M(-1) and the association constant (Ks) as 5.59 × 10(4) M(-1). Time-resolved fluorescence anisotropy decay studies show dramatic (∼170 times) increase in the rotational correlation time (τ(rot)), reflecting greatly enhanced restrictions in motion of robinetin in the protein matrix. Furthermore, prominent induced circular dichroism (ICD) bands appear, indicating that the chiral environment of HSA strongly perturbs the electronic transitions of the intrinsically achiral robinetin molecule. Molecular docking calculations suggest that robinetin binds in subdomain IIA of HSA, where specific interactions with basic residues promote ground state proton abstraction and stabilize an anionic species, which is consistent with spectroscopic observations.

  12. Molecular effects of bioactive fraction of Curcuma mangga (DLBS4847 as a downregulator of 5α-reductase activity pathways in prostatic epithelial cells

    Directory of Open Access Journals (Sweden)

    Karsono AH

    2014-06-01

    Full Text Available Agung Heru Karsono, Olivia Mayasari Tandrasasmita, Raymond R TjandrawinataSection of Molecular Pharmacology, Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, Dexa Medica, Cikarang, IndonesiaAbstract: DLBS4847 is a standardized bioactive fraction of Curcuma mangga. In this study, we used prostate cancer (PC-3 as the cell line to study the effects of DLBS4847 on prostatic cell viability, as well as related molecular changes associated with the decreased cell number. The observation revealed that DLBS4847 inhibited the growth of PC3 cells through downregulation of the 5α-reductase (5AR pathway. At the transcription level, 5AR1 and androgen-receptor gene expressions were downregulated in a dose-dependent manner. Furthermore, 5AR-1 and dihydrotestosterone expression were also downregulated at the protein level. A microarray study was also performed to see the effects of DLBS4847 on differential gene expressions in prostate cancer 3 cells. Among others, DLBS4847 downregulated genes related to prostate growth and hypertrophy. Our results suggested that DLBS4847 could potentially become an alternative treatment for prostate disorders, such as benign prostatic hyperplasia. In this regard, DLBS4847 exerts its growth inhibition partially through downregulation of the 5AR pathway.Keywords: DLBS4847, Curcuma mangga, 5α-reductase inhibitor, benign prostatic hyperplasia (BPH, prostate cancer

  13. A molecular dynamics study of the BACE1 conformational change from Apo to closed form induced by hydroxyethylamine derived compounds.

    Science.gov (United States)

    Gueto-Tettay, Carlos; Zuchniarz, Joshua; Fortich-Seca, Yeyson; Gueto-Tettay, Luis Roberto; Drosos-Ramirez, Juan Carlos

    2016-11-01

    BACE1 is an aspartyl protease which is a therapeutic target for Alzheimer's disease (AD) because of its participation in the rate-limiting step in the production of Aβ-peptide, the accumulation of which produces senile plaques and, in turn, the neurodegenerative effects associated with AD. The active site of this protease is composed in part by two aspartic residues (Asp93 and Asp289). Additionally, the catalytic site has been found to be covered by an antiparallel hairpin loop called the flap. The dynamics of this flap are fundamental to the catalytic function of the enzyme. When BACE1 is inactive (Apo), the flap adopts an open conformation, allowing a substrate or inhibitor to access the active site. Subsequent interaction with the ligand induces flap closure and the stabilization of the macromolecular complex. Further, the protonation state of the aspartic dyad is affected by the chemical nature of the species entering the active site, so that appropriate selection of protonation states for the ligand and the catalytic residues will permit the elucidation of the inhibitory pathway for BACE1. In the present study, comparative analysis of different combinations of protonation states for the BACE1-hydroxyethylamine (HEA) system is reported. HEAs are potent inhibitors of BACE1 with favorable pharmacological and kinetic properties, as well as oral bioavailability. The results of Molecular Dynamics (MD) simulations and population density calculations using 8 different parameters demonstrate that the LnAsp289 configuration (HEA with a neutral amine and the Asp289 residue protonated) is the only one which permits the expected conformational change in BACE1, from apo to closed form, after flap closure. Additionally, differences in their capacities to establish and maintain interactions with residues such as Asp93, Gly95, Thr133, Asp289, Gly291, and Asn294 during this step allow differentiation among the inhibitory activities of the HEAs. The results and methodology here

  14. Conformational behaviour of glycomimetics: NMR and molecular modelling studies of the C-glycoside analogue of the disaccharide methyl beta-D-galactopyranosyl-(1-->3)-beta-D-glucopyranoside.

    Science.gov (United States)

    Vidal, Paloma; Vauzeilles, Boris; Blériot, Yves; Sollogoub, Matthieu; Sinaÿ, Pierre; Jiménez-Barbero, Jesús; Espinosa, Juan F

    2007-09-03

    The conformational behaviour of the C-glycoside beta-C-Gal-(1-->3)-beta-Glc-OMe (1) has been studied using a combination of molecular mechanics and NMR spectroscopy (proton-proton coupling constants and nuclear Overhauser effects). It is shown that the C-disaccharide populates two distinctive conformational families in solution, the normal syn-psi conformation, which is the predominating conformation of parent O-glycoside 2, and the anti-psi conformation, which has not been detected for the O-disaccharide.

  15. Rescuing compound bioactivity in a secondary cell-based screening by using γ-cyclodextrin as a molecular carrier

    Science.gov (United States)

    Claveria-Gimeno, Rafael; Vega, Sonia; Grazu, Valeria; de la Fuente, Jesús M; Lanas, Angel; Velazquez-Campoy, Adrian; Abian, Olga

    2015-01-01

    In vitro primary screening for identifying bioactive compounds (inhibitors, activators or pharmacological chaperones) against a protein target results in the discovery of lead compounds that must be tested in cell-based efficacy secondary screenings. Very often lead compounds do not succeed because of an apparent low potency in cell assays, despite an excellent performance in primary screening. Primary and secondary screenings differ significantly according to the conditions and challenges the compounds must overcome in order to interact with their intended target. Cellular internalization and intracellular metabolism are some of the difficulties the compounds must confront and different strategies can be envisaged for minimizing that problem. Using a novel screening procedure we have identified 15 compounds inhibiting the hepatitis C NS3 protease in an allosteric fashion. After characterizing biophysically the interaction with the target, some of the compounds were not able to inhibit viral replication in cell assays. In order to overcome this obstacle and potentially improve cellular internalization three of these compounds were complexed with γ-cyclodextrin. Two of them showed a five- and 16-fold activity increase, compared to their activity when delivered as free compounds in solution (while γ-cyclodextrin did not show antiviral activity by itself). The most remarkable result came from a third compound that showed no antiviral activity in cell assays when delivered free in solution, but its γ-cyclodextrin complex exhibited a 50% effective concentration of 5 μM. Thus, the antiviral activity of these compounds can be significantly improved, even completely rescued, using γ-cyclodextrin as carrier molecule. PMID:25834436

  16. A coupling of homology modeling with multiple molecular dynamics simulation for identifying representative conformation of GPCR structures: a case study on human bombesin receptor subtype-3.

    Science.gov (United States)

    Nowroozi, Amin; Shahlaei, Mohsen

    2017-02-01

    In this study, a computational pipeline was therefore devised to overcome homology modeling (HM) bottlenecks. The coupling of HM with molecular dynamics (MD) simulation is useful in that it tackles the sampling deficiency of dynamics simulations by providing good-quality initial guesses for the native structure. Indeed, HM also relaxes the severe requirement of force fields to explore the huge conformational space of protein structures. In this study, the interaction between the human bombesin receptor subtype-3 and MK-5046 was investigated integrating HM, molecular docking, and MD simulations. To improve conformational sampling in typical MD simulations of GPCRs, as in other biomolecules, multiple trajectories with different initial conditions can be employed rather than a single long trajectory. Multiple MD simulations of human bombesin receptor subtype-3 with different initial atomic velocities are applied to sample conformations in the vicinity of the structure generated by HM. The backbone atom conformational space distribution of replicates is analyzed employing principal components analysis. As a result, the averages of structural and dynamic properties over the twenty-one trajectories differ significantly from those obtained from individual trajectories.

  17. Shape: automatic conformation prediction of carbohydrates using a genetic algorithm

    Directory of Open Access Journals (Sweden)

    Rosen Jimmy

    2009-09-01

    Full Text Available Abstract Background Detailed experimental three dimensional structures of carbohydrates are often difficult to acquire. Molecular modelling and computational conformation prediction are therefore commonly used tools for three dimensional structure studies. Modelling procedures generally require significant training and computing resources, which is often impractical for most experimental chemists and biologists. Shape has been developed to improve the availability of modelling in this field. Results The Shape software package has been developed for simplicity of use and conformation prediction performance. A trivial user interface coupled to an efficient genetic algorithm conformation search makes it a powerful tool for automated modelling. Carbohydrates up to a few hundred atoms in size can be investigated on common computer hardware. It has been shown to perform well for the prediction of over four hundred bioactive oligosaccharides, as well as compare favourably with previously published studies on carbohydrate conformation prediction. Conclusion The Shape fully automated conformation prediction can be used by scientists who lack significant modelling training, and performs well on computing hardware such as laptops and desktops. It can also be deployed on computer clusters for increased capacity. The prediction accuracy under the default settings is good, as it agrees well with experimental data and previously published conformation prediction studies. This software is available both as open source and under commercial licenses.

  18. Bioactivity of chemically transformed humic matter from vermicompost on plant root growth.

    Science.gov (United States)

    Dobbss, Leonardo Barros; Pasqualoto Canellas, Luciano; Lopes Olivares, Fábio; Oliveira Aguiar, Natália; Peres, Lázaro Eustáquio Pereira; Azevedo, Mariana; Spaccini, Riccardo; Piccolo, Alessandro; Façanha, Arnoldo R

    2010-03-24

    Chemical reactions (hydrolysis, oxidation, reduction, methylation, alkyl compounds detachment) were applied to modify the structure of humic substances (HS) isolated from vermicompost. Structural and conformational changes of these humic derivatives were assessed by elemental analyses, size exclusion chromatography (HPSEC), solid-state nuclear magnetic resonance ((13)C CPMAS-NMR), and diffusion ordered spectroscopy (DOSY-NMR), whereas their bioactivity was evaluated by changes in root architecture and proton pump activation of tomato and maize. All humic derivatives exhibited a large bioactivity compared to original HS, both KMnO(4)-oxidized and methylated materials being the most effective. Whereas no general relationship was found between bioactivity and humic molecular sizes, the hydrophobicity index was significantly related with proton pump stimulation. It is suggested that the hydrophobic domain can preserve bioactive molecules such as auxins in the humic matter. In contact with root-exuded organic acids the hydrophobic weak forces could be disrupted, releasing bioactive compounds from humic aggregates. These findings were further supported by the fact that HS and all derivatives used in this study activated the auxin synthetic reporter DR5::GUS.

  19. Characterization of molecular determinants of the conformational stability of macrophage migration inhibitory factor: leucine 46 hydrophobic pocket.

    Directory of Open Access Journals (Sweden)

    Farah El-Turk

    Full Text Available Macrophage Migration Inhibitory Factor (MIF is a key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer formation, is essential for its keto-enol tautomerase activity and probably mediates several of its interactions and biological activities, including its binding to its receptor CD74 and activation of certain signaling pathways. Therefore, understanding the molecular factors governing the oligomerization of MIF and the role of quaternary structure in modulating its structural stability and multifunctional properties is crucial for understanding the function of MIF in health and disease. Herein, we describe highly conserved intersubunit interactions involving the hydrophobic packing of the side chain of Leu46 onto the β-strand β3 of one monomer within a hydrophobic pocket from the adjacent monomer constituted by residues Arg11, Val14, Phe18, Leu19, Val39, His40, Val41, Val42, and Pro43. To elucidate the structural significance of these intersubunit interactions and their relative contribution to MIF's trimerization, structural stability and catalytic activity, we generated three point mutations where Leu46 was replaced by glycine (L46G, alanine (L46A and phenylalanine (L46F, and their structural properties, stability, oligomerization state, and catalytic activity were characterized using a battery of biophysical methods and X-ray crystallography. Our findings provide new insights into the role of the Leu46 hydrophobic pocket in stabilizing the conformational state of MIF in solution. Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state.

  20. Molecular Simulations of Dodecyl-β-maltoside Micelles in Water: Influence of the Headgroup Conformation and Force field Parameters

    Science.gov (United States)

    Abel, Stéphane; Dupradeau, François-Yves; Raman, E. Prabhu; MacKerell, Alexander D.; Marchi, Massimo

    2011-01-01

    This paper deals with the development and validation of new potential parameter sets, based on the CHARMM36 and GLYCAM06 force fields, to simulate micelles of the two anomeric forms (α and β) of N-Dodecyl-ß-maltoside (C12G2), a surfactant widely used in the extraction and purification of membrane proteins. In this context, properties such as size, shape, internal structure and hydration of the C12G2 anomer micelles were thoroughly investigated by molecular dynamics simulations and the results compared with experiments. Additional simulations were also performed with the older CHARMM22 force field for carbohydrates (Kuttel, M. et al. J. Comp. Chem. 2002, 23, 1236-1243). We find that our CHARMM and GLYCAM parameter sets yields similar results in case of properties related to the micelle structure, but differ for other properties such as the headgroup conformation or the micelle hydration. In agreement with experiments, our results show that for all model potentials the β-C12G2 micelles have a more pronounced ellipsoidal shape than those containing α anomers. The computed radius of gyration is 20.2 Å and 25.4 Å for the α- and β-anomer micelles, respectively. Finally, we show that depending on the potential the water translational diffusion of the interfacial water is 7 - 11.5 times slower than that of bulk water due to the entrapment of the water in the micelle crevices. This retardation is independent of the headgroup in α- or β- anomers. PMID:21192681

  1. A molecular mechanics study of the effect of substitution in position 1 on the conformational space of the oxytocin/vasopressin ring

    Science.gov (United States)

    Tarnowska, Monika; Liwo, Adam; Shenderovich, Mark D.; Liepiņa, Inta; Golbraikh, Alexander A.; Grzonka, Zbigniew; Tempczyk, Anna

    1993-12-01

    The effect of the substitution in position 1 on the low-energy conformations of the oxytocin/vasopressin 20-membered ring was investigated by means of molecular mechanics. Three representative substitutions were considered: β'-mercapto-β,β-dimethyl)propionic acid (Dmp), (β'-mercapto-β,β-cyclopentamethylene)propionic acid (Cpp), both forming strong antagonists, and (α,α-dimethyl-β-mercapto)propionic acid (α-Dmp), forming analogs of strongly reduced biological activity, with the β-mercaptopropionic (Mpa) residue taken as reference. Both ECEPP/2 (rigid valence geometry) and AMBER (flexible valence geometry) force fields were employed in the calculations. Three basic types of backbone conformations were taken into account which are distinguished by the type of β-turn at residues 3 and 4: β1/βIII, βII, and βI'/βIII', all types containing one or two intra-annular hydrogen bonds. The allowed (ring-closed) disulfide-bridge conformations were searched by an algorithm formulated in terms of scanning the disulfide-bridge torsional angle Cβ-S-S-Cβ. The ECEPP/2 and AMBER energies of the obtained conformations were found to be in reasonable agreement. Two of the low-energy conformers of the [Mpa1]-compound agreed very well with the cyclic part of the two conformers found in the crystal structure of [Mpa1]-oxytocin. An analysis of the effect of β-substitution on relative energies showed that the conformations with the N-C'-CH2-CH2 (ψ'1) and C'-CH2-CH2-S (ϰ'1) angles of the first residue around (-100°, 60°) and (100°, -60°) are not affected; this in most cases implies a left-handed disulfide bridge. In the case of α-substitution the allowed values of ψ'1 are close to ± 60°. This requirement, being in contradiction to the one concerning β-substitution, could explain the very low biological activity of the α-substituted analogs. The conformational preferences of substituted compounds can largely be explained by the analysis of local interactions

  2. Molecular Basis of Inactive B-RAF(WT) and B-RAF(V600E) Ligand Inhibition, Selectivity and Conformational Stability: An in Silico Study

    DEFF Research Database (Denmark)

    Fratev, Filip Filipov; Jonsdottir, Svava Osk; Mihaylova, E.

    2009-01-01

    The B-RAF kinase plays an important role both in tumor induction and maintenance in several cancers. The molecular basis of the inactive B-RAF(WT) and B-RAF(V600E) inhibition and selectivity of a series of inhibitors was examined with a combination of molecular dynamics (MD), free energy MM......-PBSA and local-binding energy (LBE) approaches. The conformational stability of the unbounded kinases and in particular the processes of the B-RAF(V600E) mutant activation were analyzed. A unique salt bridge network formed mainly by the catalytic residues was identified in the unbounded B-RAFs...

  3. Reproducing the conformations of protein-bound ligands: a critical evaluation of several popular conformational searching tools.

    Science.gov (United States)

    Boström, J

    2001-12-01

    Several programs (Catalyst, Confort, Flo99, MacroModel, and Omega) that are commonly used to generate conformational ensembles have been tested for their ability to reproduce bioactive conformations. The ligands from thirty-two different ligand-protein complexes determined by high-resolution (Confort) performed least well. For the seven ligands in the set having eight or more rotatable bonds, none of the bioactive conformations were ever found, save for one exception (Flo99). These ligands do not bind in a local minimum conformation according to AMBER*\\GB/SA. Taking these last two observations together, it is clear that geometrically similar structures should be collected in order to increase the probability of finding the bioactive conformation among the generated ensembles. Factors influencing bioactive conformational retrieval have been identified and are discussed.

  4. Molecular effects of bioactive fraction of Curcuma mangga (DLBS4847) as a downregulator of 5α-reductase activity pathways in prostatic epithelial cells.

    Science.gov (United States)

    Karsono, Agung Heru; Tandrasasmita, Olivia Mayasari; Tjandrawinata, Raymond R

    2014-01-01

    DLBS4847 is a standardized bioactive fraction of Curcuma mangga. In this study, we used prostate cancer (PC)-3 as the cell line to study the effects of DLBS4847 on prostatic cell viability, as well as related molecular changes associated with the decreased cell number. The observation revealed that DLBS4847 inhibited the growth of PC3 cells through downregulation of the 5α-reductase (5AR) pathway. At the transcription level, 5AR1 and androgen-receptor gene expressions were downregulated in a dose-dependent manner. Furthermore, 5AR-1 and dihydrotestosterone expression were also downregulated at the protein level. A microarray study was also performed to see the effects of DLBS4847 on differential gene expressions in prostate cancer 3 cells. Among others, DLBS4847 downregulated genes related to prostate growth and hypertrophy. Our results suggested that DLBS4847 could potentially become an alternative treatment for prostate disorders, such as benign prostatic hyperplasia. In this regard, DLBS4847 exerts its growth inhibition partially through downregulation of the 5AR pathway.

  5. Non-destructive analysis of the conformational differences among feedstock sources and their corresponding co-products from bioethanol production with molecular spectroscopy

    Science.gov (United States)

    Gamage, I. H.; Jonker, A.; Zhang, X.; Yu, P.

    2014-01-01

    The objective of this study was to determine the possibility of using molecular spectroscopy with multivariate technique as a fast method to detect the source effects among original feedstock sources of wheat and their corresponding co-products, wheat DDGS, from bioethanol production. Different sources of the bioethanol feedstock and their corresponding bioethanol co-products, three samples per source, were collected from the same newly-built bioethanol plant with current bioethanol processing technology. Multivariate molecular spectral analyses were carried out using agglomerative hierarchical cluster analysis (AHCA) and principal component analysis (PCA). The molecular spectral data of different feedstock sources and their corresponding co-products were compared at four different regions of ca. 1800-1725 cm-1 (carbonyl Cdbnd O ester, mainly related to lipid structure conformation), ca. 1725-1482 cm-1 (amide I and amide II region mainly related to protein structure conformation), ca. 1482-1180 cm-1 (mainly associated with structural carbohydrate) and ca. 1180-800 cm-1 (mainly related to carbohydrates) in complex plant-based system. The results showed that the molecular spectroscopy with multivariate technique could reveal the structural differences among the bioethanol feedstock sources and among their corresponding co-products. The AHCA and PCA analyses were able to distinguish the molecular structure differences associated with chemical functional groups among the different sources of the feedstock and their corresponding co-products. The molecular spectral differences indicated the differences in functional, biomolecular and biopolymer groups which were confirmed by wet chemical analysis. These biomolecular and biopolymer structural differences were associated with chemical and nutrient profiles and nutrient utilization and availability. Molecular spectral analyses had the potential to identify molecular structure difference among bioethanol feedstock sources

  6. VP40 of the Ebola Virus as a Target for EboV Therapy: Comprehensive Conformational and Inhibitor Binding Landscape from Accelerated Molecular Dynamics.

    Science.gov (United States)

    Balmith, Marissa; Soliman, Mahmoud E S

    2017-03-01

    The first account of the dynamic features of the loop region of VP40 of the Ebola virus was studied using accelerated molecular dynamics simulations and reported herein. Among the proteins of the Ebola virus, the matrix protein (VP40) plays a significant role in the virus lifecycle thereby making it a promising therapeutic target. Of interest is the newly elucidated N-terminal domain loop region of VP40 comprising residues K127, T129, and N130 which when mutated to alanine have demonstrated an unrecognized role for N-terminal domain-plasma membrane interaction for efficient VP40-plasma membrane localization, oligomerization, matrix assembly, and egress. The molecular understanding of the conformational features of VP40 in complex with a known inhibitor still remains elusive. Using accelerated molecular dynamics approaches, we conducted a comparative study on VP40 apo and bound systems to understand the conformational features of VP40 at the molecular level and to determine the effect of inhibitor binding with the aid of a number of post-dynamic analytical tools. Significant features were seen in the presence of an inhibitor as per molecular mechanics/generalized born surface area binding free energy calculations. Results revealed that inhibitor binding to VP40 reduces the flexibility and mobility of the protein as supported by root mean square fluctuation and root mean square deviation calculations. The study revealed a characteristic "twisting" motion and coiling of the loop region of VP40 accompanied by conformational changes in the dimer interface upon inhibitor binding. We believe that results presented in this study will ultimately provide useful insight into the binding landscape of VP40 which could assist researchers in the discovery of potent Ebola virus inhibitors for anti-Ebola therapies.

  7. The SRAP based molecular diversity related to antifungal and antioxidant bioactive constituents for biocontrol potentials of Trichoderma against Sclerotium rolfsii Scc.

    Science.gov (United States)

    Hirpara, Darshna G; Gajera, H P; Bhimani, R D; Golakiya, B A

    2016-08-01

    The study was performed to examine 11 isolates of Trichoderma for their bio-control potentials against Sclerotium rolfsii Sacc. causing stem rot in groundnut. The antagonists Trichoderma were subjected to sequence related amplified polymorphism (SRAP) based molecular diversity analysis and compared with their hardness to S. rolfsii with respect to secretary antifungal and antioxidant profile. T. virens NBAII Tvs 12 evident highest (87.91 %) growth inhibition of test pathogen followed by T. koningii MTCC 796 (67.03 %) at 7 days after inoculation (DAI). Microscopic study confirmed biocontrol mechanism as mycoparasitism for Tvs 12 and antibiosis for MTCC 796. The growth inhibition of test pathogen was significantly negatively correlated with sclerotia formation and lipid peroxidation during antagonism due to release of secretary bioactive antioxidants by antagonists to terminate oxidative burst generated by S. rolfsii and causing inhibition of sclerotium formation. The GC-MS profile identified antifungal and antioxidant constituents hexadecane, 1,2-benzenedicarboxylic acid, mono (2-ethylhexyl) ester, 1-hexadecanesulfonyl chloride, and octadecane in potent antagonists Tvs 12; and nonacosane and octadecane in MTCC 796 along with two novel compounds 1-pentadecene and 1-heneicosyl formate for biocontrol activity. Molecular diversity of Trichoderma isolates associated with antagonistic activity was assessed by SRAP markers. The 115 primer combinations generate total 1328 amplified products of which, 1095 are shared polymorphic and 199 are unique polymorphic. The 15 SRAP combinations produced 18 bands to diagnose best antagonist Tvs 12 and 13 SRAP combinations generated 19 unique bands for identification of MTCC 796. The mycoparasitic antagonist Tvs 12 would be the best antagonist and released unique antifungal and antioxidant constituents to combat pathogen infection. The SRAP based genetic diversity indicates Tvs12 strain clustered with T. viride NBAII Tv23 and shared

  8. Analysis of in vitro bioactivity data extracted from drug discovery literature and patents: Ranking 1654 human protein targets by assayed compounds and molecular scaffolds

    Directory of Open Access Journals (Sweden)

    Southan Christopher

    2011-05-01

    Full Text Available Abstract Background Since the classic Hopkins and Groom druggable genome review in 2002, there have been a number of publications updating both the hypothetical and successful human drug target statistics. However, listings of research targets that define the area between these two extremes are sparse because of the challenges of collating published information at the necessary scale. We have addressed this by interrogating databases, populated by expert curation, of bioactivity data extracted from patents and journal papers over the last 30 years. Results From a subset of just over 27,000 documents we have extracted a set of compound-to-target relationships for biochemical in vitro binding-type assay data for 1,736 human proteins and 1,654 gene identifiers. These are linked to 1,671,951 compound records derived from 823,179 unique chemical structures. The distribution showed a compounds-per-target average of 964 with a maximum of 42,869 (Factor Xa. The list includes non-targets, failed targets and cross-screening targets. The top-278 most actively pursued targets cover 90% of the compounds. We further investigated target ranking by determining the number of molecular frameworks and scaffolds. These were compared to the compound counts as alternative measures of chemical diversity on a per-target basis. Conclusions The compounds-per-protein listing generated in this work (provided as a supplementary file represents the major proportion of the human drug target landscape defined by published data. We supplemented the simple ranking by the number of compounds assayed with additional rankings by molecular topology. These showed significant differences and provide complementary assessments of chemical tractability.

  9. Influence of oral contraceptive use on growth hormone in vivo bioactivity following resistance exercise: responses of molecular mass variants.

    Science.gov (United States)

    Kraemer, William J; Nindl, Bradley C; Volek, Jeff S; Marx, James O; Gotshalk, Lincoln A; Bush, Jill A; Welsch, Jill R; Vingren, Jakob L; Spiering, Barry A; Fragala, Maren S; Hatfield, Disa L; Ho, Jen-Yu; Maresh, Carl M; Mastro, Andrea M; Hymer, Wesley C

    2008-06-01

    The purpose was to examine effects of oral contraceptive (OC) use on plasma growth hormone (GH) responses to heavy resistance exercise. Sixty untrained women were placed into one of two groups: currently using OC (Ortho Tri-Cyclen) (n=25; mean+/-SD: 24.5+/-4.2y, 160.4+/-7.1cm, 64.1+/-11.3kg) or not currently using OC (NOC) (n=35; 23.6+/-4.6y, 165.9+/-6.0cm, 65.7+/-10.3kg). Participants performed an acute heavy resistance exercise test (AHRET; six sets of 10 repetition squats; 2min rest between sets) during days 2-4 of the follicular phase (NOC group) or of inactive oral contraceptive intake (OC group). Plasma was obtained before and immediately after AHRET and subsequently fractionated based on apparent molecular weight (>60kD, 30-60kD, and exercise-induced GH for the IFA, Nichols, and NIDDK in unfractionated plasma and >60kD subfraction compared to NOC group. No differences were observed for the tibial line bioassay. OC use augmented immunological GH response to AHRET in unfractionated plasma and >60kD molecular weight subfraction. However, OC use only increased biological activity of GH in one of two bioassays. These data demonstrated that GH concentrations at rest and following exercise are assay-dependent.

  10. {sup 13}CHD{sub 2}–CEST NMR spectroscopy provides an avenue for studies of conformational exchange in high molecular weight proteins

    Energy Technology Data Exchange (ETDEWEB)

    Rennella, Enrico; Huang, Rui; Velyvis, Algirdas; Kay, Lewis E., E-mail: kay@pound.med.utoronto.ca [The University of Toronto, Departments of Molecular Genetics, Biochemistry and Chemistry (Canada)

    2015-10-15

    An NMR experiment for quantifying slow (millisecond) time-scale exchange processes involving the interconversion between visible ground state and invisible, conformationally excited state conformers is presented. The approach exploits chemical exchange saturation transfer (CEST) and makes use of {sup 13}CHD{sub 2} methyl group probes that can be readily incorporated into otherwise highly deuterated proteins. The methodology is validated with an application to a G48A Fyn SH3 domain that exchanges between a folded conformation and a sparsely populated and transiently formed unfolded ensemble. Experiments on a number of different protein systems, including a 360 kDa half-proteasome, establish that the sensitivity of this {sup 13}CHD{sub 2}{sup 13}C–CEST technique can be upwards of a factor of 5 times higher than for a previously published {sup 13}CH{sub 3}{sup 13}C–CEST approach (Bouvignies and Kay in J Biomol NMR 53:303–310, 2012), suggesting that the methodology will be powerful for studies of conformational exchange in high molecular weight proteins.

  11. Molecular Dynamics Simulations of Ligand-Induced Flap Conformational Changes in Cathepsin-D-A Comparative Study.

    Science.gov (United States)

    Arodola, Olayide A; Soliman, Mahmoud E S

    2016-11-01

    The flap region in aspartic proteases is a unique structural feature to this class of enzymes, and found to have a profound impact on protein overall structure, function, and dynamics. Understanding the structure and dynamic behavior of the flap regions is crucial in the design of selective inhibitors against aspartic proteases. Cathepsin-D, an aspartic protease enzyme, has been implicated in a long list of degenerative diseases as well as breast cancer progression. Presented herein, for the first time, is a comprehensive description of the conformational flap dynamics of cathepsin-D using a comparative 50 ns "multiple" molecular dynamics simulations. Diverse collective metrics were proposed to accurately define flap dynamics. These are distance d1 between the flap tips residues (Gly79 and Met301); dihedral angle ϕ; in addition to TriCα angles Gly79-Asp33-Asp223, θ1 , and Gly79-Asp223-Met301, θ2 . The maximum distance attained throughout the simulation was 17.42 and 11.47 Å for apo and bound cathepsin-D, respectively, while the minimum distance observed was 8.75 and 6.32 Å for apo and bound cathepsin-D, respectively. The movement of the flap as well as the twist of the active pocket can properly be explained by measuring the angle, θ1 , between Gly79-Asp33-Met301 and correlating it with the distance Cα of the flap tip residues. The asymmetrical opening of the binding cavity was best described by the large shift of -6.26° to +20.94° in the dihedral angle, ϕ, corresponding to the full opening of the flap at a range of 31-33 ns. A wide-range of post-dynamic analyses was also applied in this report to supplement our findings. We believe that this report would augment current efforts in designing potent structure-based inhibitors against cathepsin-D in the treatment of breast cancer and other degenerative diseases. J. Cell. Biochem. 117: 2643-2657, 2016. © 2016 Wiley Periodicals, Inc.

  12. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-03-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  13. Conformational sensitivity of conjugated poly(ethylene oxide)-poly(amidoamine) molecules to cations adducted upon electrospray ionization – A mass spectrometry, ion mobility and molecular modeling study

    Energy Technology Data Exchange (ETDEWEB)

    Tintaru, Aura [Aix-Marseille Université – CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille (France); Chendo, Christophe [Aix-Marseille Université – CNRS, FR 1739, Fédération des Sciences Chimiques de Marseille, Spectropole, Marseille (France); Wang, Qi [Aix-Marseille Université – CNRS, UMR 6114, Centre Interdisciplinaire de Nanosciences de Marseille, Marseille (France); Viel, Stéphane [Aix-Marseille Université – CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille (France); Quéléver, Gilles; Peng, Ling [Aix-Marseille Université – CNRS, UMR 6114, Centre Interdisciplinaire de Nanosciences de Marseille, Marseille (France); Posocco, Paola [University of Trieste, Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), Trieste (Italy); National Interuniversity Consortium for Material Science and Technology (INSTM), Research Unit MOSE-DEA, University of Trieste, Trieste (Italy); Pricl, Sabrina, E-mail: sabrina.pricl@di3.units.it [University of Trieste, Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), Trieste (Italy); National Interuniversity Consortium for Material Science and Technology (INSTM), Research Unit MOSE-DEA, University of Trieste, Trieste (Italy); Charles, Laurence, E-mail: laurence.charles@univ-amu.fr [Aix-Marseille Université – CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille (France)

    2014-01-15

    Graphical abstract: -- Highlights: •ESI-MS/MS, IMS and molecular modeling were combined to study PEO-PAMAM conformation. •Protonated and lithiated molecules were studied, with charge states from 2 to 4. •Protonation mostly occurred on PAMAM, with PEO units enclosing the protonated group. •Lithium adduction on PEO units lead to more expanded conformations. •Charge location strongly influenced PEO-PAMAM dissociation behavior. -- Abstract: Tandem mass spectrometry and ion mobility spectrometry experiments were performed on multiply charged molecules formed upon conjugation of a poly(amidoamine) (PAMAM) dendrimer with a poly(ethylene oxide) (PEO) linear polymer to evidence any conformational modification as a function of their charge state (2+ to 4+) and of the adducted cation (H{sup +}vs Li{sup +}). Experimental findings were rationalized by molecular dynamics simulations. The G0 PAMAM head-group could accommodate up to three protons, with protonated terminal amine group enclosed in a pseudo 18-crown-6 ring formed by the PEO segment. This particular conformation enabled a hydrogen bond network which allowed long-range proton transfer to occur during collisionally activated dissociation. In contrast, lithium adduction was found to mainly occur onto oxygen atoms of the polyether, each Li{sup +} cation being coordinated by a 12-crown-4 pseudo structure. As a result, for the studied polymeric segment (M{sub n} = 1500 g mol{sup −1}), PEO-PAMAM hybrid molecules exhibited a more expanded shape when adducted to lithium as compared to proton.

  14. Quantitative conformational analysis of the core region of N-glycans using residual dipolar couplings, aqueous molecular dynamics, and steric alignment

    Energy Technology Data Exchange (ETDEWEB)

    Almond, Andrew; Duus, Jens O. [Carlsberg Laboratory (Denmark)

    2001-08-15

    A method is described for quantitatively investigating the dynamic conformation of small oligosaccharides containing an {alpha}(1{sup {yields}}6) linkage. It was applied to the oligosaccharide Man-{alpha}(1{sup {yields}}3) {l_brace}Man-{alpha} (1{sup {yields}}6){r_brace}Man-{alpha}-O-Me, which is a core region frequently observed in N-linked glycans. The approach tests an aqueous molecular dynamics simulation, capable of predicting microscopic dynamics, against experimental residual dipolar couplings, by assuming that alignment is caused purely by steric hindrance. The experimental constraints were heteronuclear and homonuclear residual dipolar couplings, and in particular those within the {alpha}(1{sup {yields}}6) linkage itself. Powerful spin-state-selective pulse sequences and editing schemes were used to obtain the most relevant couplings for testing the model. Molecular dynamics simulations in water over a period of 50 ns were not able to predict the correct rotamer population at the {alpha}(1{sup {yields}}6) linkage to agree with the experimental data. However, this sampling problem could be corrected using a simple maximum likelihood optimisation, indicating that the simulation was modelling local dynamics correctly. The maximum likelihood prediction of the residual dipolar couplings was found to be an almost equal population of the gg and gt rotamer conformations at the {alpha}(1{sup {yields}}6) linkage, and the tg conformation was predicted to be unstable and unpopulated in aqueous solution. In this case all twelve measured residual dipolar couplings could be satisfied. This conformer population could also be used to make predictions of scalar couplings with the use of a previously derived empirical equation, and is qualitatively in agreement with previous predictions based on NMR, X-ray crystallography and optical data.

  15. Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics

    Science.gov (United States)

    Guimarães, Maria C; Duarte, Mariene H; Silla, Josué M

    2016-01-01

    Summary An intriguing question in 3D-QSAR lies on which conformation(s) to use when generating molecular descriptors (MD) for correlation with bioactivity values. This is not a simple task because the bioactive conformation in molecule data sets is usually unknown and, therefore, optimized structures in a receptor-free environment are often used to generate the MD´s. In this case, a wrong conformational choice can cause misinterpretation of the QSAR model. The present computational work reports the conformational analysis of the volatile anesthetic isoflurane (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane) in the gas phase and also in polar and nonpolar implicit and explicit solvents to show that stable minima (ruled by intramolecular interactions) do not necessarily coincide with the bioconformation (ruled by enzyme induced fit). Consequently, a QSAR model based on two-dimensional chemical structures was built and exhibited satisfactory modeling/prediction capability and interpretability, then suggesting that these 2D MD´s can be advantageous over some three-dimensional descriptors. PMID:27340468

  16. STRUCTURE, MOLECULAR WEIGHT AND BIOACTIVITIES OF (1→3)-β-D- GLUCANS AND ITS SULFATED DERIVATIVES FROM FOUR KINDS OF LENTINUS EDODES

    Institute of Scientific and Technical Information of China (English)

    Unursaikhan Surenjav; Li-na Zhang; Xiao-juan Xu; Mei Zhang; Peter Chi Keung Cheung; Fan-bo Zeng

    2005-01-01

    Lentinan samples, (1→3)-β-D-glucans containing 4.6-15.2 wt% proteins, coded as L-I1, L-I2, L-I3 and L-I4 (L-I)were isolated from four kinds of Lentinus edodes. These glucans were treated with acetone to remove the protein in order to obtain free protein glucans coded as LNP-I1, LNP-I2, LNP-I3 and LNP-I4 (LNP-I). The free-protein polysaccharides were sulfated to give derivatives (S-LNP-I) with degree of substitution (DS) from 0.4-0.8. The structural features and weight- average molecular weight (Mw) of the samples were investigated by using infrared spectroscopy, elemental analysis,13C-NMR, size exclusion chromatography combined with laser light scattering (SEC-LLS) and viscometry. The effects of structure and conformation of the polysaccharides on antitumor activities were assayed in vivo (Sarcoma 180 solid tumors)and in vitro (Sarcoma 180, HL-60, MCF-7 and Vero tumors). The results indicated that the predominant species of the samples L-I and LNP-I in 0.2 mol/L NaCl aqueous solution existed as triple-helical chains with high rigidity and in dimethyl sulfoxide (DMSO) as single-flexible chains. Interestingly, the antitumor activities of LNP-I are lower than those of the native glucans (L-I), whereas their sulfated derivatives have higher inhibition ratio against Sarcoma 180 than LNP-I. The results reveal that the binding of protein, sulfated modification and the triple helix conformation are important factors in the enhancement of the antitumor activities of polysaccharides on the whole.

  17. The future of bioactive ceramics.

    Science.gov (United States)

    Hench, Larry L

    2015-02-01

    Two important worldwide needs must be satisfied in the future; (1) treatment of the deteriorating health of an aging population and, (2) decreasing healthcare costs to meet the needs of an increased population. The ethical and economic dilemma is how to achieve equality in quality of care while at the same time decreasing cost of care for an ever-expanding number of people. The limited lifetime of prosthetic devices made from first-generation nearly inert biomaterials requires new approaches to meet these two large needs. This paper advises an expanded emphasis on: (1) regeneration of tissues and (2) prevention of tissue deterioration to meet this growing need. Innovative use of bioactive ceramics with genetic control of in situ tissue responses offers the potential to achieve both tissue regeneration and prevention. Clinical success of use of bioactive glass for bone regeneration is evidence that this concept works. Likewise the use of micron sized bioactive glass powders in a dentifrice for re-mineralization of teeth provides evidence that prevention of tissue deterioration is also possible. This opinion paper outlines clinical needs that could be met by innovative use of bioactive glasses and ceramics in the near future; including: regeneration of skeletal tissues that is patient specific and genetic based, load-bearing bioactive glass-ceramics for skeletal and ligament and tendon repair, repair and regeneration of soft tissues, and rapid low-cost analysis of human cell-biomaterial interactions leading to patient specific diagnoses and treatments using molecularly tailored bioceramics.

  18. Flavonoids from Agrimonia pilosa Ledeb: Free Radical Scavenging and DNA Oxidative Damage Protection Activities and Analysis of Bioactivity-Structure Relationship Based on Molecular and Electronic Structures

    Directory of Open Access Journals (Sweden)

    Liancai Zhu

    2017-02-01

    Full Text Available To clarify the substantial basis of the excellent antioxidant capacity of Agrimonia pilosa Ledeb. Fourteen flavonoids were isolated and identified from Agrimonia pilosa Ledeb, seven of which have notable DPPH radical scavenging activities, i.e., catechin, luteolin, quercetin, quercitrin, hyperoside, rutin, luteolin-7-O-β-glucoside with IC50 values of 5.06, 7.29, 4.36, 7.12, 6.34, 6.36 and 8.12 µM, respectively. The DNA nicking assay showed that five flavonoids from Agrimonia pilosa Ledeb—taxifolin, catechin, hyperoside, quercitrin and rutin—have good protective activity against DNA oxidative damage. Further, we analyzed the bioactivity-structure relationship of these 14 flavonoids by applying quantum theory. According to their O-H bond dissociation enthalpy (BDE, C ring’s spin density and stable molecular structure, the relationship between their structures and radical scavenging capacities was evaluated and clarified. We found that among flavonoid aglycones from Agrimonia pilosa Ledeb, the O-H BDE of quercetin is lowest with the values of 69.02 and the O-H BDE of apigenin is highest with the values of 79.77. It is interesting that the O-H BDE value of isovitexin (78.55 with glycoside at C-6 position is lower than that of its aglycone (79.77 and vitexin (99.20 with glycoside at C-8 position. Further analysis indicated that the glycosidation of flavonoids at C-6 in the A-ring makes a more uniform distribution of spin density and improves the stability of free radicals leading to the increase in antioxidant capacity. Flavonoids with good antioxidant capacity might contribute to the pharmacological effects of Agrimonia pilosa Ledeb.

  19. Quantitative conformational analysis of partially folded proteins from residual dipolar couplings: application to the molecular recognition element of Sendai virus nucleoprotein.

    Science.gov (United States)

    Jensen, Malene Ringkjøbing; Houben, Klaartje; Lescop, Ewen; Blanchard, Laurence; Ruigrok, Rob W H; Blackledge, Martin

    2008-06-25

    A significant fraction of proteins coded in the human proteome do not fold into stable three-dimensional structures but are either partially or completely unfolded. A key feature of this family of proteins is their proposed capacity to undergo a disorder-to-order transition upon interaction with a physiological partner. The mechanisms governing protein folding upon interaction, in particular the extent to which recognition elements are preconfigured prior to formation of molecular complexes, can prove difficult to resolve in highly flexible systems. Here, we develop a conformational model of this type of protein, using an explicit description of the unfolded state, specifically modified to allow for the presence of transient secondary structure, and combining this with extensive measurement of residual dipolar couplings throughout the chain. This combination of techniques allows us to quantitatively analyze the level and nature of helical sampling present in the interaction site of the partially folded C-terminal domain of Sendai virus nucleoprotein (N(TAIL)). Rather than fraying randomly, the molecular recognition element of N(TAIL) preferentially populates three specific overlapping helical conformers, each stabilized by an N-capping interaction. The unfolded strands adjacent to the helix are thereby projected in the direction of the partner protein, identifying a mechanism by which they could achieve nonspecific encounter interactions prior to binding. This study provides experimental evidence for the molecular basis of helix formation in partially folded peptide chains, carrying clear implications for understanding early steps of protein folding.

  20. Conformal house

    DEFF Research Database (Denmark)

    Ryttov, Thomas Aaby; Sannino, Francesco

    2010-01-01

    fixed point. As a consistency check we recover the previously investigated bounds of the conformal windows when restricting to a single matter representation. The earlier conformal windows can be imagined to be part now of the new conformal house. We predict the nonperturbative anomalous dimensions...... at the infrared fixed points. We further investigate the effects of adding mass terms to the condensates on the conformal house chiral dynamics and construct the simplest instanton induced effective Lagrangian terms...

  1. Conformational and entropy analyses of extended molecular dynamics simulations of α-, β- and γ-cyclodextrins and of the β-cyclodextrin/nabumetone complex.

    Science.gov (United States)

    Suárez, Dimas; Díaz, Natalia

    2017-01-04

    Herein, we report the results of 5.0 μs molecular dynamics simulations of native α-, β- and γ-cyclodextrins (CDs) in explicit water solvent that are useful to describe, in a comparative manner, the distorted geometry of the CD molecules in aqueous solution, the width and fluctuations of their cavities, and the number of cavity waters. By discretizing the time evolution of the dihedral angles, the rate of conformational change of the torsional motions and the conformational entropy are calculated for the three CDs, thus allowing the analysis of the extent of the MD sampling and the entropic significance of the CD flexibility. To obtain a first estimation of the conformational and entropy changes in the host molecule upon ligand binding, the inclusion complex formed between β-CD and nabumetone is also studied. Overall, the simulations complement previous experimental results on the structure and dynamics of native CDs, and together with the results obtained for the inclusion complex, provide insight into the entropic effects at work on the binding equilibria between CDs and guest ligands.

  2. Application of time series analysis on molecular dynamics simulations of proteins: A study of different conformational spaces by principal component analysis

    Science.gov (United States)

    Alakent, Burak; Doruker, Pemra; Camurdan, Mehmet C.

    2004-09-01

    Time series analysis is applied on the collective coordinates obtained from principal component analysis of independent molecular dynamics simulations of α-amylase inhibitor tendamistat and immunity protein of colicin E7 based on the Cα coordinates history. Even though the principal component directions obtained for each run are considerably different, the dynamics information obtained from these runs are surprisingly similar in terms of time series models and parameters. There are two main differences in the dynamics of the two proteins: the higher density of low frequencies and the larger step sizes for the interminima motions of colicin E7 than those of α-amylase inhibitor, which may be attributed to the higher number of residues of colicin E7 and/or the structural differences of the two proteins. The cumulative density function of the low frequencies in each run conforms to the expectations from the normal mode analysis. When different runs of α-amylase inhibitor are projected on the same set of eigenvectors, it is found that principal components obtained from a certain conformational region of a protein has a moderate explanation power in other conformational regions and the local minima are similar to a certain extent, while the height of the energy barriers in between the minima significantly change. As a final remark, time series analysis tools are further exploited in this study with the motive of explaining the equilibrium fluctuations of proteins.

  3. Molecular modeling on the recognition of DNA sequence and conformational repair of sheared DNA by novel chiral metal complex D, L-[Co(phen)2hpip]3+

    Institute of Scientific and Technical Information of China (English)

    WU; Yanbo; ZHANG; Cuiping

    2006-01-01

    A study on the recognition of DNA sequence and conformational repair of sheared DNA by Novel Chiral Metal complex D,L-[Co(phen)2hpip]3+ (phen=1,10 phenanthroline, hpip=2-[2-hydroxyphenyl] imidazole [4,5-f][1,10] phenanthroline) is carried out with molecular simulations. The results reveal that two isomers of the complex could both recognize the normal DNA in the minor groove orientation, while recognize the sheared DNA in the major groove orientation and both isomers could convert the conformation of mismatched bases from sheared form to parallel form. Further analysis shows that the steric details of complex's intercalation to base stack determine the results of recognition, which is induced by the steric collision among ancillary ligand phen, bases and DNA backbone, and by the steric crowding occurring in the process of structural expansion of bases and DNA backbone. Detailed analysis reveals that the conformational repair of mismatched bases relates not only to the steric interactions, but also to the π-π stack among normal bases, mismatched bases and hpip ligand.

  4. Long-Range Conformational Response of a PDZ Domain to Ligand Binding and Release: A Molecular Dynamics Study.

    Science.gov (United States)

    Lu, Cheng; Knecht, Volker; Stock, Gerhard

    2016-02-09

    The binding of a ligand to a protein may induce long-range structural or dynamical changes in the biomacromolecule even at sites physically well separated from the binding pocket. A system for which such behavior has been widely discussed is the PDZ2 domain of human tyrosine phosphatase 1E. Here, we present results from equilibrium trajectories of the PDZ2 domain in the free and ligand-bound state, as well as nonequilibrium simulations of the relaxation of PDZ2 after removal of its peptide ligand. The study reveals changes in inter-residue contacts, backbone dihedral angles, and C(α) positions upon ligand release. Our findings show a long-range conformational response of the PDZ2 domain to ligand release in the form of a collective shift of the secondary structure elements α2, β2, β3, α1-β4, and the C terminal loop relative to the rest of the protein away from the N-terminus, and a shift of the loops β2-β3 and β1-β2 in the opposite direction. The shifts lead to conformational changes in the backbone, especially in the β2-β3 loop but also in the β5-α2 and the α2-β6 loop, and are accompanied by changes of inter-residue contacts mainly within the β2-β3 loop as well as between the α2 helix and other segments. The residues showing substantial changes of inter-residue contacts, backbone conformations, or C(α) positions are considered "key residues" for the long-range conformational response of PDZ2. By comparing these residues with various sets of residues highlighted by previous studies of PDZ2, we investigate the statistical correlation of the various approaches. Interestingly, we find a considerable correlation of our findings with several works considering structural changes but no significant correlations with approaches considering energy flow or networks based on inter-residue energies.

  5. 35Cl NQR spectra of phosphorus chlorides and their molecular conformations in crystals. Part 1. Phosphorus (III) chlorides RPCl 2

    Science.gov (United States)

    Kozlov, E. S.; Kapustin, E. G.; Soifer, G. B.

    2000-09-01

    For the phosphorus chlorides RPCl 2 (R=Cl, Me, ClCH 2, CF 3, Et, i-Pr, Me 2C=CH, PhCH=CH, Me 2N, Et 2N, Pr 2N, MeO, PhO) and R'PCl 2 (R'=Ar, 2-thienyl) two linear correlations between the 35Cl NQR frequencies and charges on the chlorine atoms of the PCl 2 groups calculated by the MNDO procedure have been found. It was shown that the 35Cl NQR spectra and the relative magnitudes of the charges on the chlorine atoms of the PCl 2 groups can be used to determine conformation of the RPCl 2 molecules in crystal. Ab initio (RHF/6-31 G ∗ and MP2/6-31 G ∗) calculations showed that the gauche conformation of Me 2NPCl 2 molecule is more stable than trans conformation. In light of ab initio calculations electron diffraction results (Vilkov L.V., Khaikin L.S., Dokl. Akad. Nauk SSSR, 168 (1966) 810) are erroneous. The NBO analysis confirmed the presence of donor-acceptor interactions between the lone pair orbital of the nitrogen atom and the antibonding orbitals of the P-Cl bonds.

  6. Conformational Analysis, Molecular Structure and Solid State Simulation of the Antiviral Drug Acyclovir (Zovirax Using Density Functional Theory Methods

    Directory of Open Access Journals (Sweden)

    Margarita Clara Alvarez-Ros

    2014-06-01

    Full Text Available The five tautomers of the drug acyclovir (ACV were determined and optimised at the MP2 and B3LYP quantum chemical levels of theory. The stability of the tautomers was correlated with different parameters. On the most stable tautomer N1 was carried out a comprehensive conformational analysis, and the whole conformational parameters (R, β, Φ, φ1, φ2, φ3, φ4, φ5 were studied as well as the NBO Natural atomic charges. The calculations were carried out with full relaxation of all geometrical parameters. The search located at least 78 stable structures within 8.5 kcal/mol electronic energy range of the global minimum, and classified in two groups according to the positive or negative value of the torsional angle j1. In the nitrogen atoms and in the O2' and O5' oxygen atoms of the most stable conformer appear a higher reactivity than in the natural nucleoside deoxyguanosine. The solid state was simulated through a dimer and tetramer forms and the structural parameters were compared with the X-ray crystal data available. Several general conclusions were emphasized.

  7. Conformational stability, molecular orbital studies (chemical hardness and potential), vibrational investigation and theoretical NBO analysis of 4-tert-butyl-3-methoxy-2,6-dinitrotoluene.

    Science.gov (United States)

    Saravanan, S; Balachandran, V; Vishwanathan, K

    2014-04-24

    The FT-IR and FT-Raman spectra of 4-tert-butyl-3-methoxy-2,6-dinitrotoluene (musk ambrette) have been recorded in the regions 4000-400 cm(-1) and 3500-100 cm(-1), respectively. The total energy calculations of musk ambrette were tried for the possible conformers. The molecular structure, geometry optimization, vibrational frequencies were obtained by the density functional theory (DFT) using B3LYP and LSDA method with 6-311G(d,p) basis set for the most stable conformer "C1". The complete assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes, calculated and the scaled values were compared with experimental FT-IR and FT-Raman spectra. The observed and the calculated frequencies are found to be in good agreement. The stability of the molecule arising from hyper conjugate interactions and the charge delocalization has been analyzed using bond orbital (NBO) analysis. The HOMO and LUMO energy gap reveals that the energy gap reflects the chemical activity of the molecule. The dipole moment (μ), polarizability (α), anisotropy polarizability (Δα) and first hyperpolarizability (βtot) of the molecule have been reported. The thermodynamic functions (heat capacity, entropy and enthalpy) were obtained for the range of temperature 100-1000 K. Information about the size, shape, charge density distribution and site of chemical reactivity of the molecule has been obtained by mapping electron density isosurface with molecular electrostatic potential (MEP).

  8. Effects of hesperidin, a flavanone glycoside interaction on the conformation, stability, and aggregation of lysozyme: multispectroscopic and molecular dynamic simulation studies?

    Science.gov (United States)

    Ratnaparkhi, Aditi; Muthu, Shivani A; Shiriskar, Sonali M; Pissurlenkar, Raghuvir R S; Choudhary, Sinjan; Ahmad, Basir

    2015-09-01

    Hesperidin (HESP), a flavanone glycoside, shows high antioxidant properties and possess ability to go through the blood-brain barrier. Therefore, it could be a potential drug molecule against aggregation based diseases such as Alzheimer's, Parkinson's, and systemic amyloidoses. In this work, we investigated the potential of HESP to interact with hen egg-white lysozyme (HEWL) monomer and prevent its aggregation. The HESP-HEWL binding studies were performed using a fluorescence quenching technique, molecular docking and molecular dynamics simulations. We found a strong interaction of HESP with the lysozyme monomer (Ka, ~ 5 × 10(4) M(-1)) mainly through hydrogen bonding, water bridges, and hydrophobic interactions. We showed that HESP molecule spanned the highly aggregation prone region (amino acid residues 48-101) of HEWL and prevented its fibrillar aggregation. Further, we found that HESP binding completely inhibited amorphous aggregation of the protein induced by disulfide-reducing agent tries-(2-carboxyethyl) phosphine. Conformational and stability studies as followed by various tertiary and secondary structure probes revealed that HESP binding only marginally affected the lysozyme monomer conformation and increased both stability and reversibility of the protein against thermal denaturation. Future studies should investigate detail effects of HESP on solvent dynamics, structure, and toxicity of various aggregates. The answers to these questions will not only target the basic sciences, but also have application in biomedical and biotechnological sciences.

  9. Molecular typing of isolates of the fish pathogen, Flavobacterium columnare, by single-strand conformation polymorphism analysis.

    Science.gov (United States)

    Olivares-Fuster, Oscar; Shoemaker, Craig A; Klesius, Phillip H; Arias, Covadonga R

    2007-04-01

    Flavobacterium columnare intraspecies diversity was revealed by analyzing the 16S rRNA gene and the 16S-23S internal spacer region (ISR). Standard restriction fragment length polymorphism (RFLP) of these sequences was compared with single-strand conformation polymorphism (SSCP). Diversity indexes showed that both 16S-SSCP and ISR-SSCP improved resolution (D>or=0.9) when compared with standard RFLP. ISR-SSCP offered a simpler banding pattern than 16S-SSCP while providing high discrimination between isolates. SSCP analysis of rRNA genes proved to be a simple, rapid, and cost-effective method for routine fingerprinting of F. columnare.

  10. Conformational Changes in the GM-CSF Receptor Suggest a Molecular Mechanism for Affinity Conversion and Receptor Signaling.

    Science.gov (United States)

    Broughton, Sophie E; Hercus, Timothy R; Nero, Tracy L; Dottore, Mara; McClure, Barbara J; Dhagat, Urmi; Taing, Houng; Gorman, Michael A; King-Scott, Jack; Lopez, Angel F; Parker, Michael W

    2016-08-02

    The GM-CSF, IL-3, and IL-5 receptors constitute the βc family, playing important roles in inflammation, autoimmunity, and cancer. Typical of heterodimeric type I cytokine receptors, signaling requires recruitment of the shared subunit to the initial cytokine:α subunit binary complex through an affinity conversion mechanism. This critical process is poorly understood due to the paucity of crystal structures of both binary and ternary receptor complexes for the same cytokine. We have now solved the structure of the binary GM-CSF:GMRα complex at 2.8-Å resolution and compared it with the structure of the ternary complex, revealing distinct conformational changes. Guided by these differences we performed mutational and functional studies that, importantly, show GMRα interactions playing a major role in receptor signaling while βc interactions control high-affinity binding. These results support the notion that conformational changes underlie the mechanism of GM-CSF receptor activation and also suggest how related type I cytokine receptors signal.

  11. Workers’ Conformism

    Directory of Open Access Journals (Sweden)

    Nikolay Ivantchev

    2013-10-01

    Full Text Available Conformism was studied among 46 workers with different kinds of occupations by means of two modified scales measuring conformity by Santor, Messervey, and Kusumakar (2000 – scale for perceived peer pressure and scale for conformism in antisocial situations. The hypothesis of the study that workers’ conformism is expressed in a medium degree was confirmed partly. More than a half of the workers conform in a medium degree for taking risk, and for the use of alcohol and drugs, and for sexual relationships. More than a half of the respondents conform in a small degree for anti-social activities (like a theft. The workers were more inclined to conform for risk taking (10.9%, then – for the use of alcohol, drugs and for sexual relationships (8.7%, and in the lowest degree – for anti-social activities (6.5%. The workers who were inclined for the use of alcohol and drugs tended also to conform for anti-social activities.

  12. Single-strand conformation polymorphism (SSCP) of oligodeoxyribonucleotides: an insight into solution structural dynamics of DNAs provided by gel electrophoresis and molecular dynamics simulations.

    Science.gov (United States)

    Biyani, Manish; Nishigaki, Koichi

    2005-10-01

    Studies on the solution structure dynamics of RNA/DNA are becoming crucially important. The phenomena of SSCP (single-strand conformation polymorphism), small RNA dynamics in a cell, and others can be related to the conformational changes of single-stranded (ss) RNAs/DNAs in solution. However, little is known about those dynamics. Only the intra-structural transition of ssDNAs in solution has been reported based on Watson-Crick (W-C) base-pairing. Here, we found a general feature of the SSCP phenomenon by studying the simpler molecules of ss-oligodeoxyribonucleotides. A single base substitution or a positional exchange of nucleotide in a highly homologous series of ss-dodecanucleotides led to a change in the mobility-in-gel. This was unexpected, since most of these nucleotides [such as d(A(11)G) or d(A(11)C)] have no possibility of forming W-C base-pairing. MD (molecular dynamics) experiments revealed differences in shape and size between the dynamic structures of these molecules which could affect their mobility-in-gel. In addition, a high correlation was observed between the electrophoretic mobility and the size-related parameters such as end-to-end distance obtained from MD simulations. Because the simulation was considerably shorter (nanosecond) than the experimental time-scale (second), the result must be considered conservatively; but it is nevertheless encouraging for utilizing MD simulation for structural analysis of oligonucleotides.

  13. Conformational analysis of a polyconjugated protein-binding ligand by joint quantum chemistry and polarizable molecular mechanics. Addressing the issues of anisotropy, conjugation, polarization, and multipole transferability.

    Science.gov (United States)

    Goldwaser, Elodie; de Courcy, Benoit; Demange, Luc; Garbay, Christiane; Raynaud, Françoise; Hadj-Slimane, Reda; Piquemal, Jean-Philip; Gresh, Nohad

    2014-11-01

    We investigate the conformational properties of a potent inhibitor of neuropilin-1, a protein involved in cancer processes and macular degeneration. This inhibitor consists of four aromatic/conjugated fragments: a benzimidazole, a methylbenzene, a carboxythiourea, and a benzene-linker dioxane, and these fragments are all linked together by conjugated bonds. The calculations use the SIBFA polarizable molecular mechanics procedure. Prior to docking simulations, it is essential to ensure that variations in the ligand conformational energy upon rotations around its six main-chain torsional bonds are correctly represented (as compared to high-level ab initio quantum chemistry, QC). This is done in two successive calibration stages and one validation stage. In the latter, the minima identified following independent stepwise variations of each of the six main-chain torsion angles are used as starting points for energy minimization of all the torsion angles simultaneously. Single-point QC calculations of the minimized structures are then done to compare their relative energies ΔE conf to the SIBFA ones. We compare three different methods of deriving the multipoles and polarizabilities of the central, most critical moiety of the inhibitor: carboxythiourea (CTU). The representation that gives the best agreement with QC is the one that includes the effects of the mutual polarization energy E pol between the amide and thioamide moieties. This again highlights the critical role of this contribution. The implications and perspectives of these findings are discussed.

  14. Influence of bonded-phase coverage in reversed-phase liquid chromatography via molecular simulation I. Effects on chain conformation and interfacial properties.

    Science.gov (United States)

    Rafferty, Jake L; Siepmann, J Ilja; Schure, Mark R

    2008-09-12

    Particle-based Monte Carlo simulations were employed to examine the effects of bonding density on molecular structure in reversed-phase liquid chromatography. Octadecylsilane stationary phases with five different bonding densities (1.6, 2.3, 2.9, 3.5, and 4.2 micromol/m(2)) in contact with a water/methanol (50/50 mol%) mobile phase were simulated at a temperature of 323 K. The simulations indicate that the alkyl chains become more aligned and form a more uniform alkyl layer as coverage is increased. However, this does not imply that the chains are highly ordered (e.g., all-trans conformation or uniform tilt angle), but rather exhibit a broad distribution of conformations and tilt angles at all bonding densities. At lower densities, significant amounts of the silica surface are exposed leading to an enhanced wetting of the stationary phase. At high densities, the solvent is nearly excluded from the bonded phase and persists only near the residual silanols. An enrichment in the methanol concentration and a disruption in the mobile phase's hydrogen bond network are observed at the interface as bonding density is increased.

  15. The Effect of Molecular Conformation on the Accuracy of Theoretical (1)H and (13)C Chemical Shifts Calculated by Ab Initio Methods for Metabolic Mixture Analysis.

    Science.gov (United States)

    Chikayama, Eisuke; Shimbo, Yudai; Komatsu, Keiko; Kikuchi, Jun

    2016-04-14

    NMR spectroscopy is a powerful method for analyzing metabolic mixtures. The information obtained from an NMR spectrum is in the form of physical parameters, such as chemical shifts, and construction of databases for many metabolites will be useful for data interpretation. To increase the accuracy of theoretical chemical shifts for development of a database for a variety of metabolites, the effects of sets of conformations (structural ensembles) and the levels of theory on computations of theoretical chemical shifts were systematically investigated for a set of 29 small molecules in the present study. For each of the 29 compounds, 101 structures were generated by classical molecular dynamics at 298.15 K, and then theoretical chemical shifts for 164 (1)H and 123 (13)C atoms were calculated by ab initio quantum chemical methods. Six levels of theory were used by pairing Hartree-Fock, B3LYP (density functional theory), or second order Møller-Plesset perturbation with 6-31G or aug-cc-pVDZ basis set. The six average fluctuations in the (1)H chemical shift were ±0.63, ± 0.59, ± 0.70, ± 0.62, ± 0.75, and ±0.66 ppm for the structural ensembles, and the six average errors were ±0.34, ± 0.27, ± 0.32, ± 0.25, ± 0.32, and ±0.25 ppm. The results showed that chemical shift fluctuations with changes in the conformation because of molecular motion were larger than the differences between computed and experimental chemical shifts for all six levels of theory. In conclusion, selection of an appropriate structural ensemble should be performed before theoretical chemical shift calculations for development of an accurate database for a variety of metabolites.

  16. Characterization of the conformational space of a triple-stranded beta-sheet forming peptide with molecular dynamics simulations

    NARCIS (Netherlands)

    Soto, P; Colombo, G

    2004-01-01

    Molecular dynamics (MD) simulations have been performed on a series of mutants of the 20 amino acid peptide Betanova in order to critically assess the ability of MD simulations to reproduce the folding and stability of small beta-sheet-forming peptides on currently accessible timescales. Simulations

  17. Synthesis, Molecular and Crystal Structure Analysis of 1-(4-Methylbenzenesulfonylindole-3-carbaldehyde and DFT Investigation of Its Rotational Conformers

    Directory of Open Access Journals (Sweden)

    Julio Zukerman-Schpector

    2014-02-01

    Full Text Available Two independent molecules that differ in terms of rotation about the central S-N bond comprise the asymmetric unit of the title compound 1. The molecules have a V-shape with the dihedral angles between the fused ring system and benzene ring being 79.08(6° and 72.83(5°, respectively. The packing is mostly driven by p···p interactions occurring between the tolyl ring of one molecule and the C6 ring of the indole fused ring system of the other. DFT and IRC calculations for these and related 1-(arylsulfonylindole molecules showed that the rotational barrier about the S-N bond between conformers is within the 2.5–5.5 kcal/mol range. Crystal data for C16H13NO3S (1: Mr = 299.33, space group Pna21, a = 19.6152(4 Å, b = 11.2736(4 Å, c = 12.6334(3 Å, V = 2793.67(13 Å3, Z = 8, Z' = 2, R = 0.034.

  18. Water drives peptide conformational transitions

    CERN Document Server

    Nerukh, Dmitry

    2011-01-01

    Transitions between metastable conformations of a dipeptide are investigated using classical molecular dynamics simulation with explicit water molecules. The distribution of the surrounding water at different moments before the transitions and the dynamical correlations of water with the peptide's configurational motions indicate that water is the main driving force of the conformational changes.

  19. Deciphering fine molecular details of proteins' structure and function with a Protein Surface Topography (PST) method.

    Science.gov (United States)

    Koromyslova, Anna D; Chugunov, Anton O; Efremov, Roman G

    2014-04-28

    Molecular surfaces are the key players in biomolecular recognition and interactions. Nowadays, it is trivial to visualize a molecular surface and surface-distributed properties in three-dimensional space. However, such a representation trends to be biased and ambiguous in case of thorough analysis. We present a new method to create 2D spherical projection maps of entire protein surfaces and manipulate with them--protein surface topography (PST). It permits visualization and thoughtful analysis of surface properties. PST helps to easily portray conformational transitions, analyze proteins' properties and their dynamic behavior, improve docking performance, and reveal common patterns and dissimilarities in molecular surfaces of related bioactive peptides. This paper describes basic usage of PST with an example of small G-proteins conformational transitions, mapping of caspase-1 intersubunit interface, and intrinsic "complementarity" in the conotoxin-acetylcholine binding protein complex. We suggest that PST is a beneficial approach for structure-function studies of bioactive peptides and small proteins.

  20. Conformal Infinity

    Science.gov (United States)

    Frauendiener, Jörg

    2004-12-01

    The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  1. Conformal Infinity

    Directory of Open Access Journals (Sweden)

    Frauendiener Jörg

    2000-08-01

    Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, ``conformal infinity'' is related with almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved out of physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation and how it lends itself very naturally to solve radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  2. Conformal Infinity

    Directory of Open Access Journals (Sweden)

    Frauendiener Jörg

    2004-01-01

    Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, 'conformal infinity' is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  3. Representation of target-bound drugs by computed conformers: implications for conformational libraries

    Directory of Open Access Journals (Sweden)

    Goede Andrean

    2006-06-01

    Full Text Available Abstract Background The increasing number of known protein structures provides valuable information about pharmaceutical targets. Drug binding sites are identifiable and suitable lead compounds can be proposed. The flexibility of ligands is a critical point for the selection of potential drugs. Since computed 3D structures of millions of compounds are available, the knowledge of their binding conformations would be a great benefit for the development of efficient screening methods. Results Integration of two public databases allowed superposition of conformers for 193 approved drugs with 5507 crystallised target-bound counterparts. The generation of 9600 drug conformers using an atomic force field was carried out to obtain an optimal coverage of the conformational space. Bioactive conformations are best described by a conformational ensemble: half of all drugs exhibit multiple active states, distributed over the entire range of the reachable energy and conformational space. A number of up to 100 conformers per drug enabled us to reproduce the bound states within a similarity threshold of 1.0 Å in 70% of all cases. This fraction rises to about 90% for smaller or average sized drugs. Conclusion Single drugs adopt multiple bioactive conformations if they interact with different target proteins. Due to the structural diversity of binding sites they adopt conformations that are distributed over a broad conformational space and wide energy range. Since the majority of drugs is well represented by a predefined low number of conformers (up to 100 this procedure is a valuable method to compare compounds by three-dimensional features or for fast similarity searches starting with pharmacophores. The underlying 9600 generated drug conformers are downloadable from the Super Drug Web site 1. All superpositions are visualised at the same source. Additional conformers (110,000 of 2400 classified WHO-drugs are also available.

  4. Conformational changes and slow dynamics through microsecond polarized atomistic molecular simulation of an integral Kv1.2 ion channel

    DEFF Research Database (Denmark)

    Bjelkmar, Pär; Niemelä, Perttu S; Vattulainen, Ilpo;

    2009-01-01

    Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how...... transitions occur in membrane proteins-not to mention numerous applications in drug design. Here, we present a full 1 micros atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements...... process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5-1 micros). Together with lipids binding in matching positions...

  5. MOLECULAR VARIABILITY OF THREE GENES OF POTATO VEIN YELLOW VIRUS INFECTING Solanum tuberosum, USING SINGLE STRAND CONFORMATIONAL POLYMORPHISM

    Directory of Open Access Journals (Sweden)

    Karen Andrea CUBILLOS-ABELLO

    2015-01-01

    Full Text Available Potato yellow vein virus o virus del amarillamiento de venas de la hoja de la papa (PYVV es un virus RNA tripartito (ss+ de la familia Closteroviridae género Crinivirus que causa la enfermedad de amarillamiento de nervaduras de la hoja de papa (PYVD reduciendo la productividad, entre el 25 % y 50 %. La técnica de polimorfismo conformacional de cadena sencilla (SSCP ha sido usada para estimar la variabilidad en diferentes especies de virus. En el presente trabajo se analizó la variabilidad molecular de 60 aislados de PYVV a partir de la comparación de tres genes: el gen de la proteína mayor de la cápside (CP, proteína menor de la cápside (CPm y la proteína de choque térmico (Hsp70. Los aislados se obtuvieron de dos grupos de Solanum tuberosum : 30 del Grupo Phureja (GPh y 30 del Grupo Andígena (GA, provenientes del departamento de Nariño, Colombia. Los genes se amplificaron por RT-PCR y los productos purificados se emplearon para SSCP en geles de poliacrilamida. Se detectaron tres perfiles de SSCP para el gen CP, 12 para el CPm y 12 para el Hsp70. Para el GA el perfil más frecuente del gen Hsp70 fue el perfil C (66,6 % y para el gen CPm fue el IV (33,3 %. Para el gen CP, el patrón uno se encontró en el 93,3 % de los aislados, indicando menor variabilidad. Esta es la primera estimación de variabilidad de PYVV en diferentes genes y a través de una técnica molecular simple.

  6. Understanding the Differences in Molecular Conformation of Carbohydrate and Protein in Endosperm Tissues of Grains with Different Biodegradation Kinetics Using Advanced Synchrotron Technology

    Energy Technology Data Exchange (ETDEWEB)

    Yu, P.; Block, H; Doiron, K

    2009-01-01

    Conventional 'wet' chemical analyses rely heavily on the use of harsh chemicals and derivatization, thereby altering native seed structures leaving them unable to detect any original inherent structures within an intact tissue sample. A synchrotron is a giant particle accelerator that turns electrons into light (million times brighter than sunlight) which can be used to study the structure of materials at the molecular level. Synchrotron radiation-based Fourier transform IR microspectroscopy (SR-FTIRM) has been developed as a rapid, direct, non-destructive and bioanalytical technique. This technique, taking advantage of the brightness of synchrotron light and a small effective source size, is capable of exploring the molecular chemistry within the microstructures of a biological tissue without the destruction of inherent structures at ultraspatial resolutions within cellular dimensions. This is in contrast to traditional 'wet' chemical methods, which, during processing for analysis, often result in the destruction of the intrinsic structures of feeds. To date there has been very little application of this technique to the study of plant seed tissue in relation to nutrient utilization. The objective of this study was to use novel synchrotron radiation-based technology (SR-FTIRM) to identify the differences in the molecular chemistry and conformation of carbohydrate and protein in various plant seed endosperms within intact tissues at cellular and subcellular level from grains with different biodegradation kinetics. Barley grain (cv. Harrington) with a high rate (31.3%/h) and extent (78%), corn grain (cv. Pioneer) with a low rate (9.6%/h) and extent of (57%), and wheat grain (cv. AC Barrie) with an intermediate rate (23%/h) and extent (72%) of ruminal DM degradation were selected for evaluation. SR-FTIRM evaluations were performed at the National Synchrotron Light Source at the Brookhaven National Laboratory (Brookhaven, NY). These results suggest

  7. Molecular structures and conformations of 1-benzenesulphonyl-2-oxo-5-alkoxypyrrolidines with anti-amnesic activity. X-ray, 1H-NMR and quantum mechanical (PM3) studies

    Science.gov (United States)

    Amato, Maria E.; Bandoli, Giuliano; Dolmella, Alessandro; Grassi, Antonio; Pappalardo, Giuseppe C.; Toja, Emilio

    1991-04-01

    The crystal and molecular structures of the nootropic agents RU-47001 ((±) 1-(4-nitrobenzenesulphonyl)-2-oxo-5-ethoxypyrrolidine) and RU-47064 ((±) 1-(4-nitrobenzenesulphonyl)-2-oxo-5-isopropyloxypyrrolidine) have been determined by X-ray analysis and their solution conformation has been investigated using 1H NMR spectroscopy. The conformations of these molecules together with those of their analogues RU-35929 ((±) 1-benzenesulphonyl-2-oxo-5-ethoxypyrrolidine), RU-47010 ((±) 1-(3-pyridinylsulphonyl)-2-oxo-5-ethoxypyrrolidine) and RU-35965 ((±) 1-benzenesulphonyl-2-oxo-5-isopropyloxypyrrolidine) have been deduced from semi-quantitative PM3 type theoretical calculations. The main feature of all compounds consists of a common envelope conformation with C (4) at the flap of the pyrrolidinone ring in the solid, that in solution changes into the analogous, but opposite, possible puckered conformational isomer. The 5-alkoxy groups were found rather flexible in solution. Theoretical preferred conformations about NS and SC bonds were in acceptable agreement with those of the solid state. The calculated torsional energetics suggested that 1- 5 do not undergo conformational interconversion.

  8. Reproducing the conformations of protein-bound ligands: A critical evaluation of several popular conformational searching tools

    Science.gov (United States)

    Boström, Jonas

    2001-12-01

    Several programs (Catalyst, Confort, Flo99, MacroModel, and Omega) that are commonly used to generate conformational ensembles have been tested for their ability to reproduce bioactive conformations. The ligands from thirty-two different ligand-protein complexes determined by high-resolution ( le2.0 Å) X-ray crystallography have been analyzed. The Low-Mode Conformational Search method (with AMBER* and the GB/SA hydration model), as implemented in MacroModel, was found to perform better than the other algorithms. The rule-based method Omega, which is orders of magnitude faster than the other methods, also gave reasonable results but were found to be dependent on the input structure. The methods supporting diverse sampling (Catalyst, Confort) performed least well. For the seven ligands in the set having eight or more rotatable bonds, none of the bioactive conformations were ever found, save for one exception (Flo99). These ligands do not bind in a local minimum conformation according to AMBER*GB/SA. Taking these last two observations together, it is clear that geometrically similar structures should be collected in order to increase the probability of finding the bioactive conformation among the generated ensembles. Factors influencing bioactive conformational retrieval have been identified and are discussed.

  9. Conformational flexibility of aspartame.

    Science.gov (United States)

    Toniolo, Claudio; Temussi, Pierandrea

    2016-05-01

    L-Aspartyl-L-phenylalanine methyl ester, better known as aspartame, is not only one of the most used artificial sweeteners, but also a very interesting molecule with respect to the correlation between molecular structure and taste. The extreme conformational flexibility of this dipeptide posed a huge difficulty when researchers tried to use it as a lead compound to design new sweeteners. In particular, it was difficult to take advantage of its molecular model as a mold to infer the shape of the, then unknown, active site of the sweet taste receptor. Here, we follow the story of the 3D structural aspects of aspartame from early conformational studies to recent docking into homology models of the receptor. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 376-384, 2016.

  10. Denaturing gradient electrophoresis (DGE) and single-strand conformation polymorphism (SSCP) molecular fingerprintings revisited by simulation and used as a tool to measure microbial diversity.

    Science.gov (United States)

    Loisel, Patrice; Harmand, Jérôme; Zemb, Olivier; Latrille, Eric; Lobry, Claude; Delgenès, Jean-Philippe; Godon, Jean-Jacques

    2006-04-01

    The exact extent of microbial diversity remains unknowable. Nevertheless, fingerprinting patterns [denaturing gradient electrophoresis (DGE), single-strand conformation polymorphism (SSCP)] provide an image of a microbial ecosystem and contain diversity data. We generated numerical simulation fingerprinting patterns based on three types of distribution (uniform, geometric and lognormal) with a range of units from 10 to 500,000. First, simulated patterns containing a diversity of around 1000 units or more gave patterns similar to those obtained in experiments. Second, the number of bands or peaks saturated quickly to about 35 and were unrelated to the degree of diversity. Finally, assuming lognormal distribution, we used an estimator of diversity on in silico and experimental fingerprinting patterns. Results on in silico patterns corresponded to the simulation inputs. Diversity results in experimental patterns were in the same range as those obtained from the same DNA sample in molecular inventories. Thus, fingerprinting patterns contain extractable data about diversity although not on the basis of a number of bands or peaks, as is generally assumed to be the case.

  11. Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site [v2; ref status: indexed, http://f1000r.es/3pc

    Directory of Open Access Journals (Sweden)

    Kate A. Stafford

    2014-06-01

    Full Text Available Ribonuclease H1 (RNase H enzymes are well-conserved endonucleases that are present in all domains of life and are particularly important in the life cycle of retroviruses as domains within reverse transcriptase. Despite extensive study, especially of the E. coli homolog, the interaction of the highly negatively charged active site with catalytically required magnesium ions remains poorly understood. In this work, we describe molecular dynamics simulations of the E. coli homolog in complex with magnesium ions, as well as simulations of other homologs in their apo states. Collectively, these results suggest that the active site is highly rigid in the apo state of all homologs studied and is conformationally preorganized to favor the binding of a magnesium ion. Notably, representatives of bacterial, eukaryotic, and retroviral RNases H all exhibit similar active-site rigidity, suggesting that this dynamic feature is only subtly modulated by amino acid sequence and may primarily be imposed by the distinctive RNase H protein fold.

  12. Conformational restrictions in ligand binding to the human intestinal di-/tripeptide transporter

    DEFF Research Database (Denmark)

    Våbenø, Jon; Nielsen, Carsten Uhd; Steffansen, Bente

    2005-01-01

    The aim of the present study was to develop a computational method aiding the design of dipeptidomimetic pro-moieties targeting the human intestinal di-/tripeptide transporter hPEPT1. First, the conformation in which substrates bind to hPEPT1 (the bioactive conformation) was identified by conform...

  13. Bioactives from microalgal dinoflagellates.

    Science.gov (United States)

    Gallardo-Rodríguez, J; Sánchez-Mirón, A; García-Camacho, F; López-Rosales, L; Chisti, Y; Molina-Grima, E

    2012-01-01

    Dinoflagellate microalgae are an important source of marine biotoxins. Bioactives from dinoflagellates are attracting increasing attention because of their impact on the safety of seafood and potential uses in biomedical, toxicological and pharmacological research. Here we review the potential applications of dinoflagellate toxins and the methods for producing them. Only sparing quantities of dinoflagellate toxins are generally available and this hinders bioactivity characterization and evaluation in possible applications. Approaches to production of increased quantities of dinoflagellate bioactives are discussed. Although many dinoflagellates are fragile and grow slowly, controlled culture in bioreactors appears to be generally suitable for producing many of the metabolites of interest.

  14. Understanding the differences in molecular conformation of carbohydrate and protein in endosperm tissues of grains with different biodegradation kinetics using advanced synchrotron technology

    Science.gov (United States)

    Yu, P.; Block, H. C.; Doiron, K.

    2009-01-01

    Conventional "wet" chemical analyses rely heavily on the use of harsh chemicals and derivatization, thereby altering native seed structures leaving them unable to detect any original inherent structures within an intact tissue sample. A synchrotron is a giant particle accelerator that turns electrons into light (million times brighter than sunlight) which can be used to study the structure of materials at the molecular level. Synchrotron radiation-based Fourier transform IR microspectroscopy (SR-FTIRM) has been developed as a rapid, direct, non-destructive and bioanalytical technique. This technique, taking advantage of the brightness of synchrotron light and a small effective source size, is capable of exploring the molecular chemistry within the microstructures of a biological tissue without the destruction of inherent structures at ultraspatial resolutions within cellular dimensions. This is in contrast to traditional 'wet' chemical methods, which, during processing for analysis, often result in the destruction of the intrinsic structures of feeds. To date there has been very little application of this technique to the study of plant seed tissue in relation to nutrient utilization. The objective of this study was to use novel synchrotron radiation-based technology (SR-FTIRM) to identify the differences in the molecular chemistry and conformation of carbohydrate and protein in various plant seed endosperms within intact tissues at cellular and subcellular level from grains with different biodegradation kinetics. Barley grain (cv. Harrington) with a high rate (31.3%/h) and extent (78%), corn grain (cv. Pioneer) with a low rate (9.6%/h) and extent of (57%), and wheat grain (cv. AC Barrie) with an intermediate rate (23%/h) and extent (72%) of ruminal DM degradation were selected for evaluation. SR-FTIRM evaluations were performed at the National Synchrotron Light Source at the Brookhaven National Laboratory (Brookhaven, NY). The molecular structure spectral analysis

  15. Poly(glycidyl ether)-Based Monolayers on Gold Surfaces: Control of Grafting Density and Chain Conformation by Grafting Procedure, Surface Anchor, and Molecular Weight.

    Science.gov (United States)

    Heinen, Silke; Weinhart, Marie

    2017-03-07

    For a meaningful correlation of surface coatings with their respective biological response reproducible coating procedures, well-defined surface coatings, and thorough surface characterization with respect to layer thickness and grafting density are indispensable. The same applies to polymeric monolayer coatings which are intended to be used for, e.g., fundamental studies on the volume phase transition of surface end-tethered thermoresponsive polymer chains. Planar gold surfaces are frequently used as model substrates, since they allow a variety of straightforward surface characterization methods. Herein we present reproducible grafting-to procedures performed with thermoresponsive poly(glycidyl ether) copolymers composed of glycidyl methyl ether (GME) and ethyl glycidyl ether (EGE). The copolymers feature different molecular weights (2 kDa, 9 kDa, 24 kDa) and are equipped with varying sulfur-containing anchor groups in order to achieve adjustable grafting densities on gold surfaces and hence control the tethered polymers' chain conformation. We determined "wet" and "dry" thicknesses of these coatings by QCM-D and ellipsometry measurements and deduced anchor distances and degrees of chain overlap of the polymer chains assembled on gold. Grafting under cloud point conditions allowed for higher degrees of chain overlap compared to grafting from a good solvent like ethanol, independent of the used sulfur-containing anchor group for polymers with low (2 kDa) and medium (9 kDa) molecular weights. By contrast, the achieved grafting densities and thus chain overlaps of surface-tethered polymers with high (24 kDa) molecular weights were identical for both grafting methods. Monolayers prepared from an ethanolic solution of poly(glycidyl ether)s equipped with sterically demanding disulfide-containing anchors revealed the lowest degrees of chain overlap. The ratio of the radius of gyration to the anchor distance (2 Rg/l) of the latter coating was found to be lower than 1

  16. The Conformational Behaviour of Glucosamine

    Science.gov (United States)

    Peña, Isabel; Kolesniková, Lucie; Cabezas, Carlos; Bermúdez, Celina; Berdakin, Matías; Simao, Alcides; Alonso, José L.

    2014-06-01

    A laser ablation method has been successfully used to vaporize the bioactive amino monosaccharide D-glucosamine. Three cyclic α-4C1 pyranose forms have been identified using a combination of CP-FTMW and LA-MB-FTMW spectroscopy. Stereoelectronic hyperconjugative factors, like those associated with anomeric or gauche effects, as well as the cooperative OH\\cdotsO, OH\\cdotsN and NH\\cdotsO chains, extended along the entire molecule, are the main factors driving the conformational behavior. All observed conformers exhibit a counter-clockwise arrangement (cc) of the network of intramolecular hydrogen bonds. The results are compared with those recently obtained for D-glucose. J. L. Alonso, M. A. Lozoya, I. Peña, J. C. López, C. Cabezas, S. Mata, S. Blanco, Chem. Sci. 2014, 5, 515.

  17. A carbon-13 NMR spin-lattice relaxation study of the molecular conformation of the nootropic drug 2-oxopyrrolidin-1-ylacetamide

    Science.gov (United States)

    Baldo, M.; Grassi, A.; Guidoni, L.; Nicolini, M.; Pappalardo, G. C.; Viti, V.

    The spin-lattice relaxation times ( T1) of carbon-13 resonances of the drug 2-oxopyrrolidin- 1-ylacetamide ( 2OPYAC) were determined in CDCl 3 + DMSO and H 2O solutions to investigate the internal conformational flexibility. The measured T1s for the hydrogen-bearing carbon atoms of the 2-pyrrolidone ring fragment were diagnostic of a rigid conformation with respect to the acetamide linked moiety. The model of anisotropic reorientation of a rigid body was used to analyse the measured relaxation data in terms of a single conformation. Owing to the small number of T1 data available the fitting procedure for each of the possible conformations failed. The structure corresponding to the rigid conformation was therefore considered to be the one that is strongly stabilized by internal hydrogen bonding as predicted on the basis of theoretical MO ab initio quantum chemical calculations.

  18. Optically active mixed phthalocyaninato-porphyrinato rare-earth double-decker complexes: synthesis, spectroscopy, and solvent-dependent molecular conformations.

    Science.gov (United States)

    Zhang, Xiaomei; Muranaka, Atsuya; Lv, Wei; Zhang, Yuexing; Bian, Yongzhong; Jiang, Jianzhuang; Kobayashi, Nagao

    2008-01-01

    Reaction between the optically active metal-free phthalocyanine with a pi system with noncentrosymmetrical C(2) [corrected] symmetry ((S)- and (R)-H(2){Pc(OBNP)(2)}; OBNP=binaphthylphthalocyanine) and half-sandwich complexes [M(III)(acac)(TClPP)] (M=Y, Eu; TClPP=meso-tetrakis(4-chlorophenyl)porphyrinate; acac=acetylacetonate), which were generated in situ from [M(acac)(3)].n H(2)O and H(2)(TClPP) in n-octanol at reflux, provided the first optically active protonated mixed phthalocyaninato-porphyrinato rare-earth double-decker complexes [M(III)H{Pc(OBNP)(2)}(TClPP)] (M=Y, Eu) in good yield. In addition to electronic absorption spectroscopy and magnetic circular dichroism results, circular dichroism shows different spectroscopic features of these mixed-ring rare-earth double-decker compounds in different solvents, such as DMF and CHCl(3), which was well-reproduced on the basis of time-dependent density functional theory calculation results for the yttrium species (S)-[Y(III){Pc(OBNP)(2)}(Por)](-) (Por=porphyrinate, which is obtained by removing the four chlorophenyl groups from the TClPP ligand) in terms of the change in the rotation angle between the two macrocyclic ligands in the double-decker molecules. These results revealed the solvent-dependent nature of the molecular conformation of mixed-ring rare-earth double-decker complexes, which suggests a new way of tuning the optical and the electrochemical properties of sandwich-type bis(tetrapyrrole)-metal double-decker complexes in solution by changing the solvent.

  19. Magnitude Differences in Bioactive Compounds, Chemical Functional Groups, Fatty Acid Profiles, Nutrient Degradation and Digestion, Molecular Structure, and Metabolic Characteristics of Protein in Newly Developed Yellow-Seeded and Black-Seeded Canola Lines.

    Science.gov (United States)

    Theodoridou, Katerina; Zhang, Xuewei; Vail, Sally; Yu, Peiqiang

    2015-06-10

    Recently, new lines of yellow-seeded (CS-Y) and black-seeded canola (CS-B) have been developed with chemical and structural alteration through modern breeding technology. However, no systematic study was found on the bioactive compounds, chemical functional groups, fatty acid profiles, inherent structure, nutrient degradation and absorption, or metabolic characteristics between the newly developed yellow- and black-seeded canola lines. This study aimed to systematically characterize chemical, structural, and nutritional features in these canola lines. The parameters accessed include bioactive compounds and antinutrition factors, chemical functional groups, detailed chemical and nutrient profiles, energy value, nutrient fractions, protein structure, degradation kinetics, intestinal digestion, true intestinal protein supply, and feed milk value. The results showed that the CS-Y line was lower (P ≤ 0.05) in neutral detergent fiber (122 vs 154 g/kg DM), acid detergent fiber (61 vs 99 g/kg DM), lignin (58 vs 77 g/kg DM), nonprotein nitrogen (56 vs 68 g/kg DM), and acid detergent insoluble protein (11 vs 35 g/kg DM) than the CS-B line. There was no difference in fatty acid profiles except C20:1 eicosenoic acid content (omega-9) which was in lower in the CS-Y line (P compounds differed (P bioactive compounds, total polyphenols tended to be different (6.3 vs 7.2 g/kg DM), but there were no differences in erucic acid and condensed tannins with averages of 0.3 and 3.1 g/kg DM, respectively. When protein was portioned into five subfractions, significant differences were found in PA, PB1 (65 vs 79 g/kg CP), PB2, and PC fractions (10 vs 33 g/kg CP), indicating protein degradation and supply to small intestine differed between two new lines. In terms of protein structure spectral profile, there were no significant differences in functional groups of amides I and II, α helix, and β-sheet structure as well as their ratio between the two new lines, indicating no difference in

  20. DFT Studies of the Molecular Structures and Conformational Processes of 1,2-, 1,3- and 1,4-Dithiepane

    Institute of Scientific and Technical Information of China (English)

    HAGHDADI Mina; HAMZEHLUIYAN Mahshid

    2008-01-01

    In this study density functional theory (DFT) calculations at B3LYP/6-31G(d), B3LYP/6-31+G(d) and B3LYP/6-311+G(2df,2p) levels for geometry optimization and total energy calculation were applied for investigation of the important energy-minimum conformations and transition-state of 1,2-, 1,3-, and 1,4-dithiepanes. Moreover, ab initio calculations at HF/6-31G(d) level of theory for geometry optimization and MP2/6-311G(d)//HF/6-31G(d) level for a single-point total energy calculation were reported for different conformers. The obtained resuits reveal that, the twist-chair conformer is a global minimum for all of these compounds. Also, two local minimum were found in each case, which are twisted-chair and twisted-boat conformers. The boat and chair geometries are transition states. The minimum energy conformation of 1,2-dithiepane is more stable than the lowest energyforms of 1,3-dithiepane and 1,4-dithiepane. Furthermore, the anomeric effect was investigated for 1,3-dithiepane by the natural bond orbital method. The computational results of this study shows that all conformers of 1,3-dithiepane have a hypercojugation system. Finally, the 13C NMR chemical shifts for the conformers of 1,4-dithiepane were calculated, which have good correlation with their experimental values.

  1. Bioactive glasses: Importance of structure and properties in bone regeneration

    Science.gov (United States)

    Hench, Larry L.; Roki, Niksa; Fenn, Michael B.

    2014-09-01

    This review provides a brief background on the applications, mechanisms and genetics involved with use of bioactive glass to stimulate regeneration of bone. The emphasis is on the role of structural changes of the bioactive glasses, in particular Bioglass, which result in controlled release of osteostimulative ions. The review also summarizes the use of Raman spectroscopy, referred to hereto forward as bio-Raman spectroscopy, to obtain rapid, real time in vitro analysis of human cells in contact with bioactive glasses, and the osteostimulative dissolution ions that lead to osteogenesis. The bio-Raman studies support the results obtained from in vivo studies of bioactive glasses, as well as extensive cell and molecular biology studies, and thus offers an innovative means for rapid screening of new bioactive materials while reducing the need for animal testing.

  2. Chemical composition and bioactivity properties of size-fractions separated from a vermicompost humic acid.

    Science.gov (United States)

    Canellas, Luciano P; Piccolo, Alessandro; Dobbss, Leonardo B; Spaccini, Riccardo; Olivares, Fábio L; Zandonadi, Daniel B; Façanha, Arnoldo R

    2010-01-01

    Preparative high performance size-exclusion chromatography (HPSEC) was applied to humic acids (HA) extracted from vermicompost in order to separate humic matter of different molecular dimension and evaluate the relationship between chemical properties of size-fractions (SF) and their effects on plant root growth. Molecular dimensions of components in humic SF was further achieved by diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY-NMR) based on diffusion coefficients (D), while carbon distribution was evaluated by solid state (CP/MAS) (13)C NMR. Seedlings of maize and Arabidopsis were treated with different concentrations of SF to evaluate root growth. Six different SF were obtained and their carbohydrate-like content and alkyl chain length decreased with decreasing molecular size. Progressive reduction of aromatic carbon was also observed with decreasing molecular size of separated fractions. Diffusion-ordered spectroscopy (DOSY) spectra showed that SF were composed of complex mixtures of aliphatic, aromatic and carbohydrates constituents that could be separated on the basis of their diffusion. All SF promoted root growth in Arabidopsis and maize seedlings but the effects differed according to molecular size and plant species. In Arabidopsis seedlings, the bulk HA and its SF revealed a classical large auxin-like exogenous response, i.e.: shortened the principal root axis and induced lateral roots, while the effects in maize corresponded to low auxin-like levels, as suggested by enhanced principal axis length and induction of lateral roots. The reduction of humic heterogeneity obtained in HPSEC separated size-fractions suggested that their physiological influence on root growth and architecture was less an effect of their size than their content of specific bioactive molecules. However, these molecules may be dynamically released from humic superstructures and exert their bioactivity when weaker is the humic conformational stability as that obtained

  3. Raman spectra and molecular conformation of 2,4,4-trimethyl-2-pentanethiol as a model compound of a hydrophobic group of triton X-100 surfactant

    Science.gov (United States)

    Matsuura, Hiroatsu; Fukuhara, Koichi

    1986-05-01

    Raman spectra of 2,4,4-trimethyl-2-pentanethiol were measured. The spectral analysis with the normal coordinate treatment indicated that this molecule takes the gauche conformation about the CCCS bond in the solid state and the trans and gauche conformations in the liquid state. The Raman bands due to the totally symmetric C&.zdbnd;C streching vibration of the t-butyl part of the 1,1,3,3-tetramethylbutyl group were found to be important to distinguish the two conformations. These key bands were applied to the interpretation of the Raman spectra of Triton X-100 surfactant which contains the p-(1,1,3,3-tetramethylbutyl)phenoxyl group as a hydrophobic moiety. The 1,1,3,3-tetramethylbutyl group of Triton X-100 molecules is shown to be predominantly in the gauche conformation in the liquid state and in aquaeous solution.

  4. Bioactive behaviour of sol-gel derived antibacterial bioactive glass

    Energy Technology Data Exchange (ETDEWEB)

    Bellantone, M.; Hench, L.L. [Imperial Coll. of Science, Technology and Medicine, London (United Kingdom). Dept. of Materials

    2001-07-01

    A new four-component bioactive glass containing Ag{sub 2}O was produced via the sol-gel process. This system releases Ag{sup +} which is a powerful antibacterial agent. The work reported herein is a comparative study of the bioactivity levels of conventional bioactive glass and of the new antibacterial glass. On the basis of XRD patterns, FTIR spectra, and ICP data, the bioactive behaviour of the two biomaterials is nearly equivalent. (orig.)

  5. Bioavailability of bioactive food compounds: a challenging journey to bioefficacy.

    Science.gov (United States)

    Rein, Maarit J; Renouf, Mathieu; Cruz-Hernandez, Cristina; Actis-Goretta, Lucas; Thakkar, Sagar K; da Silva Pinto, Marcia

    2013-03-01

    Bioavailability is a key step in ensuring bioefficacy of bioactive food compounds or oral drugs. Bioavailability is a complex process involving several different stages: liberation, absorption, distribution, metabolism and elimination phases (LADME). Bioactive food compounds, whether derived from various plant or animal sources, need to be bioavailable in order to exert any beneficial effects. Through a better understanding of the digestive fate of bioactive food compounds we can impact the promotion of health and improvement of performance. Many varying factors affect bioavailability, such as bioaccessibility, food matrix effect, transporters, molecular structures and metabolizing enzymes. Bioefficacy may be improved through enhanced bioavailability. Therefore, several technologies have been developed to improve the bioavailability of xenobiotics, including structural modifications, nanotechnology and colloidal systems. Due to the complex nature of food bioactive compounds and also to the different mechanisms of absorption of hydrophilic and lipophilic bioactive compounds, unravelling the bioavailability of food constituents is challenging. Among the food sources discussed during this review, coffee, tea, citrus fruit and fish oil were included as sources of food bioactive compounds (e.g. (poly)phenols and polyunsaturated fatty acids (PUFAs)) since they are examples of important ingredients for the food industry. Although there are many studies reporting on bioavailability and bioefficacy of these bioactive food components, understanding their interactions, metabolism and mechanism of action still requires extensive work. This review focuses on some of the major factors affecting the bioavailability of the aforementioned bioactive food compounds.

  6. SISTEMA DE GESTIÓN DE NO CONFORMIDADES PARA LOS PRODUCTOS COMERCIALES DEL CENTRO DE INMUNOLOGÍA MOLECULAR / NON-CONFORMITIES MANAGEMENT SYSTEM FOR COMMERCIAL PRODUCTS IN THE MOLECULAR IMMUNOLOGY CENTER

    Directory of Open Access Journals (Sweden)

    Yuliet Romero-Ruiz

    2011-03-01

    Full Text Available

    Este artículo describe el diseño y la implementación de un sistema de gestión para las no conformidades generadas durante la fabricación y la distribución de los productos biotecnológicos comerciales en el Centro de Inmunología Molecular. El trabajo abarcó desde la etapa de planificación, con el establecimiento de los indicadores de eficiencia y eficacia del sistema, hasta la evaluación del mismo. Para el control del sistema se emplearon técnicas de ingeniería de la calidad. El diseño del sistema se basó en los principios de la gestión por procesos, la administración del riesgo y el enfoque de sistema. Al año de implementación del sistema se habían gestionado 129 no conformidades y el 83% de ellas estaban cerradas. Además, se observó una disminución en el número de las no conformidades detectadas por las inspecciones regulatorias.

    Abstract

    This article describes the design and implementation of a management system for nonconformities generated during the manufacture and distribution of commercial biotechnological products in the Molecular Immunology Centre. The work ranged from the planning stage, with the establishment of indicators of efficiency and effectiveness of the system, to its assessment. Quality engineering techniques were used for monitoring the system. The system design was based on the principles of process management, risk management and systems approach. One year after the implementation of the system, 129 non-conformities had been managed and 83% of them were closed. In addition, there was a decrease in the number of nonconformities identified by regulatory inspections.

  7. Synthesis, crystal structure analysis, spectral investigations, DFT computations and molecular dynamics and docking study of 4-benzyl-5-oxomorpholine-3-carbamide, a potential bioactive agent

    Science.gov (United States)

    Murthy, P. Krishna; Sheena Mary, Y.; Shyma Mary, Y.; Panicker, C. Yohannan; Suneetha, V.; Armaković, Stevan; Armaković, Sanja J.; Van Alsenoy, C.; Suchetan, P. A.

    2017-04-01

    4-benzyl-5-oxomorpholine-3-carbamide has been synthesized; single crystals were grown by slow evaporation solution growth technique at room temperature and characterized by single crystal X-ray diffraction, FT-IR, FT-Raman and 1H-NMR. The compound crystallizes in the monoclinic space group P21/n. The molecular geometry of the compound was optimized by using Density Functional Theory (DFT/B3LYP) method with 6-311++G(d,p) basis set in the ground state and geometric parameters are in agreement with the X-ray analysis results of the structure. The experimental vibrational spectra were compared with the calculated spectra and each vibrational wave number was assigned on the basis of potential energy distribution (PED). The electronic and charge transfer properties have been explained on the basis of highest occupied molecular orbital's (HOMOs) and lowest unoccupied molecular orbital's (LUMOs). Besides molecular electrostatic potential (MEP), frontier molecular orbital's (FMOs), some global reactivity descriptors, thermodynamic properties, non-linear optical (NLO) behavior and Mullikan charge analysis of the title compound were computed with the same method in gas phase, theoretically. Potential reactive sites of the title compound have been identified by average local ionization energy and Fukui functions, both mapped to the electron density surface. Bond dissociation energies for all single acyclic bonds have been calculated in order to investigate autoxidation and degradation properties of the title compound. Atoms with pronounced interactions with water molecules have been detected by calculations of radial distribution functions after molecular dynamics simulations. The experimental results are compared with the theoretical calculations using DFT methods for the fortification of the paper. Further the docking studies revealed that the title compound as a docked ligand forms a stable complex with pyrrole inhibitor with a binding affinity value of -7.5 kcal/mol. This

  8. Rescuing compound bioactivity in a secondary cell-based screening by using γ-cyclodextrin as a molecular carrier

    Directory of Open Access Journals (Sweden)

    Claveria-Gimeno R

    2015-03-01

    Full Text Available Rafael Claveria-Gimeno,1–3 Sonia Vega,3 Valeria Grazu,4 Jesús M de la Fuente,4–6 Angel Lanas,2,8–10 Adrian Velazquez-Campoy,2,3,7 Olga Abian1–3,8 1Instituto Aragonés de Ciencias de la Salud (IACS, Zaragoza, Spain; 2IIS Aragón, Zaragoza, Spain; 3Institute of Biocomputation and Physics of Complex Systems (BIFI, Joint Unit IQFR-CSIC-BIFI, Universidad de Zaragoza, Zaragoza, Spain; 4Instituto de Nanociencia de Aragon (INA, Universidad de Zaragoza, Zaragoza, Spain; 5Instituto de Ciencia de Materiales de Aragón (ICMA, CSIC-Universidad de Zaragoza, Zaragoza, Spain; 6Institute NanoBiomedicine and Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 7Fundacion ARAID, Government of Aragon, Spain; 8Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd, Barcelona, Spain; 9Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; 10Department of Medicine, University of Zaragoza, Zaragoza, Spain Abstract: In vitro primary screening for identifying bioactive compounds (inhibitors, activators or pharmacological chaperones against a protein target results in the discovery of lead compounds that must be tested in cell-based efficacy secondary screenings. Very often lead compounds do not succeed because of an apparent low potency in cell assays, despite an excellent performance in primary screening. Primary and secondary screenings differ significantly according to the conditions and challenges the compounds must overcome in order to interact with their intended target. Cellular internalization and intracellular metabolism are some of the difficulties the compounds must confront and different strategies can be envisaged for minimizing that problem. Using a novel screening procedure we have identified 15 compounds inhibiting the hepatitis C NS3 protease in an allosteric fashion. After characterizing biophysically the interaction

  9. Porous bioactive materials

    Science.gov (United States)

    Zhang, Kai

    Bioactive materials chemically bond to tissues through the development of biologically active apatite. Porous structures in biomaterials are designed to enhance bioactivity, grow artificial tissues and achieve better integration with host tissues in the body. The goal of this research is to design, fabricate and characterize novel porous bioactive materials. 3D ordered macroporous bioactive glasses (3DOM-BGs, pore size: 200--1000 nm) were prepared using a sol-gel process and colloidal crystal templates. 3DOM-BGs are more bioactive and degradable than mesoporous (pore size simulated body fluid (SBF). Apatite formation and 3DOM-BG degradation rates increased with the decrease of soaking ratio. Apatite induction time in SBF increased with 3DOM-BG calcination temperature (600--800°C). Apatite formation and 3DOMBG degradation were slightly enhanced for a phosphate containing composition. Large 3DOM-BG particles formed less apatite and degraded less completely as compared with small particles. An increase in macropore size slowed down 3DOM-BG degradation and apatite formation processes. After heating the converted apatite at a temperature higher than 700°C, highly crystalline hydroxyapatite and a minor tri-calcium phosphate phase formed. 3DOM-BGs have potential applications as bone/periodontal fillers, and drugs and biological factors delivery agents. Anchoring artificial soft tissues (e.g., cartilage) to native bone presents a challenge. Porous polymer/bioactive glass composites are candidate materials for engineering artificial soft tissue/bone interfaces. Porous composites consisting of polymer matrices (e.g., polysulfone, polylactide, and polyurethane) and bioactive glass particles were prepared by polymer phase separation techniques adapted to include ceramic particles. Composites (thickness: 200--500 mum) have asymmetric structures with dense top layers and porous structures beneath. Porous structures consist of large pores (>100 mum) in a network of smaller (<10

  10. Design, synthesis and bioactivity of novel ALS enzyme inhibitors (II)——Molecular mechanics, quantum chemistry and structure-activity relationship studies on the herbicidal heterocyclic sulfonamide

    Institute of Scientific and Technical Information of China (English)

    陆荣健; 杨华铮; 尚贞锋; 汪惟为; 潘荫明; 赵学庄

    1996-01-01

    In view of quantum pharmacology, the structure-activity relationships of different kinds of fused heterocydic sulfonamides with the same mode of action were first investigated using molecular mechanics, quantum chemistry and discriminatory analysis. It has been found that the process of the interaction of the fused heterocydic sulfonamide with ALS enzyme involves the electropositive region of the sulfonyl bridge chain and the electronegative region of the heterocydic moiety. The herbicidal activity is related to the potency of electric charge translocation of the related regions.

  11. The tubulin-bound conformation of paclitaxel: T-taxol vs "PTX-NY".

    Science.gov (United States)

    Yang, Yutao; Alcaraz, Ana A; Snyder, James P

    2009-03-27

    Nearly 35 years after its discovery and 11 years after FDA approval of paclitaxel (PTX) as a breakthrough anticancer drug, the 3-D structure of the agent bound to its beta-tubulin target was proposed to be T-Taxol. The latter bioactive form has recently been challenged by the Ojima group with a structure, "PTX-NY" ("REDOR Taxol"), in which the C-13 side chain is proposed to adopt a different conformation and an alternative hydrogen-bonding pattern in the tubulin binding site. Previously, the two conformers were compared to show that only T-Taxol fits the PTX-derived electron crystallographic density. That work has been extended by molecular mechanics and quantum chemical methods to reveal that the PTX-NY conformation is relatively less stable, on average, by 10-11 kcal/mol. In agreement with NMR studies, an 11 ns molecular dynamics treatment for PTX in an explicit water pool locates T-Taxol along the trajectory, but not PTX-NY. Docking of various PTX conformers into the electron crystallographic binding site of tubulin demonstrates that PTX-NY cannot be accommodated unless the pocket is reorganized in violation of the experimental constraints. Finally, analysis of the structures of T-Taxol and PTX-NY for their capacity to predict the existence of superpotent PTX analogues discloses that only the former forecasts such analogues, as now established by the T-Taxol-inspired synthesis of bridged taxanes. In sum, all empirical criteria support T-Taxol as the bound conformation of PTX on beta-tubulin in microtubules.

  12. Non-conformable, partial and conformable transposition

    DEFF Research Database (Denmark)

    König, Thomas; Mäder, Lars Kai

    2013-01-01

    Although member states are obliged to transpose directives into domestic law in a conformable manner and receive considerable time for their transposition activities, we identify three levels of transposition outcomes for EU directives: conformable, partially conformable and non-conformable...... and the Commission regarding a directive’s outcome, play a much more strategic role than has to date acknowledged in the transposition literature. Whereas disagreement of a member state delays conformable transposition, it speeds up non-conformable transposition. Disagreement of the Commission only prolongs...

  13. Multiple conformations of proteins in native state

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Examples of protein sequences that can adopt multiple native states are recently accumulated. Characterization of the protein multiple conformations will have important implications for our understanding of the relationship between structure and function, and their folding kinetics. In present review, the experimental evidence for the existence of multiple conformations in the native state of proteins, the molecular basis and the biological significance of multiple conformations of proteins are focused.

  14. A Study of Bioactivity of Corn Peptides with Low Molecular Weight Ⅱ: Effect on Plasma Free Amino Acid Concentrations in Rats

    Institute of Scientific and Technical Information of China (English)

    XU Li; ZHANG Li-qiang; WU Xiao-xia; WANG Na; ZHANG Xue-zhong

    2003-01-01

    The effects of the ingestion of corn peptides with a low molecular weight(LMCP) prepared from zein on some plasma free amino acid concentrations in rats that had taken ethanol were investigated. LMCP(1.0 g/kg body weight) in 15% ethanol(10 mL/kg body weight) was given to Wister rats by intragastrical administration. The amino acid analysis showed that the concentrations of alanine, leucine, and proline in the plasma reached their maximum levels at 30 min for the LMCP-intake group. They are 582.39, 99.60 and 272.51 μg/L, respectively. But in the control group, the plasma free amino acid levels were not changed obviously. Therefore, LMCP could cause an increase in concentration of some free amino acids such as alanine, leucine and proline etc. in plasma of the rats that have taken ethanol.

  15. Micellar and structural stability of nanoscale amphiphilic polymers: Implications for anti-atherosclerotic bioactivity.

    Science.gov (United States)

    Zhang, Yingyue; Li, Qi; Welsh, William J; Moghe, Prabhas V; Uhrich, Kathryn E

    2016-04-01

    Atherosclerosis, a leading cause of mortality in developed countries, is characterized by the buildup of oxidized low-density lipoprotein (oxLDL) within the vascular intima, unregulated oxLDL uptake by macrophages, and ensuing formation of arterial plaque. Amphiphilic polymers (AMPs) comprised of a branched hydrophobic domain and a hydrophilic poly(ethylene glycol) (PEG) tail have shown promising anti-atherogenic effects through direct inhibition of oxLDL uptake by macrophages. In this study, five AMPs with controlled variations were evaluated for their micellar and structural stability in the presence of serum and lipase, respectively, to develop underlying structure-atheroprotective activity relations. In parallel, molecular dynamics simulations were performed to explore the AMP conformational preferences within an aqueous environment. Notably, AMPs with ether linkages between the hydrophobic arms and sugar backbones demonstrated enhanced degradation stability and storage stability, and also elicited enhanced anti-atherogenic bioactivity. Additionally, AMPs with increased hydrophobicity elicited increased atheroprotective bioactivity in the presence of serum. These studies provide key insights for designing more serum-stable polymeric micelles as prospective cardiovascular nanotherapies.

  16. Conformal transformations and conformal invariance in gravitation

    CERN Document Server

    Dabrowski, Mariusz P; Blaschke, David B

    2008-01-01

    Conformal transformations are frequently used tools in order to study relations between various theories of gravity and Einstein relativity. Because of that, in this paper we discuss the rules of conformal transformations for geometric quantities in general relativity. In particular, we discuss the conformal transformations of the matter energy-momentum tensor. We thoroughly discuss the latter and show the subtlety of the conservation law (i.e., the geometrical Bianchi identity) imposed in one of the conformal frames in reference to the other. The subtlety refers to the fact that conformal transformation ``creates'' an extra matter term composed of the conformal factor which enters the conservation law. In an extreme case of the flat original spacetime the matter is ``created'' due to work done by the conformal transformation to bend the spacetime which was originally flat. We also discuss how to construct the conformally invariant gravity which, in the simplest version, is a special case of the Brans-Dicke t...

  17. Antibacterial action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles against Escherichia coli correlated with molecular chain conformation

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Yan [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); School of Science, Tianjin University of Commerce, Tianjin 300134 (China); Yao, Fanglian, E-mail: yaofanglian@tju.edu.cn [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Sun, Fang [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Tan, Zhilei [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300222 (China); Tian, Liang [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Xie, Lei; Song, Qingchao [College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300222 (China)

    2015-03-01

    The action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles (CM-HTCC/PAMAM) against Escherichia coli (E. coli) was investigated via a combination of approaches including measurements of cell membrane integrity, outer membrane (OM) and inner membrane (IM) permeability, and scanning electron microscopy (SEM). CM-HTCC/PAMAM dendrimer nanoparticles likely acted in a sequent event-driven mechanism, beginning with the binding of positively charged groups from nanoparticle surface with negative cell surface, thereby causing the disorganization of cell membrane, and subsequent leakage of intracellular components which might ultimately lead to cell death. Moreover, the chain conformation of polymers was taken into account for a better understanding of the antibacterial action mode by means of viscosity and GPC measurements. High utilization ratio of positive charge and large specific surface area generated from a compacted conformation of CM-HTCC/PAMAM, significantly different from the extended conformation of HTCC, were proposed to be involved in the antibacterial action. - Highlights: • The nanoparticles exerted antibacterial activity in a sequent event-driven manner. • Electrostatic interaction and surface adsorption shared roles in antibacterial mode. • The two factors were controlled by the compacted conformation of nanoparticles.

  18. Conformational choreography of a molecular switch region in myelin basic protein--molecular dynamics shows induced folding and secondary structure type conversion upon threonyl phosphorylation in both aqueous and membrane-associated environments.

    Science.gov (United States)

    Polverini, Eugenia; Coll, Eoin P; Tieleman, D Peter; Harauz, George

    2011-03-01

    The 18.5 kDa isoform of myelin basic protein is essential to maintaining the close apposition of myelin membranes in central nervous system myelin, but its intrinsic disorder (conformational dependence on environment), a variety of post-translational modifications, and a diversity of protein ligands (e.g., actin and tubulin) all indicate it to be multifunctional. We have performed molecular dynamics simulations of a conserved central segment of 18.5 kDa myelin basic protein (residues Glu80-Gly103, murine sequence numbering) in aqueous and membrane-associated environments to ascertain the stability of constituent secondary structure elements (α-helix from Glu80-Val91 and extended poly-proline type II from Thr92-Gly103) and the effects of phosphorylation of residues Thr92 and Thr95, individually and together. In aqueous solution, all four forms of the peptide bent in the middle to form a hydrophobic cluster. The phosphorylated variants were stabilized further by electrostatic interactions and formation of β-structures, in agreement with previous spectroscopic data. In simulations performed with the peptide in association with a dimyristoylphosphatidylcholine bilayer, the amphipathic α-helical segment remained stable and membrane-associated, although the degree of penetration was less in the phosphorylated variants, and the tilt of the α-helix with respect to the plane of the membrane also changed significantly with the modifications. The extended segment adjacent to this α-helix represents a putative SH3-ligand and remained exposed to the cytoplasm (and thus accessible to binding partners). The results of these simulations demonstrate how this segment of the protein can act as a molecular switch: an amphipathic α-helical segment of the protein is membrane-associated and presents a subsequent proline-rich segment to the cytoplasm for interaction with other proteins. Phosphorylation of threonyl residues alters the degree of membrane penetration of the

  19. Quinoxaline based bio-active mixed ligand transition metal complexes: Synthesis, characterization, electrochemical, antimicrobial, DNA binding, cleavage, antioxidant and molecular docking studies.

    Science.gov (United States)

    Dhanaraj, C Justin; Johnson, Jijo

    2015-10-01

    Co(II), Ni(II), Cu(II) and Zn(II) mixed ligand complexes have been synthesized from N(2), N(3)-bis(4-nitrophenyl)quinoxaline-2,3-diamine and 1,10-phenanthroline. The compounds were characterized by elemental analyses, molar conductance, magnetic susceptibility, IR, UV-Vis., (1)H NMR, mass and ESR spectra. Octahedral geometry has been assigned for Co(II), Ni(II) and Zn(II) complexes and distorted octahedral geometry for Cu(II) complex. Electrochemical behavior of the synthesized complexes was studied using cyclic voltammetry. Grain size and surface morphologies of the complexes were determined by powder XRD and SEM analyses. The mixed ligand metal complexes were screened for antimicrobial activity against bacterial species Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus; fungal species Aspergillus niger, and Candida albicans by disc diffusion method. The DNA binding and DNA cleavage activities of the compounds were determined using electronic absorption titration and agarose gel electrophoresis respectively. The superoxide radical scavenging and free radical scavenging activities of the Cu(II) complex was also evaluated. Molecular docking studies of the synthesized mixed ligand metal complexes were carried out against B-DNA dodecamer and the protein Plasmodium falciparum dihydrofolate reductase (pf DHFR).

  20. A Study on bioactivity of Corn Peptides with Low Molecular Weight(Ⅰ)——Effect of an Intake of them on Alcohol Metabolism in Rats

    Institute of Scientific and Technical Information of China (English)

    XULi; FEIXiao-fang; ZHANGLi-qiang; ZHANGXue-zhong

    2003-01-01

    This study aims at the effects of an intake of low molecular weight corn peptides(LMCP5)prepared from zein on alcohol mentablism in rats.LMCPs(1.0g/kg dody weight)in 15% ethanol(10mL/kg body weight) were given to Wister rats by intragastric gavage.The assay of blood ethanol was conducted by using the enzyme-based assay kit.The amino acid analysis was made with an amino acid analyzer.The data of the animal experiments showed that LMCPs could accelerate the metabolism of alcohol in rats.In the control group,the blood ethanol concentration reached the maximun level of (827.0±77.3)mg/L after ethanol loading for 30min,then gradually decreased.In contrast,the blood ethanol concentration only reached (527.25±47.0)mg/L after 30 min in the group of LMCPs taken.These results indicate that LMCPs could decrease ethanol concentration in blood rapidly.

  1. A Study on Bioactivity of Corn Peptides with Low Molecular Weight(Ⅰ) --Effect of an Intake of them on Alcohol Metabolism in Rats

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    This study aims at the effects of an intake of low molecular weight corn peptides(LMCPs) prepared from zein on alcohol metablism in rats. LMCPs(1.0 g/kg body weight) in 15% ethanol(10 mL/kg body weight) were given to Wister rats by intragastric gavage. The assay of blood ethanol was conducted by using the enzyme-based assay kit. The amino acid analysis was made with an amino acid analyzer. The data of the animal experiments showed that LMCPs could accelerate the metabolism of alcohol in rats. In the control group, the blood ethanol concentration reached the maximum level of (827.0±77.3) mg/L after ethanol loading for 30 min, then gradually decreased. In contrast, the blood ethanol concentration only reached (527.25±47.0) mg/L after 30 min in the group of LMCPs taken. These results indicate that LMCPs could decrease ethanol concentration in blood rapidly.

  2. Applied bioactive polymeric materials

    CERN Document Server

    Carraher, Charles; Foster, Van

    1988-01-01

    The biological and biomedical applications of polymeric materials have increased greatly in the past few years. This book will detail some, but not all, of these recent developments. There would not be enough space in this book to cover, even lightly, all of the major advances that have occurred. Some earlier books and summaries are available by two of this book's Editors (Gebelein & Carraher) and these should be consul ted for additional information. The books are: "Bioactive Polymeric Systems" (Plenum, 1985); "Polymeric Materials In Medication" (Plenum, 1985); "Biological Acti vi ties of Polymers" (American Chemical Society, 1982). Of these three, "Bioacti ve Polymeric Systems" should be the most useful to a person who is new to this field because it only contains review articles written at an introductory level. The present book primarily consists of recent research results and applications, with only a few review or summary articles. Bioactive polymeric materials have existed from the creation of life...

  3. Bioactive phytochemicals in flaxseed

    OpenAIRE

    Johnsson, Pernilla

    2009-01-01

    Flaxseed (Linum usitatissimum L.) is rich in health-promoting bioactive compounds. Among plant foods, flaxseed has the highest content of lignans, mainly in the form of secoisolariciresinol diglucoside (SDG). Flaxseed oil also has a very high concentration of the essential omega-3 fatty acid alpha-linolenic acid (ALA). This thesis presents studies on both SDG and ALA. An HPLC method for quantification of SDG in hydrolysed flaxseed extracts was developed and used to compare the SDG content in ...

  4. Conformal isoparametric hypersurfaces with two distinct conformal principal curvatures in conformal space

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The conformal geometry of regular hypersurfaces in the conformal space is studied.We classify all the conformal isoparametric hypersurfaces with two distinct conformal principal curvatures in the conformal space up to conformal equivalence.

  5. Conformational properties of oxazoline-amino acids

    Science.gov (United States)

    Staś, Monika; Broda, Małgorzata A.; Siodłak, Dawid

    2016-04-01

    Oxazoline-amino acids (Xaa-Ozn) occur in natural peptides of potentially important bioactivity. The conformations of the model compounds: Ac-(S)-Ala-Ozn(4R-Me), Ac-(S)-Ala-Ozn(4S-Me), and (gauche+, gauche-, anti) Ac-(S)-Val-Ozn(4R-Me) were studied at meta-hybrid M06-2X/6-311++G(d,p) method including solvent effect. Boc-L-Ala-L-Ozn-4-COOMe and Boc-L-Val-L-Ozn-4-COOMe were synthesized and studied by FT-IR and NMR-NOE methods. The conformations in crystal state were gathered from the Cambridge Structural Data Base. The main conformational feature of the oxazoline amino acids is the conformation β2 (ϕ,ψ ∼ -161°, -6°), which predominates in weakly polar environment and still is accessible in polar surrounding. The changes of the conformational preferences towards the conformations αR (ϕ,ψ ∼ -70°, -15°) and then β (ϕ,ψ ∼ -57°, -155°) are observed with increase of the environment polarity.

  6. Structural studies on a non toxic homologue of type II RIPs from bitter gourd: Molecular basis of non toxicity, conformational selection and glycan structure

    Indian Academy of Sciences (India)

    Thyageshwar Chandran; Alok Sharma; M Vijayan

    2015-12-01

    The structures of nine independent crystals of bitter gourd seed lectin (BGSL), a non-toxic homologue of type II RIPS, and its sugar complexes have been determined. The four-chain, two-fold symmetric, protein is made up of two identical two-chain modules, each consisting of a catalytic chain and a lectin chain, connected by a disulphide bridge. The lectin chain is made up of two domains. Each domain carries a carbohydrate binding site in type II RIPS of known structure. BGSL has a sugar binding site only on one domain, thus impairing its interaction at the cell surface. The adenine binding site in the catalytic chain is defective. Thus, defects in sugar binding as well as adenine binding appear to contribute to the non-toxicity of the lectin. The plasticity of the molecule is mainly caused by the presence of two possible well defined conformations of a surface loop in the lectin chain. One of them is chosen in the sugar complexes, in a case of conformational selection, as the chosen conformation facilitates an additional interaction with the sugar, involving an arginyl residue in the loop. The -glycosylation of the lectin involves a plant-specific glycan while that in toxic type H RIPS of known structure involves a glycan which is animal as well as plant specific.

  7. Identification of Distinct Conformations of the Angiotensin-II Type 1 Receptor Associated with the Gq/11 Protein Pathway and the β-Arrestin Pathway Using Molecular Dynamics Simulations*

    Science.gov (United States)

    Cabana, Jérôme; Holleran, Brian; Leduc, Richard; Escher, Emanuel; Guillemette, Gaétan; Lavigne, Pierre

    2015-01-01

    Biased signaling represents the ability of G protein-coupled receptors to engage distinct pathways with various efficacies depending on the ligand used or on mutations in the receptor. The angiotensin-II type 1 (AT1) receptor, a prototypical class A G protein-coupled receptor, can activate various effectors upon stimulation with the endogenous ligand angiotensin-II (AngII), including the Gq/11 protein and β-arrestins. It is believed that the activation of those two pathways can be associated with distinct conformations of the AT1 receptor. To verify this hypothesis, microseconds of molecular dynamics simulations were computed to explore the conformational landscape sampled by the WT-AT1 receptor, the N111G-AT1 receptor (constitutively active and biased for the Gq/11 pathway), and the D74N-AT1 receptor (biased for the β-arrestin1 and -2 pathways) in their apo-forms and in complex with AngII. The molecular dynamics simulations of the AngII-WT-AT1, N111G-AT1, and AngII-N111G-AT1 receptors revealed specific structural rearrangements compared with the initial and ground state of the receptor. Simulations of the D74N-AT1 receptor revealed that the mutation stabilizes the receptor in the initial ground state. The presence of AngII further stabilized the ground state of the D74N-AT1 receptor. The biased agonist [Sar1,Ile8]AngII also showed a preference for the ground state of the WT-AT1 receptor compared with AngII. These results suggest that activation of the Gq/11 pathway is associated with a specific conformational transition stabilized by the agonist, whereas the activation of the β-arrestin pathway is linked to the stabilization of the ground state of the receptor. PMID:25934394

  8. Aquasomes: A Self Assembling Nanobiopharmaceutical Carrier System for Bio-Active Molecules: A Review

    Directory of Open Access Journals (Sweden)

    Patel JK

    2012-02-01

    Full Text Available Aquasomes are the self-assembling nanobiopharmaceutical carrier system, contains nanocrystallinecalcium phosphate or ceramic diamond, is covered by a glassy polyhydroxyl oligomeric film.Aquasomes are spherical (5–925nm particles used for drug and antigen delivery. Aquasomes are calledas “bodies of water" their water like properties protect and preserve fragile biological molecules. Its highdegree of surface exposure is used in targeting of bio-active molecules to specific sites. Three types ofcore materials are mainly used for producing aquasomes: Tin oxide, Nanocrystalline carbon ceramicsand Brushite. Calcium phosphate is the core of interest, due to its natural presence in the body. Thebrushite is unstable and converts to hydroxyapatite upon prolong storage and seems a better core for thepreparation of aquasomes. It is widely used for the preparation of implants. Aquasomes exploited as aRBC substitutes, vaccines for delivery of viral antigen and as targeted system for intracellular genetherapy. Enzyme activity and sensitivity towards molecular conformation made aquasome as a novelcarrier for enzymes like DNAses and pigment/dyes. This report reviews the principles of self assembly,the challenges of maintaining both the conformational integrity and biochemical activity of immobilizedsurface pairs.

  9. Molecular Dynamics Characterization of the Conformational Landscape of Small Peptides: A Series of Hands-On Collaborative Practical Sessions for Undergraduate Students

    Science.gov (United States)

    Rodrigues, João P. G. L. M.; Melquiond, Adrien S. J.; Bonvin, Alexandre M. J. J.

    2016-01-01

    Molecular modelling and simulations are nowadays an integral part of research in areas ranging from physics to chemistry to structural biology, as well as pharmaceutical drug design. This popularity is due to the development of high-performance hardware and of accurate and efficient molecular mechanics algorithms by the scientific community. These…

  10. Molecular dynamics characterization of the conformational landscape of small peptides : A series of hands-on collaborative practical sessions for undergraduate students

    NARCIS (Netherlands)

    Garcia Lopes Maia Rodrigues, João; Melquiond, Adrien S J; Bonvin, Alexandre M J J

    2016-01-01

    Molecular modelling and simulations are nowadays an integral part of research in areas ranging from physics to chemistry to structural biology, as well as pharmaceutical drug design. This popularity is due to the development of high-performance hardware and of accurate and efficient molecular mechan

  11. Atropisomerism: the effect of the axial chirality in bioactive compounds; Atropoisomerismo: o efeito da quiralidade axial em substancias bioativas

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Anderson Rouge dos; Pinheiro, Alessandra Campbell; Sodero, Ana Carolina Renno; Cunha, Andrea Sousa da; Padilha, Monica Costa; Sousa, Priscila Mesquita de; Fontes, Silvia Paredes [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Quimica. Dept. de Quimica Organica; Veloso, Marcia Paranho [Universidade Federal de Alfenas, MG (Brazil); Fraga, Carlos Alberto Manssour [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Faculdade de Farmacia. Lab. de Avaliacao e Sintese de Substancias Bioativas (LASSBio)]. E-mail: cmfraga@pharma.ufrj.br

    2007-01-15

    Atropisomerism is a special kind of stereoisomeric relationship that arises from the freezing of a certain conformation of an organic molecule, associated with a high rotational barrier about a single covalent bond. Atropisomerism has been originally described in orto-functionalized biphenyl derivatives, but a lot of other organic functionalities can present this structural phenomenon, characterized by the presence of chiral properties in compounds that do not present classical stereogenic centers. Atropisomeric compounds, intermediates and catalysts have well-know importance in organic synthesis, but the influence of the axial chirality in substances able to modulate biological systems is still not very exploited in drug design and development. In this context, the present account describes the importance of this structural property in the medicinal chemistry of different classes of bioactive compounds or therapeutic agents, emphasizing how atropisomerism could affect the molecular recognition of a ligand or a prototype by the target bioreceptor. (author)

  12. Conformational stability, molecular structure, vibrational, electronic, 1H and 13C spectral analysis of 3-pyridinemethanol using ab-initio/DFT method

    Science.gov (United States)

    Sivaranjani, T.; Periandy, S.; Xavier, S.

    2016-03-01

    The FT-IR and FT-Raman spectra of 3-pyridinemethanol (3PYRM) have been recorded in the regions 4000-400 and 4000-100 cm-1 respectively. The vibrational analysis of 3PYRM was carried out using wavenumbers computed by HF and DFT (B3LYP) methods with 6-311++G (d, p) basis set, along with experimental values. The conformational analyses were performed and the energies of the different possible conformers were determined. The total electron density and MESP surfaces of the molecules were constructed using B3LYP/6-311++G (d, p) method to display nucleophilic and electrophilic region globally. The HOMO and LUMO energies were measured and different reactivity descriptors are discussed the active sites of the molecule. Natural Bond Orbital Analysis is discussed and possible transition are correlated with the electronic transitions. Milliken's net charges and the atomic natural charges are also predicted. The 13C and 1H NMR chemical shifts were computed at the B3LYP/6-311++G (2d, p) level by applying GIAO theory and compared with the experimental spectra recorded using the high resolution of 100 MHz and 400 MHz NMR spectrometer with electromagnetic field strength 9.1T, respectively. The temperature dependence of the thermodynamic properties; heat capacity, entropy and enthalpy for the title compounds were also determined by B3LYP/6-311++G (d, p) method.

  13. Nanotech: propensity in foods and bioactives.

    Science.gov (United States)

    Kuan, Chiu-Yin; Yee-Fung, Wai; Yuen, Kah-Hay; Liong, Min-Tze

    2012-01-01

    Nanotechnology is seeing higher propensity in various industries, including food and bioactives. New nanomaterials are constantly being developed from both natural biodegradable polymers of plant and animal origins such as polysaccharides and derivatives, peptides and proteins, lipids and fats, and biocompatible synthetic biopolyester polymers such as polylactic acid (PLA), polyhydroxyalkonoates (PHA), and polycaprolactone (PCL). Applications in food industries include molecular synthesis of new functional food compounds, innovative food packaging, food safety, and security monitoring. The relevance of bioactives includes targeted delivery systems with improved bioavailability using nanostructure vehicles such as association colloids, lipid based nanoencapsulator, nanoemulsions, biopolymeric nanoparticles, nanolaminates, and nanofibers. The extensive use of nanotechnology has led to the need for parallel safety assessment and regulations to protect public health and adverse effects to the environment. This review covers the use of biopolymers in the production of nanomaterials and the propensity of nanotechnology in food and bioactives. The exposure routes of nanoparticles, safety challenges, and measures undertaken to ensure optimal benefits that outweigh detriments are also discussed.

  14. Conformational Analysis of Seven Membered Nitrogen Heterocycles Employing Molecular Modeling. Part II: 1-(ONitrophenyl-2-Phenyl-1h-4,5,6,7-Tetrahydro-1,3-Diazepine

    Directory of Open Access Journals (Sweden)

    Mónica E. Hedrera

    2000-03-01

    Full Text Available Geometry optimization of 1-(o-nitrophenyl-2-phenyl-1H-4,5,6,7-tetrahydro-1,3-diazepine is performed by means of molecular modeling. Results are correlated with theoretical and experimental UV spectra.

  15. Anti-fouling bioactive surfaces.

    Science.gov (United States)

    Yu, Qian; Zhang, Yanxia; Wang, Hongwei; Brash, John; Chen, Hong

    2011-04-01

    Bioactive surfaces refer to surfaces with immobilized bioactive molecules aimed specifically at promoting or supporting particular interactions. Such surfaces are of great importance for various biomedical and biomaterials applications. In the past few years, considerable effort has been made to create bioactive surfaces by forming specific biomolecule-modified surfaces on a non-biofouling "base" or "background". Hydrophilic and bioinert polymers have been widely used as anti-fouling layers that resist non-specific protein interactions. They can also serve as "spacers" to effectively move the immobilized biomolecule away from the surface, thus enhancing its bioactivity. In this review we summarize several successful approaches for the design and preparation of bioactive surfaces based on different types of anti-fouling/spacer materials. Some perspectives on future research in this area are also presented.

  16. Bridging converts a noncytotoxic nor-paclitaxel derivative to a cytotoxic analogue by constraining it to the T-Taxol conformation.

    Science.gov (United States)

    Tang, Shoubin; Yang, Chao; Brodie, Peggy; Bane, Susan; Ravindra, Rudravajhala; Sharma, Shubhada; Jiang, Yi; Snyder, James P; Kingston, David G I

    2006-08-31

    The synthesis of the bridged A-nor-paclitaxel 4 has been achieved from paclitaxel in a key test of the T-Taxol conformational hypothesis. Although the unbridged A-nor-paclitaxel 3 is essentially noncytotoxic, the bridged analogue 4 is strongly cytotoxic. This result provides strong evidence for the T-Taxol conformation as the bioactive tubulin-binding conformation of paclitaxel.

  17. Three closely related 4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridines: synthesis, molecular conformations and hydrogen bonding in zero, one and two dimensions.

    Science.gov (United States)

    Sagar, Belakavadi K; Harsha, Kachigere B; Yathirajan, Hemmige S; Rangappa, Kanchugarakoppal S; Rathore, Ravindranath S; Glidewell, Christopher

    2017-03-01

    In each of 1-(4-fluorophenyl)-5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine, C21H19F4N3O2S, (I), 1-(4-chlorophenyl)-5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine, C21H19ClF3N3O2S, (II), and 1-(3-methylphenyl)-5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine, C22H22F3N3O2S, (III), the reduced pyridine ring adopts a half-chair conformation with the methylsulfonyl substituent occupying an equatorial site. Although compounds (I) and (II) are not isostructural, having the space groups Pbca and P212121, respectively, their molecular conformations are very similar, but the conformation of compound (III) differs from those of (I) and (II) in the relative orientation of the N-benzyl and methylsulfonyl substituents. In compounds (II) and (III), but not in (I), the trifluoromethyl groups are disordered over two sets of atomic sites. Molecules of (I) are linked into centrosymmetric dimers by C-H...π(arene) hydrogen bonds, molecules of (II) are linked by two C-H...O hydrogen bonds to form ribbons of R3(3)(18) rings, which are themselves further linked by a C-Cl...π(arene) interaction, and a combination of C-H...O and C-H...π(arene) hydrogen bonds links the molecules of (III) into sheets. Comparisons are made with the structures of some related compounds.

  18. Molecular recognition studies on supramolecular systems (XXIV)——Conformations and complexation abilities of chemically modified cyclodextrins in aqueous solution

    Institute of Scientific and Technical Information of China (English)

    刘育; 尤长城

    2000-01-01

    Circular dichroism spectral and fluorescence decay methods have been employed to determine the conformations of mono[6-(p-tolylseleno)-6-deoxy]-p-CD(1), mono(6-anilino-6-deoxy) β -CD (2) and mono[6-(L-tryptophan)-6-deoxy]-β-CD (3) in phosphate buffer solution (pH 7.2, 0.1 mol dm-3) at 298.15 K. The results indicate that compounds 2 and 3 formed self-inclusion complexes in aqueous buffer solution, while the substituent of compound 1 was not included into cyclodextrin cavity at all. Furthermore, the complex stability constant (logKs) and Gibbs free energy change (-ΔG° ) of these three cylcodextrin derivatives with several cycloalkanols have been determined by circular dichroism spectral titration in phosphate buffer solution at 298.15 K. It is found that the location of the substituent affects the stability of host-guest complex in aqueous solution.

  19. Bioactivity and structural properties of chimeric analogs of the starfish SALMFamide neuropeptides S1 and S2.

    Science.gov (United States)

    Jones, Christopher E; Otara, Claire B; Younan, Nadine D; Viles, John H; Elphick, Maurice R

    2014-10-01

    The starfish SALMFamide neuropeptides S1 (GFNSALMFamide) and S2 (SGPYSFNSGLTFamide) are the prototypical members of a family of neuropeptides that act as muscle relaxants in echinoderms. Comparison of the bioactivity of S1 and S2 as muscle relaxants has revealed that S2 is ten times more potent than S1. Here we investigated a structural basis for this difference in potency by comparing the bioactivity and solution conformations (using NMR and CD spectroscopy) of S1 and S2 with three chimeric analogs of these peptides. A peptide comprising S1 with the addition of S2's N-terminal tetrapeptide (Long S1 or LS1; SGPYGFNSALMFamide) was not significantly different to S1 in its bioactivity and did not exhibit concentration-dependent structuring seen with S2. An analog of S1 with its penultimate residue substituted from S2 (S1(T); GFNSALTFamide) exhibited S1-like bioactivity and structure. However, an analog of S2 with its penultimate residue substituted from S1 (S2(M); SGPYSFNSGLMFamide) exhibited loss of S2-type bioactivity and structural properties. Collectively, our data indicate that the C-terminal regions of S1 and S2 are the key determinants of their differing bioactivity. However, the N-terminal region of S2 may influence its bioactivity by conferring structural stability in solution. Thus, analysis of chimeric SALMFamides has revealed how neuropeptide bioactivity is determined by a complex interplay of sequence and conformation.

  20. Synthesis, Structure, and Molecular Recognition of S6 - and (SO2 )6 -Corona[6](het)arenes: Control of Macrocyclic Conformation and Properties by the Oxidation State of the Bridging Heteroatoms.

    Science.gov (United States)

    Guo, Qing-Hui; Zhao, Liang; Wang, Mei-Xiang

    2016-05-10

    We report herein the synthesis, structure, and molecular recognition of S6 - and (SO2 )6 -corona[6](het)arenes, and demonstrate a unique and efficient strategy of regulating macrocyclic conformation and properties by adjusting the oxidation state of the heteroatom linkages. The one-pot nucleophilic aromatic substitution reaction of 1,4-benzenedithiol derivatives, biphenyl-4,4'-dithiol and 9,9-dipropyl-9H-fluorene-2,7-dithiol with 3,6-dichlorotetrazine afforded S6 -corona[3]arene[3]tetrazines. These compounds underwent inverse-electron-demand Diels-Alder reaction with enamines and norbornadiene to produce S6 -corona[3]arene[3]pyridazines. Facile oxidation of sulfide linkages yielded (SO2 )6 -corona[3]arene[3]pyridazines. All corona[6](het)arenes adopted generally hexagonal macrocyclic ring structures; however, their electronic properties and conformation could be fine-tuned by altering the oxidation state of the sulfur linkages. Whereas (SO2 )6 -corona[3]arene[3]pyridazines were electron-deficient, S6 -corona[3]arene[3]pyridazines acted as electron-rich macrocyclic hosts that recognized various organic cations in both aqueous and organic solutions.

  1. Imaging of conformational changes

    Energy Technology Data Exchange (ETDEWEB)

    Michl, Josef [Univ. of Colorado, Boulder, CO (United States)

    2016-03-13

    Control of intramolecular conformational change in a small number of molecules or even a single one by an application of an outside electric field defined by potentials on nearby metal or dielectric surfaces has potential applications in both 3-D and 2-D nanotechnology. Specifically, the synthesis, characterization, and understanding of designed solids with controlled built-in internal rotational motion of a dipole promises a new class of materials with intrinsic dielectric, ferroelectric, optical and optoelectronic properties not found in nature. Controlled rotational motion is of great interest due to its expected utility in phenomena as diverse as transport, current flow in molecular junctions, diffusion in microfluidic channels, and rotary motion in molecular machines. A direct time-resolved observation of the dynamics of motion on ps or ns time scale in a single molecule would be highly interesting but is also very difficult and has yet to be accomplished. Much can be learned from an easier but still challenging comparison of directly observed initial and final orientational states of a single molecule, which is the basis of this project. The project also impacts the understanding of surface-enhanced Raman spectroscopy (SERS) and single-molecule spectroscopic detection, as well as the synthesis of solid-state materials with tailored properties from designed precursors.

  2. Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site [v1; ref status: indexed, http://f1000r.es/2z7

    Directory of Open Access Journals (Sweden)

    Kate A. Stafford

    2014-03-01

    Full Text Available Ribonuclease H1 (RNase H enzymes are well-conserved endonucleases that are present in all domains of life and are particularly important in the life cycle of retroviruses as domains within reverse transcriptase. Despite extensive study, especially of the E. coli homolog, the interaction of the highly negatively charged active site with catalytically required magnesium ions remains poorly understood. In this work, we describe molecular dynamics simulations of the E. coli homolog in complex with magnesium ions, as well as simulations of other homologs in their apo states. Collectively, these results suggest that the active site is highly rigid in the apo state of all homologs studied and is conformationally preorganized to favor the binding of a magnesium ion. Notably, representatives of bacterial, eukaryotic, and retroviral RNases H all exhibit similar active-site rigidity, suggesting that this dynamic feature is only subtly modulated by amino acid sequence and is primarily imposed by the distinctive RNase H protein fold.

  3. Conformation and atropisomeric properties of indometacin derivatives.

    Science.gov (United States)

    Wakamatsu, Shintaro; Takahashi, Yuka; Tabata, Hidetsugu; Oshitari, Tetsuta; Tani, Norihiko; Azumaya, Isao; Katsumoto, Yukiteru; Tanaka, Takeyuki; Hosoi, Shinzo; Natsugari, Hideaki; Takahashi, Hideyo

    2013-05-27

    The stereochemistry around the N-benzoylated indole moiety of indometacin was studied by restricting the rotation about the N-C7' and/or C7'-C1' bond. In the 2',6'-disubstituted ones, an atropisomeric property was found and the atropoisomers were separated and isolated as stable forms. Their biological abilities to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were examined. Only the aR-isomer showed specific inhibition of COX-1, and COX-2 was not inhibited by either atropisomer. Conformational analysis in NMR studies and X-ray crystallography, and CD spectra in combination with calculations were utilized to elucidate the bioactive conformations.

  4. Superspace conformal field theory

    Energy Technology Data Exchange (ETDEWEB)

    Quella, Thomas [Koeln Univ. (Germany). Inst. fuer Theoretische Physik; Schomerus, Volker [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2013-07-15

    Conformal sigma models and WZW models on coset superspaces provide important examples of logarithmic conformal field theories. They possess many applications to problems in string and condensed matter theory. We review recent results and developments, including the general construction of WZW models on type I supergroups, the classification of conformal sigma models and their embedding into string theory.

  5. Molecular Orbital and Density Functional Study of the Formation, Charge Transfer, Bonding and the Conformational Isomerism of the Boron Trifluoride (BF3 and Ammonia (NH3 Donor-Acceptor Complex

    Directory of Open Access Journals (Sweden)

    Dulal C. Ghosh

    2004-09-01

    Full Text Available The formation of the F3B–NH3 supermolecule by chemical interaction of its fragment parts, BF3 and NH3, and the dynamics of internal rotation about the ‘B–N’ bond have been studied in terms of parameters provided by the molecular orbital and density functional theories. It is found that the pairs of frontier orbitals of the interacting fragments have matching symmetry and are involved in the charge transfer interaction. The donation process stems from the HOMO of the donor into the LUMO of the acceptor and simultaneously, back donation stems from the HOMO of acceptor into the LUMO of the donor. The density functional computation of chemical activation in the donor and acceptor fragments, associated with the physical process of structural reorganization just prior to the event of chemical reaction, indicates that BF3 becomes more acidic and NH3 becomes more basic, compared to their separate equilibrium states. Theoretically it is observed that the chemical reaction event of the formation of the supermolecule from its fragment parts is in accordance with the chemical potential equalization principle of the density functional theory and the electronegativity equalization principle of Sanderson. The energetics of the chemical reaction, the magnitude of the net charge transfer and the energy of the newly formed bond are quite consistent, both internally and with the principle of maximum hardness, PMH. The dynamics of the internal rotation of one part with respect to the other part of the supermolecule about the ‘B–N’ bond mimics the pattern of the conformational isomerism of the isostructural ethane molecule. It is also observed that the dynamics and evolution of molecular conformations as a function of dihedral angles is also in accordance with the principle of maximum hardness, PMH. Quite consistent with spectroscopic predictions, the height of the molecule

  6. Bioactivities of fish protein hydrolysates from defatted salmon backbones

    Directory of Open Access Journals (Sweden)

    Rasa Slizyte

    2016-09-01

    Full Text Available Bioactivities of bulk fish protein hydrolysates (FPH from defatted salmon backbones obtained with eight different commercial enzymes and their combinations were tested. All FPH showed antioxidative activity in vitro. DPPH scavenging activity increased, while iron chelating ability decreased with increasing time of hydrolysis. All FPH showed ACE inhibiting effect which depended on type of enzyme and increased with time of hydrolysis. The highest effect was found for FPH produced with Trypsin. Bromelain + Papain hydrolysates reduced the uptake of radiolabelled glucose into CaCo-2 cells, a model of human enterocytes, indicating a potential antidiabetic effect of FPH. FPH obtained by Trypsin, Bromelain + Papain and Protamex showed the highest ACE inhibitory, cellular glucose transporter (GLUT/SGLT inhibitory and in vitro antioxidative activities, respectively. Correlation was observed between the measured bioactivities, degree of hydrolysis and molecular weight profiles, supporting prolonged hydrolysis to obtain high bioactivities.

  7. Bioactive glasses: Frontiers and challenges

    Directory of Open Access Journals (Sweden)

    Larry L. Hench

    2015-11-01

    Full Text Available Bioactive glasses were discovered in 1969 and provided for the first time an alternative to nearly inert implant materials. Bioglass formed a rapid, strong and stable bond with host tissues. This article examines the frontiers of research crossed to achieve clinical use of bioactive glasses and glass-ceramics. In the 1980’s it was discovered that bioactive glasses could be used in particulate form to stimulate osteogenesis, which thereby led to the concept of regeneration of tissues. Later, it was discovered that the dissolution ions from the glasses behaved like growth factors, providing signals to the cells. This article summarizes the frontiers of knowledge crossed during four eras of development of bioactive glasses that have led from concept of bioactivity to widespread clinical and commercial use, with emphasis on the first composition, 45S5 Bioglass®. The four eras are: a discovery; b clinical application; c tissue regeneration; and d innovation. Questions still to be answered for the fourth era are included to stimulate innovation in the field and exploration of new frontiers that can be the basis for a general theory of bioactive stimulation of regeneration of tissues and application to numerous clinical needs.

  8. Lanthanide paramagnetic probes for NMR spectroscopic studies of fast molecular conformational dynamics and temperature control. Effective six-site proton exchange in 18-crown-6 by exchange spectroscopy.

    Science.gov (United States)

    Babailov, Sergey P

    2012-02-06

    (1)H and (13)C NMR measurements are reported for the CDCl(3) and CD(2)Cl(2) solutions of [La(18-crown-6)(NO(3))(3)] (I), [Pr(18-crown-6) (NO(3))(3)] (II), [Ce(18-crown-6)(NO(3))(3)] (III), and [Nd(18-crown-6)(NO(3))(3)] (IV) complexes. Temperature dependencies of the (1)H NMR spectra of paramagnetic II-IV have been analyzed using the dynamic NMR (DNMR) methods for six-site exchange. Two types of conformational dynamic processes were identified (the first one is conditioned by interconversion of complex enantiomeric forms and pseudorotation of a macrocycle molecule upon the C(2) symmetry axis; the second one is conditioned by macrocycle molecule inversion). Application of exchange spectroscopy (2D-EXSY) of DNMR for investigation of this dynamic system (II-IV) simplifies the assignment of the NMR signals and represents the first experimental study of multisite exchange. In the present work, the methodology of paramagnetic 4f (Ce, Pr, and Nd) probe applications for the study of free-energy, enthalpy, and entropy changes in chemical exchange processes, as well as the advantages of this method in a comparison with DNMR studies of diamagnetic substances, is discussed. In particular, as a result of paramagnetic chemical shifts in 4f complexes, the range of measurable rate constants expands considerably compared to the analogous range in diamagnetic compounds. Coordination compounds investigated in the paper represent new types of thermometric NMR sensors and lanthanide paramagnetic probes for in situ temperature control in solution.

  9. Binding, conformational transition and dimerization of amyloid-β peptide on GM1-containing ternary membrane: insights from molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Moutusi Manna

    Full Text Available Interactions of amyloid-β (Aβ with neuronal membrane are associated with the progression of Alzheimer's disease (AD. Ganglioside GM1 has been shown to promote the structural conversion of Aβ and increase the rate of peptide aggregation; but the exact nature of interaction driving theses processes remains to be explored. In this work, we have carried out atomistic-scale computer simulations (totaling 2.65 µs to investigate the behavior of Aβ monomer and dimers in GM1-containing raft-like membrane. The oligosaccharide head-group of GM1 was observed to act as scaffold for Aβ-binding through sugar-specific interactions. Starting from the initial helical peptide conformation, a β-hairpin motif was formed at the C-terminus of the GM1-bound Aβ-monomer; that didn't appear in absence of GM1 (both in fluid POPC and liquid-ordered cholesterol/POPC bilayers and also in aqueous medium within the simulation time span. For Aβ-dimers, the β-structure was further enhanced by peptide-peptide interactions, which might influence the propensity of Aβ to aggregate into higher-ordered structures. The salt-bridges and inter-peptide hydrogen bonds were found to account for dimer stability. We observed spontaneous formation of intra-peptide D(23-K(28 salt-bridge and a turn at V(24GSN(27 region - long been accepted as characteristic structural-motifs for amyloid self-assembly. Altogether, our results provide atomistic details of Aβ-GM1 and Aβ-Aβ interactions and demonstrate their importance in the early-stages of GM1-mediated Aβ-oligomerisation on membrane surface.

  10. Bioactive proteins from pipefishes

    Institute of Scientific and Technical Information of China (English)

    E. Rethna Priya; S. Ravichandran; R. Ezhilmathi

    2013-01-01

    Objective: To screen antimicrobial potence of some pipefish species collected from Tuticorin coastal environment.Methods:Antimicrobial activity of pipefishes in methanol extract was investigated against 10 bacterial and 10 fungal human pathogenic strains.Results:Among the tested strains, in Centriscus scutatus, pipefish showed maximum zone of inhibition against Vibrio cholerae (8 mm) and minimum in the sample of Hippichthys cyanospilos against Klebseilla pneumoniae (2 mm). In positive control, maximum zone of inhibition was recorded in Vibrio cholerae (9 mm) and minimum in Klebseilla pneumoniae, and Salmonella paratyphi (5 mm). Chemical investigation indicated the presence of peptides as evidenced by ninhydrin positive spots on thin layer chromatography and presence of peptide. In SDS PAGE, in Centriscus scutatus, four bands were detected in the gel that represented the presence of proteins in the range nearly 25.8-75 kDa. In Hippichthys cyanospilos, five bands were detected in the gel that represented the presence of proteins in the range nearly 20.5-78 kDa. The result of FT-IR spectrum revealed that the pipe fishes extracts compriseed to have peptide derivatives as their predominant chemical groups.Conclusions:It can be conclude that this present investigation suggests the tested pipe fishes will be a potential source of natural bioactive compounds.

  11. Study of Molecular Conformation and Activity-Related Properties of Lipase Immobilized onto Core-Shell Structured Polyacrylic Acid-Coated Magnetic Silica Nanocomposite Particles.

    Science.gov (United States)

    Esmaeilnejad-Ahranjani, Parvaneh; Kazemeini, Mohammad; Singh, Gurvinder; Arpanaei, Ayyoob

    2016-04-01

    A facile approach for the preparation of core-shell structured poly(acrylic acid) (PAA)-coated Fe3O4 cluster@SiO2 nanocomposite particles as the support materials for the lipase immobilization is reported. Low- or high-molecular-weight (1800 and 100,000, respectively) PAA molecules were covalently attached onto the surface of amine-functionalized magnetic silica nanoacomposite particles. The successful preparation of particles were verified by scanning transmission electron microscopy (STEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), thermogravimetric analysis (TGA), zeta potential measurement, and Fourier-transform infrared (FTIR) techniques. Once lipase is covalently immobilized onto the particles with an average diameter of 210 ± 50 nm, resulting from high binding sites concentrations on the low- and high-molecular-weight PAA-coated particles, high lipase immobilization efficiencies (86.2% and 89.9%, respectively), and loading capacities (786 and 816 mg g(-1), respectively) are obtained. Results from circular dichroism (CD) analysis and catalytic activity tests reveal an increase in the β-sheet content of lipase molecules upon immobilization, along with an enhancement in their activities and stabilities. The lipases immobilized onto the low- and high-molecular-weight PAA-coated particles show maximum activities at 55 and 50 °C, respectively, which are ∼28% and ∼15% higher than that of the free lipase at its own optimum temperature (40 °C), respectively. The immobilized lipases exhibit excellent performance at broader temperature and pH ranges and high thermal and storage stabilities, as well as superior reusability. These prepared magnetic nanocomposite particles can be offered as suitable support materials for efficient immobilization of enzymes and improvement of the immobilized enzymes properties.

  12. Mechanisms underlying the antihypertensive effects of garlic bioactives.

    Science.gov (United States)

    Shouk, Reem; Abdou, Aya; Shetty, Kalidas; Sarkar, Dipayan; Eid, Ali H

    2014-02-01

    Cardiovascular disease remains the leading cause of death worldwide with hypertension being a major contributing factor to cardiovascular disease-associated mortality. On a population level, non-pharmacological approaches, such as alternative/complementary medicine, including phytochemicals, have the potential to ameliorate cardiovascular risk factors, including high blood pressure. Several epidemiological studies suggest an antihypertensive effect of garlic (Allium sativum) and of many its bioactive components. The aim of this review is to present an in-depth discussion regarding the molecular, biochemical and cellular rationale underlying the antihypertensive properties of garlic and its bioactive constituents with a primary focus on S-allyl cysteine and allicin. Key studies, largely from PubMed, were selected and screened to develop a comprehensive understanding of the specific role of garlic and its bioactive constituents in the management of hypertension. We also reviewed recent advances focusing on the role of garlic bioactives, S-allyl cysteine and allicin, in modulating various parameters implicated in the pathogenesis of hypertension. These parameters include oxidative stress, nitric oxide bioavailability, hydrogen sulfide production, angiotensin converting enzyme activity, expression of nuclear factor-κB and the proliferation of vascular smooth muscle cells. This review suggests that garlic and garlic derived bioactives have significant medicinal properties with the potential for ameliorating hypertension and associated morbidity; however, further clinical and epidemiological studies are required to determine completely the specific physiological and biochemical mechanisms involved in disease prevention and management.

  13. Highly bioactive polysiloxane modified bioactive glass-poly(ethylene glycol) hybrids monoliths with controlled surface structure for bone tissue regeneration

    Science.gov (United States)

    Chen, Jing; Que, Wenxiu; Xing, Yonglei; Lei, Bo

    2015-03-01

    Crack-free monoliths with controllable surface microstructure have high bioactivities and therefore potential applications in bone tissue regeneration. In this paper, crack-free polydimethylsiloxane-modified bioactive glass-poly (ethylene glycol) (PDMS-BG-PEG) hybrids monoliths were fabricated via using a modified sol-gel process. Results show that the addition of PEG plays an important part in the formation of crack-free and gelation of the monoliths, and surface microstructures of the as-prepared hybrid monoliths were significantly influenced by the concentration and molecular weight of PEG. The samples obtained from PEG 300 had porous surface result in higher bioactivity (apatite formation) in simulated body fluid (SBF), while the samples obtained from PEG 600 had the smooth surface and inhibited the formation of apatite layer in SBF. These as-prepared hybrid monoliths can be used as a good candidate of implant and scaffold for highly efficient bone tissue regeneration.

  14. Investigating the Conformational Structure and Potential Site Interactions of SOD Inhibitors on Ec-SOD in Marine Mud Crab Scylla serrata: A Molecular Modeling Approach.

    Science.gov (United States)

    Paital, Biswaranjan; Sablok, Gaurav; Kumar, Sunil; Singh, Sanjeev Kumar; Chainy, G B N

    2016-09-01

    Superoxide dismutases (SODs) act as a first line of the enzymatic antioxidant defense system to control cellular superoxide anion toxicity. Previously, several inhibitors have been widely identified and catalogued for inhibition of SOD activity; however, still the information about the mechanism of interaction and points toward the inhibitor interactions in structures of SODs in general and in extracellular (Ec)-SOD in particular is still in naive. In the present research, we present an insight to elucidate the molecular basis of interactions of SOD inhibitors with Ec-SOD in mud crab Scylla serrata using molecular modeling and docking approaches. Different inhibitors of SOD such as hydrogen peroxide [Formula: see text], potassium cyanide, sodium dodecyl sulfate (SDS), [Formula: see text]-mercaptoethanol and dithiocarbamate were screened to understand the potential sites that may act as sites for cleavage or blocking in the protein. SOD-SDS and [Formula: see text] complex interactions indicate residues Pro72 and Asp102 of the predicted crab Ec-SOD as common targets. The GOLD result indicates that Pro72, Asp102 and Thr103 are commonly acting as the site of interaction in Ec-SOD of S. serrata with SOD inhibitors. For the first time, the results of this study provide an insight into the structural properties of Ec-SOD of S. serrata and define the possible involvements between the amino acids present in its active sites, i.e., in the regions from 70 to 84 and from 101 to 103 and different inhibitors.

  15. Influence of hyperthermophilic protein Cren7 on the stability and conformation of DNA: insights from molecular dynamics simulation and free energy analysis.

    Science.gov (United States)

    Chen, Lin; Zhang, Ji-Long; Yu, Li-Ying; Zheng, Qing-Chuan; Chu, Wen-Ting; Xue, Qiao; Zhang, Hong-Xing; Sun, Chia-Chung

    2012-10-18

    Cren7, a novel chromatin protein highly conserved among crenarchaea, plays an important role in genome packaging and gene regulation. However, the detail dynamical structural characteristic of the Cren7-DNA complex and the detail study of the DNA in the complex have not been done. Focused on two specific Cren7-DNA complexes (PDB codes 3LWH and 3LWI ), we applied molecular dynamics (MD) simulations at four different temperatures (300, 350, 400, and 450 K) and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) free energy calculation at 300 and 350 K to examine the role of Cren7 protein in enhancing the stability of DNA duplexes via protein-DNA interactions, and to study the structural transition in DNA. The simulation results indicate that Cren7 stabilizes DNA duplex in a certain temperature range in the binary complex compared with the unbound DNA molecules. At the same time, DNA molecules were found to undergo B-like to A-like form transitions with increased temperature. The results of statistical analyses of the H-bond and hydrophobic contacts show that some residues have significant influence on the structure of DNA molecules. Our work can give important information to understand the interactions of proteins with nucleic acids and other ligands.

  16. Transitive conformal holonomy groups

    CERN Document Server

    Alt, Jesse

    2011-01-01

    For $(M,[g])$ a conformal manifold of signature $(p,q)$ and dimension at least three, the conformal holonomy group $\\mathrm{Hol}(M,[g]) \\subset O(p+1,q+1)$ is an invariant induced by the canonical Cartan geometry of $(M,[g])$. We give a description of all possible connected conformal holonomy groups which act transitively on the M\\"obius sphere $S^{p,q}$, the homogeneous model space for conformal structures of signature $(p,q)$. The main part of this description is a list of all such groups which also act irreducibly on $\\R^{p+1,q+1}$. For the rest, we show that they must be compact and act decomposably on $\\R^{p+1,q+1}$, in particular, by known facts about conformal holonomy the conformal class $[g]$ must contain a metric which is locally isometric to a so-called special Einstein product.

  17. The Effect of Conformational Variability of Phosphotriesterase upon N-acyl-L-homoserine Lactone and Paraoxon Binding: Insights from Molecular Dynamics Studies

    Directory of Open Access Journals (Sweden)

    Dongling Zhan

    2013-12-01

    Full Text Available The organophosphorous hydrolase (PTE from Brevundimonas diminuta is capable of degrading extremely toxic organophosphorous compounds with a high catalytic turnover and broad substrate specificity. Although the natural substrate for PTE is unknown, its loop remodeling (loop 7-2/H254R led to the emergence of a homoserine lactonase (HSL activity that is undetectable in PTE (kcat/km values of up to 2 × 104, with only a minor decrease in PTE paraoxonase activity. In this study, homology modeling and molecular dynamics simulations have been undertaken seeking to explain the reason for the substrate specificity for the wild-type and the loop 7-2/H254R variant. The cavity volume estimated results showed that the active pocket of the variant was almost two fold larger than that of the wild-type (WT enzyme. pKa calculations for the enzyme (the WT and the variant showed a significant pKa shift from WT standard values (ΔpKa = 3.5 units for the His254residue (in the Arg254 variant. Molecular dynamics simulations indicated that the displacement of loops 6 and 7 over the active site in loop 7-2/H254R variant is useful for N-acyl-L-homoserine lactone (C4-HSL with a large aliphatic chain to site in the channels easily. Thence the expanding of the active pocket is beneficial to C4-HSL binding and has a little effect on paraoxon binding. Our results provide a new theoretical contribution of loop remodeling to the rapid divergence of new enzyme functions.

  18. New methodologies for the extraction and fractionation of bioactive carbohydrates from mulberry (Morus alba) leaves.

    Science.gov (United States)

    Rodríguez-Sánchez, Sonia; Ruiz-Aceituno, Laura; Sanz, María L; Soria, Ana C

    2013-05-15

    Pressurized liquid extraction (PLE) was applied for the first time to extract bioactive low molecular weight carbohydrates (iminosugars and inositols) from mulberry ( Morus alba ) leaves. Under optimized conditions, PLE provided a similar yield to the conventional process used to extract these bioactives, but in less time (5 vs 90 min). To remove carbohydrates that interfere with the bioactivity of iminosugars from PLE extracts, two fractionation treatments were evaluated: yeast ( Saccharomyces cerevisiae ) incubation and cation-exchange chromatography (CEC). Both methods allowed complete removal of major soluble carbohydrates (fructose, glucose, galactose, and sucrose), without affecting the content of mulberry bioactives. As an advantage over CEC, the yeast treatment preserves bioactive inositols, and it is an affordable methodology that employs food grade solvents. This work found PLE followed by yeast treatment to be an easily scalable and automatable procedure that can be implemented in the food industry.

  19. Vibrational, spectroscopic, molecular docking and density functional theory studies on N-(5-aminopyridin-2-yl)acetamide

    Science.gov (United States)

    Asath, R. Mohamed; Rekha, T. N.; Premkumar, S.; Mathavan, T.; Benial, A. Milton Franklin

    2016-12-01

    Conformational analysis was carried out for N-(5-aminopyridin-2-yl)acetamide (APA) molecule. The most stable, optimized structure was predicted by the density functional theory calculations using the B3LYP functional with cc-pVQZ basis set. The optimized structural parameters and vibrational frequencies were calculated. The experimental and theoretical vibrational frequencies were assigned and compared. Ultraviolet-visible spectrum was simulated and validated experimentally. The molecular electrostatic potential surface was simulated. Frontier molecular orbitals and related molecular properties were computed, which reveals that the higher molecular reactivity and stability of the APA molecule and further density of states spectrum was simulated. The natural bond orbital analysis was also performed to confirm the bioactivity of the APA molecule. Antidiabetic activity was studied based on the molecular docking analysis and the APA molecule was identified that it can act as a good inhibitor against diabetic nephropathy.

  20. Synthesis and in vitro bioactivity of mesoporous bioactive glass scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Shih, C.J., E-mail: cjshih@kmu.edu.tw [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chen, H.T. [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Huang, L.F. [School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Lu, P.S.; Chang, H.F. [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, I.L., E-mail: 84004@cch.org.tw [Department of Orthopaedic Surgery, Chang-Hua Christian Hospital, Changhua 500, Taiwan (China)

    2010-06-15

    The main objective of the present study was to determine the effect of thermal treatment procedures (calcination temperature, heating rate and duration time) on the synthesis of SiO{sub 2}-CaO-P{sub 2}O{sub 5} mesoporous bioactive glass scaffolds. This is accomplished by thermogravimetric analyses, Fourier transform infrared (FTIR) absorption spectra, X-ray diffraction (XRD) and by analysis of nitrogen adsorption/desorption isotherms. In vitro bioactivity can also be assessed by the cytotoxic effect of the glasses on the NIH-3T3 cell line, and by characterization of MC-3T3-E1 cell attachment.

  1. Atropoisomerismo: o efeito da quiralidade axial em substâncias bioativas Atropisomerism: the effect of the axial chirality in bioactive compounds

    Directory of Open Access Journals (Sweden)

    Anderson Rouge dos Santos

    2007-02-01

    Full Text Available Atropisomerism is a special kind of stereoisomeric relationship that arises from the freezing of a certain conformation of an organic molecule, associated with a high rotational barrier about a single covalent bond. Atropisomerism has been originally described in orto-functionalyzed biphenyl derivatives, but a lot of other organic functionalities can present this structural phenomenon, characterized by the presence of chiral properties in compounds that don't present classical stereogenic centers. Atropisomeric compounds, intermediates and catalysts have well-know importance in organic synthesis, but the influence of the axial chirality in substances able to modulate biological systems is still not very exploited in drug design and development. In this context, the present account describes the importance of this structural property in the medicinal chemistry of different classes of bioactive compounds or therapeutic agents, emphasizing how atropisomerism could affect the molecular recognition of a ligand or a prototype by the target bioreceptor.

  2. Conformational elasticity theory of chain molecules

    Institute of Scientific and Technical Information of China (English)

    YANG; Xiaozhen

    2001-01-01

    This paper develops a conformational elasticity theory of chain molecules, which is based on three key points: (ⅰ) the molecular model is the rotational isomeric state (RIS) model; (ⅱ) the conformational distribution function of a chain molecule is described by a function of two variables, the end-to-end distance of a chain conformation and the energy of the conformation; (ⅲ) the rule of changes in the chain conformational states during deformation is that a number of chain conformations would vanish. The ideal deformation behavior calculated by the theory shows that the change in chain conformations is physically able to make the upward curvature of the stress-strain curve at the large-scale deformation of natural rubber. With the theory, different deformation behaviors between polymers with different chemical structures can be described, the energy term of the stress in the deformations can be predicted, and for natural rubber the fraction of the energy term is around 13%, coinciding with the experimental results.

  3. Bioactive Polymeric Materials for Tissue Repair

    Directory of Open Access Journals (Sweden)

    Diane R. Bienek

    2017-01-01

    Full Text Available Bioactive polymeric materials based on calcium phosphates have tremendous appeal for hard tissue repair because of their well-documented biocompatibility. Amorphous calcium phosphate (ACP-based ones additionally protect against unwanted demineralization and actively support regeneration of hard tissue minerals. Our group has been investigating the structure/composition/property relationships of ACP polymeric composites for the last two decades. Here, we present ACP’s dispersion in a polymer matrix and the fine-tuning of the resin affects the physicochemical, mechanical, and biological properties of ACP polymeric composites. These studies illustrate how the filler/resin interface and monomer/polymer molecular structure affect the material’s critical properties, such as ion release and mechanical strength. We also present evidence of the remineralization efficacy of ACP composites when exposed to accelerated acidic challenges representative of oral environment conditions. The utility of ACP has recently been extended to include airbrushing as a platform technology for fabrication of nanofiber scaffolds. These studies, focused on assessing the feasibility of incorporating ACP into various polymer fibers, also included the release kinetics of bioactive calcium and phosphate ions from nanofibers and evaluate the biorelevance of the polymeric ACP fiber networks. We also discuss the potential for future integration of the existing ACP scaffolds into therapeutic delivery systems used in the precision medicine field.

  4. Investigating the influence of effective parameters on molecular characteristics of bovine serum albumin nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Rohiwal, S.S.; Satvekar, R.K.; Tiwari, A.P.; Raut, A.V.; Kumbhar, S.G.; Pawar, S.H., E-mail: pawar_s_h@yahoo.com

    2015-04-15

    Graphical abstract: The physiochemical properties of nanoparticles provide the basic aspects about the conformational transitions which could have a strong bearing on the bioavailability for bioactive molecules such as peptides and hormones. - Highlights: • Synthesis and surface and structural properties of Bovine Serum Albumin nanoparticles (BSANPs). • Study of conformational transitions of BSANPs by spectroscopic techniques. • Studies on the effect of pH and protein concentration on formulation of BSANPs. - Abstract: The protein nanoparticles formulation is a challenging task as they are prone to undergo conformational transitions while processing which may affect bioavailability for bioactive compounds. Herein, a modified desolvation method is employed to prepare Bovine Serum Albumin nanoparticles, with controllable particle size ranging from 100 to 300 nm and low polydispersity index. The factors influencing the size and structure of BSA NPs viz. protein concentration, pH and the conditions for purification are well investigated. The structure of BSA NPs is altered due to processing, and may affect the effective binding ability with drugs and bioactive compounds. With that aims, investigations of molecular characteristics of BSA NPs are carried out in detail by using spectroscopic techniques. UV–visible absorption and Fourier Transform Infrared demonstrate the alteration in protein structure of BSA NPs whereas the FT-Raman spectroscopy investigates changes in the secondary and tertiary structures of the protein. The conformational changes of BSA NPs are observed by change in fluorescence intensity and emission maximum wavelength of tryptophan residue by fluorescence spectroscopy. The field emission scanning electron and atomic force microscopy micrographs confirm the size and semi-spherical morphology of the BSA NPs. The effect of concentration and pH on particle size distribution is studied by particle size analyzer.

  5. Bioactive Nutrients and Nutrigenomics in Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Tania Rescigno

    2017-01-01

    Full Text Available The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the “omics” technologies (transcriptomics, proteomics and metabolomics are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

  6. S-Adenosylmethionine conformations in solution and in protein complexes: Conformational influences of the sulfonium group

    DEFF Research Database (Denmark)

    Markham, George D.; Norrby, Per-Ola; Bock, Charles W.

    2002-01-01

    S-Adenosylmethionine (AdoMet) and other sulfonium ions play central roles in the metabolism of all organisms. The conformational preferences of AdoMet and two other biologically important sulfonium ions, S-methylmethionine and dimethylsulfonioproprionic acid, have been investigated by NMR...... and computational studies. Molecular mechanics parameters for the sulfonium center have been developed for the AMBER force field to permit analysis of NMR results and to enable comparison of the relative energies of the different conformations of AdoMet that have been found in crystal structures of complexes...... with proteins. S-Methylmethionine and S-dimethylsulfonioproprionate adopt a variety of conformations in aqueous solution; a conformation with an electrostatic interaction between the sulfonium sulfur and the carboxylate group is not noticeably favored, in contrast to the preferred conformation found by in vacuo...

  7. Bioactivity of Minor Milk Components

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh

    . In particular, 3-15% of very low birth weight preterm infants suffer from the most servere form of intestinal inflammation, known as necrotizing enterocolitis (NEC). This disease is incurable with a high mortality rate of 15-30%. Mother’s breast milk consists of different bioactive constituents...... several steps of thermal processing, which are known to decrease/abolish bioactivity of milk constituents. This may explain for high NEC incidence in formula-fed preterm infants. We therefore in this PhD project investigated whether gentle thermal processing conditions increase the bioavailability...... of infant formula. Thereafter, bioactive milk components which were preserved in gently-processed infant formula were selected for further investigation of their immunomodulatory activity in cell and preterm pig models. We hope this project will contribute to the research on the development of new...

  8. [Dosimetric evaluation of conformal radiotherapy: conformity factor].

    Science.gov (United States)

    Oozeer, R; Chauvet, B; Garcia, R; Berger, C; Felix-Faure, C; Reboul, F

    2000-01-01

    The aim of three-dimensional conformal therapy (3DCRT) is to treat the Planning Target Volume (PTV) to the prescribed dose while reducing doses to normal tissues and critical structures, in order to increase local control and reduce toxicity. The evaluation tools used for optimizing treatment techniques are three-dimensional visualization of dose distributions, dose-volume histograms, tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP). These tools, however, do not fully quantify the conformity of dose distributions to the PTV. Specific tools were introduced to measure this conformity for a given dose level. We have extended those definitions to different dose levels, using a conformity index (CI). CI is based on the relative volumes of PTV and outside the PTV receiving more than a given dose. This parameter has been evaluated by a clinical study including 82 patients treated for lung cancer and 82 patients treated for prostate cancer. The CI was low for lung dosimetric studies (0.35 at the prescribed dose 66 Gy) due to build-up around the GTV and to spinal cord sparing. For prostate dosimetric studies, the CI was higher (0.57 at the prescribed dose 70 Gy). The CI has been used to compare treatment plans for lung 3DCRT (2 vs 3 beams) and prostate 3DCRT (4 vs 7 beams). The variation of CI with dose can be used to optimize dose prescription.

  9. Conformational stability of calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, C.S.; Trandum, C.; Larsen, N.

    2005-01-01

    The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (T-m) increased from 31 degrees C at pH 5 to 51 degrees C at pH 9, but electrophoretic analysis revealed that calreticulin oligomerized instead of unfolding. Structural analyses showed that the single C......-terminal a-helix was of major importance to the conformational stability of calreticulin....

  10. Conformational stability of calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte S; Trandum, Christa; Larsen, Nanna Brink

    2005-01-01

    The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (Tm) increased from 31 degrees C at pH 5 to 51 degrees C at pH 9, but electrophoretic analysis revealed that calreticulin oligomerized instead of unfolding. Structural analyses showed that the single C......-terminal alpha-helix was of major importance to the conformational stability of calreticulin....

  11. Preparation and bioactivity of sol-gel macroporous bioactive glass

    Institute of Scientific and Technical Information of China (English)

    Zhihua Zhou; Jianming Ruan; Jianpeng Zou; Zhongcheng Zhou

    2008-01-01

    Bioactive glass is well known for its ability of bone regeneration, and sol-gel bioactive glass has many advantages com-pared with melt-derived bioactive glass. 3-D scaffold prepared by the sol-gel method is a promising substrate material for bone tissue engineering and large-scale bone repair. Porous sol-gel glass in the CaO-SiO2-P2O5 system with macropores larger than 100 μm was prepared by the addition of stearic acid as a pore former. The diameter of the pore created by the pore former varied from 100 to 300μm. The formation of a hydroxyapatite layer on the glass was analyzed by studying the surface of the porous glass by scanning elec-tron microscopy, energy dispersive spectroscopy, X-ray diffraction, and Raman spectra after they had been immersed in simulated body fluid (SBF) for some time, and the porous glass shows good bioactivity.

  12. An in silico study on antidiabetic activity of bioactive compounds in Euphorbia thymifolia Linn.

    Science.gov (United States)

    Nguyen Vo, T Hoang; Tran, Ngan; Nguyen, Dat; Le, Ly

    2016-01-01

    Herbal medicines have become strongly preferred treatment to reduce the negative impacts of diabetes mellitus (DM) and its severe complications due to lesser side effects and low cost. Recently, strong anti-hyperglycemic effect of Euphorbia thymifolia Linn. (E. thymifolia) on mice models has reported but the action mechanism of its bioactive compounds has remained unknown. This study aimed to evaluate molecular interactions existing between various bioactive compounds in E. thymifolia and targeted proteins related to Type 2 DM. This process involved the molecular docking of 3D structures of those substances into 4 targeted proteins: 11-β hydroxysteroid dehydrogenase type 1, glutamine: fructose-6-phosphate amidotransferase, protein-tyrosine phosphatase 1B and mono-ADP-ribosyltransferase sirtuin-6. In the next step, LigandScout was applied to evaluate the bonds formed between 20 ligands and the binding sites of each targeted proteins. The results identified seven bioactive compounds with high binding affinity (bioactive compounds, in silico approach is performed.

  13. Conformational, NBO, NLO, HOMO-LUMO, NMR, electronic spectral study and molecular docking study of N,N-Dimethyl-3-(10H-phenothiazin-10-yl)-1-propanamine

    Science.gov (United States)

    Resmi, K. S.; Haruna, Kabiru; Mary, Y. Sheena; Panicker, C. Yohannan; Saleh, Tawfik A.; Al-Saadi, Abdulaziz A.; Van Alsenoy, Christian

    2016-10-01

    FT-IR and FT-Raman spectra of N,N-Dimethyl-3-(10H-phenothiazin-10-yl)-1-propanamine were recorded and analyzed. The conformational behaviour is also investigated. The vibrational wave numbers were calculated using density functional quantum chemical calculations. The data obtained from wave number calculations are used to assign vibrational bands obtained experimentally. In the most stable form for N,N-Dimethyl-3-(10H-phenothiazin-10-yl)-1-propanamine, the nitrogen atom of the phenothiazine ring is predicted to adopt an expanded pyramidal configuration with an average Csbnd Nsbnd C angle of 118° while the alkylamine chain points away from the phenothiazine ring. The geometrical parameters are compared with related structures. The stability of the molecule arising from hyper conjugative interaction and charge delocalization has been analyzed using natural bonding orbital analysis. The frontier molecular orbital analysis is used to determine the charge transfer within the molecule. The theoretical NMR spectral analysis, Fukui functions and electronic transition UV-Vis spectral analysis is also reported. The docked title compound forms a stable complex with Plasmodium falciparum and gives a binding affinity value of -6.8 kcal/mol and the results suggest that the compound might exhibit inhibitory activity against Plasmodium falciparum.

  14. Bioactive proteins and peptides isolated from Chinese medicines with pharmaceutical potential

    Science.gov (United States)

    2014-01-01

    Some protein pharmaceuticals from Chinese medicine have been developed to treat cardiovascular diseases, genetic diseases, and cancer. Bioactive proteins with various pharmacological properties have been successfully isolated from animals such as Hirudo medicinalis (medicinal leech), Eisenia fetida (earthworm), and Mesobuthus martensii (Chinese scorpion), and from herbal medicines derived from species such as Cordyceps militaris, Ganoderma, Momordica cochinchinensis, Viscum album, Poria cocos, Senna obtusifolia, Panax notoginseng, Smilax glabra, Ginkgo biloba, Dioscorea batatas, and Trichosanthes kirilowii. This article reviews the isolation methods, molecular characteristics, bioactivities, pharmacological properties, and potential uses of bioactive proteins originating from these Chinese medicines. PMID:25067942

  15. Bioactive glasses potential biomaterials for future therapy

    CERN Document Server

    Kaur, Gurbinder

    2017-01-01

    This book describes the history, origin and basic characteristics of bioactive materials. It includes a chapter dedicated to hydroxyapatite mineral, its formation and its bioactive properties. The authors address how cytotoxicity is a determining step for bioactivity. Applications of bioactive materials in the contexts of tissue regeneration, bone regeneration and cancer therapy are also covered. Silicate, metallic and mesoporous glasses are described, as well as the challenges and future prospects of research in this field.

  16. [Conformation theory of polymers and biopolymers].

    Science.gov (United States)

    Volkenstein, M V

    1977-01-01

    A short review is given of the Soviet investigations in the field of physics of polymers and biopolymers based on the concept of conformational motility of macromolecules. It is shown that the ideas originally used for the treatment of the properties of the synthetic polymers and, in particular, of the rubber elasticity, have found broad applications in molecular biophysics.

  17. Case Studies of the Synthesis of Bioactive Cyclodepsipeptide Natural Products

    Directory of Open Access Journals (Sweden)

    Markus Kaiser

    2013-01-01

    Full Text Available Cyclodepsipeptide natural products often display intriguing biological activities that along with their complex molecular scaffolds, makes them interesting targets for chemical synthesis. Although cyclodepsipeptides feature highly diverse chemical structures, their synthesis is often associated with similar synthetic challenges such as the establishment of a suitable macrocyclization methodology. This review therefore compiles case studies of synthetic approaches to different bioactive cyclodepsipeptide natural products, thereby illustrating obstacles of cyclodepsipeptide synthesis as well as their overcomings.

  18. Investigation on the low energy conformational surface of tabun to probe the role of its different conformers on biological activity

    Science.gov (United States)

    Paukku, Yuliya; Michalkova, Andrea; Majumdar, D.; Leszczynski, Jerzy

    2006-05-01

    Conformational studies have been carried out on the two different enantiomers of tabun at the density functional and second order Møller-Plesset perturbation levels of theory to generate low energy potential energy surfaces in the gas phase as well as in aqueous environment. The structures of the low energy conformers together with their molecular electrostatic potential surfaces have been compared with those of the non-aged acetylcholinesterase-tabun complex to locate the active conformer of this molecule.

  19. EC declaration of conformity.

    Science.gov (United States)

    Donawa, M E

    1996-05-01

    The CE-marking procedure requires that manufacturers draw up a written declaration of conformity before placing their products on the market. However, some companies do not realize that this is a requirement for all devices. Also, there is no detailed information concerning the contents and format of the EC declaration of conformity in the medical device Directives or in EC guidance documentation. This article will discuss some important aspects of the EC declaration of conformity and some of the guidance that is available on its contents and format.

  20. Influence of Tableting on the Conformation and Thermal Stability of Trypsin as a Model Protein

    DEFF Research Database (Denmark)

    Klukkert, Marten; Van De Weert, Marco; Fanø, Mathias;

    2015-01-01

    reversible upon tablet reconstitution. Aqueous-state IR spectroscopy combined with partial least squares was shown to be a powerful tool to follow irreversible structural changes and evaluate sample bioactivity. Besides its conformation, the thermal stability of trypsin was altered as a result of the applied...

  1. Animal culture: chimpanzee conformity?

    Science.gov (United States)

    van Schaik, Carel P

    2012-05-22

    Culture-like phenomena in wild animals have received much attention, but how good is the evidence and how similar are they to human culture? New data on chimpanzees suggest their culture may even have an element of conformity.

  2. Conformal expansions and renormalons

    CERN Document Server

    Gardi, E; Gardi, Einan; Grunberg, Georges

    2001-01-01

    The large-order behaviour of QCD is dominated by renormalons. On the other hand renormalons do not occur in conformal theories, such as the one describing the infrared fixed-point of QCD at small beta_0 (the Banks--Zaks limit). Since the fixed-point has a perturbative realization, all-order perturbative relations exist between the conformal coefficients, which are renormalon-free, and the standard perturbative coefficients, which contain renormalons. Therefore, an explicit cancellation of renormalons should occur in these relations. The absence of renormalons in the conformal limit can thus be seen as a constraint on the structure of the QCD perturbative expansion. We show that the conformal constraint is non-trivial: a generic model for the large-order behaviour violates it. We also analyse a specific example, based on a renormalon-type integral over the two-loop running-coupling, where the required cancellation does occur.

  3. Conformally Coupled Inflation

    Directory of Open Access Journals (Sweden)

    Valerio Faraoni

    2013-07-01

    Full Text Available A massive scalar field in a curved spacetime can propagate along the light cone, a causal pathology, which can, in principle, be eliminated only if the scalar couples conformally to the Ricci curvature of spacetime. This property mandates conformal coupling for the field driving inflation in the early universe. During slow-roll inflation, this coupling can cause super-acceleration and, as a signature, a blue spectrum of primordial gravitational waves.

  4. Delineating the conformal window

    DEFF Research Database (Denmark)

    Frandsen, Mads Toudal; Pickup, Thomas; Teper, Michael

    2011-01-01

    We identify and characterise the conformal window in gauge theories relevant for beyond the standard model building, e.g. Technicolour, using the criteria of metric confinement and causal analytic couplings, which are known to be consistent with the phase diagram of supersymmetric QCD from Seiberg...... duality. Using these criteria we find perturbation theory to be consistent throughout the predicted conformal window for several of these gauge theories and we discuss recent lattice results in the light of our findings....

  5. Conformism and Wealth Distribution

    OpenAIRE

    Mino, Kazuo; Nakamoto, Yasuhiro

    2014-01-01

    This paper explores the role of consumption externalities in a neoclassical growth model in which households have heterogeneous preferences. We fi?nd that the degree of conformism in consumption held by each household signifi?cantly affects the speed of convergence of the aggregate economy as well as the patterns of wealth distribution in the steady state equilibrium. In particular, a higher degree of consumption conformism accelerates the convergence speed of the economy towards the steady s...

  6. Quantum massive conformal gravity

    Energy Technology Data Exchange (ETDEWEB)

    Faria, F.F. [Universidade Estadual do Piaui, Centro de Ciencias da Natureza, Teresina, PI (Brazil)

    2016-04-15

    We first find the linear approximation of the second plus fourth order derivative massive conformal gravity action. Then we reduce the linearized action to separated second order derivative terms, which allows us to quantize the theory by using the standard first order canonical quantization method. It is shown that quantum massive conformal gravity is renormalizable but has ghost states. A possible decoupling of these ghost states at high energies is discussed. (orig.)

  7. Conformally coupled inflation

    CERN Document Server

    Faraoni, Valerio

    2013-01-01

    A massive scalar field in a curved spacetime can propagate along the light cone, a causal pathology, which can, in principle, be eliminated only if the scalar couples conformally to the Ricci curvature of spacetime. This property mandates conformal coupling for the field driving inflation in the early universe. During slow-roll inflation, this coupling can cause super-acceleration and, as a signature, a blue spectrum of primordial gravitational waves.

  8. Optimization of a polymer composite employing molecular mechanic simulations and artificial neural networks for a novel intravaginal bioadhesive drug delivery device.

    Science.gov (United States)

    Ndesendo, Valence M K; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Buchmann, Eckhart; Meyer, Leith C R; Khan, Riaz A

    2012-01-01

    This study aimed at elucidating an optimal synergistic polymer composite for achieving a desirable molecular bioadhesivity and Matrix Erosion of a bioactive-loaded Intravaginal Bioadhesive Polymeric Device (IBPD) employing Molecular Mechanic Simulations and Artificial Neural Networks (ANN). Fifteen lead caplet-shaped devices were formulated by direct compression with the model bioactives zidovudine and polystyrene sulfonate. The Matrix Erosion was analyzed in simulated vaginal fluid to assess the critical integrity. Blueprinting the molecular mechanics of bioadhesion between vaginal epithelial glycoprotein (EGP), mucin (MUC) and the IBPD were performed on HyperChem 8.0.8 software (MM+ and AMBER force fields) for the quantification and characterization of correlative molecular interactions during molecular bioadhesion. Results proved that the IBPD bioadhesivity was pivoted on the conformation, orientation, and poly(acrylic acid) (PAA) composition that interacted with EGP and MUC present on the vaginal epithelium due to heterogeneous surface residue distributions (free energy= -46.33 kcalmol(-1)). ANN sensitivity testing as a connectionist model enabled strategic polymer selection for developing an IBPD with an optimally prolonged Matrix Erosion and superior molecular bioadhesivity (ME = 1.21-7.68%; BHN = 2.687-4.981 N/mm(2)). Molecular modeling aptly supported the EGP-MUC-PAA molecular interaction at the vaginal epithelium confirming the role of PAA in bioadhesion of the IBPD once inserted into the posterior fornix of the vagina.

  9. Molecular Conformations of Araneus Ventricosus Spider's Dragline Silk in the Spinning Process%大腹园蛛牵引丝在纺丝过程中的分子构象

    Institute of Scientific and Technical Information of China (English)

    潘志娟; 刘敏; 许箐

    2003-01-01

    The Circular dichroism(CD) spectrum of spider silk fibroin of Araneus Ventricosus major ampullate glands was measured,which indicated that the molecular conformations of spider silk in solution were primarily random coils and β-sheets.The Raman spectra were recorded for dragline silks next to the spigot and spun by a dropping spider.The results showed thatrandom coils were transformed into α-helix in the spider spinning process,andthat β-sheet orientation in dragline silk of a dropping spider was better than that of at the spigot because of dragging in air.The multiplicity of molecularstructures contributed excellent mechanical properties of dragline silk.%利用圆二色光谱测定大腹园蛛的丝蛋白,结果显示蜘蛛丝溶液中的构象最初是无规卷曲和β折叠,同时用拉曼光谱对蜘蛛吐丝口附近的牵引丝及垂直下落的蜘蛛牵引丝进行比较,结果表明在蜘蛛纺丝过程中无规卷曲转变为α螺旋,并且垂直下落的蜘蛛牵引丝由于受到空气中的拉伸其β折叠取向比吐丝口附近的牵引丝好.这些分子结构的多样性决定了蜘蛛牵引丝优异的机械性能.

  10. Conformational Analysis of Poly-2,5-Benzimidazole (ABPBI), Poly-2,5- Benzoxazole (ABPBO), and Poly-2,6-Benzothiazole (ABPBT) Dimers by the Modified Neglect of Diatomic Overlap (MNDO) and Austin Method 1 (AM1) Semiempirical Molecular Orbital Methods

    Science.gov (United States)

    1987-07-01

    AFWAL-TR-87-4034 A\\) CONFORMATIONAL ANALYSIS OF POLY-2,5-BENZOIMIDAZOLE (ABPBI), POLY-2,5-BENZOXAZOLE (ABPBO), AND POLY-2,6- BENZOTHIAZOLE (ABPBT... benzothiazole Molecular Orbital 19. ABSTRACT (Continue on reverse if necessar and identif-y by block number) The two repeat unit analogs of three, aromatic...SECURITY CLASSIFICATION OF THIS PAGE 11. TITLE (Cont) Poly-2,5-benzoxazole (ABPBO), and Poly-2,6- benzothiazole (ABPBT) Dimers by the Modified Neglect

  11. Conformation of 1,2-Dimethoxyethane in Water

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To understand the conformation of 1,2-dimethoxyethane (DME) in water, a system of two kinds of molecules, DME and H2O, was focused. The interaction of various conformers of DME with water was studied by means of ab initio molecular orbital calculation with 6-31G(d)basis set. It is shown that there are two forms of interactions between the two molecules in the sys tem, the close touched (H2O attaches to the two oxygen atoms of DME) and the open touched (H2O attaches to one oxygen atom of DME) structures. The conformation of DME is remark ably influenced by the interactions. Instead the ttt conformer is preferred in the gas state, with a close touched H2O the tgt conformer becomes the most stable one. The obtained hydration ener gies show that the stabilized order of DME conformers by water is tgt>tgg'>ttt.

  12. In situ regeneration of bioactive coatings enabled by an evolved Staphylococcus aureus sortase A

    Science.gov (United States)

    Ham, Hyun Ok; Qu, Zheng; Haller, Carolyn A.; Dorr, Brent M.; Dai, Erbin; Kim, Wookhyun; Liu, David R.; Chaikof, Elliot L.

    2016-04-01

    Surface immobilization of bioactive molecules is a central paradigm in the design of implantable devices and biosensors with improved clinical performance capabilities. However, in vivo degradation or denaturation of surface constituents often limits the long-term performance of bioactive films. Here we demonstrate the capacity to repeatedly regenerate a covalently immobilized monomolecular thin film of bioactive molecules through a two-step stripping and recharging cycle. Reversible transpeptidation by a laboratory evolved Staphylococcus aureus sortase A (eSrtA) enabled the rapid immobilization of an anti-thrombogenic film in the presence of whole blood and permitted multiple cycles of film regeneration in vitro that preserved its biological activity. Moreover, eSrtA transpeptidation facilitated surface re-engineering of medical devices in situ after in vivo implantation through removal and restoration film constituents. These studies establish a rapid, orthogonal and reversible biochemical scheme to regenerate selective molecular constituents with the potential to extend the lifetime of bioactive films.

  13. Target identification of natural products and bioactive compounds using affinity-based probes.

    Science.gov (United States)

    Pan, Sijun; Zhang, Hailong; Wang, Chenyu; Yao, Samantha C L; Yao, Shao Q

    2016-05-04

    Covering: 2010 to 2014.Advances in isolation, synthesis and screening strategies have made many bioactive substances available. However, in most cases their putative biological targets remain unknown. Herein, we highlight recent advances in target identification of natural products and bioactive compounds by using affinity-based probes. Aided by photoaffinity labelling, this strategy can capture potential cellular targets (on and off) of a natural product or bioactive compound in live cells directly, even when the compound-target interaction is reversible with moderate affinity. The knowledge of these targets may help uncover molecular pathways and new therapeutics for currently untreatable diseases. In this highlight, we will introduce the development of various photoactivatable groups, their synthesis and applications in target identification of natural products and bioactive compounds, with a focus on work done in recent years and from our laboratory. We will further discuss the strengths and weaknesses of each group and the outlooks for this novel proteome-wide profiling strategy.

  14. Systematic mining of generally recognized as safe (GRAS) flavor chemicals for bioactive compounds.

    Science.gov (United States)

    Martinez-Mayorga, Karina; Peppard, Terry L; López-Vallejo, Fabian; Yongye, Austin B; Medina-Franco, José L

    2013-08-07

    Bioactive food compounds can be both therapeutically and nutritionally relevant. Screening strategies are widely employed to identify bioactive compounds from edible plants. Flavor additives contained in the so-called FEMA GRAS (generally recognized as safe) list of approved flavoring ingredients is an additional source of potentially bioactive compounds. This work used the principles of molecular similarity to identify compounds with potential mood-modulating properties. The ability of certain GRAS molecules to inhibit histone deacetylase-1 (HDAC1), proposed as an important player in mood modulation, was assayed. Two GRAS chemicals were identified as HDAC1 inhibitors in the micromolar range, results similar to what was observed for the structurally related mood prescription drug valproic acid. Additional studies on bioavailability, toxicity at higher concentrations, and off-target effects are warranted. The methodology described in this work could be employed to identify potentially bioactive flavor chemicals present in the FEMA GRAS list.

  15. Hot Conformal Gauge Theories

    DEFF Research Database (Denmark)

    Mojaza, Matin; Pica, Claudio; Sannino, Francesco

    2010-01-01

    in such a way that the theory develops a perturbative stable infrared fixed point at zero temperature. Due to large distance conformality we trade the coupling constant with its fixed point value and define a reduced free energy which depends only on the number of flavors, colors and matter representation. We...... show that the reduced free energy changes sign, at the second, fifth and sixth order in the coupling, when decreasing the number of flavors from the upper end of the conformal window. If the change in sign is interpreted as signal of an instability of the system then we infer a critical number...... of flavors. Surprisingly this number, if computed to the order g^2, agrees with previous predictions for the lower boundary of the conformal window for nonsupersymmetric gauge theories. The higher order results tend to predict a higher number of critical flavors. These are universal properties, i...

  16. Boundary Conformal Field Theory

    CERN Document Server

    Cardy, J L

    2004-01-01

    Boundary conformal field theory (BCFT) is simply the study of conformal field theory (CFT) in domains with a boundary. It gains its significance because, in some ways, it is mathematically simpler: the algebraic and geometric structures of CFT appear in a more straightforward manner; and because it has important applications: in string theory in the physics of open strings and D-branes, and in condensed matter physics in boundary critical behavior and quantum impurity models. In this article, however, I describe the basic ideas from the point of view of quantum field theory, without regard to particular applications nor to any deeper mathematical formulations.

  17. Hierarchical Structures and Shaped Particles of Bioactive Glass and Its In Vitro Bioactivity

    Directory of Open Access Journals (Sweden)

    U. Boonyang

    2013-01-01

    Full Text Available In this study, bioactive glass particles with controllable structure and porosity were prepared using dual-templating methods. Block copolymers used as one template component produced mesopores in the calcined samples. Polymer colloidal crystals as the other template component yielded either three-dimensionally ordered macroporous (3DOM products or shaped bioactive glass nanoparticles. The in vitro bioactivity of these bioactive glasses was studied by soaking the samples in simulated body fluid (SBF at body temperature (37°C for varying lengths of time and monitoring the formation of bone-like apatite on the surface of the bioactive glass. A considerable bioactivity was found that all of bioactive glass samples have the ability to induce the formation of an apatite layer on its surface when in contact with SBF. The development of bone-like apatite is faster for 3DOM bioactive glasses than for nanoparticles.

  18. Synthesis and characterization of TEP-EDTA-regulated bioactive hydroxyapatite

    Science.gov (United States)

    Haders, Daniel Joseph, II

    Hydroxyapatite (HA), Ca10(PO4)6(OH) 2, the stoichiometric equivalent of the ceramic phase of bone, is the preferred material for hard tissue replacement due to its bioactivity. However, bioinert metals are utilized in load-bearing orthopedic applications due to the poor mechanical properties of HA. Consequently, attention has been given to HA coatings for metallic orthopedic implants to take advantage of the bioactivity of HA and the mechanical properties of metals. Commercially, the plasma spray process (PS-HA) is the method most often used to deposit HA films on metallic implants. Since its introduction in the 1980's, however, concerns have been raised about the consequences of PS-HA's low crystallinity, lack of phase purity, lack of film-substrate chemical adhesion, passivation properties, and difficulty in coating complex geometries. Thus, there is a need to develop inexpensive reproducible next-generation HA film deposition techniques, which deposit high crystallinity, phase pure, adhesive, passivating, conformal HA films on clinical metallic substrates. The aim of this dissertation was to intelligently synthesize and characterize the material and biological properties of HA films on metallic substrates synthesized by hydrothermal crystallization, using thermodynamic phase diagrams as the starting point. In three overlapping interdisciplinary studies the potential of using ethylenediamine-tetraacetic acid/triethyl phosphate (EDTA/TEP) doubly regulated hydrothermal crystallization to deposit HA films, the TEP-regulated, time-and-temperature-dependent process by which films were deposited, and the bioactivity of crystallographically engineered films were investigated. Films were crystallized in a 0.232 molal Ca(NO3)2-0.232 molal EDTA-0.187 molal TEP-1.852 molal KOH-H2O chemical system at 200°C. Thermodynamic phase diagrams demonstrated that the chosen conditions were expected to produce Ca-P phase pure HA, which was experimentally confirmed. EDTA regulation of

  19. Bioactive glasses materials, properties and applications

    CERN Document Server

    Ylänen, Heimo

    2011-01-01

    Due to their biocompatibility and bioactivity, bioactive glasses are used as highly effective implant materials throughout the human body to replace or repair damaged tissue. As a result, they have been in continuous use since shortly after their invention in the late 1960s and are the subject of extensive research worldwide.Bioactive glasses provides readers with a detailed review of the current status of this unique material, its properties, technologies and applications. Chapters in part one deal with the materials and mechanical properties of bioactive glass, examining topics such

  20. Conformal General Relativity

    CERN Document Server

    Pervushin, V

    2001-01-01

    The inflation-free solution of problems of the modern cosmology (horizon, cosmic initial data, Planck era, arrow of time, singularity,homogeneity, and so on) is considered in the conformal-invariant unified theory given in the space with geometry of similarity where we can measure only the conformal-invariant ratio of all quantities. Conformal General Relativity is defined as the $SU_c(3)\\times SU(2)\\times U(1)$-Standard Model where the dimensional parameter in the Higgs potential is replaced by a dilaton scalar field described by the negative Penrose-Chernikov-Tagirov action. Spontaneous SU(2) symmetry breaking is made on the level of the conformal-invariant angle of the dilaton-Higgs mixing, and it allows us to keep the structure of Einstein's theory with the equivalence principle. We show that the lowest order of the linearized equations of motion solves the problems mentioned above and describes the Cold Universe Scenario with the constant temperature T and z-history of all masses with respect to an obser...

  1. Conformal cloak for waves

    CERN Document Server

    Chen, Huanyang; Tyc, Tomas

    2011-01-01

    Conformal invisibility devices are only supposed to work within the validity range of geometrical optics. Here we show by numerical simulations and analytical arguments that for certain quantized frequencies they are nearly perfect even in a regime that clearly violates geometrical optics. The quantization condition follows from the analogy between the Helmholtz equation and the stationary Schrodinger equation.

  2. Conformal supermultiplets without superpartners

    CERN Document Server

    Jarvis, Peter

    2011-01-01

    We consider polynomial deformations of Lie superalgebras and their representations. For the class A(n-1,0) ~ sl(n/1), we identify families of superalgebras of quadratic and cubic type, consistent with Jacobi identities. For such deformed superalgebras we point out the possibility of zero step supermultiplets, carried on a single, irreducible representation of the even (Lie) subalgebra. For the conformal group SU(2,2) in 1+3-dimensional spacetime, such irreducible (unitary) representations correspond to standard conformal fields (j_1,j_2;d), where (j_1,j_2) is the spin and d the conformal dimension; in the massless class j_1 j_2=0, and d=j_1+j_2+1. We show that these repesentations are zero step supermultiplets for the superalgebra SU_(2)(2,2/1), the quadratic deformation of conformal supersymmetry SU(2,2/1). We propose to elevate SU_(2)(2,2/1) to a symmetry of the S-matrix. Under this scenario, low-energy standard model matter fields (leptons, quarks, Higgs scalars and gauge fields) descended from such confor...

  3. A CONFORMATIONAL ELASTICITY THEORY

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    A new statistical theory based on the rotational isomeric state model describing the chain conformational free energy has been proposed. This theory can be used to predict different tensions of rubber elongation for chemically different polymers, and the energy term during the elongation of natural rubber coincides with the experimental one.

  4. Conformational changes in biopolymers

    Science.gov (United States)

    Ivanov, Vassili

    2005-12-01

    Biopolymer conformational changes are involved in many biological processes. This thesis summarizes some theoretical and experimental approaches which I have taken at UCLA to explore conformational changes in biopolymers. The reversible thermal denaturation of the DNA double helix is, perhaps, the simplest example of biopolymer conformational change. I have developed a statistical mechanics model of DNA melting with reduced degrees of freedom, which allows base stacking interaction to be taken into account and treat base pairing and stacking separately. Unlike previous models, this model describes both the unpairing and unstacking parts of the experimental melting curves and explains the observed temperature dependence of the effective thermodynamic parameters used in models of the nearest neighbor type. I developed a basic kinetic model for irreversible thermal denaturation of F-actin, which incorporates depolymerization of F-actin from the ends and breaking of F-actin fiber in the middle. The model explains the cooperativity of F-actin thermal denaturation observed by D. Pavlov et al. in differential calorimetry measurements. CG-rich DNA sequences form left-handed Z-DNA at high ionic strength or upon binding of polyvalent ions and some proteins. I studied experimentally the B-to-Z transition of the (CG)6 dodecamer. Improvement of the locally linearized model used to interpret the data gives evidence for an intermediate state in the B-to-Z transition of DNA, contrary to previous research on this subject. In the past 15 years it has become possible to study the conformational changes of biomolecules using single-molecule techniques. In collaboration with other lab members I performed a single-molecule experiment, where we monitored the displacement of a micrometer-size bead tethered to a surface by a DNA probe undergoing the conformational change. This technique allows probing of conformational changes with subnanometer accuracy. We applied the method to detect

  5. CONFORMANCE IMPROVEMENT USING GELS

    Energy Technology Data Exchange (ETDEWEB)

    Randall S. Seright

    2004-09-30

    This report describes work performed during the third and final year of the project, ''Conformance Improvement Using Gels.'' Corefloods revealed throughput dependencies of permeability reduction by polymers and gels that were much more prolonged during oil flow than water flow. This behavior was explained using simple mobility ratio arguments. A model was developed that quantitatively fits the results and predicts ''clean up'' times for oil productivity when production wells are returned to service after application of a polymer or gel treatment. X-ray computed microtomography studies of gels in strongly water-wet Berea sandstone and strongly oil-wet porous polyethylene suggested that oil penetration through gel-filled pores occurs by a gel-dehydration mechanism, rather than gel-ripping or gel-displacement mechanisms. In contrast, analysis of data from the University of Kansas suggests that the gel-ripping or displacement mechanisms are more important in more permeable, strongly water-wet sandpacks. These findings help to explain why aqueous gels can reduce permeability to water more than to oil under different conditions. Since cement is the most commonly used material for water shutoff, we considered when gels are preferred over cements. Our analysis and experimental results indicated that cement cannot be expected to completely fill (top to bottom) a vertical fracture of any width, except near the wellbore. For vertical fractures with apertures less than 4 mm, the cement slurry will simply not penetrate very far into the fracture. For vertical fractures with apertures greater than 4 mm, the slurry may penetrate a substantial distance into the bottom part of the fracture. However, except near the wellbore, the upper part of the fracture will remain open due to gravity segregation. We compared various approaches to plugging fractures using gels, including (1) varying polymer content, (2) varying placement (extrusion) rate

  6. Compact conformations of human protein disulfide isomerase.

    Directory of Open Access Journals (Sweden)

    Shang Yang

    Full Text Available Protein disulfide isomerase (PDI composed of four thioredoxin-like domains a, b, b', and a', is a key enzyme catalyzing oxidative protein folding in the endoplasmic reticulum. Large scale molecular dynamics simulations starting from the crystal structures of human PDI (hPDI in the oxidized and reduced states were performed. The results indicate that hPDI adopts more compact conformations in solution than in the crystal structures, which are stabilized primarily by inter-domain interactions, including the salt bridges between domains a and b' observed for the first time. A prominent feature of the compact conformations is that the two catalytic domains a and a' can locate close enough for intra-molecular electron transfer, which was confirmed by the characterization of an intermediate with a disulfide between the two domains. Mutations, which disrupt the inter-domain interactions, lead to decreased reductase activity of hPDI. Our molecular dynamics simulations and biochemical experiments reveal the intrinsic conformational dynamics of hPDI and its biological impact.

  7. A Conformal Extension Theorem based on Null Conformal Geodesics

    CERN Document Server

    Lübbe, Christian

    2008-01-01

    In this article we describe the formulation of null geodesics as null conformal geodesics and their description in the tractor formalism. A conformal extension theorem through an isotropic singularity is proven by requiring the boundedness of the tractor curvature and its derivatives to sufficient order along a congruence of null conformal geodesic. This article extends earlier work by Tod and Luebbe.

  8. Bioactive Glasses in Dentistry: A Review

    Directory of Open Access Journals (Sweden)

    Abbasi Z

    2015-03-01

    Full Text Available Bioactive glasses are silicate-based and can form a strong chemical bond with the tissues. These biomaterials are highly biocompatible and can form a hydroxyapatite layer when implanted in the body or soaked in the simulated body fluid. Due to several disadvantages, conventional glass processing method including melting of glass components, is replaced by sol-gel method with a large number of benefits such as low processing temperature, higher purity and homogeneity and therefore better control of bioactivity. Bioactive glasses have a wide range of applications, particularly in dentistry. These glasses can be used as particulates or monolithic shapes and porous or dense constructs in different applications such as remineralization or hypersensitivity treatment. Some properties of bioactive glasses such as antibacterial properties can be promoted by adding different elements into the glass. Bioactive glasses can also be used to modify different biocompatible materials that need to be bioactive. This study reviews the significant developments of bioactive glasses in clinical application, especially dentistry. Furthermore, we will discuss the field of bioactive glasses from beginning to the current developments, which includes processing methods, applications, and properties of these glasses.

  9. Transportation Conformity Training and Presentations

    Science.gov (United States)

    EPA's OTAQ has provided multiple conformity training sessions in the past to assist state and local governments in implementing conformity requirements. As training information is prepared for other venues, it will be posted on this page.

  10. From integrable to conformal theory

    Energy Technology Data Exchange (ETDEWEB)

    Babelon, O. (Paris-6 Univ., 75 (France). Lab. de Physique Theorique et Hautes Energies)

    1990-12-01

    Working in the context of Toda field theory, we establish the relationship between their integrability properties and their conformal structure, thereby clarifying the role of the Yang-Baxter equation in conformal field theory. (orig.).

  11. Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

    Science.gov (United States)

    Zhong, Jian-Jiang; Xiao, Jian-Hui

    Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

  12. Chromatographic on-line detection of bioactives in food

    Directory of Open Access Journals (Sweden)

    Remmelt Van der Werf

    2013-08-01

    Full Text Available ABSTRACTFindings were focused on the anti-oxidative activity of numerous fruits and vegetables by means of an on-line HPLC radical scavenging detection method. The reactant used was the ABTS•+ green radical cation. The system has been optimized in terms of reactor design, and chemical reactions kinetics. It has been qualified to classify molecules in order of their increasing activity to scavenge exogenous radicals. It may be used as a powerful high resolution screening tool to investigate the radical scavenging activities of natural plants. Bioassays consisting in cellular in vitro antioxidant assay using pancreatic β-cells have been used to confirm the bioactivity of the selected micronutrients. This study demonstrated that it is possible to screen at the molecular level, the bioactivity of numerous natural samples and to point out the richness of the local biodiversity in terms of natural resource of functional food ingredients usable for their potential benefits for consumer’s health, wellbeing and wellaging.Key words: HPLC radical scavenging detection method, bioactivity of natural samples

  13. Functional properties of spinach (Spinacia oleracea L.) phytochemicals and bioactives.

    Science.gov (United States)

    Roberts, Joseph L; Moreau, Régis

    2016-08-10

    Overwhelming evidence indicates that diets rich in fruits and vegetables are protective against common chronic diseases, such as cancer, obesity and cardiovascular disease. Leafy green vegetables, in particular, are recognized as having substantial health-promoting activities that are attributed to the functional properties of their nutrients and non-essential chemical compounds. Spinach (Spinacia oleracea L.) is widely regarded as a functional food due to its diverse nutritional composition, which includes vitamins and minerals, and to its phytochemicals and bioactives that promote health beyond basic nutrition. Spinach-derived phytochemicals and bioactives are able to (i) scavenge reactive oxygen species and prevent macromolecular oxidative damage, (ii) modulate expression and activity of genes involved in metabolism, proliferation, inflammation, and antioxidant defence, and (iii) curb food intake by inducing secretion of satiety hormones. These biological activities contribute to the anti-cancer, anti-obesity, hypoglycemic, and hypolipidemic properties of spinach. Despite these valuable attributes, spinach consumption remains low in comparison to other leafy green vegetables. This review examines the functional properties of spinach in cell culture, animals and humans with a focus on the molecular mechanisms by which spinach-derived non-essential phytochemicals and bioactives, such as glycolipids and thylakoids, impart their health benefits.

  14. Multiscale conformal pattern transfer

    Science.gov (United States)

    Lodewijks, Kristof; Miljkovic, Vladimir; Massiot, Inès; Mekonnen, Addis; Verre, Ruggero; Olsson, Eva; Dmitriev, Alexandre

    2016-06-01

    We demonstrate a method for seamless transfer from a parent flat substrate of basically any lithographic top-down or bottom-up pattern onto essentially any kind of surface. The nano- or microscale patterns, spanning macroscopic surface areas, can be transferred with high conformity onto a large variety of surfaces when such patterns are produced on a thin carbon film, grown on top of a sacrificial layer. The latter allows lifting the patterns from the flat parent substrate onto a water-air interface to be picked up by the host surface of choice. We illustrate the power of this technique by functionalizing broad range of materials including glass, plastics, metals, rough semiconductors and polymers, highlighting the potential applications in in situ colorimetry of the chemistry of materials, anti-counterfeit technologies, biomolecular and biomedical studies, light-matter interactions at the nanoscale, conformal photovoltaics and flexible electronics.

  15. Conformal Complementarity Maps

    CERN Document Server

    Barbón, José L F

    2013-01-01

    We study quantum cosmological models for certain classes of bang/crunch singularities, using the duality between expanding bubbles in AdS with a FRW interior cosmology and perturbed CFTs on de Sitter space-time. It is pointed out that horizon complementarity in the AdS bulk geometries is realized as a conformal transformation in the dual deformed CFT. The quantum version of this map is described in full detail in a toy model involving conformal quantum mechanics. In this system the complementarity map acts as an exact duality between eternal and apocalyptic Hamiltonian evolutions. We calculate the commutation relation between the Hamiltonians corresponding to the different frames. It vanishes only on scale invariant states.

  16. On conformal lenses

    CERN Document Server

    Chen, Huanyang; Li, Hui

    2011-01-01

    Plane mirror can make one object into two for observers on the object's side. Yet, there seems no way to achieve the same effect for observers from all directions. In this letter, we will design a new class of gradient index lenses from multivalued optical conformal mapping. We shall call them the conformal lenses. Such lenses can transform one source into two (or even many) omnidirectionally. Like the overlapped illusion optics does, they can even transform multiple sources into one. Rather than using negative index materials, implementation here only needs isotropic positive index materials like other gradient index lenses. One obvious drawback however, is that they have singular permittivity values which restrict them to functioning at one single frequency. This however, needs not be the case when applying transmutation methods, which enable the lenses to work in a broadband frequency range.

  17. Conformal boundaries of warped products

    DEFF Research Database (Denmark)

    Kokkendorff, Simon Lyngby

    2006-01-01

    In this note we prove a result on how to determine the conformal boundary of a type of warped product of two length spaces in terms of the individual conformal boundaries. In the situation, that we treat, the warping and conformal distortion functions are functions of distance to a base point....... The result is applied to produce examples of CAT(0)-spaces, where the conformal and ideal boundaries differ in interesting ways....

  18. Effect of sulfated modification on the molecular characteristics and biological activities of polysaccharides from Hypsizigus marmoreus.

    Science.gov (United States)

    Bao, HongHui; Choi, Won-Seok; You, SangGuan

    2010-01-01

    The effect of sulfated modification on polysaccharides from Hypsizigus marmoreus was examined by determining their molecular structures and bioactivities. The sulfation, which was implemented by using an orthogonal array design, produced polysaccharides with varying degrees of substitution (DS) ranging from 0.11 to 1.06. The sulfated polysaccharides exhibited a lower average molecular weight (M(w)) and considerably higher radius of gyration (R(g)) than those of native polysaccharide, suggesting that the conformation of the sulfated polysaccharides had been changed towards a more extended type. The inhibitory activity toward cancer cell growth was enhanced by treating with the sulfated polysaccharides by up to 34%, as compared to the native polysaccharide. In addition, treating with the sulfated polysaccharides increased the nitric oxide (NO) and cytokine (IL-1beta and TNF-alpha) release to levels comparable to those detected in the positive control, lipopolysaccharide (LPS), suggesting that the sulfated polysaccharides might have strong immunomodulatory activity.

  19. Surface modification of bioactive glasses and preparation of PDLLA/bioactive glass composite films.

    Science.gov (United States)

    Gao, Yuan; Chang, Jiang

    2009-08-01

    In order to improve the homogeneous dispersion of particles in the polymeric matrix, 45S5, mesoporous 58S, and 58S bioactive glasses were surface modified by esterification reactions with dodecyl alcohol at reflux temperature of 260 degrees C (named as m-45S5, m-mesoporous 58S, and m-58S, respectively). The modified particles showed better hydrophobicity and longer time of suspension in organic matrix. The PDLLA/bioactive glass composite films were fabricated using surface modified bioactive glass particles through solvent casting-evaporation method. Surface morphology, mechanical property, and bioactivity were investigated. The results revealed that the inorganic particle distribution and tensile strength of the composite films with modified bioactive glass particles were significantly improved while great bioactive properties were maintained. Scanning electron microscopy (SEM) observation illustrated that the modified bioactive glass particles were homogeneously dispersed in the PDLLA matrix. The maximum tensile strengths of composite films with modified bioactive glass particles were higher than that of composite films with unmodified bioactive glass particles. The bioactivity of the composite films were evaluated by being soaked in the simulated body fluid (SBF) and the SEM observation of the films suggested that the modified composite films were still bioactive in that they could induce the formation of HAp on its surface and the distribution of HAp was even more homogeneous on the film. The results mentioned above indicated that the surface modification of bioactive glasses with dodecyl alcohol was an effective method to prepare PDLLA/bioactive glass composites with enhanced properties. By studying the comparisons of modification effects among the three types of bioactive glasses, we could get the conclusion that the size and morphology of the inorganic particles would greatly affect the modification effects and the properties of composites.

  20. Two Additional Remarks on Conformism

    OpenAIRE

    Schlicht, Ekkehart

    2014-01-01

    Abstract This note offers two comments on the article “Social Influences towards Conformism in Economic Experiments” by Hargreaves Heap that is to appear in the Economics e-Journal. One relates to the concept of conformism, the other lines out some phenomena where an explicit recognition of group processes, such as conformism, may be analytically helpful.

  1. Preparation, characterization, in vitro bioactivity, and cellular responses to a polyetheretherketone bioactive composite containing nanocalcium silicate for bone repair.

    Science.gov (United States)

    Ma, Rui; Tang, Songchao; Tan, Honglue; Qian, Jun; Lin, Wentao; Wang, Yugang; Liu, Changsheng; Wei, Jie; Tang, Tingting

    2014-08-13

    In this study, a nanocalcium silicate (n-CS)/polyetheretherketone (PEEK) bioactive composite was prepared using a process of compounding and injection-molding. The mechanical properties, hydrophilicity, and in vitro bioactivity of the composite, as well as the cellular responses of MC3T3-E1 cells (attachment, proliferation, spreading, and differentiation) to the composite, were investigated. The results showed that the mechanical properties and hydrophilicity of the composites were significantly improved by the addition of n-CS to PEEK. In addition, an apatite-layer formed on the composite surface after immersion in simulated body fluid (SBF) for 7 days. In cell culture tests, the results revealed that the n-CS/PEEK composite significantly promoted cell attachment, proliferation, and spreading compared with PEEK or ultrahigh molecular weight polyethylene (UHMWPE). Moreover, cells grown on the composite exhibited higher alkaline phosphatase (ALP) activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes than cells grown on PEEK or UHMWPE. These results indicated that the incorporation of n-CS to PEEK could greatly improve the bioactivity and biocompatibility of the composite. Thus, the n-CS/PEEK composite may be a promising bone repair material for use in orthopedic clinics.

  2. Investigating the influence of effective parameters on molecular characteristics of bovine serum albumin nanoparticles

    Science.gov (United States)

    Rohiwal, S. S.; Satvekar, R. K.; Tiwari, A. P.; Raut, A. V.; Kumbhar, S. G.; Pawar, S. H.

    2015-04-01

    The protein nanoparticles formulation is a challenging task as they are prone to undergo conformational transitions while processing which may affect bioavailability for bioactive compounds. Herein, a modified desolvation method is employed to prepare Bovine Serum Albumin nanoparticles, with controllable particle size ranging from 100 to 300 nm and low polydispersity index. The factors influencing the size and structure of BSA NPs viz. protein concentration, pH and the conditions for purification are well investigated. The structure of BSA NPs is altered due to processing, and may affect the effective binding ability with drugs and bioactive compounds. With that aims, investigations of molecular characteristics of BSA NPs are carried out in detail by using spectroscopic techniques. UV-visible absorption and Fourier Transform Infrared demonstrate the alteration in protein structure of BSA NPs whereas the FT-Raman spectroscopy investigates changes in the secondary and tertiary structures of the protein. The conformational changes of BSA NPs are observed by change in fluorescence intensity and emission maximum wavelength of tryptophan residue by fluorescence spectroscopy. The field emission scanning electron and atomic force microscopy micrographs confirm the size and semi-spherical morphology of the BSA NPs. The effect of concentration and pH on particle size distribution is studied by particle size analyzer.

  3. Synthesis, crystallographic characterization, and conformational prediction of a structurally unique molecular mixed-ligand U(VI) solid, Na{sub 6}[UO{sub 2}(O{sub 2}){sub 2}(OH){sub 2}](OH){sub 2} . 14H{sub 2}O

    Energy Technology Data Exchange (ETDEWEB)

    Zehnder, R.A.; Scott, B.L.; Peper, S.M.; Goff, G.S.; Runde, W.H. [Chemistry Div., Los Alamos National Lab., NM (United States); Batista, E.R. [Theoretical Div., Los Alamos National Lab., NM (United States)

    2008-07-01

    The first mononuclear molecular mixed-ligand U(VI) solid containing hydroxide and peroxide ligands, Na{sub 6}[UO{sub 2}(O{sub 2}){sub 2}(OH){sub 2}](OH){sub 2} . 14H{sub 2}O (I), was synthesized and structurally characterized using single crystal X-ray diffraction. The crystal structure of I consisted of [UO{sub 2}(O{sub 2}){sub 2}(OH){sub 2}]{sup 4-} molecular units, with a uranyl(VI) moiety perpendicular to 6 equatorial O atoms belonging to two side-on trans peroxo groups and two terminal trans hydroxo groups. Density functional theory (DFT) calculations determined that the trans-conformer of the [UO{sub 2}(O{sub 2}){sub 2}(OH){sub 2}]{sup 4-} molecular unit found in I was 24 kcal/mol lower in energy than the previously proposed cis-conformer. Crystal data: monoclinic, space group P2{sub 1}/n with a = 13.357(4) A, b = 5.8521(15) A, c = 15.948(6) A, {beta} = 112.292(4) , and Z = 2. (orig.)

  4. Capturing the essence of organic synthesis: from bioactive natural products to designed molecules in today's medicine.

    Science.gov (United States)

    Ghosh, Arun K

    2010-12-03

    In this Perspective, I outline my group's research involving the chemical syntheses of medicinally important natural products, exploration of their bioactivity, and the development of new asymmetric carbon-carbon bond-forming reactions. This paper also highlights our approach to molecular design and synthesis of conceptually novel inhibitors against target proteins involved in the pathogenesis of human diseases, including AIDS and Alzheimer's disease.

  5. Ligand-induced conformational changes: Improved predictions of ligand binding conformations and affinities

    DEFF Research Database (Denmark)

    Frimurer, T.M.; Peters, Günther H.J.; Iversen, L.F.

    2003-01-01

    A computational docking strategy using multiple conformations of the target protein is discussed and evaluated. A series of low molecular weight, competitive, nonpeptide protein tyrosine phosphatase inhibitors are considered for which the x-ray crystallographic structures in complex with protein...... tyrosine phosphatase 1 B (PTP1B) are known. To obtain a quantitative measure of the impact of conformational changes induced by the inhibitors, these were docked to the active site region of various structures of PTP1B using the docking program FlexX. Firstly, the inhibitors were docked to a PTP1B crystal...... predicted binding energy and a correct docking mode. Thirdly, to improve the predictability of the docking procedure in the general case, where only a single target protein structure is known, we evaluate an approach which takes possible protein side-chain conformational changes into account. Here, side...

  6. Correcting mitochondrial fusion by manipulating mitofusin conformations

    Science.gov (United States)

    Franco, Antonietta; Kitsis, Richard N.; Fleischer, Julie A.; Gavathiotis, Evripidis; Kornfeld, Opher S.; Gong, Guohua; Biris, Nikolaos; Benz, Ann; Qvit, Nir; Donnelly, Sara K; Chen, Yun; Mennerick, Steven; Hodgson, Louis; Mochly-Rosen, Daria; Dorn, Gerald W

    2017-01-01

    Summary Mitochondria are dynamic organelles, remodeling and exchanging contents during cyclic fusion and fission. Genetic mutations of mitofusin (Mfn) 2 interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition, Charcot Marie Tooth disease type 2A (CMT2A). It has not been possible to directly modulate mitochondrial fusion, in part because the structural basis of mitofusin function is incompletely understood. Here we show that mitofusins adopt either a fusion-constrained or fusion-permissive molecular conformation directed by specific intramolecular binding interactions, and demonstrate that mitofusin-dependent mitochondrial fusion can be regulated by targeting these conformational transitions. Based on this model we engineered a cell-permeant minipeptide to destabilize fusion-constrained mitofusin and promote the fusion-permissive conformation, reversing mitochondrial abnormalities in cultured fibroblasts and neurons harboring CMT2A gene defects. The relationship between mitofusin conformational plasticity and mitochondrial dynamism uncovers a central mechanism regulating mitochondrial fusion whose manipulation can correct mitochondrial pathology triggered by defective or imbalanced mitochondrial dynamics. PMID:27775718

  7. Vibrational spectroscopic studies, Fukui functions, HOMO-LUMO, NLO, NBO analysis and molecular docking study of (E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-one, a potential precursor to bioactive agents

    Science.gov (United States)

    Al-Wabli, Reem I.; Resmi, K. S.; Sheena Mary, Y.; Yohannan Panicker, C.; Attia, Mohamed I.; El-Emam, Ali A.; Van Alsenoy, C.

    2016-11-01

    The FT-IR and FT-Raman spectra of (E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-one were recorded and analyzed experimentally and theoretically. The observed experimental and theoretical wavenumbers were assigned using potential energy distribution. The NLO properties were evaluated by the determination of first and second hyperpolarizabilities of the title compound. From the frontier molecular orbital study, the HOMO centers over the entire molecule except the methyl groups, while the LUMO is over the entire molecule except the CH2 group with the dioxole ring and one of the methyl groups. From the MEP plot, it is evident that the negative region covers the carbonyl and Cdbnd C groups and the positive region is over CH2 groups. The Fukui functions are also reported. The calculated geometrical parameters are in agreement with the XRD results. From the molecular docking study, the docked ligand title compound forms a stable complex with the androgen receptor and gives a binding affinity value of -8.1 kcal/mol and the results suggest that the compound might exhibit inhibitory activity against androgen receptor.

  8. The effects of conformity and load in total knee replacement.

    Science.gov (United States)

    Kuster, M S; Horz, S; Spalinger, E; Stachowiak, G W; Gächter, A

    2000-06-01

    The effects of different conformity ratios and loads on the ultrahigh molecular weight polyethylene stress levels acting on knee implants were examined using a nonlinear, finite element analysis. The contact condition between a rigid cylinder with a radius of 30 mm and a polyethylene plate was modeled. Nonlinear behavior of polyethylene was assumed. The polyethylene plate was constructed with varying radii, with a minimal thickness of 6 mm and with a width of 40 mm. The ratio of the cylinder radius to the radius of the polyethylene plate was defined as the conformity ratio; a conformity ratio of 0 represented a flat tibial inlay, whereas the highest ratio modeled of 0.99 was nearly conforming. The conformity ratios modeled were 0, 0.2, 0.4, 0.6, 0.7, 0.8, 0.9, 0.95, and 0.99. The loads applied were 1000 N, 2000 N, 3000 N, 4000 N, 5000 N, and 6000 N. The effects of different conformity ratios and loads on the contact area (mm2), the compressive surface stress (MPa), the shear stress (MPa), and the von Mises stress (MPa) were investigated. It was found that all of these parameters were affected by changes to the conformity ratio and to a lesser extent by load changes. That is, increasing the load from 3000 N to 6000 N resulted in a surface and shear stress increase lower than the increase in stress caused by the small change of the conformity ratio from 0.99 to 0.95. The effect of an increasing conformity ratio on the reduction in stress was more pronounced for conformity ratios above 0.8. In addition, the effect of a load increase for a flat tibial inlay was two times greater than for one with near full conformity.

  9. Leaf growth is conformal

    Science.gov (United States)

    Alim, Karen; Armon, Shahaf; Shraiman, Boris I.; Boudaoud, Arezki

    2016-10-01

    Growth pattern dynamics lie at the heart of morphogenesis. Here, we investigate the growth of plant leaves. We compute the conformal transformation that maps the contour of a leaf at a given stage onto the contour of the same leaf at a later stage. Based on the mapping we predict the local displacement field in the leaf blade and find it to agree with the experimentally measured displacement field to 92%. This approach is applicable to any two-dimensional system with locally isotropic growth, enabling the deduction of the whole growth field just from observation of the tissue contour.

  10. Leaf growth is conformal

    CERN Document Server

    Alim, Karen; Shraiman, Boris I; Boudaoud, Arezki

    2016-01-01

    Growth pattern dynamics lie at the heart of morphogenesis. Here, we investigate the growth of plant leaves. We compute the conformal transformation that maps the contour of a leaf at a given stage onto the contour of the same leaf at a later stage. Based on the mapping we predict the local displacement field in the leaf blade and find it to agree with the experimentally measured displacement field to 92%. This approach is applicable to any two-dimensional system with locally isotropic growth, enabling the deduction of the whole growth field just from observation of the tissue contour.

  11. Conformance and Deviance

    DEFF Research Database (Denmark)

    Gjerdrum Pedersen, Esben Rahbek; Neergaard, Peter; Thusgaard Pedersen, Janni

    2013-01-01

    This paper analyses how large Danish companies are responding to new governmental regulation which requires them to report on corporate social responsibility (CSR). The paper is based on an analysis of 142 company annual reports required by the new Danish regulation regarding CSR reporting, plus ...... in CSR reporting practices. Finally, it is argued that non-conformance with the new regulatory requirements is not solely about conscious resistance but may also be caused by, for example, lack of awareness, resource limitations, misinterpretations, and practical difficulties....

  12. Conformal fluid dynamics

    CERN Document Server

    Jarvis, P D

    2006-01-01

    We present a conformal theory of a dissipationless relativistic fluid in 2 space-time dimensions. The theory carries with it a representation of the algebra of 2-$D$ area-preserving diffeomorphisms in the target space of the complex scalar potentials. A complete canonical description is given, and the central charge of the current algebra is calculated. The passage to the quantum theory is discussed in some detail; as a result of operator ordering problems, full quantization at the level of the fields is as yet an open problem.

  13. Bioactivities and Health Benefits of Wild Fruits.

    Science.gov (United States)

    Li, Ya; Zhang, Jiao-Jiao; Xu, Dong-Ping; Zhou, Tong; Zhou, Yue; Li, Sha; Li, Hua-Bin

    2016-08-04

    Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we review current knowledge about the bioactivities and health benefits of wild fruits, which is valuable for the exploitation and utilization of wild fruits.

  14. Microscopic insights into the NMR relaxation-based protein conformational entropy meter.

    Science.gov (United States)

    Kasinath, Vignesh; Sharp, Kim A; Wand, A Joshua

    2013-10-09

    Conformational entropy is a potentially important thermodynamic parameter contributing to protein function. Quantitative measures of conformational entropy are necessary for an understanding of its role but have been difficult to obtain. An empirical method that utilizes changes in conformational dynamics as a proxy for changes in conformational entropy has recently been introduced. Here we probe the microscopic origins of the link between conformational dynamics and conformational entropy using molecular dynamics simulations. Simulation of seven proteins gave an excellent correlation with measures of side-chain motion derived from NMR relaxation. The simulations show that the motion of methyl-bearing side chains are sufficiently coupled to that of other side chains to serve as excellent reporters of the overall side-chain conformational entropy. These results tend to validate the use of experimentally accessible measures of methyl motion--the NMR-derived generalized order parameters--as a proxy from which to derive changes in protein conformational entropy.

  15. Bioactivity of bioresorbable composite based on bioactive glass and poly-L-lactide

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zhi-hua; RUAN Jian-ming; ZOU Jian-peng; ZHOU Zhong-cheng; SHEN Xiong-jun

    2007-01-01

    Bioactive and bioresorbable composite was fabricated by a solvent evaporation technique using poly-L-lactide(PLLA) and bioactive glass (average particle size: 6.8 μm). Bioactive glass granules are homogeneously distributed in the composite with microcrack structure. The formation of hydroxyapatite(HA) on the composite in simulated body fluid(SBF) was analyzed by scanning electron microscopy(SEM), energy dispersive spectroscopy(EDS), X-ray diffraction(XRD), and Raman spectra. Rod-like HA crystals deposit on the surface of PLLA/bioactive glass composite after soaking for 3 d. Both rod-like crystals and HA layer form on the surface for 14 d in SBF. The high bioactivity of PLLA/bioactive glass composite indicates the potential of materials for integration with bone.

  16. New molecular scaffolds for the design of Mycobacterium tuberculosis type II dehydroquinase inhibitors identified using ligand and receptor based virtual screening.

    Science.gov (United States)

    Kumar, Ashutosh; Siddiqi, Mohammad Imran; Miertus, Stanislav

    2010-04-01

    Using ligand and receptor based virtual screening approaches we have identified potential virtual screening hits targeting type II dehydroquinase from Mycobacterium tuberculosis, an effective and validated anti-mycobacterial target. Initially, we applied a virtual screening workflow based on a combination of 2D structural fingerprints, 3D pharmacophore and molecular docking to identify compounds that rigidly match specific aspects of ligand bioactive conformation. Subsequently, the resulting compounds were ranked and prioritized using receptor interaction fingerprint based scoring and quantitative structure activity relationship model developed using already known actives. The virtual screening hits prioritized belong to several classes of molecular scaffolds with several available substitution positions that could allow chemical modification to enhance binding affinity. Finally, identified hits may be useful to a medicinal chemist or combinatorial chemist to pick up the new molecular starting points for medicinal chemistry optimization for the design of novel type II dehydroquinase inhibitors.

  17. Hot Conformal Gauge Theories

    CERN Document Server

    Mojaza, Matin; Sannino, Francesco

    2010-01-01

    We compute the nonzero temperature free energy up to the order g^6 \\ln(1/g) in the coupling constant for vector like SU(N) gauge theories featuring matter transforming according to different representations of the underlying gauge group. The number of matter fields, i.e. flavors, is arranged in such a way that the theory develops a perturbative stable infrared fixed point at zero temperature. Due to large distance conformality we trade the coupling constant with its fixed point value and define a reduced free energy which depends only on the number of flavors, colors and matter representation. We show that the reduced free energy changes sign, at the second, fifth and sixth order in the coupling, when decreasing the number of flavors from the upper end of the conformal window. If the change in sign is interpreted as signal of an instability of the system then we infer a critical number of flavors. Surprisingly this number, if computed to the order g^2, agrees with previous predictions for the lower boundary o...

  18. Conformal invariant saturation

    CERN Document Server

    Navelet, H

    2002-01-01

    We show that, in onium-onium scattering at (very) high energy, a transition to saturation happens due to quantum fluctuations of QCD dipoles. This transition starts when the order alpha^2 correction of the dipole loop is compensated by its faster energy evolution, leading to a negative interference with the tree level amplitude. After a derivation of the the one-loop dipole contribution using conformal invariance of the elastic 4-gluon amplitude in high energy QCD, we obtain an exact expression of the saturation line in the plane (Y,L) where Y is the total rapidity and L, the logarithm of the onium scale ratio. It shows universal features implying the Balitskyi - Fadin - Kuraev - Lipatov (BFKL) evolution kernel and the square of the QCD triple Pomeron vertex. For large L, only the higher BFKL Eigenvalue contributes, leading to a saturation depending on leading log perturbative QCD characteristics. For initial onium scales of same order, however, it involves an unlimited summation over all conformal BFKL Eigen...

  19. Conformation-controlled binding kinetics of antibodies

    Science.gov (United States)

    Galanti, Marta; Fanelli, Duccio; Piazza, Francesco

    2016-01-01

    Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines.

  20. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities.

    Science.gov (United States)

    Hayes, Maria; Tiwari, Brijesh K

    2015-09-17

    Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.

  1. Design and characterization of protein-quercetin bioactive nanoparticles

    Directory of Open Access Journals (Sweden)

    Leng Xiaojing

    2011-05-01

    Full Text Available Abstract Background The synthesis of bioactive nanoparticles with precise molecular level control is a major challenge in bionanotechnology. Understanding the nature of the interactions between the active components and transport biomaterials is thus essential for the rational formulation of bio-nanocarriers. The current study presents a single molecule of bovine serum albumin (BSA, lysozyme (Lys, or myoglobin (Mb used to load hydrophobic drugs such as quercetin (Q and other flavonoids. Results Induced by dimethyl sulfoxide (DMSO, BSA, Lys, and Mb formed spherical nanocarriers with sizes less than 70 nm. After loading Q, the size was further reduced by 30%. The adsorption of Q on protein is mainly hydrophobic, and is related to the synergy of Trp residues with the molecular environment of the proteins. Seven Q molecules could be entrapped by one Lys molecule, 9 by one Mb, and 11 by one BSA. The controlled releasing measurements indicate that these bioactive nanoparticles have long-term antioxidant protection effects on the activity of Q in both acidic and neutral conditions. The antioxidant activity evaluation indicates that the activity of Q is not hindered by the formation of protein nanoparticles. Other flavonoids, such as kaempferol and rutin, were also investigated. Conclusions BSA exhibits the most remarkable abilities of loading, controlled release, and antioxidant protection of active drugs, indicating that such type of bionanoparticles is very promising in the field of bionanotechnology.

  2. Structural analysis of (S)-1-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-3-(4-(2-methoxyphenyl)piperazin-1-yl)propan-2-ol and binding mechanism with α1A-adrenoceptor: TDDFT calculations, X-ray crystallography and molecular docking

    Science.gov (United States)

    Xu, Wei; Shao, Binhao; Xu, Xingjie; Jiang, Renwang; Yuan, Mu

    2016-02-01

    The title compound, (S)-1-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-3-(4-(2-methoxyphenyl)piperazi-n-1-yl)propan-2-ol (1), belongs to a class of arylpiperazine derivatives that exhibit good bioactivity against α1A-adrenoceptor. The current study describes conformational analysis of five energy-minimized conformers obtained at the B3LYP/6-31G(d) level of theory. The characteristically positive rotatory strengths at an excitation energy of 256 nm were achieved using time-dependent density functional theory (TDDFT) calculations. Molecular orbital studies clearly elucidated the origins of electronic transitions at 256 nm. The absolute configuration of (S)-1 was unambiguously determined by single crystal X-ray diffraction analysis. Molecular docking solved the binding mode of 1-α1A-adrenoceptor complex. This work can serve as a basis for better drug design of highly selective antagonists with chirality.

  3. Going viral: designing bioactive surfaces with bacteriophage.

    Science.gov (United States)

    Hosseinidoust, Zeinab; Olsson, Adam L J; Tufenkji, Nathalie

    2014-12-01

    Bacteriophage-functionalized bioactive surfaces are functional materials that can be used as antimicrobial surfaces in medical applications (e.g., indwelling medical devices or wound dressings) or as biosensors for bacterial capture and detection. Despite offering immense potential, designing efficient phage-functionalized bioactive surfaces is hampered by a number of challenges. This review offers an overview of the current state of knowledge in this field and presents a critical perspective of the technological promises and challenges.

  4. Bioactivities and Health Benefits of Wild Fruits

    OpenAIRE

    Ya Li; Jiao-Jiao Zhang; Dong-Ping Xu; Tong Zhou; Yue. Zhou; Sha Li; Hua-Bin Li

    2016-01-01

    Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we rev...

  5. Microencapsulation of bioactives for food applications

    OpenAIRE

    Dias, Maria Inês; Isabel C. F. R. Ferreira; Barreiro, M.F.

    2015-01-01

    Health issues are an emerging concern to the world population, and therefore the food industry is searching for novel food products containing health-promoting bioactive compounds, with little or no synthetic ingredients. However, there are some challenges in the development of functional foods, particularly in which the direct use of some bioactives is involved. They can show problems of instability, react with other food matrix ingredients or present strong odour and/or flavours. In this co...

  6. Subtleties Concerning Conformal Tractor Bundles

    CERN Document Server

    Graham, C Robin

    2012-01-01

    The realization of tractor bundles as associated bundles in conformal geometry is studied. It is shown that different natural choices of principal bundle with normal Cartan connection corresponding to a given conformal manifold can give rise to topologically distinct associated tractor bundles for the same inducing representation. Consequences for homogeneous models and conformal holonomy are described. A careful presentation is made of background material concerning standard tractor bundles and equivalence between parabolic geometries and underlying structures.

  7. Dimensional Reduction for Conformal Blocks

    CERN Document Server

    Hogervorst, Matthijs

    2016-01-01

    We consider the dimensional reduction of a CFT, breaking multiplets of the d-dimensional conformal group SO(d+1,1) up into multiplets of SO(d,1). This leads to an expansion of d-dimensional conformal blocks in terms of blocks in d-1 dimensions. In particular, we obtain a formula for 3d conformal blocks as an infinite sum over 2F1 hypergeometric functions with closed-form coefficients.

  8. Biomolecule immobilization techniques for bioactive paper fabrication.

    Science.gov (United States)

    Kong, Fanzhi; Hu, Yim Fun

    2012-04-01

    Research into paper-based sensors or functional materials that can perform analytical functions with active recognition capabilities is rapidly expanding, and significant research effort has been made into the design and fabrication of bioactive paper at the biosensor level to detect potential health hazards. A key step in the fabrication of bioactive paper is the design of the experimental and operational procedures for the immobilization of biomolecules such as antibodies, enzymes, phages, cells, proteins, synthetic polymers and DNA aptamers on a suitably prepared paper membrane. The immobilization methods are concisely categorized into physical absorption, bioactive ink entrapment, bioaffinity attachment and covalent chemical bonding immobilization. Each method has individual immobilization characteristics. Although every biomolecule-paper combination has to be optimized before use, the bioactive ink entrapment method is the most commonly used approach owing to its general applicability and biocompatibility. Currently, there are four common applications of bioactive paper: (1) paper-based bioassay or paper-based analytical devices for sample conditioning; (2) counterfeiting and countertempering in the packaging and construction industries; (3) pathogen detection for food and water quality monitoring; and (4) deactivation of pathogenic bacteria using antimicrobial paper. This article reviews and compares the different biomolecule immobilization techniques and discusses current trends. Current, emerging and future applications of bioactive paper are also discussed.

  9. Advances on Bioactive Polysaccharides from Medicinal Plants.

    Science.gov (United States)

    Xie, Jian-Hua; Jin, Ming-Liang; Morris, Gordon A; Zha, Xue-Qiang; Chen, Han-Qing; Yi, Yang; Li, Jing-En; Wang, Zhi-Jun; Gao, Jie; Nie, Shao-Ping; Shang, Peng; Xie, Ming-Yong

    2016-07-29

    In recent decades, the polysaccharides from the medicinal plants have attracted a lot of attention due to their significant bioactivities, such as anti-tumor activity, antioxidant activity, anticoagulant activity, antidiabetic activity, radioprotection effect, anti-viral activity, hypolipidemic and immunomodulatory activities, which make them suitable for medicinal applications. Previous studies have also shown that medicinal plant polysaccharides are non-toxic and show no side effects. Based on these encouraging observations, most researches have been focusing on the isolation and identification of polysaccharides, as well as their bioactivities. A large number of bioactive polysaccharides with different structural features and biological effects from medicinal plants have been purified and characterized. This review provides a comprehensive summary of the most recent developments in physiochemical, structural features and biological activities of bioactive polysaccharides from a number of important medicinal plants, such as polysaccharides from Astragalus membranaceus, Dendrobium plants, Bupleurum, Cactus fruits, Acanthopanax senticosus, Angelica sinensis (Oliv.) Diels, Aloe barbadensis Miller, and Dimocarpus longan Lour. Moreover, the paper has also been focused on the applications of bioactive polysaccharides for medicinal applications. Recent studies have provided evidence that polysaccharides from medicinal plants can play a vital role in bioactivities. The contents and data will serve as a useful reference material for further investigation, production, and application of these polysaccharides in functional foods and therapeutic agents.

  10. Loop Virasoro Lie conformal algebra

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Henan, E-mail: wuhenanby@163.com; Chen, Qiufan; Yue, Xiaoqing [Department of Mathematics, Tongji University, Shanghai 200092 (China)

    2014-01-15

    The Lie conformal algebra of loop Virasoro algebra, denoted by CW, is introduced in this paper. Explicitly, CW is a Lie conformal algebra with C[∂]-basis (L{sub i} | i∈Z) and λ-brackets [L{sub i} {sub λ} L{sub j}] = (−∂−2λ)L{sub i+j}. Then conformal derivations of CW are determined. Finally, rank one conformal modules and Z-graded free intermediate series modules over CW are classified.

  11. Reflections on Conformal Spectra

    CERN Document Server

    CERN. Geneva

    2015-01-01

    We use modular invariance and crossing symmetry of conformal field theory to reveal approximate reflection symmetries in the spectral decompositions of the partition function in two dimensions in the limit of large central charge and of the four-point function in any dimension in the limit of large scaling dimensions Δ0 of external operators. We use these symmetries to motivate universal upper bounds on the spectrum and the operator product expansion coefficients, which we then derive by independent techniques. Some of the bounds for four-point functions are valid for finite Δ0 as well as for large Δ0. We discuss a similar symmetry in a large spacetime dimension limit. Finally, we comment on the analogue of the Cardy formula and sparse light spectrum condition for the four-point function. (based on 1510.08772 with Kim & Ooguri). This seminar will be given via videolink

  12. Conformal frames in cosmology

    CERN Document Server

    Domènech, Guillem

    2016-01-01

    From higher dimensional theories, e.g. string theory, one expects the presence of non-minimally coupled scalar fields. We review the notion of conformal frames in cosmology and emphasize their physical equivalence, which holds at least at a classical level. Furthermore, if there is a field, or fields, which dominates the universe, as it is often the case in cosmology, we can use such notion of frames to treat our system, matter and gravity, as two different sectors. On one hand, the gravity sector which describes the dynamics of the geometry and on the other hand the matter sector which has such geometry as a playground. We use this interpretation to build a model where the fact that a curvaton couples to a particular frame metric could leave an imprint in the CMB.

  13. Reflections on Conformal Spectra

    CERN Document Server

    Kim, Hyungrok; Ooguri, Hirosi

    2015-01-01

    We use modular invariance and crossing symmetry of conformal field theory to reveal approximate reflection symmetries in the spectral decompositions of the partition function in two dimensions in the limit of large central charge and of the four-point function in any dimension in the limit of large scaling dimensions $\\Delta_0$ of external operators. We use these symmetries to motivate universal upper bounds on the spectrum and the operator product expansion coefficients, which we then derive by independent techniques. Some of the bounds for four-point functions are valid for finite $\\Delta_0$ as well as for large $\\Delta_0$. We discuss a similar symmetry in a large spacetime dimension limit. Finally, we comment on the analogue of the Cardy formula and sparse light spectrum condition for the four-point function.

  14. Neural network methods for identification and optimization of quantum mechanical features needed for bioactivity.

    Science.gov (United States)

    Braunheim, B B; Schwartz, S D

    2000-09-01

    This paper presents a new approach to the discovery and design of bioactive compounds. The focus of this application will be on the analysis of enzymatic inhibitors. At present the discovery of enzymatic inhibitors for therapeutic use is often accomplished through random searches. The first phase of discovery is a random search through a large pre-fabricated chemical library. Many molecules are tested with refined enzyme for signs of inhibition. Once a group of lead compounds have been discovered the chemical intuition of biochemists is used to find structurally related compounds that are more effective. This step requires new molecules to be conceived and synthesized, and it is the most time-consuming and expensive step. The development of computational and theoretical methods for prediction of the molecular structure that would bind most tightly prior to synthesis and testing, would facilitate the design of novel inhibitors. In the past, our work has focused on solving the problem of predicting the bioactivity of a molecule prior to synthesis. We used a neural network trained with the bioactivity of known compounds to predict the bioactivity of unknown compounds. In our current work, we use a separate neural network in conjunction with a trained neural network in an attempt to gain insight as to how to modify existing compounds and increase their bioactivity.

  15. Replacement between conformity and counter-conformity in consumption decisions.

    Science.gov (United States)

    Chou, Ting-Jui; Chang, En-Chung; Dai, Qi; Wong, Veronica

    2013-02-01

    This study assessed, in a Chinese context, how self-esteem interacts with perceived similarity and uniqueness to yield cognitive dissonance, and whether the dissonance leads to self-reported conformity or counter-conformity behavior. Participants were 408 respondents from 4 major Chinese cities (M age = 33.0 yr., SD = 4.3; 48% men). Self-perceptions of uniqueness, similarity, cognitive dissonance, self-esteem and need to behave in conformity or counter-conformity were measured. A theoretical model was assessed in four situations, relating the ratings of self-esteem and perceived similarity/uniqueness to the way other people at a wedding were dressed, and the resultant cognitive dissonance and conformity/ counter-conformity behavior. Regardless of high or low self-esteem, all participants reported cognitive dissonance when they were told that they were dressed extremely similarly to or extremely differently from the other people attending the wedding. However, the conforming/counter-conforming strategies used by participants to resolve the cognitive dissonance differed. When encountering dissonance induced by the perceived extreme uniqueness of dress, participants with low self-esteem tended to say they would dress next time so as to conform with the way others were dressed, while those with high self-esteem indicated they would continue their counter-conformity in attire. When encountering dissonance induced by the perceived extreme similarity to others, both those with high and low self-esteem tended to say they would dress in an unorthodox manner to surprise other people in the future.

  16. Conformation of α,α,α'-Trisubstituted Cyclododecanone

    Institute of Scientific and Technical Information of China (English)

    WANG,Ming-An; ZHANG,Ning; LU,Hui-Zhe; WANG,Dao-Quan

    2007-01-01

    Ten α,α,α'-trisubstituted cyclododecanones were synthesized and characterized by elemental analyses, infrared,1H NMR and 13C NMR spectra, and X-ray diffraction. NMR data could not give conformational information clearly,but some of their ring skeleton conformations of cyclododecanone moiety were showed to remain the unchanged [3333]-2-one conformation with little distortion, while the others were changed to the [3324]-2-one conformation in their crystal structures. These are consistent with the results of molecular mechanics calculation with Sybyl 6.9 software and Tripos force field, and semi-empirical quantum calculation with AM1 method in Gaussian 98 software.Two geminal substituting groups are located at α-comer carbon atom, and the third group is at α-side-exo carbon atom in both conformations. Both [3333]-2-one and [3324]-2-one conformations are present in a dynamic equilibrium in the solution, but only one preferred conformation exists in the crystal solid.

  17. In silico Exploration of the Conformational Universe of GPCRs.

    Science.gov (United States)

    Rodríguez-Espigares, Ismael; Kaczor, Agnieszka A; Selent, Jana

    2016-07-01

    The structural plasticity of G protein coupled receptors (GPCRs) leads to a conformational universe going from inactive to active receptor states with several intermediate states. Many of them have not been captured yet and their role for GPCR activation is not well understood. The study of this conformational space and the transition dynamics between different receptor populations is a major challenge in molecular biophysics. The rational design of effector molecules that target such receptor populations allows fine-tuning receptor signalling with higher specificity to produce drugs with safer therapeutic profiles. In this minireview, we outline highly conserved receptor regions which are considered determinant for the establishment of distinct receptor states. We then discuss in-silico approaches such as dimensionality reduction methods and Markov State Models to explore the GPCR conformational universe and exploit the obtained conformations through structure-based drug design.

  18. The conformational dynamics of the mitochondrial Hsp70 chaperone.

    Science.gov (United States)

    Mapa, Koyeli; Sikor, Martin; Kudryavtsev, Volodymyr; Waegemann, Karin; Kalinin, Stanislav; Seidel, Claus A M; Neupert, Walter; Lamb, Don C; Mokranjac, Dejana

    2010-04-09

    Heat shock proteins 70 (Hsp70) represent a ubiquitous and conserved family of molecular chaperones involved in a plethora of cellular processes. The dynamics of their ATP hydrolysis-driven and cochaperone-regulated conformational cycle are poorly understood. We used fluorescence spectroscopy to analyze, in real time and at single-molecule resolution, the effects of nucleotides and cochaperones on the conformation of Ssc1, a mitochondrial member of the family. We report that the conformation of its ADP state is unexpectedly heterogeneous, in contrast to a uniform ATP state. Substrates are actively involved in determining the conformation of Ssc1. The J protein Mdj1 does not interact transiently with the chaperone, as generally believed, but rather is released slowly upon ATP hydrolysis. Analysis of the major bacterial Hsp70 revealed important differences between highly homologous members of the family, possibly explaining tuning of Hsp70 chaperones to meet specific functions in different organisms and cellular compartments.

  19. Design, synthesis, α-glucosidase inhibitory activity, molecular docking and QSAR studies of benzimidazole derivatives

    Science.gov (United States)

    Dinparast, Leila; Valizadeh, Hassan; Bahadori, Mir Babak; Soltani, Somaieh; Asghari, Behvar; Rashidi, Mohammad-Reza

    2016-06-01

    In this study the green, one-pot, solvent-free and selective synthesis of benzimidazole derivatives is reported. The reactions were catalyzed by ZnO/MgO containing ZnO nanoparticles as a highly effective, non-toxic and environmentally friendly catalyst. The structure of synthesized benzimidazoles was characterized using spectroscopic technics (FT-IR, 1HNMR, 13CNMR). Synthesized compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 3c, 3e, 3l and 4n were potent inhibitors with IC50 values ranging from 60.7 to 168.4 μM. In silico studies were performed to explore the binding modes and interactions between enzyme and synthesized benzimidazoles. Developed linear QSAR model based on density and molecular weight could predict bioactivity of newly synthesized compounds well. Molecular docking studies revealed the availability of some hydrophobic interactions. In addition, the bioactivity of most potent compounds had good correlation with estimated free energy of binding (ΔGbinding) which was calculated according to docked best conformations.

  20. Microtubule's conformational cap

    DEFF Research Database (Denmark)

    Chretien, D.; Janosi, I.; Taveau, J.C.

    1999-01-01

    The molecular mechanisms that allow elongation of the unstable microtubule lattice remain unclear. It is usually thought that the GDP-liganded tubulin lattice is capped by a small layer of GTP- or GDP-P(i)-liganded molecules, the so called "GTP-cap". Here, we point-out that the elastic properties...

  1. Counselor Identity: Conformity or Distinction?

    Science.gov (United States)

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  2. Self-assembly, Dynamics and Chirality of Conformational Switches on Metal Surfaces Studied by UHV-STM

    DEFF Research Database (Denmark)

    Nuermaimaiti, Ajiguli

    2013-01-01

    Molecular self-assembly is essential in the bottom-up design of nanostructures. Molecular conformational switches are highly interesting both from the basic science of view to enhance our understanding of molecular dynamics in adsorption systems, and also due to potential applications such as mol......Molecular self-assembly is essential in the bottom-up design of nanostructures. Molecular conformational switches are highly interesting both from the basic science of view to enhance our understanding of molecular dynamics in adsorption systems, and also due to potential applications...... structures formed by the conformational switches and statistical analysis of conformational states, a detailed study of dynamic processes is performed by acquiring time-resolved STM data. Furthermore, one of the possible applications of conformational switches towards inducing chirality in surface assemblies...

  3. Initial conformation of kinesin's neck linker

    CERN Document Server

    Geng, Yi-Zhao; Liu, Shu-Xia; Yan, Shiwei

    2013-01-01

    How ATP binding initiates the docking process of kinesin's neck linker is a key question in understanding kinesin mechanism. It is believed that the formation of an extra turn structure by the first three amino acids of neck linker (LYS325, THR326, ILE327 in 2KIN) is crucial for initiating the docking process. But the initial conformation of neck linker (specially the three amino acids of the extra turn) and the neck linker docking initiation mechanism remain unclear. By using molecular dynamics method, we investigate the initial conformation of kinesin's neck linker in the docking process. We find that, in the initial state of NL docking process, NL still has interactions with {\\beta}0 and forms a conformation similar to the "cover-neck bundle" structure proposed by Hwang et al. [Structure 2008, 16(1): 62-71]. From this initial structure, the docking of the "cover-neck bundle" structure can be achieved. The motor head provides a forward force on the initial cover-neck bundle structure through ATP-induced rot...

  4. Eikonalization of Conformal Blocks

    CERN Document Server

    Fitzpatrick, A Liam; Walters, Matthew T; Wang, Junpu

    2015-01-01

    Classical field configurations such as the Coulomb potential and Schwarzschild solution are built from the $t$-channel exchange of many light degrees of freedom. We study the CFT analog of this phenomenon, which we term the `eikonalization' of conformal blocks. We show that when an operator $T$ appears in the OPE $\\mathcal{O}(x) \\mathcal{O}(0)$, then the large spin $\\ell$ Fock space states $[TT \\cdots T]_{\\ell}$ also appear in this OPE with a computable coefficient. The sum over the exchange of these Fock space states in an $\\langle \\mathcal{O} \\mathcal{O} \\mathcal{O} \\mathcal{O} \\rangle$ correlator build the classical `$T$ field' in the dual AdS description. In some limits the sum of all Fock space exchanges can be represented as the exponential of a single $T$ exchange in the 4-pt correlator of $\\mathcal{O}$. Our results should be useful for systematizing $1/\\ell$ perturbation theory in general CFTs and simplifying the computation of large spin OPE coefficients. As examples we obtain the leading $\\log \\ell$...

  5. The Conformal Standard Model

    CERN Document Server

    Latosinski, Adam; Meissner, Krzysztof A; Nicolai, Hermann

    2015-01-01

    We present an extended version of the Conformal Standard Model (characterized by the absence of any new intermediate scales between the electroweak scale and the Planck scale) with an enlarged scalar sector coupling to right-chiral neutrinos in such a way that the scalar potential and the Yukawa couplings involving only right-chiral neutrinos are invariant under a new global symmetry SU(3)$_N$ which is broken explicitly only by the Yukawa interaction coupling right-chiral neutrinos and the electroweak lepton doublets. We point out four main advantages of such an enlargement, namely: (1) the economy of the (non-supersymmetric) Standard Model, and thus its observational success, is preserved; (2) thanks to the enlarged scalar sector the RG improved one-loop effective potential is everywhere positive with a stable global minimum, thereby avoiding the notorious instability of the Standard Model vacuum; (3) the pseudo-Goldstone bosons resulting from spontaneous breaking of the SU(3)$_N$ symmetry are natural Dark M...

  6. Screening and target identification of bioactive compounds that modulate cell migration and autophagy.

    Science.gov (United States)

    Tashiro, Etsu; Imoto, Masaya

    2016-08-01

    Cell migration is a fundamental step for embryonic development, wound repair, immune responses, and tumor cell invasion and metastasis. It is well known that protrusive structures, namely filopodia and lamellipodia, can be observed at the leading edge of migrating cells. The formation of these structures is necessary for cell migration; however, the molecular mechanisms behind the formation of these structures remain largely unclear. Therefore, bioactive compounds that modulate protrusive structures are extremely powerful tools for studying the mechanisms behind the formation of these structures and subsequent cell migration. Therefore, we have screened for bioactive compounds that inhibit the formation of filopodia, lamellipodia, or cell migration from natural products, and attempted to identify the target molecules of our isolated compounds. Additionally, autophagy is a bulk, non-specific protein degradation system that is involved in the pathogenesis of cancer and neurodegenerative disorders. Recent extensive studies have revealed the molecular mechanisms of autophagy, however, they also remain largely unclear. Thus, we also have screened for bioactive compounds that modulate autophagy, and identified the target molecules. In the present article, we introduce the phenotypic screening system and target identification of four bioactive compounds.

  7. Conformation-dependent DNA attraction

    Science.gov (United States)

    Li, Weifeng; Nordenskiöld, Lars; Zhou, Ruhong; Mu, Yuguang

    2014-05-01

    Understanding how DNA molecules interact with other biomolecules is related to how they utilize their functions and is therefore critical for understanding their structure-function relationships. For a long time, the existence of Z-form DNA (a left-handed double helical version of DNA, instead of the common right-handed B-form) has puzzled the scientists, and the definitive biological significance of Z-DNA has not yet been clarified. In this study, the effects of DNA conformation in DNA-DNA interactions are explored by molecular dynamics simulations. Using umbrella sampling, we find that for both B- and Z-form DNA, surrounding Mg2+ ions always exert themselves to screen the Coulomb repulsion between DNA phosphates, resulting in very weak attractive force. On the contrary, a tight and stable bound state is discovered for Z-DNA in the presence of Mg2+ or Na+, benefiting from their hydrophobic nature. Based on the contact surface and a dewetting process analysis, a two-stage binding process of Z-DNA is outlined: two Z-DNA first attract each other through charge screening and Mg2+ bridges to phosphate groups in the same way as that of B-DNA, after which hydrophobic contacts of the deoxyribose groups are formed via a dewetting effect, resulting in stable attraction between two Z-DNA molecules. The highlighted hydrophobic nature of Z-DNA interaction from the current study may help to understand the biological functions of Z-DNA in gene transcription.Understanding how DNA molecules interact with other biomolecules is related to how they utilize their functions and is therefore critical for understanding their structure-function relationships. For a long time, the existence of Z-form DNA (a left-handed double helical version of DNA, instead of the common right-handed B-form) has puzzled the scientists, and the definitive biological significance of Z-DNA has not yet been clarified. In this study, the effects of DNA conformation in DNA-DNA interactions are explored by

  8. Regular Submanifolds in Conformal Space Qnp

    Institute of Scientific and Technical Information of China (English)

    Changxiong NIE; Chuanxi WU

    2012-01-01

    The authors study the regular submanifolds in the conformal space Qnp and introduce the submanifold theory in the conformal space Qnp.The first variation formula of the Willmore volume functional of pseudo-Riemannian submanifolds in the conformal space Qnp is given.Finally,the conformal isotropic submanifolds in the conformal space Qnp are classified.

  9. Milk proteins as precursors of bioactive peptides

    Directory of Open Access Journals (Sweden)

    Marta Dziuba

    2009-03-01

    Full Text Available Milk proteins, a source of bioactive peptides, are the subject of numerous research studies aiming to, among others, evaluate their properties as precursors of biologically active peptides. Physiologically active peptides released from their precursors may interact with selected receptors and affect the overall condition and health of humans. By relying on the BIOPEP database of proteins and bioactive peptides, developed by the Department of Food Biochemistry at the University of Warmia and Mazury in Olsztyn (www.uwm.edu.pl/biochemia, the profiles of potential activity of milk proteins were determined and the function of those proteins as bioactive peptide precursors was evaluated based on a quantitative criterion, i.e. the occurrence frequency of bioactive fragments (A. The study revealed that milk proteins are mainly a source of peptides with the following types of activity: antihypertensive (Amax = 0.225, immunomodulating (0.024, smooth muscle contracting (0.011, antioxidative (0.029, dipeptidyl peptidase IV inhibitors (0.148, opioid (0.073, opioid antagonistic (0.053, bonding and transporting metals and metal ions (0.024, antibacterial and antiviral (0.024, and antithrombotic (0.029. The enzymes capable of releasing bioactive peptides from precursor proteins were determined for every type of activity. The results of the experiment indicate that milk proteins such as lactoferrin, α-lactalbumin, β-casein and κ-casein hydrolysed by trypsin can be a relatively abundant source of biologically active peptides.

  10. Microencapsulation of bioactives for food applications.

    Science.gov (United States)

    Dias, Maria Inês; Ferreira, Isabel C F R; Barreiro, Maria Filomena

    2015-04-01

    Health issues are an emerging concern to the world population, and therefore the food industry is searching for novel food products containing health-promoting bioactive compounds, with little or no synthetic ingredients. However, there are some challenges in the development of functional foods, particularly in which the direct use of some bioactives is involved. They can show problems of instability, react with other food matrix ingredients or present strong odour and/or flavours. In this context, microencapsulation emerges as a potential approach to overcome these problems and, additionally, to provide controlled or targeted delivery or release. This work intends to contribute to the field of functional food development by performing a comprehensive review on the microencapsulation methods and materials, the bioactives used (extracts and isolated compounds) and the final application development. Although several studies dealing with microencapsulation of bioactives exist, they are mainly focused on the process development and the majority lack proof of concept for final applications. These factors, together with the lack of regulation, in Europe and in the United States, delay the development of new functional foods and, consequently, their market entry. In conclusion, the potential of microencapsulation to protect bioactive compounds ensuring their bioavailability is shown, but further studies are required, considering both its applicability and incentives by regulatory agencies.

  11. Bioactive glass-ceramics coatings on alumina

    Energy Technology Data Exchange (ETDEWEB)

    Vitale Brovarone, C.; Verne, E.; Lupo, F. [Politecnico di Torino (Italy). Materials Science and Chemical Eng. Dept.; Moisescu, C. [Jena Univ. (Germany). Otto-Schott-Inst. fuer Glaschemie; Zanardi, L.; Bosetti, M.; Cannas, M. [Eastern Piemont Univ., Novara (Italy). Medical Science Dept.

    2001-07-01

    In this work, aiming to combine the mechanical performances of alumina with the surface properties of a bioactive material, we coated full density alumina substrates by a bioactive glass-ceramic GC. This latter was specially tailored, in term of costituents and specific quantity to have a thermal expansion coefficient close to that of alumina (8.5-9{sup *}10{sup -6}/ C) which is lower than most of the bioactive glasses and glass-ceramics already in use. In this way, we sought to avoid, as much as possible, the crack formation and propagation due to residual stresses generated by the thermal expansion coefficients mismatch. Furthermore, the high reactivity of alumina toward the glass-ceramic was carefully controlled to avoid deep compositional modification of the GC that will negatively affect its bioactivity. At this purpose, an intermediate layer of an appropriate glass G was coated prior to coat the bioactive glass-ceramic. On the materials obtained, preliminary biological tests have been done to evaluate glass-ceramic biocompatibility respect to alumina. (orig.)

  12. Photoregulation of polymer conformation. A modelstudy for biology

    NARCIS (Netherlands)

    Veen, Gerlof van der

    1972-01-01

    SUMMARY A conformational transition of a macromolecule is often postulated to occur in biological energy transductions. When +he energy of a photon is transduced, a photochromic ligand mediates in the transfer of energy from the sun to the macromolecule. In this thesis the molecular mechanism of tho

  13. Conformational fluctuations affect protein alignment in dilute liquid crystal media

    DEFF Research Database (Denmark)

    Louhivuori, M.; Otten, R.; Lindorff-Larsen, Kresten

    2006-01-01

    The discovery of dilute liquid crystalline media to align biological macromolecules has opened many new possibilities to study protein and nucleic acid structures by NMR spectroscopy. We inspect the basic alignment phenomenon for an ensemble of protein conformations to deduce relative contributions...... molecular surfaces. Furthermore, we consider the implications of a dynamic bias to structure determination using data from the weak alignment method....

  14. Applications of biochromatography in the screening of bioactive natural products.

    Science.gov (United States)

    Chen, Cen; Yang, Feng-Qing; Zuo, Hua-Li; Song, Yue-Lin; Xia, Zhi-Ning; Xiao, Wen

    2013-09-01

    Searching for bioactive compounds from natural resources such as plant materials has become a focus for study. Several models, such as animal (biofluid, organ and tissue) and cellular (several kinds of cell lines), have traditionally been used for this purpose. As a fast, economic and effective way to identify or predict bioactive compounds in complex matrices, biochromatography has developed rapidly during the past years. Combing the properties of traditional chromatography and biomaterials, biochromatographic analysis possesses features of simultaneous screening, separation and structural identification for active compounds in a complex matrix. According to the process, biochromatography can be divided into offline and online approaches. For offline bioextraction, the biomaterials are used as the extraction phase and followed by routine chromatographic analysis. For online biochromatography, the biomaterials are directly used as the stationary phase for chromatographic analysis. This paper reviews the applications of offline bioextraction followed by chromatographic analysis and online biochromatography, including molecular, cell membrane and cell, and artificial biomembrane chromatography in the screening or predicting active compounds from natural sources.

  15. PREPARATION AND CATALYTIC ACTIVITY OF BIOACTIVE FIBERS

    Institute of Scientific and Technical Information of China (English)

    Yu-yuan Yao; Wen-xing Chen; Bao-yan Zhao; Shen-shui Lü

    2006-01-01

    Two kinds of water-soluble metallophthalocyanines, binuclear cobalt phthalocyanine (Co2Pc2) and binuclear ferric phthalocyanine (Fe2Pc2), were synthesized through phenylanhydride-urea route and characterized by elemental analysis and FT-IR spectra. Binuclear metallophthalocyanine derivatives (Mt2Pc2) were immobilized on silk fibers and modified viscose fibers to construct bioactive fibers of mimic enzyme. Mt2Pc2 was used as the active center ofbioactive fibers, viscose and silk fibers as the microenvironments. The catalytic oxidation ability of bioactive fibers on the malodors of methanthiol and hydrogen sulfide was investigated at room temperature. The experimental results indicated that the catalytic activity of such bioactive fibers was closely correlative to the types ofbioactive fibers and substrates.

  16. Conformal Patterson-Walker metrics

    CERN Document Server

    Hammerl, Matthias; Šilhan, Josef; Taghavi-Chabert, Arman; Žádník, Vojtěch

    2016-01-01

    The classical Patterson-Walker construction of a split-signature (pseudo-)Riemannian structure from a given torsion-free affine connection is generalized to a construction of a split-signature conformal structure from a given projective class of connections. A characterization of the induced structures is obtained. We achieve a complete description of Einstein metrics in the conformal class formed by the Patterson-Walker metric. Finally, we describe all symmetries of the conformal Patterson-Walker metric. In both cases we obtain descriptions in terms of geometric data on the original structure.

  17. Conformational study of neutral histamine monomer and their vibrational spectra

    Science.gov (United States)

    Mukherjee, V.; Yadav, T.

    2016-08-01

    Molecular modeling and potential energy scanning of histamine molecule, which is an important neurotransmitter, with respect to the dihedral angle of methylamine side chain have done which prefer three different conformers of histamine monomer. We have calculated molecular structures and vibrational spectra with IR and Raman intensities of these conformers using Density Functional Theory (DFT) with the exchange functional B3LYP incorporated with the basis set 6-31 ++G(d,p) and Hartree-Fock (HF) with the same basis set. We have also employed normal coordinate analysis (NCA) to scale the theoretical frequencies and to calculate potential energy distributions (PEDs) for the conspicuous assignments. Normal modes assignments of some of the vibrational frequencies of all the three conformers are in good agreement with the earlier reported experimental frequencies of histamine whereas others have modified. The standard deviations between the theoretical and experimental frequencies fall in the region 13-20 cm- 1 for the three conformers. NBO analyses of histamine conformers were also performed. The net charge transfers from ethylamine side chain to the imidazole ring. The intensive interactions between bonding and anti-bonding orbitals are found in imidazole ring. The HOMO-LUMO energy gap is nearly 5.50 eV.

  18. Logarithmic conformal field theory

    Science.gov (United States)

    Gainutdinov, Azat; Ridout, David; Runkel, Ingo

    2013-12-01

    Conformal field theory (CFT) has proven to be one of the richest and deepest subjects of modern theoretical and mathematical physics research, especially as regards statistical mechanics and string theory. It has also stimulated an enormous amount of activity in mathematics, shaping and building bridges between seemingly disparate fields through the study of vertex operator algebras, a (partial) axiomatisation of a chiral CFT. One can add to this that the successes of CFT, particularly when applied to statistical lattice models, have also served as an inspiration for mathematicians to develop entirely new fields: the Schramm-Loewner evolution and Smirnov's discrete complex analysis being notable examples. When the energy operator fails to be diagonalisable on the quantum state space, the CFT is said to be logarithmic. Consequently, a logarithmic CFT is one whose quantum space of states is constructed from a collection of representations which includes reducible but indecomposable ones. This qualifier arises because of the consequence that certain correlation functions will possess logarithmic singularities, something that contrasts with the familiar case of power law singularities. While such logarithmic singularities and reducible representations were noted by Rozansky and Saleur in their study of the U (1|1) Wess-Zumino-Witten model in 1992, the link between the non-diagonalisability of the energy operator and logarithmic singularities in correlators is usually ascribed to Gurarie's 1993 article (his paper also contains the first usage of the term 'logarithmic conformal field theory'). The class of CFTs that were under control at this time was quite small. In particular, an enormous amount of work from the statistical mechanics and string theory communities had produced a fairly detailed understanding of the (so-called) rational CFTs. However, physicists from both camps were well aware that applications from many diverse fields required significantly more

  19. Conformation of antifreeze glycoproteins as determined from conformational energy calculations and fully assigned proton NMR spectra

    Energy Technology Data Exchange (ETDEWEB)

    Bush, C.A.; Rao, B.N.N.

    1986-05-01

    The /sup 1/H NMR spectra of AFGP's ranging in molecular weight from 2600 to 30,000 Daltons isolated from several different species of polar fish have been measured. The spectrum of AFGP 1-4 from Pagothenia borchgrevinki with an average of 30 repeating subunits has a single resonance for each proton of the glycotripeptide repeating unit, (ala-(gal-(..beta..-1..-->..3) galNAc-(..cap alpha..--O-)thr-ala)/sub n/. Its /sup 1/H NMR spectrum including resonances of the amide protons has been completely assigned. Coupling constants and nuclear Overhauser enhancements (n.O.e.) between protons on distant residues imply conformational order. The 2600 dalton molecular weight glycopeptides (AFGP-8) have pro in place of ala at certain specific points in the sequence and AFGP-8R of Eleginus gracilis has arg in place of one thr. The resonances of pro and arg were assigned by decoupling. The resonances of the carboxy and amino terminals have distinct chemical shifts and were assigned in AFGP-8 of Boreogadus saida by titration. n.O.e. between ..cap alpha..--protons and amide protons of the adjacent residue (sequential n.O.e.) were used in assignments of additional resonances and to assign the distinctive resonances of thr followed by pro. Conformational energy calculations on the repeating glycotripeptide subunit of AFGP show that the ..cap alpha..--glucosidic linkage has a fixed conformation while the ..beta..--linkage is less rigid. A conformational model for AFGP 1-4, which is based on the calculations has the peptide in an extended left-handed helix with three residues per turn similar to polyproline II. The model is consistent with CD data, amide proton coupling constants, temperature dependence of amide proton chemical shifts.

  20. Some Progress in Conformal Geometry

    Directory of Open Access Journals (Sweden)

    Sun-Yung A. Chang

    2007-12-01

    Full Text Available This is a survey paper of our current research on the theory of partial differential equations in conformal geometry. Our intention is to describe some of our current works in a rather brief and expository fashion. We are not giving a comprehensive survey on the subject and references cited here are not intended to be complete. We introduce a bubble tree structure to study the degeneration of a class of Yamabe metrics on Bach flat manifolds satisfying some global conformal bounds on compact manifolds of dimension 4. As applications, we establish a gap theorem, a finiteness theorem for diffeomorphism type for this class, and diameter bound of the $sigma_2$-metrics in a class of conformal 4-manifolds. For conformally compact Einstein metrics we introduce an eigenfunction compactification. As a consequence we obtain some topological constraints in terms of renormalized volumes.

  1. Graphene-based conformal devices.

    Science.gov (United States)

    Park, Yong Ju; Lee, Seoung-Ki; Kim, Min-Seok; Kim, Hyunmin; Ahn, Jong-Hyun

    2014-08-26

    Despite recent progress in bendable and stretchable thin-film transistors using novel designs and materials, the development of conformal devices remains limited by the insufficient flexibility of devices. Here, we demonstrate the fabrication of graphene-based conformal and stretchable devices such as transistor and tactile sensor on a substrate with a convoluted surface by scaling down the device thickness. The 70 nm thick graphene-based conformal devices displayed a much lower bending stiffness than reported previously. The demonstrated devices provided excellent conformal coverage over an uneven animal hide surface without the need for an adhesive. In addition, the ultrathin graphene devices formed on the three-dimensionally curved animal hide exhibited stable electrical characteristics, even under repetitive bending and twisting. The advanced performance and flexibility demonstrated here show promise for the development and adoption of wearable electronics in a wide range of future applications.

  2. National Automated Conformity Inspection Process -

    Data.gov (United States)

    Department of Transportation — The National Automated Conformity Inspection Process (NACIP) Application is intended to expedite the workflow process as it pertains to the FAA Form 81 0-10 Request...

  3. Conformational dynamics of a ligand-free adenylate kinase.

    Directory of Open Access Journals (Sweden)

    Hyun Deok Song

    Full Text Available Adenylate kinase (AdK is a phosphoryl-transfer enzyme with important physiological functions. Based on a ligand-free open structure and a ligand-bound closed structure solved by crystallography, here we use molecular dynamics simulations to examine the stability and dynamics of AdK conformations in the absence of ligands. We first perform multiple simulations starting from the open or the closed structure, and observe their free evolutions during a simulation time of 100 or 200 nanoseconds. In all seven simulations starting from the open structure, AdK remained stable near the initial conformation. The eight simulations initiated from the closed structure, in contrast, exhibited large variation in the subsequent evolutions, with most (seven undergoing large-scale spontaneous conformational changes and approaching or reaching the open state. To characterize the thermodynamics of the transition, we propose and apply a new sampling method that employs a series of restrained simulations to calculate a one-dimensional free energy along a curved pathway in the high-dimensional conformational space. Our calculated free energy profile features a single minimum at the open conformation, and indicates that the closed state, with a high (∼13 kcal/mol free energy, is not metastable, consistent with the observed behaviors of the unrestrained simulations. Collectively, our simulations suggest that it is energetically unfavorable for the ligand-free AdK to access the closed conformation, and imply that ligand binding may precede the closure of the enzyme.

  4. Different molecular conformations co-exist in each of three 2-aryl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamides: hydrogen bonding in zero, one and two dimensions.

    Science.gov (United States)

    Narayana, Badiadka; Yathirajan, Hemmige S; Rathore, Ravindranath S; Glidewell, Christopher

    2016-09-01

    4-Antipyrine [4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one] and its derivatives exhibit a range of biological activities, including analgesic, antibacterial and anti-inflammatory, and new examples are always of potential interest and value. 2-(4-Chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, C19H18ClN3O2, (I), crystallizes with Z' = 2 in the space group P\\overline{1}, whereas its positional isomer 2-(2-chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, (II), crystallizes with Z' = 1 in the space group C2/c; the molecules of (II) are disordered over two sets of atomic sites having occupancies of 0.6020 (18) and 0.3980 (18). The two independent molecules of (I) adopt different molecular conformations, as do the two disorder components in (II), where the 2-chlorophenyl substituents adopt different orientations. The molecules of (I) are linked by a combination of N-H...O and C-H...O hydrogen bonds to form centrosymmetric four-molecule aggregates, while those of (II) are linked by the same types of hydrogen bonds forming sheets. The related compound N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-(3-methoxyphenyl)acetamide, C20H21N3O3, (III), is isomorphous with (I) but not strictly isostructural; again the two independent molecules adopt different molecular conformations, and the molecules are linked by N-H...O and C-H...O hydrogen bonds to form ribbons. Comparisons are made with some related structures, indicating that a hydrogen-bonded R2(2)(10) ring is the common structural motif.

  5. Mushroom Lectins: Specificity, Structure and Bioactivity Relevant to Human Disease

    Directory of Open Access Journals (Sweden)

    Mohamed Ali Abol Hassan

    2015-04-01

    Full Text Available Lectins are non-immunoglobulin proteins that bind diverse sugar structures with a high degree of selectivity. Lectins play crucial role in various biological processes such as cellular signaling, scavenging of glycoproteins from the circulatory system, cell–cell interactions in the immune system, differentiation and protein targeting to cellular compartments, as well as in host defence mechanisms, inflammation, and cancer. Among all the sources of lectins, plants have been most extensively studied. However, more recently fungal lectins have attracted considerable attention due to their antitumor, antiproliferative and immunomodulatory activities. Given that only 10% of mushroom species are known and have been taxonomically classified, mushrooms represent an enormous unexplored source of potentially useful and novel lectins. In this review we provide an up-to-date summary on the biochemical, molecular and structural properties of mushroom lectins, as well as their versatile applications specifically focusing on mushroom lectin bioactivity.

  6. Bioactivities of Novel Metal Complexes Involving B Vitamins and Glycine

    Directory of Open Access Journals (Sweden)

    Fazary Ahmed E.

    2016-01-01

    Full Text Available In this work twelve novel mixed ligand complexes were synthesized. The complexes were formed between a metal ion (Cu(II, Cd(II, Mn(II, Fe(III, Ni(II, Pb(II and vitamins (B 3 and B 9 as primary ligands, and glycine as secondary ligand. Melting points, conductivities, and magnetic susceptibilities of the synthesized complexes were determined and the complexes were subjected to elemental analyses. The presence of coordination water molecules in the complex was also supported by TG/DTG thermal analysis. Full elucidation of the molecular structures for the synthesized mixed ligand complexes were confirmed using detailed spectroscopic IR, 1H-, 13C-NMR, and XRD techniques. In addition, cytotoxic and antioxidant activities of the twelve synthesized solid complexes were tested to evaluate their bioactivities.

  7. Effect of Gastrointestinal Protease Digestion on Bioactivity of Marine Peptides

    DEFF Research Database (Denmark)

    Jensen, Ida-Johanne; Andersen, Lisa Lystbæk; Ossum, Carlo Gunnar;

    2014-01-01

    executed without concerning subsequent digestion after intake and the aim of this work was hence to investigate how the in vitro antioxidative, antihypertensive and caspase activating activities of peptides are affected by digestion with gastrointestinal (GI) proteases. Five different fish protein...... hydrolysates were chosen to study the effect of in vitro digestion on bioactivity. The protein concentration decreased in all samples during digestion and the molecular weight distribution of the peptides shifted towards lower values. Thus, in vitro digestion with GI proteases resulted in a further degradation...... of the peptides obtained by hydrolysis. The antihypertensive effect increased in all samples after digestion with GI proteases whereas the antioxidative capacity decreased. The effect on the caspase activity depended on the proteases used in the preparation of hydrolysates. In conclusion, the caspase activity...

  8. Encapsulation for preservation of functionality and targeted delivery of bioactive food components

    NARCIS (Netherlands)

    de Vos, Paul; Faas, Marijke M.; Spasojevic, Milica; Sikkema, Jan

    2010-01-01

    There has been a tremendous increase in the number of food products containing bioactive components with a health promoting or disease preventing effect. Bioactive food components can be divided into bioactive molecules and bioactive living cells (probiotics). Both bioactive molecules and bioactive

  9. Simple, yet powerful methodologies for conformational sampling of proteins.

    Science.gov (United States)

    Harada, Ryuhei; Takano, Yu; Baba, Takeshi; Shigeta, Yasuteru

    2015-03-07

    Several biological functions, such as molecular recognition, enzyme catalysis, signal transduction, allosteric regulation, and protein folding, are strongly related to conformational transitions of proteins. These conformational transitions are generally induced as slow dynamics upon collective motions, including biologically relevant large-amplitude fluctuations of proteins. Although molecular dynamics (MD) simulation has become a powerful tool for extracting conformational transitions of proteins, it might still be difficult to reach time scales of the biological functions because the accessible time scales of MD simulations are far from biological time scales, even if straightforward conventional MD (CMD) simulations using massively parallel computers are employed. Thus, it is desirable to develop efficient methods to achieve canonical ensembles with low computational costs. From this perspective, we review several enhanced conformational sampling techniques of biomolecules developed by us. In our methods, multiple independent short-time MD simulations are employed instead of single straightforward long-time CMD simulations. Our basic strategy is as follows: (i) selection of initial seeds (initial structures) for the conformational sampling in restarting MD simulations. Here, the seeds should be selected as candidates with high potential to transit. (ii) Resampling from the selected seeds by initializing velocities in restarting short-time MD simulations. A cycle of these simple protocols might drastically promote the conformational transitions of biomolecules. (iii) Once reactive trajectories extracted from the cycles of short-time MD simulations are obtained, a free energy profile is evaluated by means of umbrella sampling (US) techniques with the weighted histogram analysis method (WHAM) as a post-processing technique. For the selection of the initial seeds, we proposed four different choices: (1) Parallel CaScade molecular dynamics (PaCS-MD), (2) Fluctuation

  10. Role of bioactive lipid mediators in obese adipose tissue inflammation and endocrine dysfunction.

    OpenAIRE

    Lopategi, Aritz; López-Vicario, Cristina; Alcaraz-Quiles, José; García-Alonso, Verónica; Rius, Bibiana; Titos Rodríguez, Esther; Clària i Enrich, Joan

    2015-01-01

    White adipose tissue is recognized as an active endocrine organ implicated in the maintenance of metabolic homeostasis. However, adipose tissue function, which has a crucial role in the development of obesity-related comorbidities including insulin resistance and non-alcoholic fatty liver disease, is dysregulated in obese individuals. This review explores the physiological functions and molecular actions of bioactive lipids biosynthesized in adipose tissue including sphingolipids and phosphol...

  11. Energy levels and quantum states of [Leu]enkephalin conformations based on theoretical and experimental investigations

    DEFF Research Database (Denmark)

    Abdali, Salim; Jensen, Morten Østergaard; Bohr, Henrik

    2003-01-01

    This paper describes a theoretical and experimental study of [Leu]enkephalin conformations with respect to the quantum estates of the atomic structure of the peptide. Results from vibrational absorption measurements and quantum calculations are used to outline a quantum picture and to assign...... vibrational modes to the different conformations. The energy landscape of the conformations is reported as a function of a Hamming distance in Ramachandran space. Molecular dynamics simulations reveal a pronounced stability of the so-called single-bend low-energy conformation, which supports the derived...... quantum picture of this peptide....

  12. The two conformers of acetanilide unraveled using LA-MB-FTMW spectroscopy

    Science.gov (United States)

    Cabezas, C.; Varela, M.; Caminati, W.; Mata, S.; López, J. C.; Alonso, J. L.

    2011-07-01

    Acetanilide has been investigated by laser ablation molecular beam Fourier transform microwave LA-MB-FTMW spectroscopy. The rotational spectrum of both trans and cis conformers have been analyzed to determine the rotational and 14N quadrupole coupling the constants. The spectrum of the less abundant cis conformer has been assigned for the first time. The doublets observed for this conformer have been interpreted in terms of the tunneling motion between two equivalent non-planar conformations through a small barrier in which the acetamide group and phenyl ring plane are perpendicular. The results are compared with those of the related formanilide.

  13. Bioactive alkaloids in vertically transmitted fungal endophytes

    Science.gov (United States)

    Plants form mutualistic symbioses with a variety of microorganisms, including endophytic fungi that live inside the plant and cause no symptoms of infection. Some endophytic fungi form defensive mutualisms based on the production of bioactive metabolites that protect the plant from herbivores in exc...

  14. Marine bioactives and potential application in sports.

    Science.gov (United States)

    Gammone, Maria Alessandra; Gemello, Eugenio; Riccioni, Graziano; D'Orazio, Nicolantonio

    2014-04-30

    An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

  15. Glutathione conjugation as a bioactivation reaction

    NARCIS (Netherlands)

    Bladeren, P.J. van

    2000-01-01

    In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate

  16. Bioactive compounds in whole grain wheat

    NARCIS (Netherlands)

    Mateo Anson, N.

    2010-01-01

    Bread can be healthier! Consuming whole-grain foods can prevent cardiovascular diseases, type-2 diabetes and metabolic syndrome. This is due to bioactive compounds in whole grain, such as antioxidants and anti-inflammatory compounds. We found that the different fractions of a wheat grain vary much i

  17. Citrus Limonoids: Analysis, Bioactivity, and Biomedical Prospects

    Science.gov (United States)

    This publication is a review of the chemistry, biochemistry and bioactivity of limonoids occurring in citrus. The review chronologically relates the evolution of research in citrus limonoids beginning with their association with bitterness development in citrus juices. The chemical and biochemical...

  18. Bioactive motifs of agouti signal protein.

    Science.gov (United States)

    Virador, V M; Santis, C; Furumura, M; Kalbacher, H; Hearing, V J

    2000-08-25

    The switch between the synthesis of eu- and pheomelanins is modulated by the interaction of two paracrine signaling molecules, alpha-melanocyte stimulating hormone (MSH) and agouti signal protein (ASP), which interact with melanocytes via the MSH receptor (MC1R). Comparison of the primary sequence of ASP with the known MSH pharmacophore provides no suggestion about the putative bioactive domain(s) of ASP. To identify such bioactive motif(s), we synthesized 15-mer peptides that spanned the primary sequence of ASP and determined their effects on the melanogenic activities of murine melanocytes. Northern and Western blotting were used, together with chemical analysis of melanins and enzymatic assays, to identify three distinct bioactive regions of ASP that down-regulate eumelanogenesis. The decrease in eumelanin production was mediated by down-regulation of mRNA levels for tyrosinase and other melanogenic enzymes, as occurs in vivo, and these effects were comparable to those elicited by intact recombinant ASP. Shorter peptides in those motifs were synthesized and their effects on melanogenesis were further investigated. The amino acid arginine, which is present in the MSH peptide pharmacophore (HFRW), is also in the most active domain of ASP (KVARP). Our data suggest that lysines and an arginine (in motifs such as KxxxxKxxR or KxxRxxxxK) are important for the bioactivity of ASP. Identification of the specific ASP epitope that interacts with the MC1R has potential pharmacological applications in treating dysfunctions of skin pigmentation.

  19. Marine Bioactives and Potential Application in Sports

    Directory of Open Access Journals (Sweden)

    Maria Alessandra Gammone

    2014-04-01

    Full Text Available An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP, such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB, macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

  20. Bioactive Terpenes from Marine-Derived Fungi

    Directory of Open Access Journals (Sweden)

    Ahmed M. Elissawy

    2015-04-01

    Full Text Available Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years’ reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities.