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Sample records for protein structure calculation

  1. Automated protein structure calculation from NMR data

    International Nuclear Information System (INIS)

    Williamson, Mike P.; Craven, C. Jeremy

    2009-01-01

    Current software is almost at the stage to permit completely automatic structure determination of small proteins of <15 kDa, from NMR spectra to structure validation with minimal user interaction. This goal is welcome, as it makes structure calculation more objective and therefore more easily validated, without any loss in the quality of the structures generated. Moreover, it releases expert spectroscopists to carry out research that cannot be automated. It should not take much further effort to extend automation to ca 20 kDa. However, there are technological barriers to further automation, of which the biggest are identified as: routines for peak picking; adoption and sharing of a common framework for structure calculation, including the assembly of an automated and trusted package for structure validation; and sample preparation, particularly for larger proteins. These barriers should be the main target for development of methodology for protein structure determination, particularly by structural genomics consortia

  2. Principal components analysis of protein structure ensembles calculated using NMR data

    International Nuclear Information System (INIS)

    Howe, Peter W.A.

    2001-01-01

    One important problem when calculating structures of biomolecules from NMR data is distinguishing converged structures from outlier structures. This paper describes how Principal Components Analysis (PCA) has the potential to classify calculated structures automatically, according to correlated structural variation across the population. PCA analysis has the additional advantage that it highlights regions of proteins which are varying across the population. To apply PCA, protein structures have to be reduced in complexity and this paper describes two different representations of protein structures which achieve this. The calculated structures of a 28 amino acid peptide are used to demonstrate the methods. The two different representations of protein structure are shown to give equivalent results, and correct results are obtained even though the ensemble of structures used as an example contains two different protein conformations. The PCA analysis also correctly identifies the structural differences between the two conformations

  3. Effects of NMR spectral resolution on protein structure calculation.

    Directory of Open Access Journals (Sweden)

    Suhas Tikole

    Full Text Available Adequate digital resolution and signal sensitivity are two critical factors for protein structure determinations by solution NMR spectroscopy. The prime objective for obtaining high digital resolution is to resolve peak overlap, especially in NOESY spectra with thousands of signals where the signal analysis needs to be performed on a large scale. Achieving maximum digital resolution is usually limited by the practically available measurement time. We developed a method utilizing non-uniform sampling for balancing digital resolution and signal sensitivity, and performed a large-scale analysis of the effect of the digital resolution on the accuracy of the resulting protein structures. Structure calculations were performed as a function of digital resolution for about 400 proteins with molecular sizes ranging between 5 and 33 kDa. The structural accuracy was assessed by atomic coordinate RMSD values from the reference structures of the proteins. In addition, we monitored also the number of assigned NOESY cross peaks, the average signal sensitivity, and the chemical shift spectral overlap. We show that high resolution is equally important for proteins of every molecular size. The chemical shift spectral overlap depends strongly on the corresponding spectral digital resolution. Thus, knowing the extent of overlap can be a predictor of the resulting structural accuracy. Our results show that for every molecular size a minimal digital resolution, corresponding to the natural linewidth, needs to be achieved for obtaining the highest accuracy possible for the given protein size using state-of-the-art automated NOESY assignment and structure calculation methods.

  4. Determination of structural fluctuations of proteins from structure-based calculations of residual dipolar couplings

    International Nuclear Information System (INIS)

    Montalvao, Rinaldo W.; De Simone, Alfonso; Vendruscolo, Michele

    2012-01-01

    Residual dipolar couplings (RDCs) have the potential of providing detailed information about the conformational fluctuations of proteins. It is very challenging, however, to extract such information because of the complex relationship between RDCs and protein structures. A promising approach to decode this relationship involves structure-based calculations of the alignment tensors of protein conformations. By implementing this strategy to generate structural restraints in molecular dynamics simulations we show that it is possible to extract effectively the information provided by RDCs about the conformational fluctuations in the native states of proteins. The approach that we present can be used in a wide range of alignment media, including Pf1, charged bicelles and gels. The accuracy of the method is demonstrated by the analysis of the Q factors for RDCs not used as restraints in the calculations, which are significantly lower than those corresponding to existing high-resolution structures and structural ensembles, hence showing that we capture effectively the contributions to RDCs from conformational fluctuations.

  5. A tool for calculating binding-site residues on proteins from PDB structures

    Directory of Open Access Journals (Sweden)

    Hu Jing

    2009-08-01

    Full Text Available Abstract Background In the research on protein functional sites, researchers often need to identify binding-site residues on a protein. A commonly used strategy is to find a complex structure from the Protein Data Bank (PDB that consists of the protein of interest and its interacting partner(s and calculate binding-site residues based on the complex structure. However, since a protein may participate in multiple interactions, the binding-site residues calculated based on one complex structure usually do not reveal all binding sites on a protein. Thus, this requires researchers to find all PDB complexes that contain the protein of interest and combine the binding-site information gleaned from them. This process is very time-consuming. Especially, combing binding-site information obtained from different PDB structures requires tedious work to align protein sequences. The process becomes overwhelmingly difficult when researchers have a large set of proteins to analyze, which is usually the case in practice. Results In this study, we have developed a tool for calculating binding-site residues on proteins, TCBRP http://yanbioinformatics.cs.usu.edu:8080/ppbindingsubmit. For an input protein, TCBRP can quickly find all binding-site residues on the protein by automatically combining the information obtained from all PDB structures that consist of the protein of interest. Additionally, TCBRP presents the binding-site residues in different categories according to the interaction type. TCBRP also allows researchers to set the definition of binding-site residues. Conclusion The developed tool is very useful for the research on protein binding site analysis and prediction.

  6. Ab Initio Calculations of the Electronic Structures and Biological Functions of Protein Molecules

    Science.gov (United States)

    Zheng, Haoping

    2003-04-01

    The self-consistent cluster-embedding (SCCE) calculation method reduces the computational effort from M3 to about M1 (M is the number of atoms in the system) with unchanged calculation precision. So the ab initio, all-electron calculation of the electronic structure and biological function of protein molecule becomes a reality, which will promote new proteomics considerably. The calculated results of two real protein molecules, the trypsin inhibitor from the seeds of squash Cucurbita maxima (CMTI-I, 436 atoms) and the Ascaris trypsin inhibitor (912 atoms, two three-dimensional structures), are presented. The reactive sites of the inhibitors are determined and explained. The precision of structure determination of inhibitors are tested theoretically.

  7. VMD-SS: A graphical user interface plug-in to calculate the protein secondary structure in VMD program.

    Science.gov (United States)

    Yahyavi, Masoumeh; Falsafi-Zadeh, Sajad; Karimi, Zahra; Kalatarian, Giti; Galehdari, Hamid

    2014-01-01

    The investigation on the types of secondary structure (SS) of a protein is important. The evolution of secondary structures during molecular dynamics simulations is a useful parameter to analyze protein structures. Therefore, it is of interest to describe VMD-SS (a software program) for the identification of secondary structure elements and its trajectories during simulation for known structures available at the Protein Data Bank (PDB). The program helps to calculate (1) percentage SS, (2) SS occurrence in each residue, (3) percentage SS during simulation, and (4) percentage residues in all SS types during simulation. The VMD-SS plug-in was designed using TCL script and stride to calculate secondary structure features. The database is available for free at http://science.scu.ac.ir/HomePage.aspx?TabID=13755.

  8. Quantum mechanical electronic structure calculation reveals orientation dependence of hydrogen bond energy in proteins.

    Science.gov (United States)

    Mondal, Abhisek; Datta, Saumen

    2017-06-01

    Hydrogen bond plays a unique role in governing macromolecular interactions with exquisite specificity. These interactions govern the fundamental biological processes like protein folding, enzymatic catalysis, molecular recognition. Despite extensive research work, till date there is no proper report available about the hydrogen bond's energy surface with respect to its geometric parameters, directly derived from proteins. Herein, we have deciphered the potential energy landscape of hydrogen bond directly from the macromolecular coordinates obtained from Protein Data Bank using quantum mechanical electronic structure calculations. The findings unravel the hydrogen bonding energies of proteins in parametric space. These data can be used to understand the energies of such directional interactions involved in biological molecules. Quantitative characterization has also been performed using Shannon entropic calculations for atoms participating in hydrogen bond. Collectively, our results constitute an improved way of understanding hydrogen bond energies in case of proteins and complement the knowledge-based potential. Proteins 2017; 85:1046-1055. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Conformational energy calculations on polypeptides and proteins: use of a statistical mechanical procedure for evaluating structure and properties.

    Science.gov (United States)

    Scheraga, H A; Paine, G H

    1986-01-01

    We are using a variety of theoretical and computational techniques to study protein structure, protein folding, and higher-order structures. Our earlier work involved treatments of liquid water and aqueous solutions of nonpolar and polar solutes, computations of the stabilities of the fundamental structures of proteins and their packing arrangements, conformations of small cyclic and open-chain peptides, structures of fibrous proteins (collagen), structures of homologous globular proteins, introduction of special procedures as constraints during energy minimization of globular proteins, and structures of enzyme-substrate complexes. Recently, we presented a new methodology for predicting polypeptide structure (described here); the method is based on the calculation of the probable and average conformation of a polypeptide chain by the application of equilibrium statistical mechanics in conjunction with an adaptive, importance sampling Monte Carlo algorithm. As a test, it was applied to Met-enkephalin.

  10. Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations.

    Science.gov (United States)

    Marcoline, Frank V; Bethel, Neville; Guerriero, Christopher J; Brodsky, Jeffrey L; Grabe, Michael

    2015-08-04

    The electrostatic properties of membrane proteins often reveal many of their key biophysical characteristics, such as ion channel selectivity and the stability of charged membrane-spanning segments. The Poisson-Boltzmann (PB) equation is the gold standard for calculating protein electrostatics, and the software APBSmem enables the solution of the PB equation in the presence of a membrane. Here, we describe significant advances to APBSmem, including full automation of system setup, per-residue energy decomposition, incorporation of PDB2PQR, calculation of membrane-induced pKa shifts, calculation of non-polar energies, and command-line scripting for large-scale calculations. We highlight these new features with calculations carried out on a number of membrane proteins, including the recently solved structure of the ion channel TRPV1 and a large survey of 1,614 membrane proteins of known structure. This survey provides a comprehensive list of residues with large electrostatic penalties for being embedded in the membrane, potentially revealing interesting functional information. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. On the development of protein pKa calculation algorithms

    Science.gov (United States)

    Carstensen, Tommy; Farrell, Damien; Huang, Yong; Baker, Nathan A.; Nielsen, Jens Erik

    2011-01-01

    Protein pKa calculation methods are developed partly to provide fast non-experimental estimates of the ionization constants of protein side chains. However, the most significant reason for developing such methods is that a good pKa calculation method is presumed to provide an accurate physical model of protein electrostatics, which can be applied in methods for drug design, protein design and other structure-based energy calculation methods. We explore the validity of this presumption by simulating the development of a pKa calculation method using artificial experimental data derived from a human-defined physical reality. We examine the ability of an RMSD-guided development protocol to retrieve the correct (artificial) physical reality and find that a rugged optimization landscape and a huge parameter space prevent the identification of the correct physical reality. We examine the importance of the training set in developing pKa calculation methods and investigate the effect of experimental noise on our ability to identify the correct physical reality, and find that both effects have a significant and detrimental impact on the physical reality of the optimal model identified. Our findings are of relevance to all structure-based methods for protein energy calculations and simulation, and have large implications for all types of current pKa calculation methods. Our analysis furthermore suggests that careful and extensive validation on many types of experimental data can go some way in making current models more realistic. PMID:21744393

  12. The pKa Cooperative: a collaborative effort to advance structure-based calculations of pKa values and electrostatic effects in proteins.

    Science.gov (United States)

    Nielsen, Jens E; Gunner, M R; García-Moreno, Bertrand E

    2011-12-01

    The pK(a) Cooperative (http://www.pkacoop.org) was organized to advance development of accurate and useful computational methods for structure-based calculation of pK(a) values and electrostatic energies in proteins. The Cooperative brings together laboratories with expertise and interest in theoretical, computational, and experimental studies of protein electrostatics. To improve structure-based energy calculations, it is necessary to better understand the physical character and molecular determinants of electrostatic effects. Thus, the Cooperative intends to foment experimental research into fundamental aspects of proteins that depend on electrostatic interactions. It will maintain a depository for experimental data useful for critical assessment of methods for structure-based electrostatics calculations. To help guide the development of computational methods, the Cooperative will organize blind prediction exercises. As a first step, computational laboratories were invited to reproduce an unpublished set of experimental pK(a) values of acidic and basic residues introduced in the interior of staphylococcal nuclease by site-directed mutagenesis. The pK(a) values of these groups are unique and challenging to simulate owing to the large magnitude of their shifts relative to normal pK(a) values in water. Many computational methods were tested in this first Blind Prediction Challenge and critical assessment exercise. A workshop was organized in the Telluride Science Research Center to objectively assess the performance of many computational methods tested on this one extensive data set. This volume of Proteins: Structure, Function, and Bioinformatics introduces the pK(a) Cooperative, presents reports submitted by participants in the Blind Prediction Challenge, and highlights some of the problems in structure-based calculations identified during this exercise. Copyright © 2011 Wiley-Liss, Inc.

  13. Amino acid code of protein secondary structure.

    Science.gov (United States)

    Shestopalov, B V

    2003-01-01

    The calculation of protein three-dimensional structure from the amino acid sequence is a fundamental problem to be solved. This paper presents principles of the code theory of protein secondary structure, and their consequence--the amino acid code of protein secondary structure. The doublet code model of protein secondary structure, developed earlier by the author (Shestopalov, 1990), is part of this theory. The theory basis are: 1) the name secondary structure is assigned to the conformation, stabilized only by the nearest (intraresidual) and middle-range (at a distance no more than that between residues i and i + 5) interactions; 2) the secondary structure consists of regular (alpha-helical and beta-structural) and irregular (coil) segments; 3) the alpha-helices, beta-strands and coil segments are encoded, respectively, by residue pairs (i, i + 4), (i, i + 2), (i, i = 1), according to the numbers of residues per period, 3.6, 2, 1; 4) all such pairs in the amino acid sequence are codons for elementary structural elements, or structurons; 5) the codons are divided into 21 types depending on their strength, i.e. their encoding capability; 6) overlappings of structurons of one and the same structure generate the longer segments of this structure; 7) overlapping of structurons of different structures is forbidden, and therefore selection of codons is required, the codon selection is hierarchic; 8) the code theory of protein secondary structure generates six variants of the amino acid code of protein secondary structure. There are two possible kinds of model construction based on the theory: the physical one using physical properties of amino acid residues, and the statistical one using results of statistical analysis of a great body of structural data. Some evident consequences of the theory are: a) the theory can be used for calculating the secondary structure from the amino acid sequence as a partial solution of the problem of calculation of protein three

  14. Compare local pocket and global protein structure models by small structure patterns

    KAUST Repository

    Cui, Xuefeng

    2015-09-09

    Researchers proposed several criteria to assess the quality of predicted protein structures because it is one of the essential tasks in the Critical Assessment of Techniques for Protein Structure Prediction (CASP) competitions. Popular criteria include root mean squared deviation (RMSD), MaxSub score, TM-score, GDT-TS and GDT-HA scores. All these criteria require calculation of rigid transformations to superimpose the the predicted protein structure to the native protein structure. Yet, how to obtain the rigid transformations is unknown or with high time complexity, and, hence, heuristic algorithms were proposed. In this work, we carefully design various small structure patterns, including the ones specifically tuned for local pockets. Such structure patterns are biologically meaningful, and address the issue of relying on a sufficient number of backbone residue fragments for existing methods. We sample the rigid transformations from these small structure patterns; and the optimal superpositions yield by these small structures are refined and reported. As a result, among 11; 669 pairs of predicted and native local protein pocket models from the CASP10 dataset, the GDT-TS scores calculated by our method are significantly higher than those calculated by LGA. Moreover, our program is computationally much more efficient. Source codes and executables are publicly available at http://www.cbrc.kaust.edu.sa/prosta/

  15. Calculation of accurate small angle X-ray scattering curves from coarse-grained protein models

    Directory of Open Access Journals (Sweden)

    Stovgaard Kasper

    2010-08-01

    Full Text Available Abstract Background Genome sequencing projects have expanded the gap between the amount of known protein sequences and structures. The limitations of current high resolution structure determination methods make it unlikely that this gap will disappear in the near future. Small angle X-ray scattering (SAXS is an established low resolution method for routinely determining the structure of proteins in solution. The purpose of this study is to develop a method for the efficient calculation of accurate SAXS curves from coarse-grained protein models. Such a method can for example be used to construct a likelihood function, which is paramount for structure determination based on statistical inference. Results We present a method for the efficient calculation of accurate SAXS curves based on the Debye formula and a set of scattering form factors for dummy atom representations of amino acids. Such a method avoids the computationally costly iteration over all atoms. We estimated the form factors using generated data from a set of high quality protein structures. No ad hoc scaling or correction factors are applied in the calculation of the curves. Two coarse-grained representations of protein structure were investigated; two scattering bodies per amino acid led to significantly better results than a single scattering body. Conclusion We show that the obtained point estimates allow the calculation of accurate SAXS curves from coarse-grained protein models. The resulting curves are on par with the current state-of-the-art program CRYSOL, which requires full atomic detail. Our method was also comparable to CRYSOL in recognizing native structures among native-like decoys. As a proof-of-concept, we combined the coarse-grained Debye calculation with a previously described probabilistic model of protein structure, TorusDBN. This resulted in a significant improvement in the decoy recognition performance. In conclusion, the presented method shows great promise for

  16. Fragment-based quantum mechanical calculation of protein-protein binding affinities.

    Science.gov (United States)

    Wang, Yaqian; Liu, Jinfeng; Li, Jinjin; He, Xiao

    2018-04-29

    The electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method has been successfully utilized for efficient linear-scaling quantum mechanical (QM) calculation of protein energies. In this work, we applied the EE-GMFCC method for calculation of binding affinity of Endonuclease colicin-immunity protein complex. The binding free energy changes between the wild-type and mutants of the complex calculated by EE-GMFCC are in good agreement with experimental results. The correlation coefficient (R) between the predicted binding energy changes and experimental values is 0.906 at the B3LYP/6-31G*-D level, based on the snapshot whose binding affinity is closest to the average result from the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculation. The inclusion of the QM effects is important for accurate prediction of protein-protein binding affinities. Moreover, the self-consistent calculation of PB solvation energy is required for accurate calculations of protein-protein binding free energies. This study demonstrates that the EE-GMFCC method is capable of providing reliable prediction of relative binding affinities for protein-protein complexes. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  17. Molecular mechanics calculations of proteins. Comparison of different energy minimization strategies

    DEFF Research Database (Denmark)

    Christensen, I T; Jørgensen, Flemming Steen

    1997-01-01

    A general strategy for performing energy minimization of proteins using the SYBYL molecular modelling program has been developed. The influence of several variables including energy minimization procedure, solvation, dielectric function and dielectric constant have been investigated in order...... to develop a general method, which is capable of producing high quality protein structures. Avian pancreatic polypeptide (APP) and bovine pancreatic phospholipase A2 (BP PLA2) were selected for the calculations, because high quality X-ray structures exist and because all classes of secondary structure...... for this protein. Energy minimized structures of the trimeric PLA2 from Indian cobra (N.n.n. PLA2) were used for assessing the impact of protein-protein interactions. Based on the above mentioned criteria, it could be concluded that using the following conditions: Dielectric constant epsilon = 4 or 20; a distance...

  18. Binding free energy analysis of protein-protein docking model structures by evERdock.

    Science.gov (United States)

    Takemura, Kazuhiro; Matubayasi, Nobuyuki; Kitao, Akio

    2018-03-14

    To aid the evaluation of protein-protein complex model structures generated by protein docking prediction (decoys), we previously developed a method to calculate the binding free energies for complexes. The method combines a short (2 ns) all-atom molecular dynamics simulation with explicit solvent and solution theory in the energy representation (ER). We showed that this method successfully selected structures similar to the native complex structure (near-native decoys) as the lowest binding free energy structures. In our current work, we applied this method (evERdock) to 100 or 300 model structures of four protein-protein complexes. The crystal structures and the near-native decoys showed the lowest binding free energy of all the examined structures, indicating that evERdock can successfully evaluate decoys. Several decoys that show low interface root-mean-square distance but relatively high binding free energy were also identified. Analysis of the fraction of native contacts, hydrogen bonds, and salt bridges at the protein-protein interface indicated that these decoys were insufficiently optimized at the interface. After optimizing the interactions around the interface by including interfacial water molecules, the binding free energies of these decoys were improved. We also investigated the effect of solute entropy on binding free energy and found that consideration of the entropy term does not necessarily improve the evaluations of decoys using the normal model analysis for entropy calculation.

  19. Study of high-performance canonical molecular orbitals calculation for proteins

    Science.gov (United States)

    Hirano, Toshiyuki; Sato, Fumitoshi

    2017-11-01

    The canonical molecular orbital (CMO) calculation can help to understand chemical properties and reactions in proteins. However, it is difficult to perform the CMO calculation of proteins because of its self-consistent field (SCF) convergence problem and expensive computational cost. To certainly obtain the CMO of proteins, we work in research and development of high-performance CMO applications and perform experimental studies. We have proposed the third-generation density-functional calculation method of calculating the SCF, which is more advanced than the FILE and direct method. Our method is based on Cholesky decomposition for two-electron integrals calculation and the modified grid-free method for the pure-XC term evaluation. By using the third-generation density-functional calculation method, the Coulomb, the Fock-exchange, and the pure-XC terms can be given by simple linear algebraic procedure in the SCF loop. Therefore, we can expect to get a good parallel performance in solving the SCF problem by using a well-optimized linear algebra library such as BLAS on the distributed memory parallel computers. The third-generation density-functional calculation method is implemented to our program, ProteinDF. To achieve computing electronic structure of the large molecule, not only overcoming expensive computation cost and also good initial guess for safe SCF convergence are required. In order to prepare a precise initial guess for the macromolecular system, we have developed the quasi-canonical localized orbital (QCLO) method. The QCLO has the characteristics of both localized and canonical orbital in a certain region of the molecule. We have succeeded in the CMO calculations of proteins by using the QCLO method. For simplified and semi-automated calculation of the QCLO method, we have also developed a Python-based program, QCLObot.

  20. Proteins in vacuo. A more efficient means of calculating ...

    African Journals Online (AJOL)

    and dynamic behavior, studies of protein ions in vacuo have become popular in recent years. ... descriptors include radius of gyration Rgyr, principal moments of inertia {Ii}, and root-mean- square deviations (RMSD) from a standard structure. ..... modelling the effects of molecular fluctuations on the cross section calculations.

  1. Accurate protein structure modeling using sparse NMR data and homologous structure information.

    Science.gov (United States)

    Thompson, James M; Sgourakis, Nikolaos G; Liu, Gaohua; Rossi, Paolo; Tang, Yuefeng; Mills, Jeffrey L; Szyperski, Thomas; Montelione, Gaetano T; Baker, David

    2012-06-19

    While information from homologous structures plays a central role in X-ray structure determination by molecular replacement, such information is rarely used in NMR structure determination because it can be incorrect, both locally and globally, when evolutionary relationships are inferred incorrectly or there has been considerable evolutionary structural divergence. Here we describe a method that allows robust modeling of protein structures of up to 225 residues by combining (1)H(N), (13)C, and (15)N backbone and (13)Cβ chemical shift data, distance restraints derived from homologous structures, and a physically realistic all-atom energy function. Accurate models are distinguished from inaccurate models generated using incorrect sequence alignments by requiring that (i) the all-atom energies of models generated using the restraints are lower than models generated in unrestrained calculations and (ii) the low-energy structures converge to within 2.0 Å backbone rmsd over 75% of the protein. Benchmark calculations on known structures and blind targets show that the method can accurately model protein structures, even with very remote homology information, to a backbone rmsd of 1.2-1.9 Å relative to the conventional determined NMR ensembles and of 0.9-1.6 Å relative to X-ray structures for well-defined regions of the protein structures. This approach facilitates the accurate modeling of protein structures using backbone chemical shift data without need for side-chain resonance assignments and extensive analysis of NOESY cross-peak assignments.

  2. Solution structure and dynamics of melanoma inhibitory activity protein

    International Nuclear Information System (INIS)

    Lougheed, Julie C.; Domaille, Peter J.; Handel, Tracy M.

    2002-01-01

    Melanoma inhibitory activity (MIA) is a small secreted protein that is implicated in cartilage cell maintenance and melanoma metastasis. It is representative of a recently discovered family of proteins that contain a Src Homologous 3 (SH3) subdomain. While SH3 domains are normally found in intracellular proteins and mediate protein-protein interactions via recognition of polyproline helices, MIA is single-domain extracellular protein, and it probably binds to a different class of ligands.Here we report the assignments, solution structure, and dynamics of human MIA determined by heteronuclear NMR methods. The structures were calculated in a semi-automated manner without manual assignment of NOE crosspeaks, and have a backbone rmsd of 0.38 A over the ordered regions of the protein. The structure consists of an SH3-like subdomain with N- and C-terminal extensions of approximately 20 amino acids each that together form a novel fold. The rmsd between the solution structure and our recently reported crystal structure is 0.86 A over the ordered regions of the backbone, and the main differences are localized to the most dynamic regions of the protein. The similarity between the NMR and crystal structures supports the use of automated NOE assignments and ambiguous restraints to accelerate the calculation of NMR structures

  3. Protein structure estimation from NMR data by matrix completion.

    Science.gov (United States)

    Li, Zhicheng; Li, Yang; Lei, Qiang; Zhao, Qing

    2017-09-01

    Knowledge of protein structures is very important to understand their corresponding physical and chemical properties. Nuclear Magnetic Resonance (NMR) spectroscopy is one of the main methods to measure protein structure. In this paper, we propose a two-stage approach to calculate the structure of a protein from a highly incomplete distance matrix, where most data are obtained from NMR. We first randomly "guess" a small part of unobservable distances by utilizing the triangle inequality, which is crucial for the second stage. Then we use matrix completion to calculate the protein structure from the obtained incomplete distance matrix. We apply the accelerated proximal gradient algorithm to solve the corresponding optimization problem. Furthermore, the recovery error of our method is analyzed, and its efficiency is demonstrated by several practical examples.

  4. Introducing DInaMo: A Package for Calculating Protein Circular Dichroism Using Classical Electromagnetic Theory

    Directory of Open Access Journals (Sweden)

    Igor V. Uporov

    2015-09-01

    Full Text Available The dipole interaction model is a classical electromagnetic theory for calculating circular dichroism (CD resulting from the π-π* transitions of amides. The theoretical model, pioneered by J. Applequist, is assembled into a package, DInaMo, written in Fortran allowing for treatment of proteins. DInaMo reads Protein Data Bank formatted files of structures generated by molecular mechanics or reconstructed secondary structures. Crystal structures cannot be used directly with DInaMo; they either need to be rebuilt with idealized bond angles and lengths, or they need to be energy minimized to adjust bond lengths and bond angles because it is common for crystal structure geometries to have slightly short bond lengths, and DInaMo is sensitive to this. DInaMo reduces all the amide chromophores to points with anisotropic polarizability and all nonchromophoric aliphatic atoms including hydrogens to points with isotropic polarizability; all other atoms are ignored. By determining the interactions among the chromophoric and nonchromophoric parts of the molecule using empirically derived polarizabilities, the rotational and dipole strengths are determined leading to the calculation of CD. Furthermore, ignoring hydrogens bound to methyl groups is initially explored and proves to be a good approximation. Theoretical calculations on 24 proteins agree with experiment showing bands with similar morphology and maxima.

  5. Protein structure database search and evolutionary classification.

    Science.gov (United States)

    Yang, Jinn-Moon; Tung, Chi-Hua

    2006-01-01

    As more protein structures become available and structural genomics efforts provide structural models in a genome-wide strategy, there is a growing need for fast and accurate methods for discovering homologous proteins and evolutionary classifications of newly determined structures. We have developed 3D-BLAST, in part, to address these issues. 3D-BLAST is as fast as BLAST and calculates the statistical significance (E-value) of an alignment to indicate the reliability of the prediction. Using this method, we first identified 23 states of the structural alphabet that represent pattern profiles of the backbone fragments and then used them to represent protein structure databases as structural alphabet sequence databases (SADB). Our method enhanced BLAST as a search method, using a new structural alphabet substitution matrix (SASM) to find the longest common substructures with high-scoring structured segment pairs from an SADB database. Using personal computers with Intel Pentium4 (2.8 GHz) processors, our method searched more than 10 000 protein structures in 1.3 s and achieved a good agreement with search results from detailed structure alignment methods. [3D-BLAST is available at http://3d-blast.life.nctu.edu.tw].

  6. WatAA: Atlas of Protein Hydration. Exploring synergies between data mining and ab initio calculations.

    Science.gov (United States)

    Černý, Jiří; Schneider, Bohdan; Biedermannová, Lada

    2017-07-14

    Water molecules represent an integral part of proteins and a key determinant of protein structure, dynamics and function. WatAA is a newly developed, web-based atlas of amino-acid hydration in proteins. The atlas provides information about the ordered first hydration shell of the most populated amino-acid conformers in proteins. The data presented in the atlas are drawn from two sources: experimental data and ab initio quantum-mechanics calculations. The experimental part is based on a data-mining study of a large set of high-resolution protein crystal structures. The crystal-derived data include 3D maps of water distribution around amino-acids and probability of occurrence of each of the identified hydration sites. The quantum mechanics calculations validate and extend this primary description by optimizing the water position for each hydration site, by providing hydrogen atom positions and by quantifying the interaction energy that stabilizes the water molecule at the particular hydration site position. The calculations show that the majority of experimentally derived hydration sites are positioned near local energy minima for water, and the calculated interaction energies help to assess the preference of water for the individual hydration sites. We propose that the atlas can be used to validate water placement in electron density maps in crystallographic refinement, to locate water molecules mediating protein-ligand interactions in drug design, and to prepare and evaluate molecular dynamics simulations. WatAA: Atlas of Protein Hydration is freely available without login at .

  7. A novel Multi-Agent Ada-Boost algorithm for predicting protein structural class with the information of protein secondary structure.

    Science.gov (United States)

    Fan, Ming; Zheng, Bin; Li, Lihua

    2015-10-01

    Knowledge of the structural class of a given protein is important for understanding its folding patterns. Although a lot of efforts have been made, it still remains a challenging problem for prediction of protein structural class solely from protein sequences. The feature extraction and classification of proteins are the main problems in prediction. In this research, we extended our earlier work regarding these two aspects. In protein feature extraction, we proposed a scheme by calculating the word frequency and word position from sequences of amino acid, reduced amino acid, and secondary structure. For an accurate classification of the structural class of protein, we developed a novel Multi-Agent Ada-Boost (MA-Ada) method by integrating the features of Multi-Agent system into Ada-Boost algorithm. Extensive experiments were taken to test and compare the proposed method using four benchmark datasets in low homology. The results showed classification accuracies of 88.5%, 96.0%, 88.4%, and 85.5%, respectively, which are much better compared with the existing methods. The source code and dataset are available on request.

  8. 3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

    International Nuclear Information System (INIS)

    Cui, P.X.; Lian, F.L.; Wang, Y.; Wen, Yi; Chu, W.S.; Zhao, H.F.; Zhang, S.; Li, J.; Lin, D.H.; Wu, Z.Y.

    2014-01-01

    Prion-related protein (PrP), a cell-surface copper-binding glycoprotein, is considered to be responsible for a number of transmissible spongiform encephalopathies (TSEs). The structural conversion of PrP from the normal cellular isoform (PrP C ) to the post-translationally modified form (PrP Sc ) is thought to be relevant to Cu 2+ binding to histidine residues. Rabbits are one of the few mammalian species that appear to be resistant to TSEs, because of the structural characteristics of the rabbit prion protein (RaPrP C ) itself. Here we determined the three-dimensional local structure around the C-terminal high-affinity copper-binding sites using X-ray absorption near-edge structure combined with ab initio calculations in the framework of the multiple-scattering (MS) theory. Result shows that two amino acid resides, Gln97 and Met108, and two histidine residues, His95 and His110, are involved in binding this copper(II) ion. It might help us understand the roles of copper in prion conformation conversions, and the molecular mechanisms of prion-involved diseases. - Highlights: ► The first structure of the metal ion binding site in RaPrP fifth copper-binding site. ► Quantitative determination by XANES spectroscopy combined with ab initio calculations. ► Provide a proof of the roles of copper in prion conformation conversions. ► Provide a proof of the molecular mechanisms of prion-involved diseases

  9. A computer graphics program system for protein structure representation.

    Science.gov (United States)

    Ross, A M; Golub, E E

    1988-01-01

    We have developed a computer graphics program system for the schematic representation of several protein secondary structure analysis algorithms. The programs calculate the probability of occurrence of alpha-helix, beta-sheet and beta-turns by the method of Chou and Fasman and assign unique predicted structure to each residue using a novel conflict resolution algorithm based on maximum likelihood. A detailed structure map containing secondary structure, hydrophobicity, sequence identity, sequence numbering and the location of putative N-linked glycosylation sites is then produced. In addition, helical wheel diagrams and hydrophobic moment calculations can be performed to further analyze the properties of selected regions of the sequence. As they require only structure specification as input, the graphics programs can easily be adapted for use with other secondary structure prediction schemes. The use of these programs to analyze protein structure-function relationships is described and evaluated. PMID:2832829

  10. PSAIA – Protein Structure and Interaction Analyzer

    Directory of Open Access Journals (Sweden)

    Vlahoviček Kristian

    2008-04-01

    Full Text Available Abstract Background PSAIA (Protein Structure and Interaction Analyzer was developed to compute geometric parameters for large sets of protein structures in order to predict and investigate protein-protein interaction sites. Results In addition to most relevant established algorithms, PSAIA offers a new method PIADA (Protein Interaction Atom Distance Algorithm for the determination of residue interaction pairs. We found that PIADA produced more satisfactory results than comparable algorithms implemented in PSAIA. Particular advantages of PSAIA include its capacity to combine different methods to detect the locations and types of interactions between residues and its ability, without any further automation steps, to handle large numbers of protein structures and complexes. Generally, the integration of a variety of methods enables PSAIA to offer easier automation of analysis and greater reliability of results. PSAIA can be used either via a graphical user interface or from the command-line. Results are generated in either tabular or XML format. Conclusion In a straightforward fashion and for large sets of protein structures, PSAIA enables the calculation of protein geometric parameters and the determination of location and type for protein-protein interaction sites. XML formatted output enables easy conversion of results to various formats suitable for statistic analysis. Results from smaller data sets demonstrated the influence of geometry on protein interaction sites. Comprehensive analysis of properties of large data sets lead to new information useful in the prediction of protein-protein interaction sites.

  11. MEGADOCK-Web: an integrated database of high-throughput structure-based protein-protein interaction predictions.

    Science.gov (United States)

    Hayashi, Takanori; Matsuzaki, Yuri; Yanagisawa, Keisuke; Ohue, Masahito; Akiyama, Yutaka

    2018-05-08

    Protein-protein interactions (PPIs) play several roles in living cells, and computational PPI prediction is a major focus of many researchers. The three-dimensional (3D) structure and binding surface are important for the design of PPI inhibitors. Therefore, rigid body protein-protein docking calculations for two protein structures are expected to allow elucidation of PPIs different from known complexes in terms of 3D structures because known PPI information is not explicitly required. We have developed rapid PPI prediction software based on protein-protein docking, called MEGADOCK. In order to fully utilize the benefits of computational PPI predictions, it is necessary to construct a comprehensive database to gather prediction results and their predicted 3D complex structures and to make them easily accessible. Although several databases exist that provide predicted PPIs, the previous databases do not contain a sufficient number of entries for the purpose of discovering novel PPIs. In this study, we constructed an integrated database of MEGADOCK PPI predictions, named MEGADOCK-Web. MEGADOCK-Web provides more than 10 times the number of PPI predictions than previous databases and enables users to conduct PPI predictions that cannot be found in conventional PPI prediction databases. In MEGADOCK-Web, there are 7528 protein chains and 28,331,628 predicted PPIs from all possible combinations of those proteins. Each protein structure is annotated with PDB ID, chain ID, UniProt AC, related KEGG pathway IDs, and known PPI pairs. Additionally, MEGADOCK-Web provides four powerful functions: 1) searching precalculated PPI predictions, 2) providing annotations for each predicted protein pair with an experimentally known PPI, 3) visualizing candidates that may interact with the query protein on biochemical pathways, and 4) visualizing predicted complex structures through a 3D molecular viewer. MEGADOCK-Web provides a huge amount of comprehensive PPI predictions based on

  12. Calculating ensemble averaged descriptions of protein rigidity without sampling.

    Science.gov (United States)

    González, Luis C; Wang, Hui; Livesay, Dennis R; Jacobs, Donald J

    2012-01-01

    Previous works have demonstrated that protein rigidity is related to thermodynamic stability, especially under conditions that favor formation of native structure. Mechanical network rigidity properties of a single conformation are efficiently calculated using the integer body-bar Pebble Game (PG) algorithm. However, thermodynamic properties require averaging over many samples from the ensemble of accessible conformations to accurately account for fluctuations in network topology. We have developed a mean field Virtual Pebble Game (VPG) that represents the ensemble of networks by a single effective network. That is, all possible number of distance constraints (or bars) that can form between a pair of rigid bodies is replaced by the average number. The resulting effective network is viewed as having weighted edges, where the weight of an edge quantifies its capacity to absorb degrees of freedom. The VPG is interpreted as a flow problem on this effective network, which eliminates the need to sample. Across a nonredundant dataset of 272 protein structures, we apply the VPG to proteins for the first time. Our results show numerically and visually that the rigidity characterizations of the VPG accurately reflect the ensemble averaged [Formula: see text] properties. This result positions the VPG as an efficient alternative to understand the mechanical role that chemical interactions play in maintaining protein stability.

  13. Protein Structure Prediction by Protein Threading

    Science.gov (United States)

    Xu, Ying; Liu, Zhijie; Cai, Liming; Xu, Dong

    The seminal work of Bowie, Lüthy, and Eisenberg (Bowie et al., 1991) on "the inverse protein folding problem" laid the foundation of protein structure prediction by protein threading. By using simple measures for fitness of different amino acid types to local structural environments defined in terms of solvent accessibility and protein secondary structure, the authors derived a simple and yet profoundly novel approach to assessing if a protein sequence fits well with a given protein structural fold. Their follow-up work (Elofsson et al., 1996; Fischer and Eisenberg, 1996; Fischer et al., 1996a,b) and the work by Jones, Taylor, and Thornton (Jones et al., 1992) on protein fold recognition led to the development of a new brand of powerful tools for protein structure prediction, which we now term "protein threading." These computational tools have played a key role in extending the utility of all the experimentally solved structures by X-ray crystallography and nuclear magnetic resonance (NMR), providing structural models and functional predictions for many of the proteins encoded in the hundreds of genomes that have been sequenced up to now.

  14. On the relationship between residue structural environment and sequence conservation in proteins.

    Science.gov (United States)

    Liu, Jen-Wei; Lin, Jau-Ji; Cheng, Chih-Wen; Lin, Yu-Feng; Hwang, Jenn-Kang; Huang, Tsun-Tsao

    2017-09-01

    Residues that are crucial to protein function or structure are usually evolutionarily conserved. To identify the important residues in protein, sequence conservation is estimated, and current methods rely upon the unbiased collection of homologous sequences. Surprisingly, our previous studies have shown that the sequence conservation is closely correlated with the weighted contact number (WCN), a measure of packing density for residue's structural environment, calculated only based on the C α positions of a protein structure. Moreover, studies have shown that sequence conservation is correlated with environment-related structural properties calculated based on different protein substructures, such as a protein's all atoms, backbone atoms, side-chain atoms, or side-chain centroid. To know whether the C α atomic positions are adequate to show the relationship between residue environment and sequence conservation or not, here we compared C α atoms with other substructures in their contributions to the sequence conservation. Our results show that C α positions are substantially equivalent to the other substructures in calculations of various measures of residue environment. As a result, the overlapping contributions between C α atoms and the other substructures are high, yielding similar structure-conservation relationship. Take the WCN as an example, the average overlapping contribution to sequence conservation is 87% between C α and all-atom substructures. These results indicate that only C α atoms of a protein structure could reflect sequence conservation at the residue level. © 2017 Wiley Periodicals, Inc.

  15. 3D local structure around copper site of rabbit prion-related protein: Quantitative determination by XANES spectroscopy combined with multiple-scattering calculations

    Science.gov (United States)

    Cui, P. X.; Lian, F. L.; Wang, Y.; Wen, Yi; Chu, W. S.; Zhao, H. F.; Zhang, S.; Li, J.; Lin, D. H.; Wu, Z. Y.

    2014-02-01

    Prion-related protein (PrP), a cell-surface copper-binding glycoprotein, is considered to be responsible for a number of transmissible spongiform encephalopathies (TSEs). The structural conversion of PrP from the normal cellular isoform (PrPC) to the post-translationally modified form (PrPSc) is thought to be relevant to Cu2+ binding to histidine residues. Rabbits are one of the few mammalian species that appear to be resistant to TSEs, because of the structural characteristics of the rabbit prion protein (RaPrPC) itself. Here we determined the three-dimensional local structure around the C-terminal high-affinity copper-binding sites using X-ray absorption near-edge structure combined with ab initio calculations in the framework of the multiple-scattering (MS) theory. Result shows that two amino acid resides, Gln97 and Met108, and two histidine residues, His95 and His110, are involved in binding this copper(II) ion. It might help us understand the roles of copper in prion conformation conversions, and the molecular mechanisms of prion-involved diseases.

  16. Structural deformation upon protein-protein interaction: a structural alphabet approach.

    Science.gov (United States)

    Martin, Juliette; Regad, Leslie; Lecornet, Hélène; Camproux, Anne-Claude

    2008-02-28

    In a number of protein-protein complexes, the 3D structures of bound and unbound partners significantly differ, supporting the induced fit hypothesis for protein-protein binding. In this study, we explore the induced fit modifications on a set of 124 proteins available in both bound and unbound forms, in terms of local structure. The local structure is described thanks to a structural alphabet of 27 structural letters that allows a detailed description of the backbone. Using a control set to distinguish induced fit from experimental error and natural protein flexibility, we show that the fraction of structural letters modified upon binding is significantly greater than in the control set (36% versus 28%). This proportion is even greater in the interface regions (41%). Interface regions preferentially involve coils. Our analysis further reveals that some structural letters in coil are not favored in the interface. We show that certain structural letters in coil are particularly subject to modifications at the interface, and that the severity of structural change also varies. These information are used to derive a structural letter substitution matrix that summarizes the local structural changes observed in our data set. We also illustrate the usefulness of our approach to identify common binding motifs in unrelated proteins. Our study provides qualitative information about induced fit. These results could be of help for flexible docking.

  17. Structural deformation upon protein-protein interaction: A structural alphabet approach

    Directory of Open Access Journals (Sweden)

    Lecornet Hélène

    2008-02-01

    Full Text Available Abstract Background In a number of protein-protein complexes, the 3D structures of bound and unbound partners significantly differ, supporting the induced fit hypothesis for protein-protein binding. Results In this study, we explore the induced fit modifications on a set of 124 proteins available in both bound and unbound forms, in terms of local structure. The local structure is described thanks to a structural alphabet of 27 structural letters that allows a detailed description of the backbone. Using a control set to distinguish induced fit from experimental error and natural protein flexibility, we show that the fraction of structural letters modified upon binding is significantly greater than in the control set (36% versus 28%. This proportion is even greater in the interface regions (41%. Interface regions preferentially involve coils. Our analysis further reveals that some structural letters in coil are not favored in the interface. We show that certain structural letters in coil are particularly subject to modifications at the interface, and that the severity of structural change also varies. These information are used to derive a structural letter substitution matrix that summarizes the local structural changes observed in our data set. We also illustrate the usefulness of our approach to identify common binding motifs in unrelated proteins. Conclusion Our study provides qualitative information about induced fit. These results could be of help for flexible docking.

  18. Magic Angle Spinning NMR Structure Determination of Proteins from Pseudocontact Shifts

    KAUST Repository

    Li, Jianping

    2013-06-05

    Magic angle spinning solid-state NMR is a unique technique to study atomic-resolution structure of biomacromolecules which resist crystallization or are too large to study by solution NMR techniques. However, difficulties in obtaining sufficient number of long-range distance restraints using dipolar coupling based spectra hamper the process of structure determination of proteins in solid-state NMR. In this study it is shown that high-resolution structure of proteins in solid phase can be determined without the use of traditional dipolar-dipolar coupling based distance restraints by combining the measurements of pseudocontact shifts (PCSs) with Rosetta calculations. The PCSs were generated by chelating exogenous paramagnetic metal ions to a tag 4-mercaptomethyl-dipicolinic acid, which is covalently attached to different residue sites in a 56-residue immunoglobulin-binding domain of protein G (GB1). The long-range structural restraints with metal-nucleus distance of up to ∼20 Å are quantitatively extracted from experimentally observed PCSs, and these are in good agreement with the distances back-calculated using an X-ray structure model. Moreover, we demonstrate that using several paramagnetic ions with varied paramagnetic susceptibilities as well as the introduction of paramagnetic labels at different sites can dramatically increase the number of long-range restraints and cover different regions of the protein. The structure generated from solid-state NMR PCSs restraints combined with Rosetta calculations has 0.7 Å root-mean-square deviation relative to X-ray structure. © 2013 American Chemical Society.

  19. Magic Angle Spinning NMR Structure Determination of Proteins from Pseudocontact Shifts

    KAUST Repository

    Li, Jianping; Pilla, Kala Bharath; Li, Qingfeng; Zhang, Zhengfeng; Su, Xuncheng; Huber, Thomas; Yang, Jun

    2013-01-01

    Magic angle spinning solid-state NMR is a unique technique to study atomic-resolution structure of biomacromolecules which resist crystallization or are too large to study by solution NMR techniques. However, difficulties in obtaining sufficient number of long-range distance restraints using dipolar coupling based spectra hamper the process of structure determination of proteins in solid-state NMR. In this study it is shown that high-resolution structure of proteins in solid phase can be determined without the use of traditional dipolar-dipolar coupling based distance restraints by combining the measurements of pseudocontact shifts (PCSs) with Rosetta calculations. The PCSs were generated by chelating exogenous paramagnetic metal ions to a tag 4-mercaptomethyl-dipicolinic acid, which is covalently attached to different residue sites in a 56-residue immunoglobulin-binding domain of protein G (GB1). The long-range structural restraints with metal-nucleus distance of up to ∼20 Å are quantitatively extracted from experimentally observed PCSs, and these are in good agreement with the distances back-calculated using an X-ray structure model. Moreover, we demonstrate that using several paramagnetic ions with varied paramagnetic susceptibilities as well as the introduction of paramagnetic labels at different sites can dramatically increase the number of long-range restraints and cover different regions of the protein. The structure generated from solid-state NMR PCSs restraints combined with Rosetta calculations has 0.7 Å root-mean-square deviation relative to X-ray structure. © 2013 American Chemical Society.

  20. Calculating ensemble averaged descriptions of protein rigidity without sampling.

    Directory of Open Access Journals (Sweden)

    Luis C González

    Full Text Available Previous works have demonstrated that protein rigidity is related to thermodynamic stability, especially under conditions that favor formation of native structure. Mechanical network rigidity properties of a single conformation are efficiently calculated using the integer body-bar Pebble Game (PG algorithm. However, thermodynamic properties require averaging over many samples from the ensemble of accessible conformations to accurately account for fluctuations in network topology. We have developed a mean field Virtual Pebble Game (VPG that represents the ensemble of networks by a single effective network. That is, all possible number of distance constraints (or bars that can form between a pair of rigid bodies is replaced by the average number. The resulting effective network is viewed as having weighted edges, where the weight of an edge quantifies its capacity to absorb degrees of freedom. The VPG is interpreted as a flow problem on this effective network, which eliminates the need to sample. Across a nonredundant dataset of 272 protein structures, we apply the VPG to proteins for the first time. Our results show numerically and visually that the rigidity characterizations of the VPG accurately reflect the ensemble averaged [Formula: see text] properties. This result positions the VPG as an efficient alternative to understand the mechanical role that chemical interactions play in maintaining protein stability.

  1. Quality assessment of protein model-structures based on structural and functional similarities.

    Science.gov (United States)

    Konopka, Bogumil M; Nebel, Jean-Christophe; Kotulska, Malgorzata

    2012-09-21

    Experimental determination of protein 3D structures is expensive, time consuming and sometimes impossible. A gap between number of protein structures deposited in the World Wide Protein Data Bank and the number of sequenced proteins constantly broadens. Computational modeling is deemed to be one of the ways to deal with the problem. Although protein 3D structure prediction is a difficult task, many tools are available. These tools can model it from a sequence or partial structural information, e.g. contact maps. Consequently, biologists have the ability to generate automatically a putative 3D structure model of any protein. However, the main issue becomes evaluation of the model quality, which is one of the most important challenges of structural biology. GOBA--Gene Ontology-Based Assessment is a novel Protein Model Quality Assessment Program. It estimates the compatibility between a model-structure and its expected function. GOBA is based on the assumption that a high quality model is expected to be structurally similar to proteins functionally similar to the prediction target. Whereas DALI is used to measure structure similarity, protein functional similarity is quantified using standardized and hierarchical description of proteins provided by Gene Ontology combined with Wang's algorithm for calculating semantic similarity. Two approaches are proposed to express the quality of protein model-structures. One is a single model quality assessment method, the other is its modification, which provides a relative measure of model quality. Exhaustive evaluation is performed on data sets of model-structures submitted to the CASP8 and CASP9 contests. The validation shows that the method is able to discriminate between good and bad model-structures. The best of tested GOBA scores achieved 0.74 and 0.8 as a mean Pearson correlation to the observed quality of models in our CASP8 and CASP9-based validation sets. GOBA also obtained the best result for two targets of CASP8, and

  2. Protein NMR Structures Refined with Rosetta Have Higher Accuracy Relative to Corresponding X-ray Crystal Structures

    Science.gov (United States)

    2014-01-01

    We have found that refinement of protein NMR structures using Rosetta with experimental NMR restraints yields more accurate protein NMR structures than those that have been deposited in the PDB using standard refinement protocols. Using 40 pairs of NMR and X-ray crystal structures determined by the Northeast Structural Genomics Consortium, for proteins ranging in size from 5–22 kDa, restrained Rosetta refined structures fit better to the raw experimental data, are in better agreement with their X-ray counterparts, and have better phasing power compared to conventionally determined NMR structures. For 37 proteins for which NMR ensembles were available and which had similar structures in solution and in the crystal, all of the restrained Rosetta refined NMR structures were sufficiently accurate to be used for solving the corresponding X-ray crystal structures by molecular replacement. The protocol for restrained refinement of protein NMR structures was also compared with restrained CS-Rosetta calculations. For proteins smaller than 10 kDa, restrained CS-Rosetta, starting from extended conformations, provides slightly more accurate structures, while for proteins in the size range of 10–25 kDa the less CPU intensive restrained Rosetta refinement protocols provided equally or more accurate structures. The restrained Rosetta protocols described here can improve the accuracy of protein NMR structures and should find broad and general for studies of protein structure and function. PMID:24392845

  3. Role of protein structure and the role of individual fingers in zinc finger protein-DNA recognition: a molecular dynamics simulation study and free energy calculations

    Science.gov (United States)

    Hamed, Mazen Y.

    2018-05-01

    Molecular dynamics and MM_GBSA energy calculations on various zinc finger proteins containing three and four fingers bound to their target DNA gave insights into the role of each finger in the DNA binding process as part of the protein structure. The wild type Zif 268 (PDB code: 1AAY) gave a ΔG value of - 76.1 (14) kcal/mol. Zinc fingers ZF1, ZF2 and ZF3 were mutated in one experiment and in another experiment one finger was cut and the rest of the protein was studied for binding. The ΔΔG values for the Zinc Finger protein with both ZF1 and ZF2 mutated was + 80 kcal/mol, while mutating only ZF1 the ΔΔG value was + 52 kcal/mol (relative to the wild type). Cutting ZF3 and studying the protein consisting only of ZF1 linked to ZF2 gave a ΔΔG value of + 68 kcal/mol. Upon cutting ZF1, the resulting ZF2 linked to ZF3 protein gave a ΔΔG value of + 41 kcal/mol. The above results shed light on the importance of each finger in the binding process, especially the role of ZF1 as the anchoring finger followed in importance by ZF2 and ZF3. The energy difference between the binding of the wild type protein Zif268 (1AAY) and that for individual finger binding to DNA according to the formula: ΔΔGlinkers, otherstructuralfactors = ΔGzif268 - (ΔGF1+F2+F3) gave a value = - 44.5 kcal/mol. This stabilization can be attributed to the contribution of linkers and other structural factors in the intact protein in the DNA binding process. DNA binding energies of variant proteins of the wild type Zif268 which differ in their ZF1 amino acid sequence gave evidence of a good relationship between binding energy and recognition and specificity, this finding confirms the reported vital role of ZF1 in the ZF protein scanning and anchoring to the target DNA sequence. The role of hydrogen bonds in both specific and nonspecific amino acid-DNA contacts is discussed in relation to mutations. The binding energies of variant Zinc Finger proteins confirmed the role of ZF1 in the recognition

  4. Proteins in vacuo. A more efficient means of calculating ...

    African Journals Online (AJOL)

    given bath gas particle and the protein. Calculations of savg. , though in principle straightforward, are time consuming. In the work presented below, it was investigated whether a more efficient calculation scheme can be employed without sacrificing too much accuracy. In the new scheme, atomic-scale protein surface ...

  5. Structure refinement of flexible proteins using dipolar couplings: Application to the protein p8MTCP1

    International Nuclear Information System (INIS)

    Demene, Helene; Ducat, Thierry; Barthe, Philippe; Delsuc, Marc-Andre; Roumestand, Christian

    2002-01-01

    The present study deals with the relevance of using mobility-averaged dipolar couplings for the structure refinement of flexible proteins. The 68-residue protein p8 MTCP1 has been chosen as model for this study. Its solution state consists mainly of three α-helices. The two N-terminal helices are strapped in a well-determined α-hairpin, whereas, due to an intrinsic mobility, the position of the third helix is less well defined in the NMR structure. To further characterize the degrees of freedom of this helix, we have measured the dipolar coupling constants in the backbone of p8 MTCP1 in a bicellar medium. We show here that including D HN dip dipolar couplings in the structure calculation protocol improves the structure of the α-hairpin but not the positioning of the third helix. This is due to the motional averaging of the dipolar couplings measured in the last helix. Performing two calculations with different force constants for the dipolar restraints highlights the inconstancy of these mobility-averaged dipolar couplings. Alternatively, prior to any structure calculations, comparing the values of the dipolar couplings measured in helix III to values back-calculated from an ideal helix demonstrates that they are atypical for a helix. This can be partly attributed to mobility effects since the inclusion of the 15 N relaxation derived order parameter allows for a better fit

  6. Discrete Haar transform and protein structure.

    Science.gov (United States)

    Morosetti, S

    1997-12-01

    The discrete Haar transform of the sequence of the backbone dihedral angles (phi and psi) was performed over a set of X-ray protein structures of high resolution from the Brookhaven Protein Data Bank. Afterwards, the new dihedral angles were calculated by the inverse transform, using a growing number of Haar functions, from the lower to the higher degree. New structures were obtained using these dihedral angles, with standard values for bond lengths and angles, and with omega = 0 degree. The reconstructed structures were compared with the experimental ones, and analyzed by visual inspection and statistical analysis. When half of the Haar coefficients were used, all the reconstructed structures were not yet collapsed to a tertiary folding, but they showed yet realized most of the secondary motifs. These results indicate a substantial separation of structural information in the space of Haar transform, with the secondary structural information mainly present in the Haar coefficients of lower degrees, and the tertiary one present in the higher degree coefficients. Because of this separation, the representation of the folded structures in the space of Haar transform seems a promising candidate to encompass the problem of premature convergence in genetic algorithms.

  7. The AUDANA algorithm for automated protein 3D structure determination from NMR NOE data

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Woonghee, E-mail: whlee@nmrfam.wisc.edu [University of Wisconsin-Madison, National Magnetic Resonance Facility at Madison and Biochemistry Department (United States); Petit, Chad M. [University of Alabama at Birmingham, Department of Biochemistry and Molecular Genetics (United States); Cornilescu, Gabriel; Stark, Jaime L.; Markley, John L., E-mail: markley@nmrfam.wisc.edu [University of Wisconsin-Madison, National Magnetic Resonance Facility at Madison and Biochemistry Department (United States)

    2016-06-15

    We introduce AUDANA (Automated Database-Assisted NOE Assignment), an algorithm for determining three-dimensional structures of proteins from NMR data that automates the assignment of 3D-NOE spectra, generates distance constraints, and conducts iterative high temperature molecular dynamics and simulated annealing. The protein sequence, chemical shift assignments, and NOE spectra are the only required inputs. Distance constraints generated automatically from ambiguously assigned NOE peaks are validated during the structure calculation against information from an enlarged version of the freely available PACSY database that incorporates information on protein structures deposited in the Protein Data Bank (PDB). This approach yields robust sets of distance constraints and 3D structures. We evaluated the performance of AUDANA with input data for 14 proteins ranging in size from 6 to 25 kDa that had 27–98 % sequence identity to proteins in the database. In all cases, the automatically calculated 3D structures passed stringent validation tests. Structures were determined with and without database support. In 9/14 cases, database support improved the agreement with manually determined structures in the PDB and in 11/14 cases, database support lowered the r.m.s.d. of the family of 20 structural models.

  8. The AUDANA algorithm for automated protein 3D structure determination from NMR NOE data

    International Nuclear Information System (INIS)

    Lee, Woonghee; Petit, Chad M.; Cornilescu, Gabriel; Stark, Jaime L.; Markley, John L.

    2016-01-01

    We introduce AUDANA (Automated Database-Assisted NOE Assignment), an algorithm for determining three-dimensional structures of proteins from NMR data that automates the assignment of 3D-NOE spectra, generates distance constraints, and conducts iterative high temperature molecular dynamics and simulated annealing. The protein sequence, chemical shift assignments, and NOE spectra are the only required inputs. Distance constraints generated automatically from ambiguously assigned NOE peaks are validated during the structure calculation against information from an enlarged version of the freely available PACSY database that incorporates information on protein structures deposited in the Protein Data Bank (PDB). This approach yields robust sets of distance constraints and 3D structures. We evaluated the performance of AUDANA with input data for 14 proteins ranging in size from 6 to 25 kDa that had 27–98 % sequence identity to proteins in the database. In all cases, the automatically calculated 3D structures passed stringent validation tests. Structures were determined with and without database support. In 9/14 cases, database support improved the agreement with manually determined structures in the PDB and in 11/14 cases, database support lowered the r.m.s.d. of the family of 20 structural models.

  9. Massive calculations of electrostatic potentials and structure maps of biopolymers in a distributed computing environment

    International Nuclear Information System (INIS)

    Akishina, T.P.; Ivanov, V.V.; Stepanenko, V.A.

    2013-01-01

    Among the key factors determining the processes of transcription and translation are the distributions of the electrostatic potentials of DNA, RNA and proteins. Calculations of electrostatic distributions and structure maps of biopolymers on computers are time consuming and require large computational resources. We developed the procedures for organization of massive calculations of electrostatic potentials and structure maps for biopolymers in a distributed computing environment (several thousands of cores).

  10. Biomolecular Structure Information from High-Speed Quantum Mechanical Electronic Spectra Calculation.

    Science.gov (United States)

    Seibert, Jakob; Bannwarth, Christoph; Grimme, Stefan

    2017-08-30

    A fully quantum mechanical (QM) treatment to calculate electronic absorption (UV-vis) and circular dichroism (CD) spectra of typical biomolecules with thousands of atoms is presented. With our highly efficient sTDA-xTB method, spectra averaged along structures from molecular dynamics (MD) simulations can be computed in a reasonable time frame on standard desktop computers. This way, nonequilibrium structure and conformational, as well as purely quantum mechanical effects like charge-transfer or exciton-coupling, are included. Different from other contemporary approaches, the entire system is treated quantum mechanically and neither fragmentation nor system-specific adjustment is necessary. Among the systems considered are a large DNA fragment, oligopeptides, and even entire proteins in an implicit solvent. We propose the method in tandem with experimental spectroscopy or X-ray studies for the elucidation of complex (bio)molecular structures including metallo-proteins like myoglobin.

  11. Evaluation of variability in high-resolution protein structures by global distance scoring

    Directory of Open Access Journals (Sweden)

    Risa Anzai

    2018-01-01

    Full Text Available Systematic analysis of the statistical and dynamical properties of proteins is critical to understanding cellular events. Extraction of biologically relevant information from a set of high-resolution structures is important because it can provide mechanistic details behind the functional properties of protein families, enabling rational comparison between families. Most of the current structural comparisons are pairwise-based, which hampers the global analysis of increasing contents in the Protein Data Bank. Additionally, pairing of protein structures introduces uncertainty with respect to reproducibility because it frequently accompanies other settings for superimposition. This study introduces intramolecular distance scoring for the global analysis of proteins, for each of which at least several high-resolution structures are available. As a pilot study, we have tested 300 human proteins and showed that the method is comprehensively used to overview advances in each protein and protein family at the atomic level. This method, together with the interpretation of the model calculations, provide new criteria for understanding specific structural variation in a protein, enabling global comparison of the variability in proteins from different species.

  12. Evaluation of variability in high-resolution protein structures by global distance scoring.

    Science.gov (United States)

    Anzai, Risa; Asami, Yoshiki; Inoue, Waka; Ueno, Hina; Yamada, Koya; Okada, Tetsuji

    2018-01-01

    Systematic analysis of the statistical and dynamical properties of proteins is critical to understanding cellular events. Extraction of biologically relevant information from a set of high-resolution structures is important because it can provide mechanistic details behind the functional properties of protein families, enabling rational comparison between families. Most of the current structural comparisons are pairwise-based, which hampers the global analysis of increasing contents in the Protein Data Bank. Additionally, pairing of protein structures introduces uncertainty with respect to reproducibility because it frequently accompanies other settings for superimposition. This study introduces intramolecular distance scoring for the global analysis of proteins, for each of which at least several high-resolution structures are available. As a pilot study, we have tested 300 human proteins and showed that the method is comprehensively used to overview advances in each protein and protein family at the atomic level. This method, together with the interpretation of the model calculations, provide new criteria for understanding specific structural variation in a protein, enabling global comparison of the variability in proteins from different species.

  13. Functional structural motifs for protein-ligand, protein-protein, and protein-nucleic acid interactions and their connection to supersecondary structures.

    Science.gov (United States)

    Kinjo, Akira R; Nakamura, Haruki

    2013-01-01

    Protein functions are mediated by interactions between proteins and other molecules. One useful approach to analyze protein functions is to compare and classify the structures of interaction interfaces of proteins. Here, we describe the procedures for compiling a database of interface structures and efficiently comparing the interface structures. To do so requires a good understanding of the data structures of the Protein Data Bank (PDB). Therefore, we also provide a detailed account of the PDB exchange dictionary necessary for extracting data that are relevant for analyzing interaction interfaces and secondary structures. We identify recurring structural motifs by classifying similar interface structures, and we define a coarse-grained representation of supersecondary structures (SSS) which represents a sequence of two or three secondary structure elements including their relative orientations as a string of four to seven letters. By examining the correspondence between structural motifs and SSS strings, we show that no SSS string has particularly high propensity to be found interaction interfaces in general, indicating any SSS can be used as a binding interface. When individual structural motifs are examined, there are some SSS strings that have high propensity for particular groups of structural motifs. In addition, it is shown that while the SSS strings found in particular structural motifs for nonpolymer and protein interfaces are as abundant as in other structural motifs that belong to the same subunit, structural motifs for nucleic acid interfaces exhibit somewhat stronger preference for SSS strings. In regard to protein folds, many motif-specific SSS strings were found across many folds, suggesting that SSS may be a useful description to investigate the universality of ligand binding modes.

  14. Protein solution structure determination using distances from two-dimensional nuclear Overhauser effect experiments: Effect of approximations on the accuracy of derived structures

    International Nuclear Information System (INIS)

    Thomas, P.D.; Basus, V.J.; James, T.L.

    1991-01-01

    Solution structures for many proteins have been determined to date utilizing interproton distance constraints estimated from two-dimensional nuclear Overhauser effect (2D NOE) spectra. Although the simple isolated spin pair approximation (ISPA) generally used can result in systematic errors in distances, the large number of constraints enables proteins structure to be defined with reasonably high resolution. Effects of these systematic errors on the resulting protein structure are examined. Iterative relaxation matrix calculations, which account for dipolar interactions between all protons in a molecule, can accurately determine internuclear distances with little or no a priori knowledge of the molecular structure. The value of this additional complexity is also addressed. To assess these distance determination methods, hypothetical experimental data, including random noise and peak overlap, are calculated for an arbitrary true protein structure. Three methods of obtaining distance constraints from 2D NOE peak intensities are examined: one entails a conservative use of ISPA, one assumes the ISPA to be fairly accurate, and on utilizes an iterative relaxation matrix method called MARDIGRAS (matrix analysis of relaxation for discerning the geometry of an aqueous structure), developed in this laboratory. An R factor for evaluating fit between experimental and calculated 2D NOE intensities is proposed

  15. A pairwise residue contact area-based mean force potential for discrimination of native protein structure

    Directory of Open Access Journals (Sweden)

    Pezeshk Hamid

    2010-01-01

    Full Text Available Abstract Background Considering energy function to detect a correct protein fold from incorrect ones is very important for protein structure prediction and protein folding. Knowledge-based mean force potentials are certainly the most popular type of interaction function for protein threading. They are derived from statistical analyses of interacting groups in experimentally determined protein structures. These potentials are developed at the atom or the amino acid level. Based on orientation dependent contact area, a new type of knowledge-based mean force potential has been developed. Results We developed a new approach to calculate a knowledge-based potential of mean-force, using pairwise residue contact area. To test the performance of our approach, we performed it on several decoy sets to measure its ability to discriminate native structure from decoys. This potential has been able to distinguish native structures from the decoys in the most cases. Further, the calculated Z-scores were quite high for all protein datasets. Conclusions This knowledge-based potential of mean force can be used in protein structure prediction, fold recognition, comparative modelling and molecular recognition. The program is available at http://www.bioinf.cs.ipm.ac.ir/softwares/surfield

  16. Languages for structural calculations

    International Nuclear Information System (INIS)

    Thomas, J.B.; Chambon, M.R.

    1988-01-01

    The differences between human and computing languages are recalled. It is argued that they are to some extent structured in antagonistic ways. Languages in structural calculation, in the past, present, and future, are considered. The contribution of artificial intelligence is stressed [fr

  17. Lipid nanotechnologies for structural studies of membrane-associated proteins.

    Science.gov (United States)

    Stoilova-McPhie, Svetla; Grushin, Kirill; Dalm, Daniela; Miller, Jaimy

    2014-11-01

    We present a methodology of lipid nanotubes (LNT) and nanodisks technologies optimized in our laboratory for structural studies of membrane-associated proteins at close to physiological conditions. The application of these lipid nanotechnologies for structure determination by cryo-electron microscopy (cryo-EM) is fundamental for understanding and modulating their function. The LNTs in our studies are single bilayer galactosylceramide based nanotubes of ∼20 nm inner diameter and a few microns in length, that self-assemble in aqueous solutions. The lipid nanodisks (NDs) are self-assembled discoid lipid bilayers of ∼10 nm diameter, which are stabilized in aqueous solutions by a belt of amphipathic helical scaffold proteins. By combining LNT and ND technologies, we can examine structurally how the membrane curvature and lipid composition modulates the function of the membrane-associated proteins. As proof of principle, we have engineered these lipid nanotechnologies to mimic the activated platelet's phosphtaidylserine rich membrane and have successfully assembled functional membrane-bound coagulation factor VIII in vitro for structure determination by cryo-EM. The macromolecular organization of the proteins bound to ND and LNT are further defined by fitting the known atomic structures within the calculated three-dimensional maps. The combination of LNT and ND technologies offers a means to control the design and assembly of a wide range of functional membrane-associated proteins and complexes for structural studies by cryo-EM. The presented results confirm the suitability of the developed methodology for studying the functional structure of membrane-associated proteins, such as the coagulation factors, at a close to physiological environment. © 2014 Wiley Periodicals, Inc.

  18. Resolution-by-proxy: a simple measure for assessing and comparing the overall quality of NMR protein structures

    International Nuclear Information System (INIS)

    Berjanskii, Mark; Zhou Jianjun; Liang Yongjie; Lin Guohui; Wishart, David S.

    2012-01-01

    In protein X-ray crystallography, resolution is often used as a good indicator of structural quality. Diffraction resolution of protein crystals correlates well with the number of X-ray observables that are used in structure generation and, therefore, with protein coordinate errors. In protein NMR, there is no parameter identical to X-ray resolution. Instead, resolution is often used as a synonym of NMR model quality. Resolution of NMR structures is often deduced from ensemble precision, torsion angle normality and number of distance restraints per residue. The lack of common techniques to assess the resolution of X-ray and NMR structures complicates the comparison of structures solved by these two methods. This problem is sometimes approached by calculating “equivalent resolution” from structure quality metrics. However, existing protocols do not offer a comprehensive assessment of protein structure as they calculate equivalent resolution from a relatively small number (<5) of protein parameters. Here, we report a development of a protocol that calculates equivalent resolution from 25 measurable protein features. This new method offers better performance (correlation coefficient of 0.92, mean absolute error of 0.28 Å) than existing predictors of equivalent resolution. Because the method uses coordinate data as a proxy for X-ray diffraction data, we call this measure “Resolution-by-Proxy” or ResProx. We demonstrate that ResProx can be used to identify under-restrained, poorly refined or inaccurate NMR structures, and can discover structural defects that the other equivalent resolution methods cannot detect. The ResProx web server is available at http://www.resprox.cahttp://www.resprox.ca.

  19. Calculation of accurate small angle X-ray scattering curves from coarse-grained protein models

    DEFF Research Database (Denmark)

    Stovgaard, Kasper; Andreetta, Christian; Ferkinghoff-Borg, Jesper

    2010-01-01

    , which is paramount for structure determination based on statistical inference. Results: We present a method for the efficient calculation of accurate SAXS curves based on the Debye formula and a set of scattering form factors for dummy atom representations of amino acids. Such a method avoids......DBN. This resulted in a significant improvement in the decoy recognition performance. In conclusion, the presented method shows great promise for use in statistical inference of protein structures from SAXS data....

  20. Correlated mutations in protein sequences: Phylogenetic and structural effects

    Energy Technology Data Exchange (ETDEWEB)

    Lapedes, A.S. [Los Alamos National Lab., NM (United States). Theoretical Div.]|[Santa Fe Inst., NM (United States); Giraud, B.G. [C.E.N. Saclay, Gif/Yvette (France). Service Physique Theorique; Liu, L.C. [Los Alamos National Lab., NM (United States). Theoretical Div.; Stormo, G.D. [Univ. of Colorado, Boulder, CO (United States). Dept. of Molecular, Cellular and Developmental Biology

    1998-12-01

    Covariation analysis of sets of aligned sequences for RNA molecules is relatively successful in elucidating RNA secondary structure, as well as some aspects of tertiary structure. Covariation analysis of sets of aligned sequences for protein molecules is successful in certain instances in elucidating certain structural and functional links, but in general, pairs of sites displaying highly covarying mutations in protein sequences do not necessarily correspond to sites that are spatially close in the protein structure. In this paper the authors identify two reasons why naive use of covariation analysis for protein sequences fails to reliably indicate sequence positions that are spatially proximate. The first reason involves the bias introduced in calculation of covariation measures due to the fact that biological sequences are generally related by a non-trivial phylogenetic tree. The authors present a null-model approach to solve this problem. The second reason involves linked chains of covariation which can result in pairs of sites displaying significant covariation even though they are not spatially proximate. They present a maximum entropy solution to this classic problem of causation versus correlation. The methodologies are validated in simulation.

  1. EFFECT OF PLANT PROTEIN ISOLATES ON THE STRUCTURAL – MECHANICAL PROPERTIES OF WHEAT DOUGH

    Directory of Open Access Journals (Sweden)

    Valeriy MAKHYNKO

    2017-06-01

    Full Text Available The results of using isolates of soya, pea and rice flour as well as of dry wheat gluten in the making of bread dough have been presented. Taking into account the high water absorption capacity of these products, effect of the protein isolates on the structural-mechanical properties of the dough has been investigated. On the basis of farinogram curves the additional quantity of water needed to obtain proper structure of dough made from all types of raw materials has been determined. A formula of calculation the additional quantity of water has been proposed. It proves that most quantity of water is needed for dough with isolate of soya protein – 2.3 g per 1 g of added isolate. Isolate of pea protein needs additionally 1.5 g of water, dry wheat gluten – 1.3 g, and isolate of rice protein – 0.9 g of water. The proposed calculation has been checked for mixes with different proportion of raw materials and its effectiveness has been proven. The calculation method was used to determine the additional quantity of water required to obtain wheat dough with necessary structural and mechanical properties.

  2. Validation of Molecular Dynamics Simulations for Prediction of Three-Dimensional Structures of Small Proteins.

    Science.gov (United States)

    Kato, Koichi; Nakayoshi, Tomoki; Fukuyoshi, Shuichi; Kurimoto, Eiji; Oda, Akifumi

    2017-10-12

    Although various higher-order protein structure prediction methods have been developed, almost all of them were developed based on the three-dimensional (3D) structure information of known proteins. Here we predicted the short protein structures by molecular dynamics (MD) simulations in which only Newton's equations of motion were used and 3D structural information of known proteins was not required. To evaluate the ability of MD simulationto predict protein structures, we calculated seven short test protein (10-46 residues) in the denatured state and compared their predicted and experimental structures. The predicted structure for Trp-cage (20 residues) was close to the experimental structure by 200-ns MD simulation. For proteins shorter or longer than Trp-cage, root-mean square deviation values were larger than those for Trp-cage. However, secondary structures could be reproduced by MD simulations for proteins with 10-34 residues. Simulations by replica exchange MD were performed, but the results were similar to those from normal MD simulations. These results suggest that normal MD simulations can roughly predict short protein structures and 200-ns simulations are frequently sufficient for estimating the secondary structures of protein (approximately 20 residues). Structural prediction method using only fundamental physical laws are useful for investigating non-natural proteins, such as primitive proteins and artificial proteins for peptide-based drug delivery systems.

  3. Oligomeric protein structure networks: insights into protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Brinda KV

    2005-12-01

    Full Text Available Abstract Background Protein-protein association is essential for a variety of cellular processes and hence a large number of investigations are being carried out to understand the principles of protein-protein interactions. In this study, oligomeric protein structures are viewed from a network perspective to obtain new insights into protein association. Structure graphs of proteins have been constructed from a non-redundant set of protein oligomer crystal structures by considering amino acid residues as nodes and the edges are based on the strength of the non-covalent interactions between the residues. The analysis of such networks has been carried out in terms of amino acid clusters and hubs (highly connected residues with special emphasis to protein interfaces. Results A variety of interactions such as hydrogen bond, salt bridges, aromatic and hydrophobic interactions, which occur at the interfaces are identified in a consolidated manner as amino acid clusters at the interface, from this study. Moreover, the characterization of the highly connected hub-forming residues at the interfaces and their comparison with the hubs from the non-interface regions and the non-hubs in the interface regions show that there is a predominance of charged interactions at the interfaces. Further, strong and weak interfaces are identified on the basis of the interaction strength between amino acid residues and the sizes of the interface clusters, which also show that many protein interfaces are stronger than their monomeric protein cores. The interface strengths evaluated based on the interface clusters and hubs also correlate well with experimentally determined dissociation constants for known complexes. Finally, the interface hubs identified using the present method correlate very well with experimentally determined hotspots in the interfaces of protein complexes obtained from the Alanine Scanning Energetics database (ASEdb. A few predictions of interface hot

  4. Modularity in protein structures: study on all-alpha proteins.

    Science.gov (United States)

    Khan, Taushif; Ghosh, Indira

    2015-01-01

    Modularity is known as one of the most important features of protein's robust and efficient design. The architecture and topology of proteins play a vital role by providing necessary robust scaffolds to support organism's growth and survival in constant evolutionary pressure. These complex biomolecules can be represented by several layers of modular architecture, but it is pivotal to understand and explore the smallest biologically relevant structural component. In the present study, we have developed a component-based method, using protein's secondary structures and their arrangements (i.e. patterns) in order to investigate its structural space. Our result on all-alpha protein shows that the known structural space is highly populated with limited set of structural patterns. We have also noticed that these frequently observed structural patterns are present as modules or "building blocks" in large proteins (i.e. higher secondary structure content). From structural descriptor analysis, observed patterns are found to be within similar deviation; however, frequent patterns are found to be distinctly occurring in diverse functions e.g. in enzymatic classes and reactions. In this study, we are introducing a simple approach to explore protein structural space using combinatorial- and graph-based geometry methods, which can be used to describe modularity in protein structures. Moreover, analysis indicates that protein function seems to be the driving force that shapes the known structure space.

  5. Estimating structure quality trends in the Protein Data Bank by equivalent resolution.

    Science.gov (United States)

    Bagaria, Anurag; Jaravine, Victor; Güntert, Peter

    2013-10-01

    The quality of protein structures obtained by different experimental and ab-initio calculation methods varies considerably. The methods have been evolving over time by improving both experimental designs and computational techniques, and since the primary aim of these developments is the procurement of reliable and high-quality data, better techniques resulted on average in an evolution toward higher quality structures in the Protein Data Bank (PDB). Each method leaves a specific quantitative and qualitative "trace" in the PDB entry. Certain information relevant to one method (e.g. dynamics for NMR) may be lacking for another method. Furthermore, some standard measures of quality for one method cannot be calculated for other experimental methods, e.g. crystal resolution or NMR bundle RMSD. Consequently, structures are classified in the PDB by the method used. Here we introduce a method to estimate a measure of equivalent X-ray resolution (e-resolution), expressed in units of Å, to assess the quality of any type of monomeric, single-chain protein structure, irrespective of the experimental structure determination method. We showed and compared the trends in the quality of structures in the Protein Data Bank over the last two decades for five different experimental techniques, excluding theoretical structure predictions. We observed that as new methods are introduced, they undergo a rapid method development evolution: within several years the e-resolution score becomes similar for structures obtained from the five methods and they improve from initially poor performance to acceptable quality, comparable with previously established methods, the performance of which is essentially stable. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Mapping monomeric threading to protein-protein structure prediction.

    Science.gov (United States)

    Guerler, Aysam; Govindarajoo, Brandon; Zhang, Yang

    2013-03-25

    The key step of template-based protein-protein structure prediction is the recognition of complexes from experimental structure libraries that have similar quaternary fold. Maintaining two monomer and dimer structure libraries is however laborious, and inappropriate library construction can degrade template recognition coverage. We propose a novel strategy SPRING to identify complexes by mapping monomeric threading alignments to protein-protein interactions based on the original oligomer entries in the PDB, which does not rely on library construction and increases the efficiency and quality of complex template recognitions. SPRING is tested on 1838 nonhomologous protein complexes which can recognize correct quaternary template structures with a TM score >0.5 in 1115 cases after excluding homologous proteins. The average TM score of the first model is 60% and 17% higher than that by HHsearch and COTH, respectively, while the number of targets with an interface RMSD benchmark proteins. Although the relative performance of SPRING and ZDOCK depends on the level of homology filters, a combination of the two methods can result in a significantly higher model quality than ZDOCK at all homology thresholds. These data demonstrate a new efficient approach to quaternary structure recognition that is ready to use for genome-scale modeling of protein-protein interactions due to the high speed and accuracy.

  7. Protein structure based prediction of catalytic residues.

    Science.gov (United States)

    Fajardo, J Eduardo; Fiser, Andras

    2013-02-22

    Worldwide structural genomics projects continue to release new protein structures at an unprecedented pace, so far nearly 6000, but only about 60% of these proteins have any sort of functional annotation. We explored a range of features that can be used for the prediction of functional residues given a known three-dimensional structure. These features include various centrality measures of nodes in graphs of interacting residues: closeness, betweenness and page-rank centrality. We also analyzed the distance of functional amino acids to the general center of mass (GCM) of the structure, relative solvent accessibility (RSA), and the use of relative entropy as a measure of sequence conservation. From the selected features, neural networks were trained to identify catalytic residues. We found that using distance to the GCM together with amino acid type provide a good discriminant function, when combined independently with sequence conservation. Using an independent test set of 29 annotated protein structures, the method returned 411 of the initial 9262 residues as the most likely to be involved in function. The output 411 residues contain 70 of the annotated 111 catalytic residues. This represents an approximately 14-fold enrichment of catalytic residues on the entire input set (corresponding to a sensitivity of 63% and a precision of 17%), a performance competitive with that of other state-of-the-art methods. We found that several of the graph based measures utilize the same underlying feature of protein structures, which can be simply and more effectively captured with the distance to GCM definition. This also has the added the advantage of simplicity and easy implementation. Meanwhile sequence conservation remains by far the most influential feature in identifying functional residues. We also found that due the rapid changes in size and composition of sequence databases, conservation calculations must be recalibrated for specific reference databases.

  8. MolTalk--a programming library for protein structures and structure analysis.

    Science.gov (United States)

    Diemand, Alexander V; Scheib, Holger

    2004-04-19

    Two of the mostly unsolved but increasingly urgent problems for modern biologists are a) to quickly and easily analyse protein structures and b) to comprehensively mine the wealth of information, which is distributed along with the 3D co-ordinates by the Protein Data Bank (PDB). Tools which address this issue need to be highly flexible and powerful but at the same time must be freely available and easy to learn. We present MolTalk, an elaborate programming language, which consists of the programming library libmoltalk implemented in Objective-C and the Smalltalk-based interpreter MolTalk. MolTalk combines the advantages of an easy to learn and programmable procedural scripting with the flexibility and power of a full programming language. An overview of currently available applications of MolTalk is given and with PDBChainSaw one such application is described in more detail. PDBChainSaw is a MolTalk-based parser and information extraction utility of PDB files. Weekly updates of the PDB are synchronised with PDBChainSaw and are available for free download from the MolTalk project page http://www.moltalk.org following the link to PDBChainSaw. For each chain in a protein structure, PDBChainSaw extracts the sequence from its co-ordinates and provides additional information from the PDB-file header section, such as scientific organism, compound name, and EC code. MolTalk provides a rich set of methods to analyse and even modify experimentally determined or modelled protein structures. These methods vary in complexity and are thus suitable for beginners and advanced programmers alike. We envision MolTalk to be most valuable in the following applications:1) To analyse protein structures repetitively in large-scale, i.e. to benchmark protein structure prediction methods or to evaluate structural models. The quality of the resulting 3D-models can be assessed by e.g. calculating a Ramachandran-Sasisekharan plot.2) To quickly retrieve information for (a limited number of

  9. Protein enriched pasta: structure and digestibility of its protein network.

    Science.gov (United States)

    Laleg, Karima; Barron, Cécile; Santé-Lhoutellier, Véronique; Walrand, Stéphane; Micard, Valérie

    2016-02-01

    Wheat (W) pasta was enriched in 6% gluten (G), 35% faba (F) or 5% egg (E) to increase its protein content (13% to 17%). The impact of the enrichment on the multiscale structure of the pasta and on in vitro protein digestibility was studied. Increasing the protein content (W- vs. G-pasta) strengthened pasta structure at molecular and macroscopic scales but reduced its protein digestibility by 3% by forming a higher covalently linked protein network. Greater changes in the macroscopic and molecular structure of the pasta were obtained by varying the nature of protein used for enrichment. Proteins in G- and E-pasta were highly covalently linked (28-32%) resulting in a strong pasta structure. Conversely, F-protein (98% SDS-soluble) altered the pasta structure by diluting gluten and formed a weak protein network (18% covalent link). As a result, protein digestibility in F-pasta was significantly higher (46%) than in E- (44%) and G-pasta (39%). The effect of low (55 °C, LT) vs. very high temperature (90 °C, VHT) drying on the protein network structure and digestibility was shown to cause greater molecular changes than pasta formulation. Whatever the pasta, a general strengthening of its structure, a 33% to 47% increase in covalently linked proteins and a higher β-sheet structure were observed. However, these structural differences were evened out after the pasta was cooked, resulting in identical protein digestibility in LT and VHT pasta. Even after VHT drying, F-pasta had the best amino acid profile with the highest protein digestibility, proof of its nutritional interest.

  10. An approach for high-throughput structure determination of proteins by NMR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Medek, Ales; Olejniczak, Edward T.; Meadows, Robert P.; Fesik, Stephen W. [Abbott Laboratories, Pharmaceutical Discovery Division (United States)

    2000-11-15

    An approach is described for rapidly determining protein structures by NMR that utilizes proteins containing {sup 13}C-methyl labeled Val, Leu, and Ile ({delta}1) and protonated Phe and Tyr in a deuterated background. Using this strategy, the key NOEs that define the hydrophobic core and overall fold of the protein are easily obtained. NMR data are acquired using cryogenic probe technology which markedly reduces the spectrometer time needed for data acquisition. The approach is demonstrated by determining the overall fold of the antiapoptotic protein, Bcl-xL, from data collected in only 4 days. Refinement of the Bcl-xL structure to a backbone rmsd of 0.95 A was accomplished with data collected in an additional 3 days. A distance analysis of 180 different proteins and structure calculations using simulated data suggests that our method will allow the global folds of a wide variety of proteins to be determined.

  11. Structure-based barcoding of proteins.

    Science.gov (United States)

    Metri, Rahul; Jerath, Gaurav; Kailas, Govind; Gacche, Nitin; Pal, Adityabarna; Ramakrishnan, Vibin

    2014-01-01

    A reduced representation in the format of a barcode has been developed to provide an overview of the topological nature of a given protein structure from 3D coordinate file. The molecular structure of a protein coordinate file from Protein Data Bank is first expressed in terms of an alpha-numero code and further converted to a barcode image. The barcode representation can be used to compare and contrast different proteins based on their structure. The utility of this method has been exemplified by comparing structural barcodes of proteins that belong to same fold family, and across different folds. In addition to this, we have attempted to provide an illustration to (i) the structural changes often seen in a given protein molecule upon interaction with ligands and (ii) Modifications in overall topology of a given protein during evolution. The program is fully downloadable from the website http://www.iitg.ac.in/probar/. © 2013 The Protein Society.

  12. Taking advantage of local structure descriptors to analyze interresidue contacts in protein structures and protein complexes.

    Science.gov (United States)

    Martin, Juliette; Regad, Leslie; Etchebest, Catherine; Camproux, Anne-Claude

    2008-11-15

    Interresidue protein contacts in proteins structures and at protein-protein interface are classically described by the amino acid types of interacting residues and the local structural context of the contact, if any, is described using secondary structures. In this study, we present an alternate analysis of interresidue contact using local structures defined by the structural alphabet introduced by Camproux et al. This structural alphabet allows to describe a 3D structure as a sequence of prototype fragments called structural letters, of 27 different types. Each residue can then be assigned to a particular local structure, even in loop regions. The analysis of interresidue contacts within protein structures defined using Voronoï tessellations reveals that pairwise contact specificity is greater in terms of structural letters than amino acids. Using a simple heuristic based on specificity score comparison, we find that 74% of the long-range contacts within protein structures are better described using structural letters than amino acid types. The investigation is extended to a set of protein-protein complexes, showing that the similar global rules apply as for intraprotein contacts, with 64% of the interprotein contacts best described by local structures. We then present an evaluation of pairing functions integrating structural letters to decoy scoring and show that some complexes could benefit from the use of structural letter-based pairing functions.

  13. The cellular approach to band structure calculations

    International Nuclear Information System (INIS)

    Verwoerd, W.S.

    1982-01-01

    A short introduction to the cellular approach in band structure calculations is given. The linear cellular approach and its potantial applicability in surface structure calculations is given some consideration in particular

  14. CMsearch: simultaneous exploration of protein sequence space and structure space improves not only protein homology detection but also protein structure prediction

    KAUST Repository

    Cui, Xuefeng

    2016-06-15

    Motivation: Protein homology detection, a fundamental problem in computational biology, is an indispensable step toward predicting protein structures and understanding protein functions. Despite the advances in recent decades on sequence alignment, threading and alignment-free methods, protein homology detection remains a challenging open problem. Recently, network methods that try to find transitive paths in the protein structure space demonstrate the importance of incorporating network information of the structure space. Yet, current methods merge the sequence space and the structure space into a single space, and thus introduce inconsistency in combining different sources of information. Method: We present a novel network-based protein homology detection method, CMsearch, based on cross-modal learning. Instead of exploring a single network built from the mixture of sequence and structure space information, CMsearch builds two separate networks to represent the sequence space and the structure space. It then learns sequence–structure correlation by simultaneously taking sequence information, structure information, sequence space information and structure space information into consideration. Results: We tested CMsearch on two challenging tasks, protein homology detection and protein structure prediction, by querying all 8332 PDB40 proteins. Our results demonstrate that CMsearch is insensitive to the similarity metrics used to define the sequence and the structure spaces. By using HMM–HMM alignment as the sequence similarity metric, CMsearch clearly outperforms state-of-the-art homology detection methods and the CASP-winning template-based protein structure prediction methods.

  15. A novel strategy for NMR resonance assignment and protein structure determination

    International Nuclear Information System (INIS)

    Lemak, Alexander; Gutmanas, Aleksandras; Chitayat, Seth; Karra, Murthy; Farès, Christophe; Sunnerhagen, Maria; Arrowsmith, Cheryl H.

    2011-01-01

    The quality of protein structures determined by nuclear magnetic resonance (NMR) spectroscopy is contingent on the number and quality of experimentally-derived resonance assignments, distance and angular restraints. Two key features of protein NMR data have posed challenges for the routine and automated structure determination of small to medium sized proteins; (1) spectral resolution – especially of crowded nuclear Overhauser effect spectroscopy (NOESY) spectra, and (2) the reliance on a continuous network of weak scalar couplings as part of most common assignment protocols. In order to facilitate NMR structure determination, we developed a semi-automated strategy that utilizes non-uniform sampling (NUS) and multidimensional decomposition (MDD) for optimal data collection and processing of selected, high resolution multidimensional NMR experiments, combined it with an ABACUS protocol for sequential and side chain resonance assignments, and streamlined this procedure to execute structure and refinement calculations in CYANA and CNS, respectively. Two graphical user interfaces (GUIs) were developed to facilitate efficient analysis and compilation of the data and to guide automated structure determination. This integrated method was implemented and refined on over 30 high quality structures of proteins ranging from 5.5 to 16.5 kDa in size.

  16. Structural studies of bacterial transcriptional regulatory proteins by multidimensional heteronuclear NMR

    Energy Technology Data Exchange (ETDEWEB)

    Volkman, Brian Finley [Univ. of California, Berkeley, CA (United States)

    1995-02-01

    Nuclear magnetic resonance spectroscopy was used to elucidate detailed structural information for peptide and protein molecules. A small peptide was designed and synthesized, and its three-dimensional structure was calculated using distance information derived from two-dimensional NMR measurements. The peptide was used to induce antibodies in mice, and the cross-reactivity of the antibodies with a related protein was analyzed with enzyme-linked immunosorbent assays. Two proteins which are involved in regulation of transcription in bacteria were also studied. The ferric uptake regulation (Fur) protein is a metal-dependent repressor which controls iron uptake in bacteria. Two- and three-dimensional NMR techniques, coupled with uniform and selective isotope labeling allowed the nearly complete assignment of the resonances of the metal-binding domain of the Fur protein. NTRC is a transcriptional enhancer binding protein whose N-terminal domain is a "receiver domain" in the family of "two-component" regulatory systems. Phosphorylation of the N-terminal domain of NTRC activates the initiation of transcription of aeries encoding proteins involved in nitrogen regulation. Three- and four-dimensional NMR spectroscopy methods have been used to complete the resonance assignments and determine the solution structure of the N-terminal receiver domain of the NTRC protein. Comparison of the solution structure of the NTRC receiver domain with the crystal structures of the homologous protein CheY reveals a very similar fold, with the only significant difference being the position of helix 4 relative to the rest of the protein. The determination of the structure of the NTRC receiver domain is the first step toward understanding a mechanism of signal transduction which is common to many bacterial regulatory systems.

  17. Difficulties in applying pure Kohn-Sham density functional theory electronic structure methods to protein molecules

    Science.gov (United States)

    Rudberg, Elias

    2012-02-01

    Self-consistency-based Kohn-Sham density functional theory (KS-DFT) electronic structure calculations with Gaussian basis sets are reported for a set of 17 protein-like molecules with geometries obtained from the Protein Data Bank. It is found that in many cases such calculations do not converge due to vanishing HOMO-LUMO gaps. A sequence of polyproline I helix molecules is also studied and it is found that self-consistency calculations using pure functionals fail to converge for helices longer than six proline units. Since the computed gap is strongly correlated to the fraction of Hartree-Fock exchange, test calculations using both pure and hybrid density functionals are reported. The tested methods include the pure functionals BLYP, PBE and LDA, as well as Hartree-Fock and the hybrid functionals BHandHLYP, B3LYP and PBE0. The effect of including solvent molecules in the calculations is studied, and it is found that the inclusion of explicit solvent molecules around the protein fragment in many cases gives a larger gap, but that convergence problems due to vanishing gaps still occur in calculations with pure functionals. In order to achieve converged results, some modeling of the charge distribution of solvent water molecules outside the electronic structure calculation is needed. Representing solvent water molecules by a simple point charge distribution is found to give non-vanishing HOMO-LUMO gaps for the tested protein-like systems also for pure functionals.

  18. Difficulties in applying pure Kohn-Sham density functional theory electronic structure methods to protein molecules

    International Nuclear Information System (INIS)

    Rudberg, Elias

    2012-01-01

    Self-consistency-based Kohn-Sham density functional theory (KS-DFT) electronic structure calculations with Gaussian basis sets are reported for a set of 17 protein-like molecules with geometries obtained from the Protein Data Bank. It is found that in many cases such calculations do not converge due to vanishing HOMO-LUMO gaps. A sequence of polyproline I helix molecules is also studied and it is found that self-consistency calculations using pure functionals fail to converge for helices longer than six proline units. Since the computed gap is strongly correlated to the fraction of Hartree-Fock exchange, test calculations using both pure and hybrid density functionals are reported. The tested methods include the pure functionals BLYP, PBE and LDA, as well as Hartree-Fock and the hybrid functionals BHandHLYP, B3LYP and PBE0. The effect of including solvent molecules in the calculations is studied, and it is found that the inclusion of explicit solvent molecules around the protein fragment in many cases gives a larger gap, but that convergence problems due to vanishing gaps still occur in calculations with pure functionals. In order to achieve converged results, some modeling of the charge distribution of solvent water molecules outside the electronic structure calculation is needed. Representing solvent water molecules by a simple point charge distribution is found to give non-vanishing HOMO-LUMO gaps for the tested protein-like systems also for pure functionals. (fast track communication)

  19. Roles of water in protein structure and function studied by molecular liquid theory.

    Science.gov (United States)

    Imai, Takashi

    2009-01-01

    The roles of water in the structure and function of proteins have not been completely elucidated. Although molecular simulation has been widely used for the investigation of protein structure and function, it is not always useful for elucidating the roles of water because the effect of water ranges from atomic to thermodynamic level. The three-dimensional reference interaction site model (3D-RISM) theory, which is a statistical-mechanical theory of molecular liquids, can yield the solvation structure at the atomic level and calculate the thermodynamic quantities from the intermolecular potentials. In the last few years, the author and coworkers have succeeded in applying the 3D-RISM theory to protein aqueous solution systems and demonstrated that the theory is useful for investigating the roles of water. This article reviews some of the recent applications and findings, which are concerned with molecular recognition by protein, protein folding, and the partial molar volume of protein which is related to the pressure effect on protein.

  20. Protein structure validation and refinement using amide proton chemical shifts derived from quantum mechanics

    DEFF Research Database (Denmark)

    Christensen, Anders Steen; Linnet, Troels Emtekær; Borg, Mikael

    2013-01-01

    We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts - sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level...

  1. Oligomerisation status and evolutionary conservation of interfaces of protein structural domain superfamilies.

    Science.gov (United States)

    Sukhwal, Anshul; Sowdhamini, Ramanathan

    2013-07-01

    Protein-protein interactions are important in carrying out many biological processes and functions. These interactions may be either permanent or of temporary nature. Several studies have employed tools like solvent accessibility and graph theory to identify these interactions, but still more studies need to be performed to quantify and validate them. Although we now have many databases available with predicted and experimental results on protein-protein interactions, we still do not have many databases which focus on providing structural details of the interacting complexes, their oligomerisation state and homologues. In this work, protein-protein interactions have been thoroughly investigated within the structural regime and quantified for their strength using calculated pseudoenergies. The PPCheck server, an in-house webserver, has been used for calculating the pseudoenergies like van der Waals, hydrogen bonds and electrostatic energy based on distances between atoms of amino acids from two interacting proteins. PPCheck can be visited at . Based on statistical data, as obtained by studying established protein-protein interacting complexes from earlier studies, we came to a conclusion that an average protein-protein interface consisted of about 51 to 150 amino acid residues and the generalized energy per residue ranged from -2 kJ mol(-1) to -6 kJ mol(-1). We found that some of the proteins have an exceptionally higher number of amino acids at the interface and it was purely because of their elaborate interface or extended topology i.e. some of their secondary structure regions or loops were either inter-mixing or running parallel to one another or they were taking part in domain swapping. Residue networks were prepared for all the amino acids of the interacting proteins involved in different types of interactions (like van der Waals, hydrogen-bonding, electrostatic or intramolecular interactions) and were analysed between the query domain-interacting partner pair

  2. MolTalk – a programming library for protein structures and structure analysis

    Science.gov (United States)

    Diemand, Alexander V; Scheib, Holger

    2004-01-01

    Background Two of the mostly unsolved but increasingly urgent problems for modern biologists are a) to quickly and easily analyse protein structures and b) to comprehensively mine the wealth of information, which is distributed along with the 3D co-ordinates by the Protein Data Bank (PDB). Tools which address this issue need to be highly flexible and powerful but at the same time must be freely available and easy to learn. Results We present MolTalk, an elaborate programming language, which consists of the programming library libmoltalk implemented in Objective-C and the Smalltalk-based interpreter MolTalk. MolTalk combines the advantages of an easy to learn and programmable procedural scripting with the flexibility and power of a full programming language. An overview of currently available applications of MolTalk is given and with PDBChainSaw one such application is described in more detail. PDBChainSaw is a MolTalk-based parser and information extraction utility of PDB files. Weekly updates of the PDB are synchronised with PDBChainSaw and are available for free download from the MolTalk project page following the link to PDBChainSaw. For each chain in a protein structure, PDBChainSaw extracts the sequence from its co-ordinates and provides additional information from the PDB-file header section, such as scientific organism, compound name, and EC code. Conclusion MolTalk provides a rich set of methods to analyse and even modify experimentally determined or modelled protein structures. These methods vary in complexity and are thus suitable for beginners and advanced programmers alike. We envision MolTalk to be most valuable in the following applications: 1) To analyse protein structures repetitively in large-scale, i.e. to benchmark protein structure prediction methods or to evaluate structural models. The quality of the resulting 3D-models can be assessed by e.g. calculating a Ramachandran-Sasisekharan plot. 2) To quickly retrieve information for (a limited

  3. MolTalk – a programming library for protein structures and structure analysis

    Directory of Open Access Journals (Sweden)

    Diemand Alexander V

    2004-04-01

    Full Text Available Abstract Background Two of the mostly unsolved but increasingly urgent problems for modern biologists are a to quickly and easily analyse protein structures and b to comprehensively mine the wealth of information, which is distributed along with the 3D co-ordinates by the Protein Data Bank (PDB. Tools which address this issue need to be highly flexible and powerful but at the same time must be freely available and easy to learn. Results We present MolTalk, an elaborate programming language, which consists of the programming library libmoltalk implemented in Objective-C and the Smalltalk-based interpreter MolTalk. MolTalk combines the advantages of an easy to learn and programmable procedural scripting with the flexibility and power of a full programming language. An overview of currently available applications of MolTalk is given and with PDBChainSaw one such application is described in more detail. PDBChainSaw is a MolTalk-based parser and information extraction utility of PDB files. Weekly updates of the PDB are synchronised with PDBChainSaw and are available for free download from the MolTalk project page http://www.moltalk.org following the link to PDBChainSaw. For each chain in a protein structure, PDBChainSaw extracts the sequence from its co-ordinates and provides additional information from the PDB-file header section, such as scientific organism, compound name, and EC code. Conclusion MolTalk provides a rich set of methods to analyse and even modify experimentally determined or modelled protein structures. These methods vary in complexity and are thus suitable for beginners and advanced programmers alike. We envision MolTalk to be most valuable in the following applications: 1 To analyse protein structures repetitively in large-scale, i.e. to benchmark protein structure prediction methods or to evaluate structural models. The quality of the resulting 3D-models can be assessed by e.g. calculating a Ramachandran-Sasisekharan plot. 2 To

  4. Three-dimensional solution structure of a DNA duplex containing the BclI restriction sequence: Two-dimensional NMR studies, distance geometry calculations, and refinement by back-calculation of the NOESY spectrum

    International Nuclear Information System (INIS)

    Banks, K.M.; Hare, D.R.; Reid, B.R.

    1989-01-01

    A three-dimensional solution structure for the self-complementary dodecanucleotide [(d-GCCTGATCAGGC)] 2 has been determined by distance geometry with further refinements being performed after back-calculation of the NOESY spectrum. This DNA dodecamer contains the hexamer [d(TGATCA)] 2 recognized and cut by the restriction endonuclease BclI, and its structure was determined in hopes of obtaining a better understanding of the sequence-specific interactions which occur between proteins and DNA. Preliminary examination of the structure indicates the structure is underwound with respect to idealized B-form DNA though some of the local structural parameters (glycosyl torsion angle and pseudorotation angle) suggest a B-family type of structure is present. This research demonstrates the requirements (resonance assignments, interproton distance measurements, distance geometry calculations, and NOESY spectra back-calculation) to generate experimentally self-consistent solution structures for short DNA sequences

  5. SDSL-ESR-based protein structure characterization.

    Science.gov (United States)

    Strancar, Janez; Kavalenka, Aleh; Urbancic, Iztok; Ljubetic, Ajasja; Hemminga, Marcus A

    2010-03-01

    As proteins are key molecules in living cells, knowledge about their structure can provide important insights and applications in science, biotechnology, and medicine. However, many protein structures are still a big challenge for existing high-resolution structure-determination methods, as can be seen in the number of protein structures published in the Protein Data Bank. This is especially the case for less-ordered, more hydrophobic and more flexible protein systems. The lack of efficient methods for structure determination calls for urgent development of a new class of biophysical techniques. This work attempts to address this problem with a novel combination of site-directed spin labelling electron spin resonance spectroscopy (SDSL-ESR) and protein structure modelling, which is coupled by restriction of the conformational spaces of the amino acid side chains. Comparison of the application to four different protein systems enables us to generalize the new method and to establish a general procedure for determination of protein structure.

  6. Structure and non-structure of centrosomal proteins.

    Science.gov (United States)

    Dos Santos, Helena G; Abia, David; Janowski, Robert; Mortuza, Gulnahar; Bertero, Michela G; Boutin, Maïlys; Guarín, Nayibe; Méndez-Giraldez, Raúl; Nuñez, Alfonso; Pedrero, Juan G; Redondo, Pilar; Sanz, María; Speroni, Silvia; Teichert, Florian; Bruix, Marta; Carazo, José M; Gonzalez, Cayetano; Reina, José; Valpuesta, José M; Vernos, Isabelle; Zabala, Juan C; Montoya, Guillermo; Coll, Miquel; Bastolla, Ugo; Serrano, Luis

    2013-01-01

    Here we perform a large-scale study of the structural properties and the expression of proteins that constitute the human Centrosome. Centrosomal proteins tend to be larger than generic human proteins (control set), since their genes contain in average more exons (20.3 versus 14.6). They are rich in predicted disordered regions, which cover 57% of their length, compared to 39% in the general human proteome. They also contain several regions that are dually predicted to be disordered and coiled-coil at the same time: 55 proteins (15%) contain disordered and coiled-coil fragments that cover more than 20% of their length. Helices prevail over strands in regions homologous to known structures (47% predicted helical residues against 17% predicted as strands), and even more in the whole centrosomal proteome (52% against 7%), while for control human proteins 34.5% of the residues are predicted as helical and 12.8% are predicted as strands. This difference is mainly due to residues predicted as disordered and helical (30% in centrosomal and 9.4% in control proteins), which may correspond to alpha-helix forming molecular recognition features (α-MoRFs). We performed expression assays for 120 full-length centrosomal proteins and 72 domain constructs that we have predicted to be globular. These full-length proteins are often insoluble: Only 39 out of 120 expressed proteins (32%) and 19 out of 72 domains (26%) were soluble. We built or retrieved structural models for 277 out of 361 human proteins whose centrosomal localization has been experimentally verified. We could not find any suitable structural template with more than 20% sequence identity for 84 centrosomal proteins (23%), for which around 74% of the residues are predicted to be disordered or coiled-coils. The three-dimensional models that we built are available at http://ub.cbm.uam.es/centrosome/models/index.php.

  7. Structure-Energy Relationships of Halogen Bonds in Proteins.

    Science.gov (United States)

    Scholfield, Matthew R; Ford, Melissa Coates; Carlsson, Anna-Carin C; Butta, Hawera; Mehl, Ryan A; Ho, P Shing

    2017-06-06

    The structures and stabilities of proteins are defined by a series of weak noncovalent electrostatic, van der Waals, and hydrogen bond (HB) interactions. In this study, we have designed and engineered halogen bonds (XBs) site-specifically to study their structure-energy relationship in a model protein, T4 lysozyme. The evidence for XBs is the displacement of the aromatic side chain toward an oxygen acceptor, at distances that are equal to or less than the sums of their respective van der Waals radii, when the hydroxyl substituent of the wild-type tyrosine is replaced by a halogen. In addition, thermal melting studies show that the iodine XB rescues the stabilization energy from an otherwise destabilizing substitution (at an equivalent noninteracting site), indicating that the interaction is also present in solution. Quantum chemical calculations show that the XB complements an HB at this site and that solvent structure must also be considered in trying to design molecular interactions such as XBs into biological systems. A bromine substitution also shows displacement of the side chain, but the distances and geometries do not indicate formation of an XB. Thus, we have dissected the contributions from various noncovalent interactions of halogens introduced into proteins, to drive the application of XBs, particularly in biomolecular design.

  8. BLAST-based structural annotation of protein residues using Protein Data Bank.

    Science.gov (United States)

    Singh, Harinder; Raghava, Gajendra P S

    2016-01-25

    In the era of next-generation sequencing where thousands of genomes have been already sequenced; size of protein databases is growing with exponential rate. Structural annotation of these proteins is one of the biggest challenges for the computational biologist. Although, it is easy to perform BLAST search against Protein Data Bank (PDB) but it is difficult for a biologist to annotate protein residues from BLAST search. A web-server StarPDB has been developed for structural annotation of a protein based on its similarity with known protein structures. It uses standard BLAST software for performing similarity search of a query protein against protein structures in PDB. This server integrates wide range modules for assigning different types of annotation that includes, Secondary-structure, Accessible surface area, Tight-turns, DNA-RNA and Ligand modules. Secondary structure module allows users to predict regular secondary structure states to each residue in a protein. Accessible surface area predict the exposed or buried residues in a protein. Tight-turns module is designed to predict tight turns like beta-turns in a protein. DNA-RNA module developed for predicting DNA and RNA interacting residues in a protein. Similarly, Ligand module of server allows one to predicted ligands, metal and nucleotides ligand interacting residues in a protein. In summary, this manuscript presents a web server for comprehensive annotation of a protein based on similarity search. It integrates number of visualization tools that facilitate users to understand structure and function of protein residues. This web server is available freely for scientific community from URL http://crdd.osdd.net/raghava/starpdb .

  9. Calculations of nucleon structure functions

    International Nuclear Information System (INIS)

    Signal, A.I.

    1990-01-01

    We present a method of calculating deep inelastic nucleon structure functions using bag model wavefunctions. Our method uses the Peierls - Yoccoz projection to form translation invariant bag states. We obtain the correct support for the structure functions and satisfy the positivity requirements for quark and anti-quark distribution functions. (orig.)

  10. Towards accurate free energy calculations in ligand protein-binding studies.

    Science.gov (United States)

    Steinbrecher, Thomas; Labahn, Andreas

    2010-01-01

    Cells contain a multitude of different chemical reaction paths running simultaneously and quite independently next to each other. This amazing feat is enabled by molecular recognition, the ability of biomolecules to form stable and specific complexes with each other and with their substrates. A better understanding of this process, i.e. of the kinetics, structures and thermodynamic properties of biomolecule binding, would be invaluable in the study of biological systems. In addition, as the mode of action of many pharmaceuticals is based upon their inhibition or activation of biomolecule targets, predictive models of small molecule receptor binding are very helpful tools in rational drug design. Since the goal here is normally to design a new compound with a high inhibition strength, one of the most important thermodynamic properties is the binding free energy DeltaG(0). The prediction of binding constants has always been one of the major goals in the field of computational chemistry, because the ability to reliably assess a hypothetical compound's binding properties without having to synthesize it first would save a tremendous amount of work. The different approaches to this question range from fast and simple empirical descriptor methods to elaborate simulation protocols aimed at putting the computation of free energies onto a solid foundation of statistical thermodynamics. While the later methods are still not suited for the screenings of thousands of compounds that are routinely performed in computational drug design studies, they are increasingly put to use for the detailed study of protein ligand interactions. This review will focus on molecular mechanics force field based free energy calculations and their application to the study of protein ligand interactions. After a brief overview of other popular methods for the calculation of free energies, we will describe recent advances in methodology and a variety of exemplary studies of molecular dynamics

  11. Final disposal room structural response calculations

    International Nuclear Information System (INIS)

    Stone, C.M.

    1997-08-01

    Finite element calculations have been performed to determine the structural response of waste-filled disposal rooms at the WIPP for a period of 10,000 years after emplacement of the waste. The calculations were performed to generate the porosity surface data for the final set of compliance calculations. The most recent reference data for the stratigraphy, waste characterization, gas generation potential, and nonlinear material response have been brought together for this final set of calculations

  12. Broyden's method in nuclear structure calculations

    International Nuclear Information System (INIS)

    Baran, Andrzej; Bulgac, Aurel; Forbes, Michael McNeil; Hagen, Gaute; Nazarewicz, Witold; Schunck, Nicolas; Stoitsov, Mario V.

    2008-01-01

    Broyden's method, widely used in quantum chemistry electronic-structure calculations for the numerical solution of nonlinear equations in many variables, is applied in the context of the nuclear many-body problem. Examples include the unitary gas problem, the nuclear density functional theory with Skyrme functionals, and the nuclear coupled-cluster theory. The stability of the method, its ease of use, and its rapid convergence rates make Broyden's method a tool of choice for large-scale nuclear structure calculations

  13. Distance matrix-based approach to protein structure prediction.

    Science.gov (United States)

    Kloczkowski, Andrzej; Jernigan, Robert L; Wu, Zhijun; Song, Guang; Yang, Lei; Kolinski, Andrzej; Pokarowski, Piotr

    2009-03-01

    dynamics. After structure matching, we apply principal component analysis (PCA) to obtain the important apparent motions for both bound and unbound structures. There are significant similarities between the first few key motions and the first few low-frequency normal modes calculated from a static representative structure with an elastic network model (ENM) that is based on the contact matrix C (related to D), strongly suggesting that the variations among the observed structures and the corresponding conformational changes are facilitated by the low-frequency, global motions intrinsic to the structure. Similarities are also found when the approach is applied to an NMR ensemble, as well as to atomic molecular dynamics (MD) trajectories. Thus, a sufficiently large number of experimental structures can directly provide important information about protein dynamics, but ENM can also provide a similar sampling of conformations. Finally, we use distance constraints from databases of known protein structures for structure refinement. We use the distributions of distances of various types in known protein structures to obtain the most probable ranges or the mean-force potentials for the distances. We then impose these constraints on structures to be refined or include the mean-force potentials directly in the energy minimization so that more plausible structural models can be built. This approach has been successfully used by us in 2006 in the CASPR structure refinement (http://predictioncenter.org/caspR).

  14. NAPS: Network Analysis of Protein Structures

    Science.gov (United States)

    Chakrabarty, Broto; Parekh, Nita

    2016-01-01

    Traditionally, protein structures have been analysed by the secondary structure architecture and fold arrangement. An alternative approach that has shown promise is modelling proteins as a network of non-covalent interactions between amino acid residues. The network representation of proteins provide a systems approach to topological analysis of complex three-dimensional structures irrespective of secondary structure and fold type and provide insights into structure-function relationship. We have developed a web server for network based analysis of protein structures, NAPS, that facilitates quantitative and qualitative (visual) analysis of residue–residue interactions in: single chains, protein complex, modelled protein structures and trajectories (e.g. from molecular dynamics simulations). The user can specify atom type for network construction, distance range (in Å) and minimal amino acid separation along the sequence. NAPS provides users selection of node(s) and its neighbourhood based on centrality measures, physicochemical properties of amino acids or cluster of well-connected residues (k-cliques) for further analysis. Visual analysis of interacting domains and protein chains, and shortest path lengths between pair of residues are additional features that aid in functional analysis. NAPS support various analyses and visualization views for identifying functional residues, provide insight into mechanisms of protein folding, domain-domain and protein–protein interactions for understanding communication within and between proteins. URL:http://bioinf.iiit.ac.in/NAPS/. PMID:27151201

  15. Modeling the Structure of SARS 3a Transmembrane Protein Using a ...

    Indian Academy of Sciences (India)

    Modeling the structure of SARS 3a Transmembrane protein using a ... for the implicit membrane molecular dynamics (MD) simulations. ... The coordinates during the simulation were saved every 500 steps, and were used for analysis. ... the pair list for calculation of nonbonded interactions being updated after every 10 steps.

  16. Improved reliability, accuracy and quality in automated NMR structure calculation with ARIA

    Energy Technology Data Exchange (ETDEWEB)

    Mareuil, Fabien [Institut Pasteur, Cellule d' Informatique pour la Biologie (France); Malliavin, Thérèse E.; Nilges, Michael; Bardiaux, Benjamin, E-mail: bardiaux@pasteur.fr [Institut Pasteur, Unité de Bioinformatique Structurale, CNRS UMR 3528 (France)

    2015-08-15

    In biological NMR, assignment of NOE cross-peaks and calculation of atomic conformations are critical steps in the determination of reliable high-resolution structures. ARIA is an automated approach that performs NOE assignment and structure calculation in a concomitant manner in an iterative procedure. The log-harmonic shape for distance restraint potential and the Bayesian weighting of distance restraints, recently introduced in ARIA, were shown to significantly improve the quality and the accuracy of determined structures. In this paper, we propose two modifications of the ARIA protocol: (1) the softening of the force field together with adapted hydrogen radii, which is meaningful in the context of the log-harmonic potential with Bayesian weighting, (2) a procedure that automatically adjusts the violation tolerance used in the selection of active restraints, based on the fitting of the structure to the input data sets. The new ARIA protocols were fine-tuned on a set of eight protein targets from the CASD–NMR initiative. As a result, the convergence problems previously observed for some targets was resolved and the obtained structures exhibited better quality. In addition, the new ARIA protocols were applied for the structure calculation of ten new CASD–NMR targets in a blind fashion, i.e. without knowing the actual solution. Even though optimisation of parameters and pre-filtering of unrefined NOE peak lists were necessary for half of the targets, ARIA consistently and reliably determined very precise and highly accurate structures for all cases. In the context of integrative structural biology, an increasing number of experimental methods are used that produce distance data for the determination of 3D structures of macromolecules, stressing the importance of methods that successfully make use of ambiguous and noisy distance data.

  17. Model for calculation of electrostatic contribution into protein stability

    Science.gov (United States)

    Kundrotas, Petras; Karshikoff, Andrey

    2003-03-01

    Existing models of the denatured state of proteins consider only one possible spatial distribution of protein charges and therefore are applicable to a limited number of cases. In this presentation a more general framework for the modeling of the denatured state is proposed. It is based on the assumption that the titratable groups of an unfolded protein can adopt a quasi-random distribution, restricted by the protein sequence. The model was tested on two proteins, barnase and N-terminal domain of the ribosomal protein L9. The calculated free energy of denaturation, Δ G( pH), reproduces the experimental data essentially better than the commonly used null approximation (NA). It was demonstrated that the seemingly good agreement with experimental data obtained by NA originates from the compensatory effect between the pair-wise electrostatic interactions and the desolvation energy of the individual sites. It was also found that the ionization properties of denatured proteins are influenced by the protein sequence.

  18. Structural interface parameters are discriminatory in recognising near-native poses of protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Sony Malhotra

    Full Text Available Interactions at the molecular level in the cellular environment play a very crucial role in maintaining the physiological functioning of the cell. These molecular interactions exist at varied levels viz. protein-protein interactions, protein-nucleic acid interactions or protein-small molecules interactions. Presently in the field, these interactions and their mechanisms mark intensively studied areas. Molecular interactions can also be studied computationally using the approach named as Molecular Docking. Molecular docking employs search algorithms to predict the possible conformations for interacting partners and then calculates interaction energies. However, docking proposes number of solutions as different docked poses and hence offers a serious challenge to identify the native (or near native structures from the pool of these docked poses. Here, we propose a rigorous scoring scheme called DockScore which can be used to rank the docked poses and identify the best docked pose out of many as proposed by docking algorithm employed. The scoring identifies the optimal interactions between the two protein partners utilising various features of the putative interface like area, short contacts, conservation, spatial clustering and the presence of positively charged and hydrophobic residues. DockScore was first trained on a set of 30 protein-protein complexes to determine the weights for different parameters. Subsequently, we tested the scoring scheme on 30 different protein-protein complexes and native or near-native structure were assigned the top rank from a pool of docked poses in 26 of the tested cases. We tested the ability of DockScore to discriminate likely dimer interactions that differ substantially within a homologous family and also demonstrate that DOCKSCORE can distinguish correct pose for all 10 recent CAPRI targets.

  19. How Many Protein Sequences Fold to a Given Structure? A Coevolutionary Analysis.

    Science.gov (United States)

    Tian, Pengfei; Best, Robert B

    2017-10-17

    Quantifying the relationship between protein sequence and structure is key to understanding the protein universe. A fundamental measure of this relationship is the total number of amino acid sequences that can fold to a target protein structure, known as the "sequence capacity," which has been suggested as a proxy for how designable a given protein fold is. Although sequence capacity has been extensively studied using lattice models and theory, numerical estimates for real protein structures are currently lacking. In this work, we have quantitatively estimated the sequence capacity of 10 proteins with a variety of different structures using a statistical model based on residue-residue co-evolution to capture the variation of sequences from the same protein family. Remarkably, we find that even for the smallest protein folds, such as the WW domain, the number of foldable sequences is extremely large, exceeding the Avogadro constant. In agreement with earlier theoretical work, the calculated sequence capacity is positively correlated with the size of the protein, or better, the density of contacts. This allows the absolute sequence capacity of a given protein to be approximately predicted from its structure. On the other hand, the relative sequence capacity, i.e., normalized by the total number of possible sequences, is an extremely tiny number and is strongly anti-correlated with the protein length. Thus, although there may be more foldable sequences for larger proteins, it will be much harder to find them. Lastly, we have correlated the evolutionary age of proteins in the CATH database with their sequence capacity as predicted by our model. The results suggest a trade-off between the opposing requirements of high designability and the likelihood of a novel fold emerging by chance. Published by Elsevier Inc.

  20. Fast loop modeling for protein structures

    Science.gov (United States)

    Zhang, Jiong; Nguyen, Son; Shang, Yi; Xu, Dong; Kosztin, Ioan

    2015-03-01

    X-ray crystallography is the main method for determining 3D protein structures. In many cases, however, flexible loop regions of proteins cannot be resolved by this approach. This leads to incomplete structures in the protein data bank, preventing further computational study and analysis of these proteins. For instance, all-atom molecular dynamics (MD) simulation studies of structure-function relationship require complete protein structures. To address this shortcoming, we have developed and implemented an efficient computational method for building missing protein loops. The method is database driven and uses deep learning and multi-dimensional scaling algorithms. We have implemented the method as a simple stand-alone program, which can also be used as a plugin in existing molecular modeling software, e.g., VMD. The quality and stability of the generated structures are assessed and tested via energy scoring functions and by equilibrium MD simulations. The proposed method can also be used in template-based protein structure prediction. Work supported by the National Institutes of Health [R01 GM100701]. Computer time was provided by the University of Missouri Bioinformatics Consortium.

  1. Temperature, pressure, and electrochemical constraints on protein speciation: Group additivity calculation of the standard molal thermodynamic properties of ionized unfolded proteins

    Directory of Open Access Journals (Sweden)

    J. M. Dick

    2006-01-01

    Full Text Available Thermodynamic calculations can be used to quantify environmental constraints on the speciation of proteins, such as the pH and temperature dependence of ionization state, and the relative chemical stabilities of proteins in different biogeochemical settings. These calculations depend in part on values of the standard molal Gibbs energies of proteins and their ionization reactions as a function of temperature and pressure. Because these values are not generally available, we calculated values of the standard molal thermodynamic properties at 25°C and 1 bar as well as the revised Helgeson-Kirkham-Flowers equations of state parameters of neutral and charged zwitterionic reference model compounds including aqueous amino acids, polypeptides, and unfolded proteins. The experimental calorimetric and volumetric data for these species taken from the literature were combined with group additivity algorithms to calculate the properties and parameters of neutral and ionized sidechain and backbone groups in unfolded proteins. The resulting set of group contributions enables the calculation of the standard molal Gibbs energy, enthalpy, entropy, isobaric heat capacity, volume, and isothermal compressibility of unfolded proteins in a range of proton ionization states to temperatures and pressures exceeding 100°C and 1000 bar. This approach provides a useful frame of reference for thermodynamic studies of protein folding and complexation reactions. It can also be used to assign provisional values of the net charge and Gibbs energy of ionized proteins as a function of temperature and pH. Using these values, an Eh-pH diagram for a reaction representing the speciation of extracellular proteins from Pyrococcus furiosus and Bacillus subtilis was generated. The predicted predominance limits of these proteins correspond with the different electrochemical conditions of hydrothermal vents and soils. More comprehensive calculations of this kind may reveal pervasive

  2. ORNL-SAS: Versatile software for calculation of small-angle x-ray and neutron scattering intensity profiles from arbitrary structures

    International Nuclear Information System (INIS)

    Heller, William T; Tjioe, Elina

    2007-01-01

    ORNL-SAS is software for calculating solution small-angle scattering intensity profiles from any structure provided in the Protein Data Bank format and can also compare the results with experimental data

  3. Prediction of protein–protein interactions: unifying evolution and structure at protein interfaces

    International Nuclear Information System (INIS)

    Tuncbag, Nurcan; Gursoy, Attila; Keskin, Ozlem

    2011-01-01

    The vast majority of the chores in the living cell involve protein–protein interactions. Providing details of protein interactions at the residue level and incorporating them into protein interaction networks are crucial toward the elucidation of a dynamic picture of cells. Despite the rapid increase in the number of structurally known protein complexes, we are still far away from a complete network. Given experimental limitations, computational modeling of protein interactions is a prerequisite to proceed on the way to complete structural networks. In this work, we focus on the question 'how do proteins interact?' rather than 'which proteins interact?' and we review structure-based protein–protein interaction prediction approaches. As a sample approach for modeling protein interactions, PRISM is detailed which combines structural similarity and evolutionary conservation in protein interfaces to infer structures of complexes in the protein interaction network. This will ultimately help us to understand the role of protein interfaces in predicting bound conformations

  4. Structural anatomy of telomere OB proteins.

    Science.gov (United States)

    Horvath, Martin P

    2011-10-01

    Telomere DNA-binding proteins protect the ends of chromosomes in eukaryotes. A subset of these proteins are constructed with one or more OB folds and bind with G+T-rich single-stranded DNA found at the extreme termini. The resulting DNA-OB protein complex interacts with other telomere components to coordinate critical telomere functions of DNA protection and DNA synthesis. While the first crystal and NMR structures readily explained protection of telomere ends, the picture of how single-stranded DNA becomes available to serve as primer and template for synthesis of new telomere DNA is only recently coming into focus. New structures of telomere OB fold proteins alongside insights from genetic and biochemical experiments have made significant contributions towards understanding how protein-binding OB proteins collaborate with DNA-binding OB proteins to recruit telomerase and DNA polymerase for telomere homeostasis. This review surveys telomere OB protein structures alongside highly comparable structures derived from replication protein A (RPA) components, with the goal of providing a molecular context for understanding telomere OB protein evolution and mechanism of action in protection and synthesis of telomere DNA.

  5. Protein Structure and the Sequential Structure of mRNA

    DEFF Research Database (Denmark)

    Brunak, Søren; Engelbrecht, Jacob

    1996-01-01

    entries in the Brookhaven Protein Data Bank produced 719 protein chains with matching mRNA sequence, amino acid sequence, and secondary structure assignment, By neural network analysis, we found strong signals in mRNA sequence regions surrounding helices and sheets, These signals do not originate from......A direct comparison of experimentally determined protein structures and their corresponding protein coding mRNA sequences has been performed, We examine whether real world data support the hypothesis that clusters of rare codons correlate with the location of structural units in the resulting...... protein, The degeneracy of the genetic code allows for a biased selection of codons which may control the translational rate of the ribosome, and may thus in vivo have a catalyzing effect on the folding of the polypeptide chain, A complete search for GenBank nucleotide sequences coding for structural...

  6. Structural and energetic study of cation-π-cation interactions in proteins.

    Science.gov (United States)

    Pinheiro, Silvana; Soteras, Ignacio; Gelpí, Josep Lluis; Dehez, François; Chipot, Christophe; Luque, F Javier; Curutchet, Carles

    2017-04-12

    Cation-π interactions of aromatic rings and positively charged groups are among the most important interactions in structural biology. The role and energetic characteristics of these interactions are well established. However, the occurrence of cation-π-cation interactions is an unexpected motif, which raises intriguing questions about its functional role in proteins. We present a statistical analysis of the occurrence, composition and geometrical preferences of cation-π-cation interactions identified in a set of non-redundant protein structures taken from the Protein Data Bank. Our results demonstrate that this structural motif is observed at a small, albeit non-negligible frequency in proteins, and suggest a preference to establish cation-π-cation motifs with Trp, followed by Tyr and Phe. Furthermore, we have found that cation-π-cation interactions tend to be highly conserved, which supports their structural or functional role. Finally, we have performed an energetic analysis of a representative subset of cation-π-cation complexes combining quantum-chemical and continuum solvation calculations. Our results point out that the protein environment can strongly screen the cation-cation repulsion, leading to an attractive interaction in 64% of the complexes analyzed. Together with the high degree of conservation observed, these results suggest a potential stabilizing role in the protein fold, as demonstrated recently for a miniature protein (Craven et al., J. Am. Chem. Soc. 2016, 138, 1543). From a computational point of view, the significant contribution of non-additive three-body terms challenges the suitability of standard additive force fields for describing cation-π-cation motifs in molecular simulations.

  7. Automated protein structure modeling with SWISS-MODEL Workspace and the Protein Model Portal.

    Science.gov (United States)

    Bordoli, Lorenza; Schwede, Torsten

    2012-01-01

    Comparative protein structure modeling is a computational approach to build three-dimensional structural models for proteins using experimental structures of related protein family members as templates. Regular blind assessments of modeling accuracy have demonstrated that comparative protein structure modeling is currently the most reliable technique to model protein structures. Homology models are often sufficiently accurate to substitute for experimental structures in a wide variety of applications. Since the usefulness of a model for specific application is determined by its accuracy, model quality estimation is an essential component of protein structure prediction. Comparative protein modeling has become a routine approach in many areas of life science research since fully automated modeling systems allow also nonexperts to build reliable models. In this chapter, we describe practical approaches for automated protein structure modeling with SWISS-MODEL Workspace and the Protein Model Portal.

  8. Automated Protein Structure Modeling with SWISS-MODEL Workspace and the Protein Model Portal

    OpenAIRE

    Bordoli, Lorenza; Schwede, Torsten

    2012-01-01

    Comparative protein structure modeling is a computational approach to build three-dimensional structural models for proteins using experimental structures of related protein family members as templates. Regular blind assessments of modeling accuracy have demonstrated that comparative protein structure modeling is currently the most reliable technique to model protein structures. Homology models are often sufficiently accurate to substitute for experimental structures in a wide variety of appl...

  9. Beta-structures in fibrous proteins.

    Science.gov (United States)

    Kajava, Andrey V; Squire, John M; Parry, David A D

    2006-01-01

    The beta-form of protein folding, one of the earliest protein structures to be defined, was originally observed in studies of silks. It was then seen in early studies of synthetic polypeptides and, of course, is now known to be present in a variety of guises as an essential component of globular protein structures. However, in the last decade or so it has become clear that the beta-conformation of chains is present not only in many of the amyloid structures associated with, for example, Alzheimer's Disease, but also in the prion structures associated with the spongiform encephalopathies. Furthermore, X-ray crystallography studies have revealed the high incidence of the beta-fibrous proteins among virulence factors of pathogenic bacteria and viruses. Here we describe the basic forms of the beta-fold, summarize the many different new forms of beta-structural fibrous arrangements that have been discovered, and review advances in structural studies of amyloid and prion fibrils. These and other issues are described in detail in later chapters.

  10. Calculation of the redox potential of the protein azurin and some mutants

    NARCIS (Netherlands)

    van den Bosch, M; Swart, M; Snijders, JG; Berendsen, HJC; Mark, AE; Oostenbrink, C; van Gunsteren, WF; Canters, GW

    Azurin from Pseudomonas aeruginosa is a small 128-residue, copper-containing protein. Its redox potential can be modified by mutating the protein. Free-energy calculations based on classical molecular-dynamics simulations of the protein and from mutants in aqueous solution at different pH values

  11. Calculation of protein-ligand binding affinities.

    Science.gov (United States)

    Gilson, Michael K; Zhou, Huan-Xiang

    2007-01-01

    Accurate methods of computing the affinity of a small molecule with a protein are needed to speed the discovery of new medications and biological probes. This paper reviews physics-based models of binding, beginning with a summary of the changes in potential energy, solvation energy, and configurational entropy that influence affinity, and a theoretical overview to frame the discussion of specific computational approaches. Important advances are reported in modeling protein-ligand energetics, such as the incorporation of electronic polarization and the use of quantum mechanical methods. Recent calculations suggest that changes in configurational entropy strongly oppose binding and must be included if accurate affinities are to be obtained. The linear interaction energy (LIE) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods are analyzed, as are free energy pathway methods, which show promise and may be ready for more extensive testing. Ultimately, major improvements in modeling accuracy will likely require advances on multiple fronts, as well as continued validation against experiment.

  12. Solution structure of the human signaling protein RACK1

    Directory of Open Access Journals (Sweden)

    Papa Priscila F

    2010-06-01

    Full Text Available Abstract Background The adaptor protein RACK1 (receptor of activated kinase 1 was originally identified as an anchoring protein for protein kinase C. RACK1 is a 36 kDa protein, and is composed of seven WD repeats which mediate its protein-protein interactions. RACK1 is ubiquitously expressed and has been implicated in diverse cellular processes involving: protein translation regulation, neuropathological processes, cellular stress, and tissue development. Results In this study we performed a biophysical analysis of human RACK1 with the aim of obtaining low resolution structural information. Small angle X-ray scattering (SAXS experiments demonstrated that human RACK1 is globular and monomeric in solution and its low resolution structure is strikingly similar to that of an homology model previously calculated by us and to the crystallographic structure of RACK1 isoform A from Arabidopsis thaliana. Both sedimentation velocity and sedimentation equilibrium analytical ultracentrifugation techniques showed that RACK1 is predominantly a monomer of around 37 kDa in solution, but also presents small amounts of oligomeric species. Moreover, hydrodynamic data suggested that RACK1 has a slightly asymmetric shape. The interaction of RACK1 and Ki-1/57 was tested by sedimentation equilibrium. The results suggested that the association between RACK1 and Ki-1/57(122-413 follows a stoichiometry of 1:1. The binding constant (KB observed for RACK1-Ki-1/57(122-413 interaction was of around (1.5 ± 0.2 × 106 M-1 and resulted in a dissociation constant (KD of (0.7 ± 0.1 × 10-6 M. Moreover, the fluorescence data also suggests that the interaction may occur in a cooperative fashion. Conclusion Our SAXS and analytical ultracentrifugation experiments indicated that RACK1 is predominantly a monomer in solution. RACK1 and Ki-1/57(122-413 interact strongly under the tested conditions.

  13. The interface of protein structure, protein biophysics, and molecular evolution

    Science.gov (United States)

    Liberles, David A; Teichmann, Sarah A; Bahar, Ivet; Bastolla, Ugo; Bloom, Jesse; Bornberg-Bauer, Erich; Colwell, Lucy J; de Koning, A P Jason; Dokholyan, Nikolay V; Echave, Julian; Elofsson, Arne; Gerloff, Dietlind L; Goldstein, Richard A; Grahnen, Johan A; Holder, Mark T; Lakner, Clemens; Lartillot, Nicholas; Lovell, Simon C; Naylor, Gavin; Perica, Tina; Pollock, David D; Pupko, Tal; Regan, Lynne; Roger, Andrew; Rubinstein, Nimrod; Shakhnovich, Eugene; Sjölander, Kimmen; Sunyaev, Shamil; Teufel, Ashley I; Thorne, Jeffrey L; Thornton, Joseph W; Weinreich, Daniel M; Whelan, Simon

    2012-01-01

    Abstract The interface of protein structural biology, protein biophysics, molecular evolution, and molecular population genetics forms the foundations for a mechanistic understanding of many aspects of protein biochemistry. Current efforts in interdisciplinary protein modeling are in their infancy and the state-of-the art of such models is described. Beyond the relationship between amino acid substitution and static protein structure, protein function, and corresponding organismal fitness, other considerations are also discussed. More complex mutational processes such as insertion and deletion and domain rearrangements and even circular permutations should be evaluated. The role of intrinsically disordered proteins is still controversial, but may be increasingly important to consider. Protein geometry and protein dynamics as a deviation from static considerations of protein structure are also important. Protein expression level is known to be a major determinant of evolutionary rate and several considerations including selection at the mRNA level and the role of interaction specificity are discussed. Lastly, the relationship between modeling and needed high-throughput experimental data as well as experimental examination of protein evolution using ancestral sequence resurrection and in vitro biochemistry are presented, towards an aim of ultimately generating better models for biological inference and prediction. PMID:22528593

  14. Accuracy issues involved in modeling in vivo protein structures using PM7.

    Science.gov (United States)

    Martin, Benjamin P; Brandon, Christopher J; Stewart, James J P; Braun-Sand, Sonja B

    2015-08-01

    Using the semiempirical method PM7, an attempt has been made to quantify the error in prediction of the in vivo structure of proteins relative to X-ray structures. Three important contributory factors are the experimental limitations of X-ray structures, the difference between the crystal and solution environments, and the errors due to PM7. The geometries of 19 proteins from the Protein Data Bank that had small R values, that is, high accuracy structures, were optimized and the resulting drop in heat of formation was calculated. Analysis of the changes showed that about 10% of this decrease in heat of formation was caused by faults in PM7, the balance being attributable to the X-ray structure and the difference between the crystal and solution environments. A previously unknown fault in PM7 was revealed during tests to validate the geometries generated using PM7. Clashscores generated by the Molprobity molecular mechanics structure validation program showed that PM7 was predicting unrealistically close contacts between nonbonding atoms in regions where the local geometry is dominated by very weak noncovalent interactions. The origin of this fault was traced to an underestimation of the core-core repulsion between atoms at distances smaller than the equilibrium distance. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published By Wiley Periodicals, Inc.

  15. GIS: a comprehensive source for protein structure similarities.

    Science.gov (United States)

    Guerler, Aysam; Knapp, Ernst-Walter

    2010-07-01

    A web service for analysis of protein structures that are sequentially or non-sequentially similar was generated. Recently, the non-sequential structure alignment algorithm GANGSTA+ was introduced. GANGSTA+ can detect non-sequential structural analogs for proteins stated to possess novel folds. Since GANGSTA+ ignores the polypeptide chain connectivity of secondary structure elements (i.e. alpha-helices and beta-strands), it is able to detect structural similarities also between proteins whose sequences were reshuffled during evolution. GANGSTA+ was applied in an all-against-all comparison on the ASTRAL40 database (SCOP version 1.75), which consists of >10,000 protein domains yielding about 55 x 10(6) possible protein structure alignments. Here, we provide the resulting protein structure alignments as a public web-based service, named GANGSTA+ Internet Services (GIS). We also allow to browse the ASTRAL40 database of protein structures with GANGSTA+ relative to an externally given protein structure using different constraints to select specific results. GIS allows us to analyze protein structure families according to the SCOP classification scheme. Additionally, users can upload their own protein structures for pairwise protein structure comparison, alignment against all protein structures of the ASTRAL40 database (SCOP version 1.75) or symmetry analysis. GIS is publicly available at http://agknapp.chemie.fu-berlin.de/gplus.

  16. Neural Networks for protein Structure Prediction

    DEFF Research Database (Denmark)

    Bohr, Henrik

    1998-01-01

    This is a review about neural network applications in bioinformatics. Especially the applications to protein structure prediction, e.g. prediction of secondary structures, prediction of surface structure, fold class recognition and prediction of the 3-dimensional structure of protein backbones...

  17. Protein Molecular Structures, Protein SubFractions, and Protein Availability Affected by Heat Processing: A Review

    International Nuclear Information System (INIS)

    Yu, P.

    2007-01-01

    The utilization and availability of protein depended on the types of protein and their specific susceptibility to enzymatic hydrolysis (inhibitory activities) in the gastrointestine and was highly associated with protein molecular structures. Studying internal protein structure and protein subfraction profiles leaded to an understanding of the components that make up a whole protein. An understanding of the molecular structure of the whole protein was often vital to understanding its digestive behavior and nutritive value in animals. In this review, recently obtained information on protein molecular structural effects of heat processing was reviewed, in relation to protein characteristics affecting digestive behavior and nutrient utilization and availability. The emphasis of this review was on (1) using the newly advanced synchrotron technology (S-FTIR) as a novel approach to reveal protein molecular chemistry affected by heat processing within intact plant tissues; (2) revealing the effects of heat processing on the profile changes of protein subfractions associated with digestive behaviors and kinetics manipulated by heat processing; (3) prediction of the changes of protein availability and supply after heat processing, using the advanced DVE/OEB and NRC-2001 models, and (4) obtaining information on optimal processing conditions of protein as intestinal protein source to achieve target values for potential high net absorbable protein in the small intestine. The information described in this article may give better insight in the mechanisms involved and the intrinsic protein molecular structural changes occurring upon processing.

  18. Calculating evolutionary dynamics in structured populations.

    Directory of Open Access Journals (Sweden)

    Charles G Nathanson

    2009-12-01

    Full Text Available Evolution is shaping the world around us. At the core of every evolutionary process is a population of reproducing individuals. The outcome of an evolutionary process depends on population structure. Here we provide a general formula for calculating evolutionary dynamics in a wide class of structured populations. This class includes the recently introduced "games in phenotype space" and "evolutionary set theory." There can be local interactions for determining the relative fitness of individuals, but we require global updating, which means all individuals compete uniformly for reproduction. We study the competition of two strategies in the context of an evolutionary game and determine which strategy is favored in the limit of weak selection. We derive an intuitive formula for the structure coefficient, sigma, and provide a method for efficient numerical calculation.

  19. Structure based alignment and clustering of proteins (STRALCP)

    Science.gov (United States)

    Zemla, Adam T.; Zhou, Carol E.; Smith, Jason R.; Lam, Marisa W.

    2013-06-18

    Disclosed are computational methods of clustering a set of protein structures based on local and pair-wise global similarity values. Pair-wise local and global similarity values are generated based on pair-wise structural alignments for each protein in the set of protein structures. Initially, the protein structures are clustered based on pair-wise local similarity values. The protein structures are then clustered based on pair-wise global similarity values. For each given cluster both a representative structure and spans of conserved residues are identified. The representative protein structure is used to assign newly-solved protein structures to a group. The spans are used to characterize conservation and assign a "structural footprint" to the cluster.

  20. Validation-driven protein-structure improvement

    NARCIS (Netherlands)

    Touw, W.G.

    2016-01-01

    High-quality protein structure models are essential for many Life Science applications, such as protein engineering, molecular dynamics, drug design, and homology modelling. The WHAT_CHECK model validation project and the PDB_REDO model optimisation project have shown that many structure models in

  1. Understanding Protein-Protein Interactions Using Local Structural Features

    DEFF Research Database (Denmark)

    Planas-Iglesias, Joan; Bonet, Jaume; García-García, Javier

    2013-01-01

    Protein-protein interactions (PPIs) play a relevant role among the different functions of a cell. Identifying the PPI network of a given organism (interactome) is useful to shed light on the key molecular mechanisms within a biological system. In this work, we show the role of structural features...... interacting and non-interacting protein pairs to classify the structural features that sustain the binding (or non-binding) behavior. Our study indicates that not only the interacting region but also the rest of the protein surface are important for the interaction fate. The interpretation...... to score the likelihood of the interaction between two proteins and to develop a method for the prediction of PPIs. We have tested our method on several sets with unbalanced ratios of interactions and non-interactions to simulate real conditions, obtaining accuracies higher than 25% in the most unfavorable...

  2. SiteBinder: an improved approach for comparing multiple protein structural motifs.

    Science.gov (United States)

    Sehnal, David; Vařeková, Radka Svobodová; Huber, Heinrich J; Geidl, Stanislav; Ionescu, Crina-Maria; Wimmerová, Michaela; Koča, Jaroslav

    2012-02-27

    There is a paramount need to develop new techniques and tools that will extract as much information as possible from the ever growing repository of protein 3D structures. We report here on the development of a software tool for the multiple superimposition of large sets of protein structural motifs. Our superimposition methodology performs a systematic search for the atom pairing that provides the best fit. During this search, the RMSD values for all chemically relevant pairings are calculated by quaternion algebra. The number of evaluated pairings is markedly decreased by using PDB annotations for atoms. This approach guarantees that the best fit will be found and can be applied even when sequence similarity is low or does not exist at all. We have implemented this methodology in the Web application SiteBinder, which is able to process up to thousands of protein structural motifs in a very short time, and which provides an intuitive and user-friendly interface. Our benchmarking analysis has shown the robustness, efficiency, and versatility of our methodology and its implementation by the successful superimposition of 1000 experimentally determined structures for each of 32 eukaryotic linear motifs. We also demonstrate the applicability of SiteBinder using three case studies. We first compared the structures of 61 PA-IIL sugar binding sites containing nine different sugars, and we found that the sugar binding sites of PA-IIL and its mutants have a conserved structure despite their binding different sugars. We then superimposed over 300 zinc finger central motifs and revealed that the molecular structure in the vicinity of the Zn atom is highly conserved. Finally, we superimposed 12 BH3 domains from pro-apoptotic proteins. Our findings come to support the hypothesis that there is a structural basis for the functional segregation of BH3-only proteins into activators and enablers.

  3. ProBiS-2012: web server and web services for detection of structurally similar binding sites in proteins.

    Science.gov (United States)

    Konc, Janez; Janezic, Dusanka

    2012-07-01

    The ProBiS web server is a web server for detection of structurally similar binding sites in the PDB and for local pairwise alignment of protein structures. In this article, we present a new version of the ProBiS web server that is 10 times faster than earlier versions, due to the efficient parallelization of the ProBiS algorithm, which now allows significantly faster comparison of a protein query against the PDB and reduces the calculation time for scanning the entire PDB from hours to minutes. It also features new web services, and an improved user interface. In addition, the new web server is united with the ProBiS-Database and thus provides instant access to pre-calculated protein similarity profiles for over 29 000 non-redundant protein structures. The ProBiS web server is particularly adept at detection of secondary binding sites in proteins. It is freely available at http://probis.cmm.ki.si/old-version, and the new ProBiS web server is at http://probis.cmm.ki.si.

  4. Understanding and Manipulating Electrostatic Fields at the Protein-Protein Interface Using Vibrational Spectroscopy and Continuum Electrostatics Calculations.

    Science.gov (United States)

    Ritchie, Andrew W; Webb, Lauren J

    2015-11-05

    Biological function emerges in large part from the interactions of biomacromolecules in the complex and dynamic environment of the living cell. For this reason, macromolecular interactions in biological systems are now a major focus of interest throughout the biochemical and biophysical communities. The affinity and specificity of macromolecular interactions are the result of both structural and electrostatic factors. Significant advances have been made in characterizing structural features of stable protein-protein interfaces through the techniques of modern structural biology, but much less is understood about how electrostatic factors promote and stabilize specific functional macromolecular interactions over all possible choices presented to a given molecule in a crowded environment. In this Feature Article, we describe how vibrational Stark effect (VSE) spectroscopy is being applied to measure electrostatic fields at protein-protein interfaces, focusing on measurements of guanosine triphosphate (GTP)-binding proteins of the Ras superfamily binding with structurally related but functionally distinct downstream effector proteins. In VSE spectroscopy, spectral shifts of a probe oscillator's energy are related directly to that probe's local electrostatic environment. By performing this experiment repeatedly throughout a protein-protein interface, an experimental map of measured electrostatic fields generated at that interface is determined. These data can be used to rationalize selective binding of similarly structured proteins in both in vitro and in vivo environments. Furthermore, these data can be used to compare to computational predictions of electrostatic fields to explore the level of simulation detail that is necessary to accurately predict our experimental findings.

  5. Structural insights, protein-ligand interactions and spectroscopic characterization of isoformononetin

    Science.gov (United States)

    Srivastava, Anubha; Singh, Harshita; Mishra, Rashmi; Dev, Kapil; Tandon, Poonam; Maurya, Rakesh

    2017-04-01

    Isoformononetin, a methoxylated isoflavone present in medicinal plants, has non-estrogenic bone forming effect via differential mitogen-activated protein kinase (MAPK) signaling. Spectroscopic (FT-Raman, FT-IR, UV-vis and NMR spectra) and quantum chemical calculations using density functional theory (DFT) and 6-311++G(d,p) as a large basis set have been employed to study the structural and electronic properties of isoformononetin. A detailed conformational analysis is performed to determine the stability among conformers and the various possibilities of intramolecular hydrogen bonding formation. Molecular docking studies with different protein kinases were performed on isoformononetin and previously studied isoflavonoid, formononetin in order to understand their inhibitory nature and the effect of functional groups on osteogenic or osteoporosis associated proteins. It is found that the oxygen atoms of methoxy, hydroxyl groups attached to phenyl rings R1, R3 and carbonyl group attached to pyran ring R2, play a major role in binding with the protein kinases that is responsible for the osteoporosis; however, no hydrophobic interactions are observed between rings of ligand and protein. The electronic properties such as HOMO and LUMO energies were determined by time-dependent TD-DFT which predict that conformer II is a little bit more stable and chemically low reactive than conformer I of isoformononetin. To estimate the structure-activity relationship, the molecular electrostatic potential (MEP) surface map, and reactivity descriptors are calculated from the optimized geometry of the molecule. From these results, it is also found that isoformononetin is kinetically more stable, less toxic, weak electrophile and chemically less reactive than formononetin. The atoms in molecules and natural bond orbital analysis are applied for the detailed analysis of intra and intermolecular hydrogen bonding interactions.

  6. Efficient protein structure search using indexing methods.

    Science.gov (United States)

    Kim, Sungchul; Sael, Lee; Yu, Hwanjo

    2013-01-01

    Understanding functions of proteins is one of the most important challenges in many studies of biological processes. The function of a protein can be predicted by analyzing the functions of structurally similar proteins, thus finding structurally similar proteins accurately and efficiently from a large set of proteins is crucial. A protein structure can be represented as a vector by 3D-Zernike Descriptor (3DZD) which compactly represents the surface shape of the protein tertiary structure. This simplified representation accelerates the searching process. However, computing the similarity of two protein structures is still computationally expensive, thus it is hard to efficiently process many simultaneous requests of structurally similar protein search. This paper proposes indexing techniques which substantially reduce the search time to find structurally similar proteins. In particular, we first exploit two indexing techniques, i.e., iDistance and iKernel, on the 3DZDs. After that, we extend the techniques to further improve the search speed for protein structures. The extended indexing techniques build and utilize an reduced index constructed from the first few attributes of 3DZDs of protein structures. To retrieve top-k similar structures, top-10 × k similar structures are first found using the reduced index, and top-k structures are selected among them. We also modify the indexing techniques to support θ-based nearest neighbor search, which returns data points less than θ to the query point. The results show that both iDistance and iKernel significantly enhance the searching speed. In top-k nearest neighbor search, the searching time is reduced 69.6%, 77%, 77.4% and 87.9%, respectively using iDistance, iKernel, the extended iDistance, and the extended iKernel. In θ-based nearest neighbor serach, the searching time is reduced 80%, 81%, 95.6% and 95.6% using iDistance, iKernel, the extended iDistance, and the extended iKernel, respectively.

  7. A 'periodic table' for protein structures.

    Science.gov (United States)

    Taylor, William R

    2002-04-11

    Current structural genomics programs aim systematically to determine the structures of all proteins coded in both human and other genomes, providing a complete picture of the number and variety of protein structures that exist. In the past, estimates have been made on the basis of the incomplete sample of structures currently known. These estimates have varied greatly (between 1,000 and 10,000; see for example refs 1 and 2), partly because of limited sample size but also owing to the difficulties of distinguishing one structure from another. This distinction is usually topological, based on the fold of the protein; however, in strict topological terms (neglecting to consider intra-chain cross-links), protein chains are open strings and hence are all identical. To avoid this trivial result, topologies are determined by considering secondary links in the form of intra-chain hydrogen bonds (secondary structure) and tertiary links formed by the packing of secondary structures. However, small additions to or loss of structure can make large changes to these perceived topologies and such subjective solutions are neither robust nor amenable to automation. Here I formalize both secondary and tertiary links to allow the rigorous and automatic definition of protein topology.

  8. Improved hybrid optimization algorithm for 3D protein structure prediction.

    Science.gov (United States)

    Zhou, Changjun; Hou, Caixia; Wei, Xiaopeng; Zhang, Qiang

    2014-07-01

    A new improved hybrid optimization algorithm - PGATS algorithm, which is based on toy off-lattice model, is presented for dealing with three-dimensional protein structure prediction problems. The algorithm combines the particle swarm optimization (PSO), genetic algorithm (GA), and tabu search (TS) algorithms. Otherwise, we also take some different improved strategies. The factor of stochastic disturbance is joined in the particle swarm optimization to improve the search ability; the operations of crossover and mutation that are in the genetic algorithm are changed to a kind of random liner method; at last tabu search algorithm is improved by appending a mutation operator. Through the combination of a variety of strategies and algorithms, the protein structure prediction (PSP) in a 3D off-lattice model is achieved. The PSP problem is an NP-hard problem, but the problem can be attributed to a global optimization problem of multi-extremum and multi-parameters. This is the theoretical principle of the hybrid optimization algorithm that is proposed in this paper. The algorithm combines local search and global search, which overcomes the shortcoming of a single algorithm, giving full play to the advantage of each algorithm. In the current universal standard sequences, Fibonacci sequences and real protein sequences are certified. Experiments show that the proposed new method outperforms single algorithms on the accuracy of calculating the protein sequence energy value, which is proved to be an effective way to predict the structure of proteins.

  9. Protein structure recognition: From eigenvector analysis to structural threading method

    Science.gov (United States)

    Cao, Haibo

    In this work, we try to understand the protein folding problem using pair-wise hydrophobic interaction as the dominant interaction for the protein folding process. We found a strong correlation between amino acid sequence and the corresponding native structure of the protein. Some applications of this correlation were discussed in this dissertation include the domain partition and a new structural threading method as well as the performance of this method in the CASP5 competition. In the first part, we give a brief introduction to the protein folding problem. Some essential knowledge and progress from other research groups was discussed. This part include discussions of interactions among amino acids residues, lattice HP model, and the designablity principle. In the second part, we try to establish the correlation between amino acid sequence and the corresponding native structure of the protein. This correlation was observed in our eigenvector study of protein contact matrix. We believe the correlation is universal, thus it can be used in automatic partition of protein structures into folding domains. In the third part, we discuss a threading method based on the correlation between amino acid sequence and ominant eigenvector of the structure contact-matrix. A mathematically straightforward iteration scheme provides a self-consistent optimum global sequence-structure alignment. The computational efficiency of this method makes it possible to search whole protein structure databases for structural homology without relying on sequence similarity. The sensitivity and specificity of this method is discussed, along with a case of blind test prediction. In the appendix, we list the overall performance of this threading method in CASP5 blind test in comparison with other existing approaches.

  10. Protein Structure Recognition: From Eigenvector Analysis to Structural Threading Method

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Haibo [Iowa State Univ., Ames, IA (United States)

    2003-01-01

    In this work, they try to understand the protein folding problem using pair-wise hydrophobic interaction as the dominant interaction for the protein folding process. They found a strong correlation between amino acid sequences and the corresponding native structure of the protein. Some applications of this correlation were discussed in this dissertation include the domain partition and a new structural threading method as well as the performance of this method in the CASP5 competition. In the first part, they give a brief introduction to the protein folding problem. Some essential knowledge and progress from other research groups was discussed. This part includes discussions of interactions among amino acids residues, lattice HP model, and the design ability principle. In the second part, they try to establish the correlation between amino acid sequence and the corresponding native structure of the protein. This correlation was observed in the eigenvector study of protein contact matrix. They believe the correlation is universal, thus it can be used in automatic partition of protein structures into folding domains. In the third part, they discuss a threading method based on the correlation between amino acid sequences and ominant eigenvector of the structure contact-matrix. A mathematically straightforward iteration scheme provides a self-consistent optimum global sequence-structure alignment. The computational efficiency of this method makes it possible to search whole protein structure databases for structural homology without relying on sequence similarity. The sensitivity and specificity of this method is discussed, along with a case of blind test prediction. In the appendix, they list the overall performance of this threading method in CASP5 blind test in comparison with other existing approaches.

  11. Protein Structure Recognition: From Eigenvector Analysis to Structural Threading Method

    International Nuclear Information System (INIS)

    Haibo Cao

    2003-01-01

    In this work, they try to understand the protein folding problem using pair-wise hydrophobic interaction as the dominant interaction for the protein folding process. They found a strong correlation between amino acid sequences and the corresponding native structure of the protein. Some applications of this correlation were discussed in this dissertation include the domain partition and a new structural threading method as well as the performance of this method in the CASP5 competition. In the first part, they give a brief introduction to the protein folding problem. Some essential knowledge and progress from other research groups was discussed. This part includes discussions of interactions among amino acids residues, lattice HP model, and the design ability principle. In the second part, they try to establish the correlation between amino acid sequence and the corresponding native structure of the protein. This correlation was observed in the eigenvector study of protein contact matrix. They believe the correlation is universal, thus it can be used in automatic partition of protein structures into folding domains. In the third part, they discuss a threading method based on the correlation between amino acid sequences and ominant eigenvector of the structure contact-matrix. A mathematically straightforward iteration scheme provides a self-consistent optimum global sequence-structure alignment. The computational efficiency of this method makes it possible to search whole protein structure databases for structural homology without relying on sequence similarity. The sensitivity and specificity of this method is discussed, along with a case of blind test prediction. In the appendix, they list the overall performance of this threading method in CASP5 blind test in comparison with other existing approaches

  12. Structures composing protein domains.

    Science.gov (United States)

    Kubrycht, Jaroslav; Sigler, Karel; Souček, Pavel; Hudeček, Jiří

    2013-08-01

    This review summarizes available data concerning intradomain structures (IS) such as functionally important amino acid residues, short linear motifs, conserved or disordered regions, peptide repeats, broadly occurring secondary structures or folds, etc. IS form structural features (units or elements) necessary for interactions with proteins or non-peptidic ligands, enzyme reactions and some structural properties of proteins. These features have often been related to a single structural level (e.g. primary structure) mostly requiring certain structural context of other levels (e.g. secondary structures or supersecondary folds) as follows also from some examples reported or demonstrated here. In addition, we deal with some functionally important dynamic properties of IS (e.g. flexibility and different forms of accessibility), and more special dynamic changes of IS during enzyme reactions and allosteric regulation. Selected notes concern also some experimental methods, still more necessary tools of bioinformatic processing and clinically interesting relationships. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  13. Current strategies for protein production and purification enabling membrane protein structural biology.

    Science.gov (United States)

    Pandey, Aditya; Shin, Kyungsoo; Patterson, Robin E; Liu, Xiang-Qin; Rainey, Jan K

    2016-12-01

    Membrane proteins are still heavily under-represented in the protein data bank (PDB), owing to multiple bottlenecks. The typical low abundance of membrane proteins in their natural hosts makes it necessary to overexpress these proteins either in heterologous systems or through in vitro translation/cell-free expression. Heterologous expression of proteins, in turn, leads to multiple obstacles, owing to the unpredictability of compatibility of the target protein for expression in a given host. The highly hydrophobic and (or) amphipathic nature of membrane proteins also leads to challenges in producing a homogeneous, stable, and pure sample for structural studies. Circumventing these hurdles has become possible through the introduction of novel protein production protocols; efficient protein isolation and sample preparation methods; and, improvement in hardware and software for structural characterization. Combined, these advances have made the past 10-15 years very exciting and eventful for the field of membrane protein structural biology, with an exponential growth in the number of solved membrane protein structures. In this review, we focus on both the advances and diversity of protein production and purification methods that have allowed this growth in structural knowledge of membrane proteins through X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM).

  14. Protein structure similarity from principle component correlation analysis

    Directory of Open Access Journals (Sweden)

    Chou James

    2006-01-01

    Full Text Available Abstract Background Owing to rapid expansion of protein structure databases in recent years, methods of structure comparison are becoming increasingly effective and important in revealing novel information on functional properties of proteins and their roles in the grand scheme of evolutionary biology. Currently, the structural similarity between two proteins is measured by the root-mean-square-deviation (RMSD in their best-superimposed atomic coordinates. RMSD is the golden rule of measuring structural similarity when the structures are nearly identical; it, however, fails to detect the higher order topological similarities in proteins evolved into different shapes. We propose new algorithms for extracting geometrical invariants of proteins that can be effectively used to identify homologous protein structures or topologies in order to quantify both close and remote structural similarities. Results We measure structural similarity between proteins by correlating the principle components of their secondary structure interaction matrix. In our approach, the Principle Component Correlation (PCC analysis, a symmetric interaction matrix for a protein structure is constructed with relationship parameters between secondary elements that can take the form of distance, orientation, or other relevant structural invariants. When using a distance-based construction in the presence or absence of encoded N to C terminal sense, there are strong correlations between the principle components of interaction matrices of structurally or topologically similar proteins. Conclusion The PCC method is extensively tested for protein structures that belong to the same topological class but are significantly different by RMSD measure. The PCC analysis can also differentiate proteins having similar shapes but different topological arrangements. Additionally, we demonstrate that when using two independently defined interaction matrices, comparison of their maximum

  15. Elastic strain and twist analysis of protein structural data and allostery of the transmembrane channel KcsA

    Science.gov (United States)

    Mitchell, Michael R.; Leibler, Stanislas

    2018-05-01

    The abundance of available static protein structural data makes the more effective analysis and interpretation of this data a valuable tool to supplement the experimental study of protein mechanics. Structural displacements can be difficult to analyze and interpret. Previously, we showed that strains provide a more natural and interpretable representation of protein deformations, revealing mechanical coupling between spatially distinct sites of allosteric proteins. Here, we demonstrate that other transformations of displacements yield additional insights. We calculate the divergence and curl of deformations of the transmembrane channel KcsA. Additionally, we introduce quantities analogous to bend, splay, and twist deformation energies of nematic liquid crystals. These transformations enable the decomposition of displacements into different modes of deformation, helping to characterize the type of deformation a protein undergoes. We apply these calculations to study the filter and gating regions of KcsA. We observe a continuous path of rotational deformations physically coupling these two regions, and, we propose, underlying the allosteric interaction between these regions. Bend, splay, and twist distinguish KcsA gate opening, filter opening, and filter-gate coupling, respectively. In general, physically meaningful representations of deformations (like strain, curl, bend, splay, and twist) can make testable predictions and yield insights into protein mechanics, augmenting experimental methods and more fully exploiting available structural data.

  16. SDSL-ESR-based protein structure characterization

    NARCIS (Netherlands)

    Strancar, J.; Kavalenka, A.A.; Urbancic, I.; Ljubetic, A.; Hemminga, M.A.

    2010-01-01

    As proteins are key molecules in living cells, knowledge about their structure can provide important insights and applications in science, biotechnology, and medicine. However, many protein structures are still a big challenge for existing high-resolution structure-determination methods, as can be

  17. Deposit3D: a tool for automating structure depositions to the Protein Data Bank

    Energy Technology Data Exchange (ETDEWEB)

    Badger, J., E-mail: jbadger@active-sight.com; Hendle, J.; Burley, S. K.; Kissinger, C. R. [SGX Inc., 10505 Roselle Street, San Diego, CA 92121 (United States)

    2005-09-01

    This paper describes a Python script that may be used to gather all required structure-annotation information into an mmCIF file for upload through the RCSB PDB ADIT structure-deposition interface. Almost all successful protein structure-determination projects in the public sector culminate in a structure deposition to the Protein Data Bank (PDB). In order to expedite the deposition proces, Deposit3D has been developed. This command-line script calculates or gathers all the required structure-deposition information and outputs this data into a mmCIF file for subsequent upload through the RCSB PDB ADIT interface. Deposit3D might be particularly useful for structural genomics pipeline projects because it allows workers involved with various stages of a structure-determination project to pool their different categories of annotation information before starting a deposition session.

  18. Deposit3D: a tool for automating structure depositions to the Protein Data Bank

    International Nuclear Information System (INIS)

    Badger, J.; Hendle, J.; Burley, S. K.; Kissinger, C. R.

    2005-01-01

    This paper describes a Python script that may be used to gather all required structure-annotation information into an mmCIF file for upload through the RCSB PDB ADIT structure-deposition interface. Almost all successful protein structure-determination projects in the public sector culminate in a structure deposition to the Protein Data Bank (PDB). In order to expedite the deposition proces, Deposit3D has been developed. This command-line script calculates or gathers all the required structure-deposition information and outputs this data into a mmCIF file for subsequent upload through the RCSB PDB ADIT interface. Deposit3D might be particularly useful for structural genomics pipeline projects because it allows workers involved with various stages of a structure-determination project to pool their different categories of annotation information before starting a deposition session

  19. Convenient method for resolving degeneracies due to symmetry of the magnetic susceptibility tensor and its application to pseudo contact shift-based protein-protein complex structure determination

    Energy Technology Data Exchange (ETDEWEB)

    Kobashigawa, Yoshihiro; Saio, Tomohide [Hokkaido University, Department of Structural Biology, Faculty of Advanced Life Science (Japan); Ushio, Masahiro [Hokkaido University, Graduate School of Life Science (Japan); Sekiguchi, Mitsuhiro [Astellas Pharma Inc., Analysis and Pharmacokinetics Research Labs, Department of Drug Discovery (Japan); Yokochi, Masashi; Ogura, Kenji; Inagaki, Fuyuhiko, E-mail: finagaki@pharm.hokudai.ac.jp [Hokkaido University, Department of Structural Biology, Faculty of Advanced Life Science (Japan)

    2012-05-15

    Pseudo contact shifts (PCSs) induced by paramagnetic lanthanide ions fixed in a protein frame provide long-range distance and angular information, and are valuable for the structure determination of protein-protein and protein-ligand complexes. We have been developing a lanthanide-binding peptide tag (hereafter LBT) anchored at two points via a peptide bond and a disulfide bond to the target proteins. However, the magnetic susceptibility tensor displays symmetry, which can cause multiple degenerated solutions in a structure calculation based solely on PCSs. Here we show a convenient method for resolving this degeneracy by changing the spacer length between the LBT and target protein. We applied this approach to PCS-based rigid body docking between the FKBP12-rapamycin complex and the mTOR FRB domain, and demonstrated that degeneracy could be resolved using the PCS restraints obtained from two-point anchored LBT with two different spacer lengths. The present strategy will markedly increase the usefulness of two-point anchored LBT for protein complex structure determination.

  20. Electronic structure calculations of calcium silicate hydrates

    International Nuclear Information System (INIS)

    Sterne, P.A.; Meike, A.

    1995-11-01

    Many phases in the calcium-silicate-hydrate system can develop in cement exposed over long periods of time to temperatures above 25 C. As a consequence, chemical reactions involving these phases can affect the relative humidity and water chemistry of a radioactive waste repository that contains significant amounts of cement. In order to predict and simulate these chemical reactions, the authors are developing an internally consistent database of crystalline Ca-Si-hydrate structures. The results of first principles electronic structure calculations on two such phases, wollastonite (CaSiO 3 ) and xonotlite (Ca 6 Si 6 O 17 (OH) 2 ), are reported here. The calculated ground state properties are in very good agreement with experiment, providing equilibrium lattice parameters within about 1--1.4% of the experimentally reported values. The roles of the different types of oxygen atoms, which are fundamental to understanding the energetics of crystalline Ca-Si-hydrates are briefly discussed in terms of their electronic state densities. The good agreement with experiment for the lattice parameters and the consistency of the electronic density of states features for the two structures demonstrate the applicability of these electronic structure methods in calculating the fundamental properties of these phases

  1. Ab-initio electronic band structure calculations for beryllium chalcogenides

    International Nuclear Information System (INIS)

    Kalpana, G.; Pari, G.; Yousuf, Mohammad

    1997-01-01

    The first principle tight-binding linear muffin-tin orbital method within the local density approximation (LDA) has been used to calculate the ground state properties, structural phase transition and pressure dependence of band gap of BeS, BeSe and BeTe. We have calculated the energy-volume relations for these compounds in the B3 and B8 phases. The calculated lattice parameters, bulk modulus and the pressure-volume relation were found to be in good agreement with the recent experimental results. The calculated B3→B8 structural transition pressure for BeS, BeSe and BeTe agree well with the recent experimental results. Our calculations show that these compounds are indirect band gap (Γ-X) semiconductors at ambient conditions. The calculated band gap values are found to be underestimated by 20-30% which is due to the usage of LDA. After the structural transition to the B8 phase, BeS continues to be indirect band gap semiconductors and ultimately above 100 GPa it metallises, BeSe and BeTe are metallic at the B3→B8 structural transition. (author)

  2. Benchmark calculation programme concerning typical LMFBR structures

    International Nuclear Information System (INIS)

    Donea, J.; Ferrari, G.; Grossetie, J.C.; Terzaghi, A.

    1982-01-01

    This programme, which is part of a comprehensive activity aimed at resolving difficulties encountered in using design procedures based on ASME Code Case N-47, should allow to get confidence in computer codes which are supposed to provide a realistic prediction of the LMFBR component behaviour. The calculations started on static analysis of typical structures made of non linear materials stressed by cyclic loads. The fluid structure interaction analysis is also being considered. Reasons and details of the different benchmark calculations are described, results obtained are commented and future computational exercise indicated

  3. Total energy calculations for structural phase transformations

    International Nuclear Information System (INIS)

    Ye, Y.Y.; Chan, C.T.; Ho, K.M.; Harmon, B.N.

    1990-01-01

    The structural integrity and physical properties of crystalline solids are frequently limited or enhanced by the occurrence of phase transformations. Martensitic transformations involve the collective displacement of atoms from one ordered state to another. Modern methods to determine the microscopic electronic changes as the atoms move are now accurate enough to evaluate the very small energy differences involved. Extensive first principles calculations for the prototypical martensitic transformation from body-centered cubic (bcc) to closepacked 9R structure in sodium metal are described. The minimum energy coordinate or configuration path between the bcc and 9R structures is determined as well as paths to other competing close-packed structures. The energy barriers and important anharmonic interactions are identified and general conclusions drawn. The calculational methods used to solve the Schrodinger equation include pseudopotentials, fast Fourier transforms, efficient matrix diagnonalization, and supercells with many atoms

  4. Calculations of proton-binding thermodynamics in proteins.

    Science.gov (United States)

    Beroza, P; Case, D A

    1998-01-01

    Computational models of proton binding can range from the chemically complex and statistically simple (as in the quantum calculations) to the chemically simple and statistically complex. Much progress has been made in the multiple-site titration problem. Calculations have improved with the inclusion of more flexibility in regard to both the geometry of the proton binding and the larger scale protein motions associated with titration. This article concentrated on the principles of current calculations, but did not attempt to survey their quantitative performance. This is (1) because such comparisons are given in the cited papers and (2) because continued developments in understanding conformational flexibility and interaction energies will be needed to develop robust methods with strong predictive power. Nevertheless, the advances achieved over the past few years should not be underestimated: serious calculations of protonation behavior and its coupling to conformational change can now be confidently pursued against a backdrop of increasing understanding of the strengths and limitations of such models. It is hoped that such theoretical advances will also spur renewed experimental interest in measuring both overall titration curves and individual pKa values or pKa shifts. Exploration of the shapes of individual titration curves (as measured by Hill coefficients and other parameters) would also be useful in assessing the accuracy of computations and in drawing connections to functional behavior.

  5. Overcoming barriers to membrane protein structure determination.

    Science.gov (United States)

    Bill, Roslyn M; Henderson, Peter J F; Iwata, So; Kunji, Edmund R S; Michel, Hartmut; Neutze, Richard; Newstead, Simon; Poolman, Bert; Tate, Christopher G; Vogel, Horst

    2011-04-01

    After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.

  6. 3dRPC: a web server for 3D RNA-protein structure prediction.

    Science.gov (United States)

    Huang, Yangyu; Li, Haotian; Xiao, Yi

    2018-04-01

    RNA-protein interactions occur in many biological processes. To understand the mechanism of these interactions one needs to know three-dimensional (3D) structures of RNA-protein complexes. 3dRPC is an algorithm for prediction of 3D RNA-protein complex structures and consists of a docking algorithm RPDOCK and a scoring function 3dRPC-Score. RPDOCK is used to sample possible complex conformations of an RNA and a protein by calculating the geometric and electrostatic complementarities and stacking interactions at the RNA-protein interface according to the features of atom packing of the interface. 3dRPC-Score is a knowledge-based potential that uses the conformations of nucleotide-amino-acid pairs as statistical variables and that is used to choose the near-native complex-conformations obtained from the docking method above. Recently, we built a web server for 3dRPC. The users can easily use 3dRPC without installing it locally. RNA and protein structures in PDB (Protein Data Bank) format are the only needed input files. It can also incorporate the information of interface residues or residue-pairs obtained from experiments or theoretical predictions to improve the prediction. The address of 3dRPC web server is http://biophy.hust.edu.cn/3dRPC. yxiao@hust.edu.cn.

  7. CMsearch: simultaneous exploration of protein sequence space and structure space improves not only protein homology detection but also protein structure prediction

    KAUST Repository

    Cui, Xuefeng; Lu, Zhiwu; Wang, Sheng; Jing-Yan Wang, Jim; Gao, Xin

    2016-01-01

    Motivation: Protein homology detection, a fundamental problem in computational biology, is an indispensable step toward predicting protein structures and understanding protein functions. Despite the advances in recent decades on sequence alignment

  8. Structural determination of intact proteins using mass spectrometry

    Science.gov (United States)

    Kruppa, Gary [San Francisco, CA; Schoeniger, Joseph S [Oakland, CA; Young, Malin M [Livermore, CA

    2008-05-06

    The present invention relates to novel methods of determining the sequence and structure of proteins. Specifically, the present invention allows for the analysis of intact proteins within a mass spectrometer. Therefore, preparatory separations need not be performed prior to introducing a protein sample into the mass spectrometer. Also disclosed herein are new instrumental developments for enhancing the signal from the desired modified proteins, methods for producing controlled protein fragments in the mass spectrometer, eliminating complex microseparations, and protein preparatory chemical steps necessary for cross-linking based protein structure determination.Additionally, the preferred method of the present invention involves the determination of protein structures utilizing a top-down analysis of protein structures to search for covalent modifications. In the preferred method, intact proteins are ionized and fragmented within the mass spectrometer.

  9. Structural basis for target protein recognition by the protein disulfide reductase thioredoxin

    DEFF Research Database (Denmark)

    Maeda, Kenji; Hägglund, Per; Finnie, Christine

    2006-01-01

    Thioredoxin is ubiquitous and regulates various target proteins through disulfide bond reduction. We report the structure of thioredoxin (HvTrxh2 from barley) in a reaction intermediate complex with a protein substrate, barley alpha-amylase/subtilisin inhibitor (BASI). The crystal structure...... of this mixed disulfide shows a conserved hydrophobic motif in thioredoxin interacting with a sequence of residues from BASI through van der Waals contacts and backbone-backbone hydrogen bonds. The observed structural complementarity suggests that the recognition of features around protein disulfides plays...... a major role in the specificity and protein disulfide reductase activity of thioredoxin. This novel insight into the function of thioredoxin constitutes a basis for comprehensive understanding of its biological role. Moreover, comparison with structurally related proteins shows that thioredoxin shares...

  10. Protein structure: geometry, topology and classification

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, William R.; May, Alex C.W.; Brown, Nigel P.; Aszodi, Andras [Division of Mathematical Biology, National Institute for Medical Research, London (United Kingdom)

    2001-04-01

    The structural principals of proteins are reviewed and analysed from a geometric perspective with a view to revealing the underlying regularities in their construction. Computer methods for the automatic comparison and classification of these structures are then reviewed with an analysis of the statistical significance of comparing different shapes. Following an analysis of the current state of the classification of proteins, more abstract geometric and topological representations are explored, including the occurrence of knotted topologies. The review concludes with a consideration of the origin of higher-level symmetries in protein structure. (author)

  11. Use of designed sequences in protein structure recognition.

    Science.gov (United States)

    Kumar, Gayatri; Mudgal, Richa; Srinivasan, Narayanaswamy; Sandhya, Sankaran

    2018-05-09

    Knowledge of the protein structure is a pre-requisite for improved understanding of molecular function. The gap in the sequence-structure space has increased in the post-genomic era. Grouping related protein sequences into families can aid in narrowing the gap. In the Pfam database, structure description is provided for part or full-length proteins of 7726 families. For the remaining 52% of the families, information on 3-D structure is not yet available. We use the computationally designed sequences that are intermediately related to two protein domain families, which are already known to share the same fold. These strategically designed sequences enable detection of distant relationships and here, we have employed them for the purpose of structure recognition of protein families of yet unknown structure. We first measured the success rate of our approach using a dataset of protein families of known fold and achieved a success rate of 88%. Next, for 1392 families of yet unknown structure, we made structural assignments for part/full length of the proteins. Fold association for 423 domains of unknown function (DUFs) are provided as a step towards functional annotation. The results indicate that knowledge-based filling of gaps in protein sequence space is a lucrative approach for structure recognition. Such sequences assist in traversal through protein sequence space and effectively function as 'linkers', where natural linkers between distant proteins are unavailable. This article was reviewed by Oliviero Carugo, Christine Orengo and Srikrishna Subramanian.

  12. PDB2CD visualises dynamics within protein structures.

    Science.gov (United States)

    Janes, Robert W

    2017-10-01

    Proteins tend to have defined conformations, a key factor in enabling their function. Atomic resolution structures of proteins are predominantly obtained by either solution nuclear magnetic resonance (NMR) or crystal structure methods. However, when considering a protein whose structure has been determined by both these approaches, on many occasions, the resultant conformations are subtly different, as illustrated by the examples in this study. The solution NMR approach invariably results in a cluster of structures whose conformations satisfy the distance boundaries imposed by the data collected; it might be argued that this is evidence of the dynamics of proteins when in solution. In crystal structures, the proteins are often in an energy minimum state which can result in an increase in the extent of regular secondary structure present relative to the solution state depicted by NMR, because the more dynamic ends of alpha helices and beta strands can become ordered at the lower temperatures. This study examines a novel way to display the differences in conformations within an NMR ensemble and between these and a crystal structure of a protein. Circular dichroism (CD) spectroscopy can be used to characterise protein structures in solution. Using the new bioinformatics tool, PDB2CD, which generates CD spectra from atomic resolution protein structures, the differences between, and possible dynamic range of, conformations adopted by a protein can be visualised.

  13. Course 12: Proteins: Structural, Thermodynamic and Kinetic Aspects

    Science.gov (United States)

    Finkelstein, A. V.

    1 Introduction 2 Overview of protein architectures and discussion of physical background of their natural selection 2.1 Protein structures 2.2 Physical selection of protein structures 3 Thermodynamic aspects of protein folding 3.1 Reversible denaturation of protein structures 3.2 What do denatured proteins look like? 3.3 Why denaturation of a globular protein is the first-order phase transition 3.4 "Gap" in energy spectrum: The main characteristic that distinguishes protein chains from random polymers 4 Kinetic aspects of protein folding 4.1 Protein folding in vivo 4.2 Protein folding in vitro (in the test-tube) 4.3 Theory of protein folding rates and solution of the Levinthal paradox

  14. Protein interfacial structure and nanotoxicology

    Energy Technology Data Exchange (ETDEWEB)

    White, John W. [Research School of Chemistry, Australian National University, Canberra (Australia)], E-mail: jww@rsc.anu.edu.au; Perriman, Adam W.; McGillivray, Duncan J.; Lin, J.-M. [Research School of Chemistry, Australian National University, Canberra (Australia)

    2009-02-21

    Here we briefly recapitulate the use of X-ray and neutron reflectometry at the air-water interface to find protein structures and thermodynamics at interfaces and test a possibility for understanding those interactions between nanoparticles and proteins which lead to nanoparticle toxicology through entry into living cells. Stable monomolecular protein films have been made at the air-water interface and, with a specially designed vessel, the substrate changed from that which the air-water interfacial film was deposited. This procedure allows interactions, both chemical and physical, between introduced species and the monomolecular film to be studied by reflectometry. The method is briefly illustrated here with some new results on protein-protein interaction between {beta}-casein and {kappa}-casein at the air-water interface using X-rays. These two proteins are an essential component of the structure of milk. In the experiments reported, specific and directional interactions appear to cause different interfacial structures if first, a {beta}-casein monolayer is attacked by a {kappa}-casein solution compared to the reverse. The additional contrast associated with neutrons will be an advantage here. We then show the first results of experiments on the interaction of a {beta}-casein monolayer with a nanoparticle titanium oxide sol, foreshadowing the study of the nanoparticle 'corona' thought to be important for nanoparticle-cell wall penetration.

  15. Protein interfacial structure and nanotoxicology

    International Nuclear Information System (INIS)

    White, John W.; Perriman, Adam W.; McGillivray, Duncan J.; Lin, J.-M.

    2009-01-01

    Here we briefly recapitulate the use of X-ray and neutron reflectometry at the air-water interface to find protein structures and thermodynamics at interfaces and test a possibility for understanding those interactions between nanoparticles and proteins which lead to nanoparticle toxicology through entry into living cells. Stable monomolecular protein films have been made at the air-water interface and, with a specially designed vessel, the substrate changed from that which the air-water interfacial film was deposited. This procedure allows interactions, both chemical and physical, between introduced species and the monomolecular film to be studied by reflectometry. The method is briefly illustrated here with some new results on protein-protein interaction between β-casein and κ-casein at the air-water interface using X-rays. These two proteins are an essential component of the structure of milk. In the experiments reported, specific and directional interactions appear to cause different interfacial structures if first, a β-casein monolayer is attacked by a κ-casein solution compared to the reverse. The additional contrast associated with neutrons will be an advantage here. We then show the first results of experiments on the interaction of a β-casein monolayer with a nanoparticle titanium oxide sol, foreshadowing the study of the nanoparticle 'corona' thought to be important for nanoparticle-cell wall penetration.

  16. The structure of a cholesterol-trapping protein

    Science.gov (United States)

    cholesterol-trapping protein Contact: Dan Krotz, dakrotz@lbl.gov Berkeley Lab Science Beat Lab website index Institute researchers determined the three-dimensional structure of a protein that controls cholesterol level in the bloodstream. Knowing the structure of the protein, a cellular receptor that ensnares

  17. Protein structure determination by exhaustive search of Protein Data Bank derived databases.

    Science.gov (United States)

    Stokes-Rees, Ian; Sliz, Piotr

    2010-12-14

    Parallel sequence and structure alignment tools have become ubiquitous and invaluable at all levels in the study of biological systems. We demonstrate the application and utility of this same parallel search paradigm to the process of protein structure determination, benefitting from the large and growing corpus of known structures. Such searches were previously computationally intractable. Through the method of Wide Search Molecular Replacement, developed here, they can be completed in a few hours with the aide of national-scale federated cyberinfrastructure. By dramatically expanding the range of models considered for structure determination, we show that small (less than 12% structural coverage) and low sequence identity (less than 20% identity) template structures can be identified through multidimensional template scoring metrics and used for structure determination. Many new macromolecular complexes can benefit significantly from such a technique due to the lack of known homologous protein folds or sequences. We demonstrate the effectiveness of the method by determining the structure of a full-length p97 homologue from Trichoplusia ni. Example cases with the MHC/T-cell receptor complex and the EmoB protein provide systematic estimates of minimum sequence identity, structure coverage, and structural similarity required for this method to succeed. We describe how this structure-search approach and other novel computationally intensive workflows are made tractable through integration with the US national computational cyberinfrastructure, allowing, for example, rapid processing of the entire Structural Classification of Proteins protein fragment database.

  18. Function and structure of GFP-like proteins in the protein data bank.

    Science.gov (United States)

    Ong, Wayne J-H; Alvarez, Samuel; Leroux, Ivan E; Shahid, Ramza S; Samma, Alex A; Peshkepija, Paola; Morgan, Alicia L; Mulcahy, Shawn; Zimmer, Marc

    2011-04-01

    The RCSB protein databank contains 266 crystal structures of green fluorescent proteins (GFP) and GFP-like proteins. This is the first systematic analysis of all the GFP-like structures in the pdb. We have used the pdb to examine the function of fluorescent proteins (FP) in nature, aspects of excited state proton transfer (ESPT) in FPs, deformation from planarity of the chromophore and chromophore maturation. The conclusions reached in this review are that (1) The lid residues are highly conserved, particularly those on the "top" of the β-barrel. They are important to the function of GFP-like proteins, perhaps in protecting the chromophore or in β-barrel formation. (2) The primary/ancestral function of GFP-like proteins may well be to aid in light induced electron transfer. (3) The structural prerequisites for light activated proton pumps exist in many structures and it's possible that like bioluminescence, proton pumps are secondary functions of GFP-like proteins. (4) In most GFP-like proteins the protein matrix exerts a significant strain on planar chromophores forcing most GFP-like proteins to adopt non-planar chromophores. These chromophoric deviations from planarity play an important role in determining the fluorescence quantum yield. (5) The chemospatial characteristics of the chromophore cavity determine the isomerization state of the chromophore. The cavities of highlighter proteins that can undergo cis/trans isomerization have chemospatial properties that are common to both cis and trans GFP-like proteins.

  19. Classification of proteins: available structural space for molecular modeling.

    Science.gov (United States)

    Andreeva, Antonina

    2012-01-01

    The wealth of available protein structural data provides unprecedented opportunity to study and better understand the underlying principles of protein folding and protein structure evolution. A key to achieving this lies in the ability to analyse these data and to organize them in a coherent classification scheme. Over the past years several protein classifications have been developed that aim to group proteins based on their structural relationships. Some of these classification schemes explore the concept of structural neighbourhood (structural continuum), whereas other utilize the notion of protein evolution and thus provide a discrete rather than continuum view of protein structure space. This chapter presents a strategy for classification of proteins with known three-dimensional structure. Steps in the classification process along with basic definitions are introduced. Examples illustrating some fundamental concepts of protein folding and evolution with a special focus on the exceptions to them are presented.

  20. Protein structural similarity search by Ramachandran codes

    Directory of Open Access Journals (Sweden)

    Chang Chih-Hung

    2007-08-01

    Full Text Available Abstract Background Protein structural data has increased exponentially, such that fast and accurate tools are necessary to access structure similarity search. To improve the search speed, several methods have been designed to reduce three-dimensional protein structures to one-dimensional text strings that are then analyzed by traditional sequence alignment methods; however, the accuracy is usually sacrificed and the speed is still unable to match sequence similarity search tools. Here, we aimed to improve the linear encoding methodology and develop efficient search tools that can rapidly retrieve structural homologs from large protein databases. Results We propose a new linear encoding method, SARST (Structural similarity search Aided by Ramachandran Sequential Transformation. SARST transforms protein structures into text strings through a Ramachandran map organized by nearest-neighbor clustering and uses a regenerative approach to produce substitution matrices. Then, classical sequence similarity search methods can be applied to the structural similarity search. Its accuracy is similar to Combinatorial Extension (CE and works over 243,000 times faster, searching 34,000 proteins in 0.34 sec with a 3.2-GHz CPU. SARST provides statistically meaningful expectation values to assess the retrieved information. It has been implemented into a web service and a stand-alone Java program that is able to run on many different platforms. Conclusion As a database search method, SARST can rapidly distinguish high from low similarities and efficiently retrieve homologous structures. It demonstrates that the easily accessible linear encoding methodology has the potential to serve as a foundation for efficient protein structural similarity search tools. These search tools are supposed applicable to automated and high-throughput functional annotations or predictions for the ever increasing number of published protein structures in this post-genomic era.

  1. Calculation of coupling factor for double-period accelerating structure

    International Nuclear Information System (INIS)

    Bian Xiaohao; Chen Huaibi; Zheng Shuxin

    2005-01-01

    In the design of the linear accelerating structure, the coupling factor between cavities is a crucial parameter. The error of coupling factor accounts for the electric or magnetic field error mainly. To accurately design the coupling iris, the accurate calculation of coupling factor is essential. The numerical simulation is widely used to calculate the coupling factor now. By using MAFIA code, two methods have been applied to calculate the dispersion characteristics of the single-period structure, one method is to simulate the traveling wave mode by the period boundary condition; another method is to simulate the standing wave mode by the electrical boundary condition. In this work, the authors develop the two methods to calculate the coupling factor of double-period accelerating structure. Compared to experiment, the results for both methods are very similar, and in agreement with measurement within 15% deviation. (authors)

  2. Functional classification of protein structures by local structure matching in graph representation.

    Science.gov (United States)

    Mills, Caitlyn L; Garg, Rohan; Lee, Joslynn S; Tian, Liang; Suciu, Alexandru; Cooperman, Gene; Beuning, Penny J; Ondrechen, Mary Jo

    2018-03-31

    As a result of high-throughput protein structure initiatives, over 14,400 protein structures have been solved by structural genomics (SG) centers and participating research groups. While the totality of SG data represents a tremendous contribution to genomics and structural biology, reliable functional information for these proteins is generally lacking. Better functional predictions for SG proteins will add substantial value to the structural information already obtained. Our method described herein, Graph Representation of Active Sites for Prediction of Function (GRASP-Func), predicts quickly and accurately the biochemical function of proteins by representing residues at the predicted local active site as graphs rather than in Cartesian coordinates. We compare the GRASP-Func method to our previously reported method, structurally aligned local sites of activity (SALSA), using the ribulose phosphate binding barrel (RPBB), 6-hairpin glycosidase (6-HG), and Concanavalin A-like Lectins/Glucanase (CAL/G) superfamilies as test cases. In each of the superfamilies, SALSA and the much faster method GRASP-Func yield similar correct classification of previously characterized proteins, providing a validated benchmark for the new method. In addition, we analyzed SG proteins using our SALSA and GRASP-Func methods to predict function. Forty-one SG proteins in the RPBB superfamily, nine SG proteins in the 6-HG superfamily, and one SG protein in the CAL/G superfamily were successfully classified into one of the functional families in their respective superfamily by both methods. This improved, faster, validated computational method can yield more reliable predictions of function that can be used for a wide variety of applications by the community. © 2018 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  3. Proteins with Novel Structure, Function and Dynamics

    Science.gov (United States)

    Pohorille, Andrew

    2014-01-01

    Recently, a small enzyme that ligates two RNA fragments with the rate of 10(exp 6) above background was evolved in vitro (Seelig and Szostak, Nature 448:828-831, 2007). This enzyme does not resemble any contemporary protein (Chao et al., Nature Chem. Biol. 9:81-83, 2013). It consists of a dynamic, catalytic loop, a small, rigid core containing two zinc ions coordinated by neighboring amino acids, and two highly flexible tails that might be unimportant for protein function. In contrast to other proteins, this enzyme does not contain ordered secondary structure elements, such as alpha-helix or beta-sheet. The loop is kept together by just two interactions of a charged residue and a histidine with a zinc ion, which they coordinate on the opposite side of the loop. Such structure appears to be very fragile. Surprisingly, computer simulations indicate otherwise. As the coordinating, charged residue is mutated to alanine, another, nearby charged residue takes its place, thus keeping the structure nearly intact. If this residue is also substituted by alanine a salt bridge involving two other, charged residues on the opposite sides of the loop keeps the loop in place. These adjustments are facilitated by high flexibility of the protein. Computational predictions have been confirmed experimentally, as both mutants retain full activity and overall structure. These results challenge our notions about what is required for protein activity and about the relationship between protein dynamics, stability and robustness. We hypothesize that small, highly dynamic proteins could be both active and fault tolerant in ways that many other proteins are not, i.e. they can adjust to retain their structure and activity even if subjected to mutations in structurally critical regions. This opens the doors for designing proteins with novel functions, structures and dynamics that have not been yet considered.

  4. Molecular recognition in a diverse set of protein-ligand interactions studied with molecular dynamics simulations and end-point free energy calculations.

    Science.gov (United States)

    Wang, Bo; Li, Liwei; Hurley, Thomas D; Meroueh, Samy O

    2013-10-28

    End-point free energy calculations using MM-GBSA and MM-PBSA provide a detailed understanding of molecular recognition in protein-ligand interactions. The binding free energy can be used to rank-order protein-ligand structures in virtual screening for compound or target identification. Here, we carry out free energy calculations for a diverse set of 11 proteins bound to 14 small molecules using extensive explicit-solvent MD simulations. The structure of these complexes was previously solved by crystallography and their binding studied with isothermal titration calorimetry (ITC) data enabling direct comparison to the MM-GBSA and MM-PBSA calculations. Four MM-GBSA and three MM-PBSA calculations reproduced the ITC free energy within 1 kcal·mol(-1) highlighting the challenges in reproducing the absolute free energy from end-point free energy calculations. MM-GBSA exhibited better rank-ordering with a Spearman ρ of 0.68 compared to 0.40 for MM-PBSA with dielectric constant (ε = 1). An increase in ε resulted in significantly better rank-ordering for MM-PBSA (ρ = 0.91 for ε = 10), but larger ε significantly reduced the contributions of electrostatics, suggesting that the improvement is due to the nonpolar and entropy components, rather than a better representation of the electrostatics. The SVRKB scoring function applied to MD snapshots resulted in excellent rank-ordering (ρ = 0.81). Calculations of the configurational entropy using normal-mode analysis led to free energies that correlated significantly better to the ITC free energy than the MD-based quasi-harmonic approach, but the computed entropies showed no correlation with the ITC entropy. When the adaptation energy is taken into consideration by running separate simulations for complex, apo, and ligand (MM-PBSAADAPT), there is less agreement with the ITC data for the individual free energies, but remarkably good rank-ordering is observed (ρ = 0.89). Interestingly, filtering MD snapshots by prescoring

  5. Structure and function of nanoparticle-protein conjugates

    International Nuclear Information System (INIS)

    Aubin-Tam, M-E; Hamad-Schifferli, K

    2008-01-01

    Conjugation of proteins to nanoparticles has numerous applications in sensing, imaging, delivery, catalysis, therapy and control of protein structure and activity. Therefore, characterizing the nanoparticle-protein interface is of great importance. A variety of covalent and non-covalent linking chemistries have been reported for nanoparticle attachment. Site-specific labeling is desirable in order to control the protein orientation on the nanoparticle, which is crucial in many applications such as fluorescence resonance energy transfer. We evaluate methods for successful site-specific attachment. Typically, a specific protein residue is linked directly to the nanoparticle core or to the ligand. As conjugation often affects the protein structure and function, techniques to probe structure and activity are assessed. We also examine how molecular dynamics simulations of conjugates would complete those experimental techniques in order to provide atomistic details on the effect of nanoparticle attachment. Characterization studies of nanoparticle-protein complexes show that the structure and function are influenced by the chemistry of the nanoparticle ligand, the nanoparticle size, the nanoparticle material, the stoichiometry of the conjugates, the labeling site on the protein and the nature of the linkage (covalent versus non-covalent)

  6. Soil structure interaction calculations: a comparison of methods

    Energy Technology Data Exchange (ETDEWEB)

    Wight, L.; Zaslawsky, M.

    1976-07-22

    Two approaches for calculating soil structure interaction (SSI) are compared: finite element and lumped mass. Results indicate that the calculations with the lumped mass method are generally conservative compared to those obtained by the finite element method. They also suggest that a closer agreement between the two sets of calculations is possible, depending on the use of frequency-dependent soil springs and dashpots in the lumped mass calculations. There is a total lack of suitable guidelines for implementing the lumped mass method of calculating SSI, which leads to the conclusion that the finite element method is generally superior for calculative purposes.

  7. Soil structure interaction calculations: a comparison of methods

    International Nuclear Information System (INIS)

    Wight, L.; Zaslawsky, M.

    1976-01-01

    Two approaches for calculating soil structure interaction (SSI) are compared: finite element and lumped mass. Results indicate that the calculations with the lumped mass method are generally conservative compared to those obtained by the finite element method. They also suggest that a closer agreement between the two sets of calculations is possible, depending on the use of frequency-dependent soil springs and dashpots in the lumped mass calculations. There is a total lack of suitable guidelines for implementing the lumped mass method of calculating SSI, which leads to the conclusion that the finite element method is generally superior for calculative purposes

  8. Modeling protein structures: construction and their applications.

    Science.gov (United States)

    Ring, C S; Cohen, F E

    1993-06-01

    Although no general solution to the protein folding problem exists, the three-dimensional structures of proteins are being successfully predicted when experimentally derived constraints are used in conjunction with heuristic methods. In the case of interleukin-4, mutagenesis data and CD spectroscopy were instrumental in the accurate assignment of secondary structure. In addition, the tertiary structure was highly constrained by six cysteines separated by many residues that formed three disulfide bridges. Although the correct structure was a member of a short list of plausible structures, the "best" structure was the topological enantiomer of the experimentally determined conformation. For many proteases, other experimentally derived structures can be used as templates to identify the secondary structure elements. In a procedure called modeling by homology, the structure of a known protein is used as a scaffold to predict the structure of another related protein. This method has been used to model a serine and a cysteine protease that are important in the schistosome and malarial life cycles, respectively. The model structures were then used to identify putative small molecule enzyme inhibitors computationally. Experiments confirm that some of these nonpeptidic compounds are active at concentrations of less than 10 microM.

  9. Breaking symmetry in the structure determination of (large) symmetric protein dimers

    Energy Technology Data Exchange (ETDEWEB)

    Gaponenko, Vadim; Altieri, Amanda S.; Li, Jess; Byrd, R. Andrew [National Cancer Institute, Structural Biophysics Laboratory (United States)], E-mail: rabyrd@ncifcrf.gov

    2002-10-15

    We demonstrate a novel methodology to disrupt the symmetry in the NMR spectra of homodimers. A paramagnetic probe is introduced sub-stoichiometrically to create an asymmetric system with the paramagnetic probe residing on only one monomer within the dimer. This creates sufficient magnetic anisotropy for resolution of symmetry-related overlapped resonances and, consequently, detection of pseudocontact shifts and residual dipolar couplings specific to each monomeric component. These pseudocontact shifts can be readily incorporated into existing structure refinement calculations and enable determination of monomer orientation within the dimeric protein. This methodology can be widely used for solution structure determination of symmetric dimers.

  10. Myristoylation as a general method for immobilization and alignment of soluble proteins for solid-state NMR structural studies

    International Nuclear Information System (INIS)

    Mesleh, M.F.; Valentine, K.G.; Opella, S.J.; Louis, J.M.; Gronenborn, A.M.

    2003-01-01

    N-terminal myristoylation of the immunoglobulin-binding domain of protein G (GB1) from group G Streptococcus provides the means to bind the protein to aligned phospholipid bilayers for solid-state NMR structural studies. The myristoylated protein is immobilized by its interactions with bilayers, and the sample alignment enables orientationally dependent 15 N chemical shifts and 1 H- 15 N-dipolar couplings to be measured. Spectra calculated for the average solution NMR structure of the protein at various orientations with respect to the magnetic field direction were compared to the experimental spectrum. The best fit identified the orientation of the myristoylated protein on the lipid bilayers, and demonstrated that the protein adopts a similar structure in both its myristoylated and non-myristoylated forms, and that the structure is not grossly distorted by its interaction with the phosholipid bilayer surface or by its location in the restricted aqueous space between bilayer leaflets. The protein is oriented such that its charged sides face the phosphatidylcholine headgroups of the lipids with the single amphiphilic helix running parallel to the bilayer surface

  11. Improving the chances of successful protein structure determination with a random forest classifier

    Energy Technology Data Exchange (ETDEWEB)

    Jahandideh, Samad [Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92307 (United States); Joint Center for Structural Genomics, (United States); Jaroszewski, Lukasz; Godzik, Adam, E-mail: adam@burnham.org [Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92307 (United States); Joint Center for Structural Genomics, (United States); University of California, San Diego, La Jolla, California (United States)

    2014-03-01

    Using an extended set of protein features calculated separately for protein surface and interior, a new version of XtalPred based on a random forest classifier achieves a significant improvement in predicting the success of structure determination from the primary amino-acid sequence. Obtaining diffraction quality crystals remains one of the major bottlenecks in structural biology. The ability to predict the chances of crystallization from the amino-acid sequence of the protein can, at least partly, address this problem by allowing a crystallographer to select homologs that are more likely to succeed and/or to modify the sequence of the target to avoid features that are detrimental to successful crystallization. In 2007, the now widely used XtalPred algorithm [Slabinski et al. (2007 ▶), Protein Sci.16, 2472–2482] was developed. XtalPred classifies proteins into five ‘crystallization classes’ based on a simple statistical analysis of the physicochemical features of a protein. Here, towards the same goal, advanced machine-learning methods are applied and, in addition, the predictive potential of additional protein features such as predicted surface ruggedness, hydrophobicity, side-chain entropy of surface residues and amino-acid composition of the predicted protein surface are tested. The new XtalPred-RF (random forest) achieves significant improvement of the prediction of crystallization success over the original XtalPred. To illustrate this, XtalPred-RF was tested by revisiting target selection from 271 Pfam families targeted by the Joint Center for Structural Genomics (JCSG) in PSI-2, and it was estimated that the number of targets entered into the protein-production and crystallization pipeline could have been reduced by 30% without lowering the number of families for which the first structures were solved. The prediction improvement depends on the subset of targets used as a testing set and reaches 100% (i.e. twofold) for the top class of predicted

  12. Improving the accuracy of protein secondary structure prediction using structural alignment

    Directory of Open Access Journals (Sweden)

    Gallin Warren J

    2006-06-01

    Full Text Available Abstract Background The accuracy of protein secondary structure prediction has steadily improved over the past 30 years. Now many secondary structure prediction methods routinely achieve an accuracy (Q3 of about 75%. We believe this accuracy could be further improved by including structure (as opposed to sequence database comparisons as part of the prediction process. Indeed, given the large size of the Protein Data Bank (>35,000 sequences, the probability of a newly identified sequence having a structural homologue is actually quite high. Results We have developed a method that performs structure-based sequence alignments as part of the secondary structure prediction process. By mapping the structure of a known homologue (sequence ID >25% onto the query protein's sequence, it is possible to predict at least a portion of that query protein's secondary structure. By integrating this structural alignment approach with conventional (sequence-based secondary structure methods and then combining it with a "jury-of-experts" system to generate a consensus result, it is possible to attain very high prediction accuracy. Using a sequence-unique test set of 1644 proteins from EVA, this new method achieves an average Q3 score of 81.3%. Extensive testing indicates this is approximately 4–5% better than any other method currently available. Assessments using non sequence-unique test sets (typical of those used in proteome annotation or structural genomics indicate that this new method can achieve a Q3 score approaching 88%. Conclusion By using both sequence and structure databases and by exploiting the latest techniques in machine learning it is possible to routinely predict protein secondary structure with an accuracy well above 80%. A program and web server, called PROTEUS, that performs these secondary structure predictions is accessible at http://wishart.biology.ualberta.ca/proteus. For high throughput or batch sequence analyses, the PROTEUS programs

  13. SCOWLP classification: Structural comparison and analysis of protein binding regions

    Directory of Open Access Journals (Sweden)

    Anders Gerd

    2008-01-01

    Full Text Available Abstract Background Detailed information about protein interactions is critical for our understanding of the principles governing protein recognition mechanisms. The structures of many proteins have been experimentally determined in complex with different ligands bound either in the same or different binding regions. Thus, the structural interactome requires the development of tools to classify protein binding regions. A proper classification may provide a general view of the regions that a protein uses to bind others and also facilitate a detailed comparative analysis of the interacting information for specific protein binding regions at atomic level. Such classification might be of potential use for deciphering protein interaction networks, understanding protein function, rational engineering and design. Description Protein binding regions (PBRs might be ideally described as well-defined separated regions that share no interacting residues one another. However, PBRs are often irregular, discontinuous and can share a wide range of interacting residues among them. The criteria to define an individual binding region can be often arbitrary and may differ from other binding regions within a protein family. Therefore, the rational behind protein interface classification should aim to fulfil the requirements of the analysis to be performed. We extract detailed interaction information of protein domains, peptides and interfacial solvent from the SCOWLP database and we classify the PBRs of each domain family. For this purpose, we define a similarity index based on the overlapping of interacting residues mapped in pair-wise structural alignments. We perform our classification with agglomerative hierarchical clustering using the complete-linkage method. Our classification is calculated at different similarity cut-offs to allow flexibility in the analysis of PBRs, feature especially interesting for those protein families with conflictive binding regions

  14. Nuclear structure calculations for astrophysical applications

    International Nuclear Information System (INIS)

    Moeller, P.; Kratz, K.L.

    1992-01-01

    Here we present calculated results on such diverse properties as nuclear energy levels, ground-state masses and shapes, β-decay properties and fission-barrier heights. Our approach to these calculations is to use a unified theoretical framework within which the above properties can all be studied. The results are obtained in the macroscopic-microscopic approach in which a microscopic nuclear-structure single-particle model with extensions is combined with a macroscopic model, such as the liquid drop model. In this model the total potential energy of the nucleus may be calculated as a function of shape. The maxima and minima in this function correspond to such features as the ground state, fission saddle points and shape-isomeric states. Various transition rate matrix elements are determined from wave-functions calculated in the single-particle model with pairing and other relevant residual interactions taken into account

  15. Structure and orientation of interfacial proteins determined by sum frequency generation vibrational spectroscopy: method and application.

    Science.gov (United States)

    Ye, Shuji; Wei, Feng; Li, Hongchun; Tian, Kangzhen; Luo, Yi

    2013-01-01

    In situ and real-time characterization of molecular structures and orientation of proteins at interfaces is essential to understand the nature of interfacial protein interaction. Such work will undoubtedly provide important clues to control biointerface in a desired manner. Sum frequency generation vibrational spectroscopy (SFG-VS) has been demonstrated to be a powerful technique to study the interfacial structures and interactions at the molecular level. This paper first systematically introduced the methods for the calculation of the Raman polarizability tensor, infrared transition dipole moment, and SFG molecular hyperpolarizability tensor elements of proteins/peptides with the secondary structures of α-helix, 310-helix, antiparallel β-sheet, and parallel β-sheet, as well as the methodology to determine the orientation of interfacial protein secondary structures using SFG amide I spectra. After that, recent progresses on the determination of protein structure and orientation at different interfaces by SFG-VS were then reviewed, which provides a molecular-level understanding of the structures and interactions of interfacial proteins, specially understanding the nature of driving force behind such interactions. Although this review has focused on analysis of amide I spectra, it will be expected to offer a basic idea for the spectral analysis of amide III SFG signals and other complicated molecular systems such as RNA and DNA. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Calculation of X-ray scattering curves and electron distance distribution functions of biological macromolecules in solution using the PROTEIN DATA BANK

    International Nuclear Information System (INIS)

    Mueller, J.J.; Friedrichowicz, E.; Nothnagel, A.; Wunderlich, T.; Ziehlsdorf, E.; Damaschun, G.

    1983-01-01

    The wide angle X-ray scattering curve, the electron distance distribution function and the solvent excluded volume of a macromolecule in solution are calculated from the atomic coordinates contained in the PROTEIN DATA BANK. The structures and the projections of the excluded volumes are depicted using molecule graphic routines. The described computer programs are used to determine the three-dimensional structure of macromolecules in solution from wide angle X-ray scattering data. (author)

  17. PRince: a web server for structural and physicochemical analysis of protein-RNA interface.

    Science.gov (United States)

    Barik, Amita; Mishra, Abhishek; Bahadur, Ranjit Prasad

    2012-07-01

    We have developed a web server, PRince, which analyzes the structural features and physicochemical properties of the protein-RNA interface. Users need to submit a PDB file containing the atomic coordinates of both the protein and the RNA molecules in complex form (in '.pdb' format). They should also mention the chain identifiers of interacting protein and RNA molecules. The size of the protein-RNA interface is estimated by measuring the solvent accessible surface area buried in contact. For a given protein-RNA complex, PRince calculates structural, physicochemical and hydration properties of the interacting surfaces. All these parameters generated by the server are presented in a tabular format. The interacting surfaces can also be visualized with software plug-in like Jmol. In addition, the output files containing the list of the atomic coordinates of the interacting protein, RNA and interface water molecules can be downloaded. The parameters generated by PRince are novel, and users can correlate them with the experimentally determined biophysical and biochemical parameters for better understanding the specificity of the protein-RNA recognition process. This server will be continuously upgraded to include more parameters. PRince is publicly accessible and free for use. Available at http://www.facweb.iitkgp.ernet.in/~rbahadur/prince/home.html.

  18. Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein.

    Science.gov (United States)

    Massiah, M A; Starich, M R; Paschall, C; Summers, M F; Christensen, A M; Sundquist, W I

    1994-11-25

    The HIV-1 matrix protein forms an icosahedral shell associated with the inner membrane of the mature virus. Genetic analyses have indicated that the protein performs important functions throughout the viral life-cycle, including anchoring the transmembrane envelope protein on the surface of the virus, assisting in viral penetration, transporting the proviral integration complex across the nuclear envelope, and localizing the assembling virion to the cell membrane. We now report the three-dimensional structure of recombinant HIV-1 matrix protein, determined at high resolution by nuclear magnetic resonance (NMR) methods. The HIV-1 matrix protein is the first retroviral matrix protein to be characterized structurally and only the fourth HIV-1 protein of known structure. NMR signal assignments required recently developed triple-resonance (1H, 13C, 15N) NMR methodologies because signals for 91% of 132 assigned H alpha protons and 74% of the 129 assignable backbone amide protons resonate within chemical shift ranges of 0.8 p.p.m. and 1 p.p.m., respectively. A total of 636 nuclear Overhauser effect-derived distance restraints were employed for distance geometry-based structure calculations, affording an average of 13.0 NMR-derived distance restraints per residue for the experimentally constrained amino acids. An ensemble of 25 refined distance geometry structures with penalties (sum of the squares of the distance violations) of 0.32 A2 or less and individual distance violations under 0.06 A was generated; best-fit superposition of ordered backbone heavy atoms relative to mean atom positions afforded root-mean-square deviations of 0.50 (+/- 0.08) A. The folded HIV-1 matrix protein structure is composed of five alpha-helices, a short 3(10) helical stretch, and a three-strand mixed beta-sheet. Helices I to III and the 3(10) helix pack about a central helix (IV) to form a compact globular domain that is capped by the beta-sheet. The C-terminal helix (helix V) projects away

  19. Exploring the universe of protein structures beyond the Protein Data Bank.

    Science.gov (United States)

    Cossio, Pilar; Trovato, Antonio; Pietrucci, Fabio; Seno, Flavio; Maritan, Amos; Laio, Alessandro

    2010-11-04

    It is currently believed that the atlas of existing protein structures is faithfully represented in the Protein Data Bank. However, whether this atlas covers the full universe of all possible protein structures is still a highly debated issue. By using a sophisticated numerical approach, we performed an exhaustive exploration of the conformational space of a 60 amino acid polypeptide chain described with an accurate all-atom interaction potential. We generated a database of around 30,000 compact folds with at least of secondary structure corresponding to local minima of the potential energy. This ensemble plausibly represents the universe of protein folds of similar length; indeed, all the known folds are represented in the set with good accuracy. However, we discover that the known folds form a rather small subset, which cannot be reproduced by choosing random structures in the database. Rather, natural and possible folds differ by the contact order, on average significantly smaller in the former. This suggests the presence of an evolutionary bias, possibly related to kinetic accessibility, towards structures with shorter loops between contacting residues. Beside their conceptual relevance, the new structures open a range of practical applications such as the development of accurate structure prediction strategies, the optimization of force fields, and the identification and design of novel folds.

  20. Solution NMR structure determination of proteins revisited

    International Nuclear Information System (INIS)

    Billeter, Martin; Wagner, Gerhard; Wuethrich, Kurt

    2008-01-01

    This 'Perspective' bears on the present state of protein structure determination by NMR in solution. The focus is on a comparison of the infrastructure available for NMR structure determination when compared to protein crystal structure determination by X-ray diffraction. The main conclusion emerges that the unique potential of NMR to generate high resolution data also on dynamics, interactions and conformational equilibria has contributed to a lack of standard procedures for structure determination which would be readily amenable to improved efficiency by automation. To spark renewed discussion on the topic of NMR structure determination of proteins, procedural steps with high potential for improvement are identified

  1. K-nearest uphill clustering in the protein structure space

    KAUST Repository

    Cui, Xuefeng; Gao, Xin

    2016-01-01

    The protein structure classification problem, which is to assign a protein structure to a cluster of similar proteins, is one of the most fundamental problems in the construction and application of the protein structure space. Early manually curated

  2. Electronic structure calculations on nitride semiconductors and their alloys

    International Nuclear Information System (INIS)

    Dugdale, D.

    2000-09-01

    Calculations of the electronic properties of AIN, GaN, InN and their alloys are presented. Initial calculations are performed using the first principles pseudopotential method to obtain accurate lattice constants. Further calculations then investigate bonding in the nitrides through population analysis and density of state calculations. The empirical pseudopotential method is also used in this work. Pseudopotentials for each of the nitrides are constructed using a functional form that allows strained material and alloys to be studied. The conventional k.p valence band parameters for both zincblende and wurtzite are obtained from the empirical band structure using two different methods. A Monte-Carlo fitting of the k.p band structure to the pseudopotential data (or an effective mass method for the zincblende structure) is used to produce one set. Another set is obtained directly from the momentum matrix elements and energy eigenvalues at the centre of the Brillouin zone. Both methods of calculating k.p parameters produce band structure in excellent agreement with the original empirical band calculations near the centre of the Brillouin zone. The advantage of the direct method is that it produces consistent sets of parameters, and can be used in studies involving a series of alloy compositions. Further empirical pseudopotential method calculations are then performed for alloys of the nitrides. In particular, the variation of the band gap with alloy composition is investigated, and good agreement with theory and experiment is found. The direct method is used to obtain k.p parameters for the alloys, and is contrasted with the fitting approach. The behaviour of the nitrides under strain is also studied. In particular. valence band offsets for nitride heterojunctions are calculated, and a strong forward- backward asymmetry in the band offset is found, in good agreement with other results in the literature. (author)

  3. The primary structure of fatty-acid-binding protein from nurse shark liver. Structural and evolutionary relationship to the mammalian fatty-acid-binding protein family.

    Science.gov (United States)

    Medzihradszky, K F; Gibson, B W; Kaur, S; Yu, Z H; Medzihradszky, D; Burlingame, A L; Bass, N M

    1992-02-01

    The primary structure of a fatty-acid-binding protein (FABP) isolated from the liver of the nurse shark (Ginglymostoma cirratum) was determined by high-performance tandem mass spectrometry (employing multichannel array detection) and Edman degradation. Shark liver FABP consists of 132 amino acids with an acetylated N-terminal valine. The chemical molecular mass of the intact protein determined by electrospray ionization mass spectrometry (Mr = 15124 +/- 2.5) was in good agreement with that calculated from the amino acid sequence (Mr = 15121.3). The amino acid sequence of shark liver FABP displays significantly greater similarity to the FABP expressed in mammalian heart, peripheral nerve myelin and adipose tissue (61-53% sequence similarity) than to the FABP expressed in mammalian liver (22% similarity). Phylogenetic trees derived from the comparison of the shark liver FABP amino acid sequence with the members of the mammalian fatty-acid/retinoid-binding protein gene family indicate the initial divergence of an ancestral gene into two major subfamilies: one comprising the genes for mammalian liver FABP and gastrotropin, the other comprising the genes for mammalian cellular retinol-binding proteins I and II, cellular retinoic-acid-binding protein myelin P2 protein, adipocyte FABP, heart FABP and shark liver FABP, the latter having diverged from the ancestral gene that ultimately gave rise to the present day mammalian heart-FABP, adipocyte FABP and myelin P2 protein sequences. The sequence for intestinal FABP from the rat could be assigned to either subfamily, depending on the approach used for phylogenetic tree construction, but clearly diverged at a relatively early evolutionary time point. Indeed, sequences proximately ancestral or closely related to mammalian intestinal FABP, liver FABP, gastrotropin and the retinoid-binding group of proteins appear to have arisen prior to the divergence of shark liver FABP and should therefore also be present in elasmobranchs

  4. Comparison of NMR and crystal structures for the proteins TM1112 and TM1367

    International Nuclear Information System (INIS)

    Mohanty, Biswaranjan; Serrano, Pedro; Pedrini, Bill; Jaudzems, Kristaps; Geralt, Michael; Horst, Reto; Herrmann, Torsten; Elsliger, Marc-André; Wilson, Ian A.; Wüthrich, Kurt

    2010-01-01

    NMR structures of the proteins TM1112 and TM1367 solved by the JCSG in solution at 298 K could be superimposed with the corresponding crystal structures at 100 K with r.m.s.d. values of <1.0 Å for the backbone heavy atoms. For both proteins the structural differences between multiple molecules in the asymmetric unit of the crystals correlated with structural variations within the bundles of conformers used to represent the NMR solution structures. A recently introduced JCSG NMR structure-determination protocol, which makes use of the software package UNIO for extensive automation, was further evaluated by comparison of the TM1112 structure obtained using these automated methods with another NMR structure that was independently solved in another PSI center, where a largely interactive approach was applied. The NMR structures of the TM1112 and TM1367 proteins from Thermotoga maritima in solution at 298 K were determined following a new protocol which uses the software package UNIO for extensive automation. The results obtained with this novel procedure were evaluated by comparison with the crystal structures solved by the JCSG at 100 K to 1.83 and 1.90 Å resolution, respectively. In addition, the TM1112 solution structure was compared with an NMR structure solved by the NESG using a conventional largely interactive methodology. For both proteins, the newly determined NMR structure could be superimposed with the crystal structure with r.m.s.d. values of <1.0 Å for the backbone heavy atoms, which provided a starting platform to investigate local structure variations, which may arise from either the methods used or from the different chemical environments in solution and in the crystal. Thereby, these comparative studies were further explored with the use of reference NMR and crystal structures, which were computed using the NMR software with input of upper-limit distance constraints derived from the molecular models that represent the results of structure

  5. Integral membrane protein structure determination using pseudocontact shifts

    Energy Technology Data Exchange (ETDEWEB)

    Crick, Duncan J.; Wang, Jue X. [University of Cambridge, Department of Biochemistry (United Kingdom); Graham, Bim; Swarbrick, James D. [Monash University, Monash Institute of Pharmaceutical Sciences (Australia); Mott, Helen R.; Nietlispach, Daniel, E-mail: dn206@cam.ac.uk [University of Cambridge, Department of Biochemistry (United Kingdom)

    2015-04-15

    Obtaining enough experimental restraints can be a limiting factor in the NMR structure determination of larger proteins. This is particularly the case for large assemblies such as membrane proteins that have been solubilized in a membrane-mimicking environment. Whilst in such cases extensive deuteration strategies are regularly utilised with the aim to improve the spectral quality, these schemes often limit the number of NOEs obtainable, making complementary strategies highly beneficial for successful structure elucidation. Recently, lanthanide-induced pseudocontact shifts (PCSs) have been established as a structural tool for globular proteins. Here, we demonstrate that a PCS-based approach can be successfully applied for the structure determination of integral membrane proteins. Using the 7TM α-helical microbial receptor pSRII, we show that PCS-derived restraints from lanthanide binding tags attached to four different positions of the protein facilitate the backbone structure determination when combined with a limited set of NOEs. In contrast, the same set of NOEs fails to determine the correct 3D fold. The latter situation is frequently encountered in polytopical α-helical membrane proteins and a PCS approach is thus suitable even for this particularly challenging class of membrane proteins. The ease of measuring PCSs makes this an attractive route for structure determination of large membrane proteins in general.

  6. The Protein Model Portal--a comprehensive resource for protein structure and model information.

    Science.gov (United States)

    Haas, Juergen; Roth, Steven; Arnold, Konstantin; Kiefer, Florian; Schmidt, Tobias; Bordoli, Lorenza; Schwede, Torsten

    2013-01-01

    The Protein Model Portal (PMP) has been developed to foster effective use of 3D molecular models in biomedical research by providing convenient and comprehensive access to structural information for proteins. Both experimental structures and theoretical models for a given protein can be searched simultaneously and analyzed for structural variability. By providing a comprehensive view on structural information, PMP offers the opportunity to apply consistent assessment and validation criteria to the complete set of structural models available for proteins. PMP is an open project so that new methods developed by the community can contribute to PMP, for example, new modeling servers for creating homology models and model quality estimation servers for model validation. The accuracy of participating modeling servers is continuously evaluated by the Continuous Automated Model EvaluatiOn (CAMEO) project. The PMP offers a unique interface to visualize structural coverage of a protein combining both theoretical models and experimental structures, allowing straightforward assessment of the model quality and hence their utility. The portal is updated regularly and actively developed to include latest methods in the field of computational structural biology. Database URL: http://www.proteinmodelportal.org.

  7. The Protein Model Portal—a comprehensive resource for protein structure and model information

    Science.gov (United States)

    Haas, Juergen; Roth, Steven; Arnold, Konstantin; Kiefer, Florian; Schmidt, Tobias; Bordoli, Lorenza; Schwede, Torsten

    2013-01-01

    The Protein Model Portal (PMP) has been developed to foster effective use of 3D molecular models in biomedical research by providing convenient and comprehensive access to structural information for proteins. Both experimental structures and theoretical models for a given protein can be searched simultaneously and analyzed for structural variability. By providing a comprehensive view on structural information, PMP offers the opportunity to apply consistent assessment and validation criteria to the complete set of structural models available for proteins. PMP is an open project so that new methods developed by the community can contribute to PMP, for example, new modeling servers for creating homology models and model quality estimation servers for model validation. The accuracy of participating modeling servers is continuously evaluated by the Continuous Automated Model EvaluatiOn (CAMEO) project. The PMP offers a unique interface to visualize structural coverage of a protein combining both theoretical models and experimental structures, allowing straightforward assessment of the model quality and hence their utility. The portal is updated regularly and actively developed to include latest methods in the field of computational structural biology. Database URL: http://www.proteinmodelportal.org PMID:23624946

  8. Prediction of protein structural classes by recurrence quantification analysis based on chaos game representation.

    Science.gov (United States)

    Yang, Jian-Yi; Peng, Zhen-Ling; Yu, Zu-Guo; Zhang, Rui-Jie; Anh, Vo; Wang, Desheng

    2009-04-21

    In this paper, we intend to predict protein structural classes (alpha, beta, alpha+beta, or alpha/beta) for low-homology data sets. Two data sets were used widely, 1189 (containing 1092 proteins) and 25PDB (containing 1673 proteins) with sequence homology being 40% and 25%, respectively. We propose to decompose the chaos game representation of proteins into two kinds of time series. Then, a novel and powerful nonlinear analysis technique, recurrence quantification analysis (RQA), is applied to analyze these time series. For a given protein sequence, a total of 16 characteristic parameters can be calculated with RQA, which are treated as feature representation of protein sequences. Based on such feature representation, the structural class for each protein is predicted with Fisher's linear discriminant algorithm. The jackknife test is used to test and compare our method with other existing methods. The overall accuracies with step-by-step procedure are 65.8% and 64.2% for 1189 and 25PDB data sets, respectively. With one-against-others procedure used widely, we compare our method with five other existing methods. Especially, the overall accuracies of our method are 6.3% and 4.1% higher for the two data sets, respectively. Furthermore, only 16 parameters are used in our method, which is less than that used by other methods. This suggests that the current method may play a complementary role to the existing methods and is promising to perform the prediction of protein structural classes.

  9. Sampling Realistic Protein Conformations Using Local Structural Bias

    DEFF Research Database (Denmark)

    Hamelryck, Thomas Wim; Kent, John T.; Krogh, A.

    2006-01-01

    The prediction of protein structure from sequence remains a major unsolved problem in biology. The most successful protein structure prediction methods make use of a divide-and-conquer strategy to attack the problem: a conformational sampling method generates plausible candidate structures, which...... are subsequently accepted or rejected using an energy function. Conceptually, this often corresponds to separating local structural bias from the long-range interactions that stabilize the compact, native state. However, sampling protein conformations that are compatible with the local structural bias encoded...... in a given protein sequence is a long-standing open problem, especially in continuous space. We describe an elegant and mathematically rigorous method to do this, and show that it readily generates native-like protein conformations simply by enforcing compactness. Our results have far-reaching implications...

  10. Exploring the universe of protein structures beyond the Protein Data Bank.

    Directory of Open Access Journals (Sweden)

    Pilar Cossio

    Full Text Available It is currently believed that the atlas of existing protein structures is faithfully represented in the Protein Data Bank. However, whether this atlas covers the full universe of all possible protein structures is still a highly debated issue. By using a sophisticated numerical approach, we performed an exhaustive exploration of the conformational space of a 60 amino acid polypeptide chain described with an accurate all-atom interaction potential. We generated a database of around 30,000 compact folds with at least of secondary structure corresponding to local minima of the potential energy. This ensemble plausibly represents the universe of protein folds of similar length; indeed, all the known folds are represented in the set with good accuracy. However, we discover that the known folds form a rather small subset, which cannot be reproduced by choosing random structures in the database. Rather, natural and possible folds differ by the contact order, on average significantly smaller in the former. This suggests the presence of an evolutionary bias, possibly related to kinetic accessibility, towards structures with shorter loops between contacting residues. Beside their conceptual relevance, the new structures open a range of practical applications such as the development of accurate structure prediction strategies, the optimization of force fields, and the identification and design of novel folds.

  11. Simultaneous determination of protein structure and dynamics

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Best, Robert B.; DePristo, M. A.

    2005-01-01

    at the atomic level about the structural and dynamical features of proteins-with the ability of molecular dynamics simulations to explore a wide range of protein conformations. We illustrate the method for human ubiquitin in solution and find that there is considerable conformational heterogeneity throughout......We present a protocol for the experimental determination of ensembles of protein conformations that represent simultaneously the native structure and its associated dynamics. The procedure combines the strengths of nuclear magnetic resonance spectroscopy-for obtaining experimental information...... the protein structure. The interior atoms of the protein are tightly packed in each individual conformation that contributes to the ensemble but their overall behaviour can be described as having a significant degree of liquid-like character. The protocol is completely general and should lead to significant...

  12. PONDEROSA, an automated 3D-NOESY peak picking program, enables automated protein structure determination.

    Science.gov (United States)

    Lee, Woonghee; Kim, Jin Hae; Westler, William M; Markley, John L

    2011-06-15

    PONDEROSA (Peak-picking Of Noe Data Enabled by Restriction of Shift Assignments) accepts input information consisting of a protein sequence, backbone and sidechain NMR resonance assignments, and 3D-NOESY ((13)C-edited and/or (15)N-edited) spectra, and returns assignments of NOESY crosspeaks, distance and angle constraints, and a reliable NMR structure represented by a family of conformers. PONDEROSA incorporates and integrates external software packages (TALOS+, STRIDE and CYANA) to carry out different steps in the structure determination. PONDEROSA implements internal functions that identify and validate NOESY peak assignments and assess the quality of the calculated three-dimensional structure of the protein. The robustness of the analysis results from PONDEROSA's hierarchical processing steps that involve iterative interaction among the internal and external modules. PONDEROSA supports a variety of input formats: SPARKY assignment table (.shifts) and spectrum file formats (.ucsf), XEASY proton file format (.prot), and NMR-STAR format (.star). To demonstrate the utility of PONDEROSA, we used the package to determine 3D structures of two proteins: human ubiquitin and Escherichia coli iron-sulfur scaffold protein variant IscU(D39A). The automatically generated structural constraints and ensembles of conformers were as good as or better than those determined previously by much less automated means. The program, in the form of binary code along with tutorials and reference manuals, is available at http://ponderosa.nmrfam.wisc.edu/.

  13. Hidden Structural Codes in Protein Intrinsic Disorder.

    Science.gov (United States)

    Borkosky, Silvia S; Camporeale, Gabriela; Chemes, Lucía B; Risso, Marikena; Noval, María Gabriela; Sánchez, Ignacio E; Alonso, Leonardo G; de Prat Gay, Gonzalo

    2017-10-17

    Intrinsic disorder is a major structural category in biology, accounting for more than 30% of coding regions across the domains of life, yet consists of conformational ensembles in equilibrium, a major challenge in protein chemistry. Anciently evolved papillomavirus genomes constitute an unparalleled case for sequence to structure-function correlation in cases in which there are no folded structures. E7, the major transforming oncoprotein of human papillomaviruses, is a paradigmatic example among the intrinsically disordered proteins. Analysis of a large number of sequences of the same viral protein allowed for the identification of a handful of residues with absolute conservation, scattered along the sequence of its N-terminal intrinsically disordered domain, which intriguingly are mostly leucine residues. Mutation of these led to a pronounced increase in both α-helix and β-sheet structural content, reflected by drastic effects on equilibrium propensities and oligomerization kinetics, and uncovers the existence of local structural elements that oppose canonical folding. These folding relays suggest the existence of yet undefined hidden structural codes behind intrinsic disorder in this model protein. Thus, evolution pinpoints conformational hot spots that could have not been identified by direct experimental methods for analyzing or perturbing the equilibrium of an intrinsically disordered protein ensemble.

  14. K-nearest uphill clustering in the protein structure space

    KAUST Repository

    Cui, Xuefeng

    2016-08-26

    The protein structure classification problem, which is to assign a protein structure to a cluster of similar proteins, is one of the most fundamental problems in the construction and application of the protein structure space. Early manually curated protein structure classifications (e.g., SCOP and CATH) are very successful, but recently suffer the slow updating problem because of the increased throughput of newly solved protein structures. Thus, fully automatic methods to cluster proteins in the protein structure space have been designed and developed. In this study, we observed that the SCOP superfamilies are highly consistent with clustering trees representing hierarchical clustering procedures, but the tree cutting is very challenging and becomes the bottleneck of clustering accuracy. To overcome this challenge, we proposed a novel density-based K-nearest uphill clustering method that effectively eliminates noisy pairwise protein structure similarities and identifies density peaks as cluster centers. Specifically, the density peaks are identified based on K-nearest uphills (i.e., proteins with higher densities) and K-nearest neighbors. To our knowledge, this is the first attempt to apply and develop density-based clustering methods in the protein structure space. Our results show that our density-based clustering method outperforms the state-of-the-art clustering methods previously applied to the problem. Moreover, we observed that computational methods and human experts could produce highly similar clusters at high precision values, while computational methods also suggest to split some large superfamilies into smaller clusters. © 2016 Elsevier B.V.

  15. SCHEMA computational design of virus capsid chimeras: calibrating how genome packaging, protection, and transduction correlate with calculated structural disruption.

    Science.gov (United States)

    Ho, Michelle L; Adler, Benjamin A; Torre, Michael L; Silberg, Jonathan J; Suh, Junghae

    2013-12-20

    Adeno-associated virus (AAV) recombination can result in chimeric capsid protein subunits whose ability to assemble into an oligomeric capsid, package a genome, and transduce cells depends on the inheritance of sequence from different AAV parents. To develop quantitative design principles for guiding site-directed recombination of AAV capsids, we have examined how capsid structural perturbations predicted by the SCHEMA algorithm correlate with experimental measurements of disruption in seventeen chimeric capsid proteins. In our small chimera population, created by recombining AAV serotypes 2 and 4, we found that protection of viral genomes and cellular transduction were inversely related to calculated disruption of the capsid structure. Interestingly, however, we did not observe a correlation between genome packaging and calculated structural disruption; a majority of the chimeric capsid proteins formed at least partially assembled capsids and more than half packaged genomes, including those with the highest SCHEMA disruption. These results suggest that the sequence space accessed by recombination of divergent AAV serotypes is rich in capsid chimeras that assemble into 60-mer capsids and package viral genomes. Overall, the SCHEMA algorithm may be useful for delineating quantitative design principles to guide the creation of libraries enriched in genome-protecting virus nanoparticles that can effectively transduce cells. Such improvements to the virus design process may help advance not only gene therapy applications but also other bionanotechnologies dependent upon the development of viruses with new sequences and functions.

  16. Structural Mass Spectrometry of Proteins Using Hydroxyl Radical Based Protein Footprinting

    OpenAIRE

    Wang, Liwen; Chance, Mark R.

    2011-01-01

    Structural MS is a rapidly growing field with many applications in basic research and pharmaceutical drug development. In this feature article the overall technology is described and several examples of how hydroxyl radical based footprinting MS can be used to map interfaces, evaluate protein structure, and identify ligand dependent conformational changes in proteins are described.

  17. Extracting knowledge from protein structure geometry

    DEFF Research Database (Denmark)

    Røgen, Peter; Koehl, Patrice

    2013-01-01

    potential from geometric knowledge extracted from native and misfolded conformers of protein structures. This new potential, Metric Protein Potential (MPP), has two main features that are key to its success. Firstly, it is composite in that it includes local and nonlocal geometric information on proteins...

  18. Relationship between Molecular Structure Characteristics of Feed Proteins and Protein Digestibility and Solubility

    Directory of Open Access Journals (Sweden)

    Mingmei Bai

    2016-08-01

    Full Text Available The nutritional value of feed proteins and their utilization by livestock are related not only to the chemical composition but also to the structure of feed proteins, but few studies thus far have investigated the relationship between the structure of feed proteins and their solubility as well as digestibility in monogastric animals. To address this question we analyzed soybean meal, fish meal, corn distiller’s dried grains with solubles, corn gluten meal, and feather meal by Fourier transform infrared (FTIR spectroscopy to determine the protein molecular spectral band characteristics for amides I and II as well as α-helices and β-sheets and their ratios. Protein solubility and in vitro digestibility were measured with the Kjeldahl method using 0.2% KOH solution and the pepsin-pancreatin two-step enzymatic method, respectively. We found that all measured spectral band intensities (height and area of feed proteins were correlated with their the in vitro digestibility and solubility (p≤0.003; moreover, the relatively quantitative amounts of α-helices, random coils, and α-helix to β-sheet ratio in protein secondary structures were positively correlated with protein in vitro digestibility and solubility (p≤0.004. On the other hand, the percentage of β-sheet structures was negatively correlated with protein in vitro digestibility (p<0.001 and solubility (p = 0.002. These results demonstrate that the molecular structure characteristics of feed proteins are closely related to their in vitro digestibility at 28 h and solubility. Furthermore, the α-helix-to-β-sheet ratio can be used to predict the nutritional value of feed proteins.

  19. Calculations of optical rotation: Influence of molecular structure

    Directory of Open Access Journals (Sweden)

    Yu Jia

    2012-01-01

    Full Text Available Ab initio Hartree-Fock (HF method and Density Functional Theory (DFT were used to calculate the optical rotation of 26 chiral compounds. The effects of theory and basis sets used for calculation, solvents influence on the geometry and values of calculated optical rotation were all discussed. The polarizable continuum model, included in the calculation, did not improve the accuracy effectively, but it was superior to γs. Optical rotation of five or sixmembered of cyclic compound has been calculated and 17 pyrrolidine or piperidine derivatives which were calculated by HF and DFT methods gave acceptable predictions. The nitrogen atom affects the calculation results dramatically, and it is necessary in the molecular structure in order to get an accurate computation result. Namely, when the nitrogen atom was substituted by oxygen atom in the ring, the calculation result deteriorated.

  20. Electronic Structure Calculation of Permanent Magnets using the KKR Green's Function Method

    Science.gov (United States)

    Doi, Shotaro; Akai, Hisazumi

    2014-03-01

    Electronic structure and magnetic properties of permanent magnetic materials, especially Nd2Fe14B, are investigated theoretically using the KKR Green's function method. Important physical quantities in magnetism, such as magnetic moment, Curie temperature, and anisotropy constant, which are obtained from electronics structure calculations in both cases of atomic-sphere-approximation and full-potential treatment, are compared with past band structure calculations and experiments. The site preference of heavy rare-earth impurities are also evaluated through the calculation of formation energy with the use of coherent potential approximations. Further, the development of electronic structure calculation code using the screened KKR for large super-cells, which is aimed at studying the electronic structure of realistic microstructures (e.g. grain boundary phase), is introduced with some test calculations.

  1. Lattice QCD Calculation of Nucleon Structure

    International Nuclear Information System (INIS)

    Liu, Keh-Fei; Draper, Terrence

    2016-01-01

    It is emphasized in the 2015 NSAC Long Range Plan that 'understanding the structure of hadrons in terms of QCD's quarks and gluons is one of the central goals of modern nuclear physics.' Over the last three decades, lattice QCD has developed into a powerful tool for ab initio calculations of strong-interaction physics. Up until now, it is the only theoretical approach to solving QCD with controlled statistical and systematic errors. Since 1985, we have proposed and carried out first-principles calculations of nucleon structure and hadron spectroscopy using lattice QCD which entails both algorithmic development and large-scale computer simulation. We started out by calculating the nucleon form factors -- electromagnetic, axial-vector, ?NN, and scalar form factors, the quark spin contribution to the proton spin, the strangeness magnetic moment, the quark orbital angular momentum, the quark momentum fraction, and the quark and glue decomposition of the proton momentum and angular momentum. The first round of calculations were done with Wilson fermions in the 'quenched' approximation where the dynamical effects of the quarks in the sea are not taken into account in the Monte Carlo simulation to generate the background gauge configurations. Beginning in 2000, we have started implementing the overlap fermion formulation into the spectroscopy and structure calculations. This is mainly because the overlap fermion honors chiral symmetry as in the continuum. It is going to be more and more important to take the symmetry into account as the simulations move closer to the physical point where the u and d quark masses are as light as a few MeV only. We began with lattices which have quark masses in the sea corresponding to a pion mass at ~ 300 MeV and obtained the strange form factors, charm and strange quark masses, the charmonium spectrum and the D_s meson decay constant f_D__s, the strangeness and charmness, the meson mass decomposition and the strange quark spin from the

  2. Solution structure of an archaeal DNA binding protein with an eukaryotic zinc finger fold.

    Directory of Open Access Journals (Sweden)

    Florence Guillière

    Full Text Available While the basal transcription machinery in archaea is eukaryal-like, transcription factors in archaea and their viruses are usually related to bacterial transcription factors. Nevertheless, some of these organisms show predicted classical zinc fingers motifs of the C2H2 type, which are almost exclusively found in proteins of eukaryotes and most often associated with transcription regulators. In this work, we focused on the protein AFV1p06 from the hyperthermophilic archaeal virus AFV1. The sequence of the protein consists of the classical eukaryotic C2H2 motif with the fourth histidine coordinating zinc missing, as well as of N- and C-terminal extensions. We showed that the protein AFV1p06 binds zinc and solved its solution structure by NMR. AFV1p06 displays a zinc finger fold with a novel structure extension and disordered N- and C-termini. Structure calculations show that a glutamic acid residue that coordinates zinc replaces the fourth histidine of the C2H2 motif. Electromobility gel shift assays indicate that the protein binds to DNA with different affinities depending on the DNA sequence. AFV1p06 is the first experimentally characterised archaeal zinc finger protein with a DNA binding activity. The AFV1p06 protein family has homologues in diverse viruses of hyperthermophilic archaea. A phylogenetic analysis points out a common origin of archaeal and eukaryotic C2H2 zinc fingers.

  3. eMatchSite: sequence order-independent structure alignments of ligand binding pockets in protein models.

    Directory of Open Access Journals (Sweden)

    Michal Brylinski

    2014-09-01

    Full Text Available Detecting similarities between ligand binding sites in the absence of global homology between target proteins has been recognized as one of the critical components of modern drug discovery. Local binding site alignments can be constructed using sequence order-independent techniques, however, to achieve a high accuracy, many current algorithms for binding site comparison require high-quality experimental protein structures, preferably in the bound conformational state. This, in turn, complicates proteome scale applications, where only various quality structure models are available for the majority of gene products. To improve the state-of-the-art, we developed eMatchSite, a new method for constructing sequence order-independent alignments of ligand binding sites in protein models. Large-scale benchmarking calculations using adenine-binding pockets in crystal structures demonstrate that eMatchSite generates accurate alignments for almost three times more protein pairs than SOIPPA. More importantly, eMatchSite offers a high tolerance to structural distortions in ligand binding regions in protein models. For example, the percentage of correctly aligned pairs of adenine-binding sites in weakly homologous protein models is only 4-9% lower than those aligned using crystal structures. This represents a significant improvement over other algorithms, e.g. the performance of eMatchSite in recognizing similar binding sites is 6% and 13% higher than that of SiteEngine using high- and moderate-quality protein models, respectively. Constructing biologically correct alignments using predicted ligand binding sites in protein models opens up the possibility to investigate drug-protein interaction networks for complete proteomes with prospective systems-level applications in polypharmacology and rational drug repositioning. eMatchSite is freely available to the academic community as a web-server and a stand-alone software distribution at http://www.brylinski.org/ematchsite.

  4. Relation between native ensembles and experimental structures of proteins

    DEFF Research Database (Denmark)

    Best, R. B.; Lindorff-Larsen, Kresten; DePristo, M. A.

    2006-01-01

    Different experimental structures of the same protein or of proteins with high sequence similarity contain many small variations. Here we construct ensembles of "high-sequence similarity Protein Data Bank" (HSP) structures and consider the extent to which such ensembles represent the structural...... Data Bank ensembles; moreover, we show that the effects of uncertainties in structure determination are insufficient to explain the results. These results highlight the importance of accounting for native-state protein dynamics in making comparisons with ensemble-averaged experimental data and suggest...... heterogeneity of the native state in solution. We find that different NMR measurements probing structure and dynamics of given proteins in solution, including order parameters, scalar couplings, and residual dipolar couplings, are remarkably well reproduced by their respective high-sequence similarity Protein...

  5. A protein relational database and protein family knowledge bases to facilitate structure-based design analyses.

    Science.gov (United States)

    Mobilio, Dominick; Walker, Gary; Brooijmans, Natasja; Nilakantan, Ramaswamy; Denny, R Aldrin; Dejoannis, Jason; Feyfant, Eric; Kowticwar, Rupesh K; Mankala, Jyoti; Palli, Satish; Punyamantula, Sairam; Tatipally, Maneesh; John, Reji K; Humblet, Christine

    2010-08-01

    The Protein Data Bank is the most comprehensive source of experimental macromolecular structures. It can, however, be difficult at times to locate relevant structures with the Protein Data Bank search interface. This is particularly true when searching for complexes containing specific interactions between protein and ligand atoms. Moreover, searching within a family of proteins can be tedious. For example, one cannot search for some conserved residue as residue numbers vary across structures. We describe herein three databases, Protein Relational Database, Kinase Knowledge Base, and Matrix Metalloproteinase Knowledge Base, containing protein structures from the Protein Data Bank. In Protein Relational Database, atom-atom distances between protein and ligand have been precalculated allowing for millisecond retrieval based on atom identity and distance constraints. Ring centroids, centroid-centroid and centroid-atom distances and angles have also been included permitting queries for pi-stacking interactions and other structural motifs involving rings. Other geometric features can be searched through the inclusion of residue pair and triplet distances. In Kinase Knowledge Base and Matrix Metalloproteinase Knowledge Base, the catalytic domains have been aligned into common residue numbering schemes. Thus, by searching across Protein Relational Database and Kinase Knowledge Base, one can easily retrieve structures wherein, for example, a ligand of interest is making contact with the gatekeeper residue.

  6. Values for digestible indispensable amino acid scores (DIAAS) for some dairy and plant proteins may better describe protein quality than values calculated using the concept for protein digestibility-corrected amino acid scores (PDCAAS).

    Science.gov (United States)

    Mathai, John K; Liu, Yanhong; Stein, Hans H

    2017-02-01

    An experiment was conducted to compare values for digestible indispensable amino acid scores (DIAAS) for four animal proteins and four plant proteins with values calculated as recommended for protein digestibility-corrected amino acid scores (PDCAAS), but determined in pigs instead of in rats. Values for standardised total tract digestibility (STTD) of crude protein (CP) and standardised ileal digestibility (SID) of amino acids (AA) were calculated for whey protein isolate (WPI), whey protein concentrate (WPC), milk protein concentrate (MPC), skimmed milk powder (SMP), pea protein concentrate (PPC), soya protein isolate (SPI), soya flour and whole-grain wheat. The PDCAAS-like values were calculated using the STTD of CP to estimate AA digestibility and values for DIAAS were calculated from values for SID of AA. Results indicated that values for SID of most indispensable AA in WPI, WPC and MPC were greater (P<0·05) than for SMP, PPC, SPI, soya flour and wheat. With the exception of arginine and tryptophan, the SID of all indispensable AA in SPI was greater (P<0·05) than in soya flour, and with the exception of threonine, the SID of all indispensable AA in wheat was less (P<0·05) than in all other ingredients. If the same scoring pattern for children between 6 and 36 months was used to calculate PDCAAS-like values and DIAAS, PDCAAS-like values were greater (P<0·05) than DIAAS values for SMP, PPC, SPI, soya flour and wheat indicating that PDCAAS-like values estimated in pigs may overestimate the quality of these proteins.

  7. Atomic structure calculations of Mo XV-XL

    International Nuclear Information System (INIS)

    Kubo, Hirotaka; Sugie, Tatsuo; Shiho, Makoto; Suzuki, Yasuo; Ishii, Keishi; Maeda, Hikosuke.

    1986-06-01

    Energy levels and oscillator strengths were calculated for Mo XV - Mo XL. The computer program for atomic structure calculation, developed by Dr. Robert D. Cowan, Los Alamos National Laboratory, was used in the present work. The scaled energy parameters were empirically determined from the observed spectral data. We present wavelengths and transition probabilities of Mo XV-XL. Energy levels and spectral patterns are presented in figures that are useful for the identification of spectral lines. (author)

  8. DNA mimic proteins: functions, structures, and bioinformatic analysis.

    Science.gov (United States)

    Wang, Hao-Ching; Ho, Chun-Han; Hsu, Kai-Cheng; Yang, Jinn-Moon; Wang, Andrew H-J

    2014-05-13

    DNA mimic proteins have DNA-like negative surface charge distributions, and they function by occupying the DNA binding sites of DNA binding proteins to prevent these sites from being accessed by DNA. DNA mimic proteins control the activities of a variety of DNA binding proteins and are involved in a wide range of cellular mechanisms such as chromatin assembly, DNA repair, transcription regulation, and gene recombination. However, the sequences and structures of DNA mimic proteins are diverse, making them difficult to predict by bioinformatic search. To date, only a few DNA mimic proteins have been reported. These DNA mimics were not found by searching for functional motifs in their sequences but were revealed only by structural analysis of their charge distribution. This review highlights the biological roles and structures of 16 reported DNA mimic proteins. We also discuss approaches that might be used to discover new DNA mimic proteins.

  9. Compare local pocket and global protein structure models by small structure patterns

    KAUST Repository

    Cui, Xuefeng; Kuwahara, Hiroyuki; Li, Shuai Cheng; Gao, Xin

    2015-01-01

    Researchers proposed several criteria to assess the quality of predicted protein structures because it is one of the essential tasks in the Critical Assessment of Techniques for Protein Structure Prediction (CASP) competitions. Popular criteria

  10. Post processing of protein-compound docking for fragment-based drug discovery (FBDD): in-silico structure-based drug screening and ligand-binding pose prediction.

    Science.gov (United States)

    Fukunishi, Yoshifumi

    2010-01-01

    For fragment-based drug development, both hit (active) compound prediction and docking-pose (protein-ligand complex structure) prediction of the hit compound are important, since chemical modification (fragment linking, fragment evolution) subsequent to the hit discovery must be performed based on the protein-ligand complex structure. However, the naïve protein-compound docking calculation shows poor accuracy in terms of docking-pose prediction. Thus, post-processing of the protein-compound docking is necessary. Recently, several methods for the post-processing of protein-compound docking have been proposed. In FBDD, the compounds are smaller than those for conventional drug screening. This makes it difficult to perform the protein-compound docking calculation. A method to avoid this problem has been reported. Protein-ligand binding free energy estimation is useful to reduce the procedures involved in the chemical modification of the hit fragment. Several prediction methods have been proposed for high-accuracy estimation of protein-ligand binding free energy. This paper summarizes the various computational methods proposed for docking-pose prediction and their usefulness in FBDD.

  11. DL_MG: A Parallel Multigrid Poisson and Poisson-Boltzmann Solver for Electronic Structure Calculations in Vacuum and Solution.

    Science.gov (United States)

    Womack, James C; Anton, Lucian; Dziedzic, Jacek; Hasnip, Phil J; Probert, Matt I J; Skylaris, Chris-Kriton

    2018-03-13

    The solution of the Poisson equation is a crucial step in electronic structure calculations, yielding the electrostatic potential-a key component of the quantum mechanical Hamiltonian. In recent decades, theoretical advances and increases in computer performance have made it possible to simulate the electronic structure of extended systems in complex environments. This requires the solution of more complicated variants of the Poisson equation, featuring nonhomogeneous dielectric permittivities, ionic concentrations with nonlinear dependencies, and diverse boundary conditions. The analytic solutions generally used to solve the Poisson equation in vacuum (or with homogeneous permittivity) are not applicable in these circumstances, and numerical methods must be used. In this work, we present DL_MG, a flexible, scalable, and accurate solver library, developed specifically to tackle the challenges of solving the Poisson equation in modern large-scale electronic structure calculations on parallel computers. Our solver is based on the multigrid approach and uses an iterative high-order defect correction method to improve the accuracy of solutions. Using two chemically relevant model systems, we tested the accuracy and computational performance of DL_MG when solving the generalized Poisson and Poisson-Boltzmann equations, demonstrating excellent agreement with analytic solutions and efficient scaling to ∼10 9 unknowns and 100s of CPU cores. We also applied DL_MG in actual large-scale electronic structure calculations, using the ONETEP linear-scaling electronic structure package to study a 2615 atom protein-ligand complex with routinely available computational resources. In these calculations, the overall execution time with DL_MG was not significantly greater than the time required for calculations using a conventional FFT-based solver.

  12. Improved protein surface comparison and application to low-resolution protein structure data

    Directory of Open Access Journals (Sweden)

    Kihara Daisuke

    2010-12-01

    Full Text Available Abstract Background Recent advancements of experimental techniques for determining protein tertiary structures raise significant challenges for protein bioinformatics. With the number of known structures of unknown function expanding at a rapid pace, an urgent task is to provide reliable clues to their biological function on a large scale. Conventional approaches for structure comparison are not suitable for a real-time database search due to their slow speed. Moreover, a new challenge has arisen from recent techniques such as electron microscopy (EM, which provide low-resolution structure data. Previously, we have introduced a method for protein surface shape representation using the 3D Zernike descriptors (3DZDs. The 3DZD enables fast structure database searches, taking advantage of its rotation invariance and compact representation. The search results of protein surface represented with the 3DZD has showngood agreement with the existing structure classifications, but some discrepancies were also observed. Results The three new surface representations of backbone atoms, originally devised all-atom-surface representation, and the combination of all-atom surface with the backbone representation are examined. All representations are encoded with the 3DZD. Also, we have investigated the applicability of the 3DZD for searching protein EM density maps of varying resolutions. The surface representations are evaluated on structure retrieval using two existing classifications, SCOP and the CE-based classification. Conclusions Overall, the 3DZDs representing backbone atoms show better retrieval performance than the original all-atom surface representation. The performance further improved when the two representations are combined. Moreover, we observed that the 3DZD is also powerful in comparing low-resolution structures obtained by electron microscopy.

  13. Improved protein surface comparison and application to low-resolution protein structure data.

    Science.gov (United States)

    Sael, Lee; Kihara, Daisuke

    2010-12-14

    Recent advancements of experimental techniques for determining protein tertiary structures raise significant challenges for protein bioinformatics. With the number of known structures of unknown function expanding at a rapid pace, an urgent task is to provide reliable clues to their biological function on a large scale. Conventional approaches for structure comparison are not suitable for a real-time database search due to their slow speed. Moreover, a new challenge has arisen from recent techniques such as electron microscopy (EM), which provide low-resolution structure data. Previously, we have introduced a method for protein surface shape representation using the 3D Zernike descriptors (3DZDs). The 3DZD enables fast structure database searches, taking advantage of its rotation invariance and compact representation. The search results of protein surface represented with the 3DZD has showngood agreement with the existing structure classifications, but some discrepancies were also observed. The three new surface representations of backbone atoms, originally devised all-atom-surface representation, and the combination of all-atom surface with the backbone representation are examined. All representations are encoded with the 3DZD. Also, we have investigated the applicability of the 3DZD for searching protein EM density maps of varying resolutions. The surface representations are evaluated on structure retrieval using two existing classifications, SCOP and the CE-based classification. Overall, the 3DZDs representing backbone atoms show better retrieval performance than the original all-atom surface representation. The performance further improved when the two representations are combined. Moreover, we observed that the 3DZD is also powerful in comparing low-resolution structures obtained by electron microscopy.

  14. Topological properties of complex networks in protein structures

    Science.gov (United States)

    Kim, Kyungsik; Jung, Jae-Won; Min, Seungsik

    2014-03-01

    We study topological properties of networks in structural classification of proteins. We model the native-state protein structure as a network made of its constituent amino-acids and their interactions. We treat four structural classes of proteins composed predominantly of α helices and β sheets and consider several proteins from each of these classes whose sizes range from amino acids of the Protein Data Bank. Particularly, we simulate and analyze the network metrics such as the mean degree, the probability distribution of degree, the clustering coefficient, the characteristic path length, the local efficiency, and the cost. This work was supported by the KMAR and DP under Grant WISE project (153-3100-3133-302-350).

  15. Structural system reliability calculation using a probabilistic fault tree analysis method

    Science.gov (United States)

    Torng, T. Y.; Wu, Y.-T.; Millwater, H. R.

    1992-01-01

    The development of a new probabilistic fault tree analysis (PFTA) method for calculating structural system reliability is summarized. The proposed PFTA procedure includes: developing a fault tree to represent the complex structural system, constructing an approximation function for each bottom event, determining a dominant sampling sequence for all bottom events, and calculating the system reliability using an adaptive importance sampling method. PFTA is suitable for complicated structural problems that require computer-intensive computer calculations. A computer program has been developed to implement the PFTA.

  16. Studying Membrane Protein Structure and Function Using Nanodiscs

    DEFF Research Database (Denmark)

    Huda, Pie

    The structure and dynamic of membrane proteins can provide valuable information about general functions, diseases and effects of various drugs. Studying membrane proteins are a challenge as an amphiphilic environment is necessary to stabilise the protein in a functionally and structurally relevant...... form. This is most typically achieved through the use of detergent based reconstitution systems. However, time and again such systems fail to provide a suitable environment causing aggregation and inactivation. Nanodiscs are self-assembled lipoproteins containing two membrane scaffold proteins...... and a lipid bilayer in defined nanometer size, which can act as a stabiliser for membrane proteins. This enables both functional and structural investigation of membrane proteins in a detergent free environment which is closer to the native situation. Understanding the self-assembly of nanodiscs is important...

  17. 3D bioprinting of structural proteins.

    Science.gov (United States)

    Włodarczyk-Biegun, Małgorzata K; Del Campo, Aránzazu

    2017-07-01

    3D bioprinting is a booming method to obtain scaffolds of different materials with predesigned and customized morphologies and geometries. In this review we focus on the experimental strategies and recent achievements in the bioprinting of major structural proteins (collagen, silk, fibrin), as a particularly interesting technology to reconstruct the biochemical and biophysical composition and hierarchical morphology of natural scaffolds. The flexibility in molecular design offered by structural proteins, combined with the flexibility in mixing, deposition, and mechanical processing inherent to bioprinting technologies, enables the fabrication of highly functional scaffolds and tissue mimics with a degree of complexity and organization which has only just started to be explored. Here we describe the printing parameters and physical (mechanical) properties of bioinks based on structural proteins, including the biological function of the printed scaffolds. We describe applied printing techniques and cross-linking methods, highlighting the modifications implemented to improve scaffold properties. The used cell types, cell viability, and possible construct applications are also reported. We envision that the application of printing technologies to structural proteins will enable unprecedented control over their supramolecular organization, conferring printed scaffolds biological properties and functions close to natural systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Calculation of surface acoustic waves in a multilayered piezoelectric structure

    International Nuclear Information System (INIS)

    Zhang Zuwei; Wen Zhiyu; Hu Jing

    2013-01-01

    The propagation properties of the surface acoustic waves (SAWs) in a ZnO—SiO 2 —Si multilayered piezoelectric structure are calculated by using the recursive asymptotic method. The phase velocities and the electromechanical coupling coefficients for the Rayleigh wave and the Love wave in the different ZnO—SiO 2 —Si structures are calculated and analyzed. The Love mode wave is found to be predominantly generated since the c-axis of the ZnO film is generally perpendicular to the substrate. In order to prove the calculated results, a Love mode SAW device based on the ZnO—SiO 2 —Si multilayered structure is fabricated by micromachining, and its frequency responses are detected. The experimental results are found to be mainly consistent with the calculated ones, except for the slightly larger velocities induced by the residual stresses produced in the fabrication process of the films. The deviation of the experimental results from the calculated ones is reduced by thermal annealing. (semiconductor physics)

  19. MODY - calculation of ordered structures by symmetry-adapted functions

    Science.gov (United States)

    Białas, Franciszek; Pytlik, Lucjan; Sikora, Wiesława

    2016-01-01

    In this paper we focus on the new version of computer program MODY for calculations of symmetryadapted functions based on the theory of groups and representations. The choice of such a functional frame of coordinates for description of ordered structures leads to a minimal number of parameters which must be used for presentation of such structures and investigations of their properties. The aim of this work is to find those parameters, which are coefficients of a linear combination of calculated functions, leading to construction of different types of structure ordering with a given symmetry. A spreadsheet script for simplification of this work has been created and attached to the program.

  20. ProteinSplit: splitting of multi-domain proteins using prediction of ordered and disordered regions in protein sequences for virtual structural genomics

    International Nuclear Information System (INIS)

    Wyrwicz, Lucjan S; Koczyk, Grzegorz; Rychlewski, Leszek; Plewczynski, Dariusz

    2007-01-01

    The annotation of protein folds within newly sequenced genomes is the main target for semi-automated protein structure prediction (virtual structural genomics). A large number of automated methods have been developed recently with very good results in the case of single-domain proteins. Unfortunately, most of these automated methods often fail to properly predict the distant homology between a given multi-domain protein query and structural templates. Therefore a multi-domain protein should be split into domains in order to overcome this limitation. ProteinSplit is designed to identify protein domain boundaries using a novel algorithm that predicts disordered regions in protein sequences. The software utilizes various sequence characteristics to assess the local propensity of a protein to be disordered or ordered in terms of local structure stability. These disordered parts of a protein are likely to create interdomain spacers. Because of its speed and portability, the method was successfully applied to several genome-wide fold annotation experiments. The user can run an automated analysis of sets of proteins or perform semi-automated multiple user projects (saving the results on the server). Additionally the sequences of predicted domains can be sent to the Bioinfo.PL Protein Structure Prediction Meta-Server for further protein three-dimensional structure and function prediction. The program is freely accessible as a web service at http://lucjan.bioinfo.pl/proteinsplit together with detailed benchmark results on the critical assessment of a fully automated structure prediction (CAFASP) set of sequences. The source code of the local version of protein domain boundary prediction is available upon request from the authors

  1. A hidden markov model derived structural alphabet for proteins.

    Science.gov (United States)

    Camproux, A C; Gautier, R; Tufféry, P

    2004-06-04

    Understanding and predicting protein structures depends on the complexity and the accuracy of the models used to represent them. We have set up a hidden Markov model that discretizes protein backbone conformation as series of overlapping fragments (states) of four residues length. This approach learns simultaneously the geometry of the states and their connections. We obtain, using a statistical criterion, an optimal systematic decomposition of the conformational variability of the protein peptidic chain in 27 states with strong connection logic. This result is stable over different protein sets. Our model fits well the previous knowledge related to protein architecture organisation and seems able to grab some subtle details of protein organisation, such as helix sub-level organisation schemes. Taking into account the dependence between the states results in a description of local protein structure of low complexity. On an average, the model makes use of only 8.3 states among 27 to describe each position of a protein structure. Although we use short fragments, the learning process on entire protein conformations captures the logic of the assembly on a larger scale. Using such a model, the structure of proteins can be reconstructed with an average accuracy close to 1.1A root-mean-square deviation and for a complexity of only 3. Finally, we also observe that sequence specificity increases with the number of states of the structural alphabet. Such models can constitute a very relevant approach to the analysis of protein architecture in particular for protein structure prediction.

  2. 3D complex: a structural classification of protein complexes.

    Directory of Open Access Journals (Sweden)

    Emmanuel D Levy

    2006-11-01

    Full Text Available Most of the proteins in a cell assemble into complexes to carry out their function. It is therefore crucial to understand the physicochemical properties as well as the evolution of interactions between proteins. The Protein Data Bank represents an important source of information for such studies, because more than half of the structures are homo- or heteromeric protein complexes. Here we propose the first hierarchical classification of whole protein complexes of known 3-D structure, based on representing their fundamental structural features as a graph. This classification provides the first overview of all the complexes in the Protein Data Bank and allows nonredundant sets to be derived at different levels of detail. This reveals that between one-half and two-thirds of known structures are multimeric, depending on the level of redundancy accepted. We also analyse the structures in terms of the topological arrangement of their subunits and find that they form a small number of arrangements compared with all theoretically possible ones. This is because most complexes contain four subunits or less, and the large majority are homomeric. In addition, there is a strong tendency for symmetry in complexes, even for heteromeric complexes. Finally, through comparison of Biological Units in the Protein Data Bank with the Protein Quaternary Structure database, we identified many possible errors in quaternary structure assignments. Our classification, available as a database and Web server at http://www.3Dcomplex.org, will be a starting point for future work aimed at understanding the structure and evolution of protein complexes.

  3. Identification of similar regions of protein structures using integrated sequence and structure analysis tools

    Directory of Open Access Journals (Sweden)

    Heiland Randy

    2006-03-01

    Full Text Available Abstract Background Understanding protein function from its structure is a challenging problem. Sequence based approaches for finding homology have broad use for annotation of both structure and function. 3D structural information of protein domains and their interactions provide a complementary view to structure function relationships to sequence information. We have developed a web site http://www.sblest.org/ and an API of web services that enables users to submit protein structures and identify statistically significant neighbors and the underlying structural environments that make that match using a suite of sequence and structure analysis tools. To do this, we have integrated S-BLEST, PSI-BLAST and HMMer based superfamily predictions to give a unique integrated view to prediction of SCOP superfamilies, EC number, and GO term, as well as identification of the protein structural environments that are associated with that prediction. Additionally, we have extended UCSF Chimera and PyMOL to support our web services, so that users can characterize their own proteins of interest. Results Users are able to submit their own queries or use a structure already in the PDB. Currently the databases that a user can query include the popular structural datasets ASTRAL 40 v1.69, ASTRAL 95 v1.69, CLUSTER50, CLUSTER70 and CLUSTER90 and PDBSELECT25. The results can be downloaded directly from the site and include function prediction, analysis of the most conserved environments and automated annotation of query proteins. These results reflect both the hits found with PSI-BLAST, HMMer and with S-BLEST. We have evaluated how well annotation transfer can be performed on SCOP ID's, Gene Ontology (GO ID's and EC Numbers. The method is very efficient and totally automated, generally taking around fifteen minutes for a 400 residue protein. Conclusion With structural genomics initiatives determining structures with little, if any, functional characterization

  4. Wavelets in self-consistent electronic structure calculations

    International Nuclear Information System (INIS)

    Wei, S.; Chou, M.Y.

    1996-01-01

    We report the first implementation of orthonormal wavelet bases in self-consistent electronic structure calculations within the local-density approximation. These local bases of different scales efficiently describe localized orbitals of interest. As an example, we studied two molecules, H 2 and O 2 , using pseudopotentials and supercells. Considerably fewer bases are needed compared with conventional plane-wave approaches, yet calculated binding properties are similar. Our implementation employs fast wavelet and Fourier transforms, avoiding evaluating any three-dimensional integral numerically. copyright 1996 The American Physical Society

  5. Continuum Electrostatics Approaches to Calculating pKas and Ems in Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Gunner, Marilyn R.; Baker, Nathan A.

    2016-06-20

    Proteins change their charge state through protonation and redox reactions as well as through binding charged ligands. The free energy of these reactions are dominated by solvation and electrostatic energies and modulated by protein conformational relaxation in response to the ionization state changes. Although computational methods for calculating these interactions can provide very powerful tools for predicting protein charge states, they include several critical approximations of which users should be aware. This chapter discusses the strengths, weaknesses, and approximations of popular computational methods for predicting charge states and understanding their underlying electrostatic interactions. The goal of this chapter is to inform users about applications and potential caveats of these methods as well as outline directions for future theoretical and computational research.

  6. Structural and dynamic characterization of eukaryotic gene regulatory protein domains in solution

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Andrew Loyd [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    1996-05-01

    Solution NMR was primarily used to characterize structure and dynamics in two different eukaryotic protein systems: the δ-Al-ε activation domain from c-jun and the Drosophila RNA-binding protein Sex-lethal. The second system is the Drosophila Sex-lethal (Sxl) protein, an RNA-binding protein which is the ``master switch`` in sex determination. Sxl contains two adjacent RNA-binding domains (RBDs) of the RNP consensus-type. The NMR spectrum of the second RBD (Sxl-RBD2) was assigned using multidimensional heteronuclear NMR, and an intermediate-resolution family of structures was calculated from primarily NOE distance restraints. The overall fold was determined to be similar to other RBDs: a βαβ-βαβ pattern of secondary structure, with the two helices packed against a 4-stranded anti-parallel β-sheet. In addition 15N T1, T2, and 15N/1H NOE relaxation measurements were carried out to characterize the backbone dynamics of Sxl-RBD2 in solution. RNA corresponding to the polypyrimidine tract of transformer pre-mRNA was generated and titrated into 3 different Sxl-RBD protein constructs. Combining Sxl-RBD1+2 (bht RBDs) with this RNA formed a specific, high affinity protein/RNA complex that is amenable to further NMR characterization. The backbone 1H, 13C, and 15N resonances of Sxl-RBD1+2 were assigned using a triple-resonance approach, and 15N relaxation experiments were carried out to characterize the backbone dynamics of this complex. The changes in chemical shift in Sxl-RBD1+2 upon binding RNA are observed using Sxl-RBD2 as a substitute for unbound Sxl-RBD1+2. This allowed the binding interface to be qualitatively mapped for the second domain.

  7. Deprotonated imidodiphosphate in AMPPNP-containing protein structures

    International Nuclear Information System (INIS)

    Dauter, Miroslawa; Dauter, Zbigniew

    2011-01-01

    In certain AMPPNP-containing protein structures, the nitrogen bridging the two terminal phosphate groups can be deprotonated. Many different proteins utilize the chemical energy provided by the cofactor adenosine triphosphate (ATP) for their proper function. A number of structures in the Protein Data Bank (PDB) contain adenosine 5′-(β,γ-imido)triphosphate (AMPPNP), a nonhydrolysable analog of ATP in which the bridging O atom between the two terminal phosphate groups is substituted by the imido function. Under mild conditions imides do not have acidic properties and thus the imide nitrogen should be protonated. However, an analysis of protein structures containing AMPPNP reveals that the imide group is deprotonated in certain complexes if the negative charges of the phosphate moieties in AMPPNP are in part neutralized by coordinating divalent metals or a guanidinium group of an arginine

  8. Fragger: a protein fragment picker for structural queries.

    Science.gov (United States)

    Berenger, Francois; Simoncini, David; Voet, Arnout; Shrestha, Rojan; Zhang, Kam Y J

    2017-01-01

    Protein modeling and design activities often require querying the Protein Data Bank (PDB) with a structural fragment, possibly containing gaps. For some applications, it is preferable to work on a specific subset of the PDB or with unpublished structures. These requirements, along with specific user needs, motivated the creation of a new software to manage and query 3D protein fragments. Fragger is a protein fragment picker that allows protein fragment databases to be created and queried. All fragment lengths are supported and any set of PDB files can be used to create a database. Fragger can efficiently search a fragment database with a query fragment and a distance threshold. Matching fragments are ranked by distance to the query. The query fragment can have structural gaps and the allowed amino acid sequences matching a query can be constrained via a regular expression of one-letter amino acid codes. Fragger also incorporates a tool to compute the backbone RMSD of one versus many fragments in high throughput. Fragger should be useful for protein design, loop grafting and related structural bioinformatics tasks.

  9. Dengue Virus Non-structural Protein 1 Modulates Infectious Particle Production via Interaction with the Structural Proteins.

    Directory of Open Access Journals (Sweden)

    Pietro Scaturro

    Full Text Available Non-structural protein 1 (NS1 is one of the most enigmatic proteins of the Dengue virus (DENV, playing distinct functions in immune evasion, pathogenesis and viral replication. The recently reported crystal structure of DENV NS1 revealed its peculiar three-dimensional fold; however, detailed information on NS1 function at different steps of the viral replication cycle is still missing. By using the recently reported crystal structure, as well as amino acid sequence conservation, as a guide for a comprehensive site-directed mutagenesis study, we discovered that in addition to being essential for RNA replication, DENV NS1 is also critically required for the production of infectious virus particles. Taking advantage of a trans-complementation approach based on fully functional epitope-tagged NS1 variants, we identified previously unreported interactions between NS1 and the structural proteins Envelope (E and precursor Membrane (prM. Interestingly, coimmunoprecipitation revealed an additional association with capsid, arguing that NS1 interacts via the structural glycoproteins with DENV particles. Results obtained with mutations residing either in the NS1 Wing domain or in the β-ladder domain suggest that NS1 might have two distinct functions in the assembly of DENV particles. By using a trans-complementation approach with a C-terminally KDEL-tagged ER-resident NS1, we demonstrate that the secretion of NS1 is dispensable for both RNA replication and infectious particle production. In conclusion, our results provide an extensive genetic map of NS1 determinants essential for viral RNA replication and identify a novel role of NS1 in virion production that is mediated via interaction with the structural proteins. These studies extend the list of NS1 functions and argue for a central role in coordinating replication and assembly/release of infectious DENV particles.

  10. In vitro versus in vivo protein digestibility techniques for calculating PDCAAS (protein digestibility-corrected amino acid score) applied to chickpea fractions.

    Science.gov (United States)

    Tavano, Olga Luisa; Neves, Valdir Augusto; da Silva Júnior, Sinézio Inácio

    2016-11-01

    Seven different in vitro methods to determine the protein digestibility for chickpea proteins were considered and also the application of these methodologies for calculating PDCAAS (protein digestibility-corrected amino acid score), seeking their correlations with the in vivo methodology. In vitro digestibility of raw and heated samples were determined using pepsin-pancreatin hydrolysis, considering soluble nitrogen via Kjeldahl (ppKJ) and hydrolysed peptide linkages using trinitrobenzenesulfonic acid and o-phthaldialdehyde. In vitro digestibility was also determined using trypsin, chymotrypsin and peptidase (3-Enz) or trypsin, chymotrypsin, peptidase and pronase solution (4-Enz). None of the correlations between in vitro and in vivo digestibilities were significant (at p<0.0500), but, strong correlations were observed between PDCAAS calculated by in vitro and in vivo results. PDCAAS-ppKJ, PDCAAS-3-Enz and PDCAAS-4-Enz presented the highest correlations with in vivo method, r=0.9316, 0.9442 and 0.9649 (p<0.0500), respectively. The use of in vitro methods for calculating PDCAAS may be promising and deserves more discussions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Electronic structure of SnS deduced from photoelectron spectra and band-structure calculations

    NARCIS (Netherlands)

    Ettema, A.R.H.F.; Groot, R.A. de; Haas, C.; Turner, T.S.

    1992-01-01

    SnS is a layer compound with a phase transition from a high-temperature β phase to a low-temperature α phase with a lower symmetry. Ab initio band-structure calculations are presented for both phases. The calculations show that the charge distributions in the two phases are very similar. However,

  12. Prediction of protein-protein interactions in dengue virus coat proteins guided by low resolution cryoEM structures

    Directory of Open Access Journals (Sweden)

    Srinivasan Narayanaswamy

    2010-06-01

    Full Text Available Abstract Background Dengue virus along with the other members of the flaviviridae family has reemerged as deadly human pathogens. Understanding the mechanistic details of these infections can be highly rewarding in developing effective antivirals. During maturation of the virus inside the host cell, the coat proteins E and M undergo conformational changes, altering the morphology of the viral coat. However, due to low resolution nature of the available 3-D structures of viral assemblies, the atomic details of these changes are still elusive. Results In the present analysis, starting from Cα positions of low resolution cryo electron microscopic structures the residue level details of protein-protein interaction interfaces of dengue virus coat proteins have been predicted. By comparing the preexisting structures of virus in different phases of life cycle, the changes taking place in these predicted protein-protein interaction interfaces were followed as a function of maturation process of the virus. Besides changing the current notion about the presence of only homodimers in the mature viral coat, the present analysis indicated presence of a proline-rich motif at the protein-protein interaction interface of the coat protein. Investigating the conservation status of these seemingly functionally crucial residues across other members of flaviviridae family enabled dissecting common mechanisms used for infections by these viruses. Conclusions Thus, using computational approach the present analysis has provided better insights into the preexisting low resolution structures of virus assemblies, the findings of which can be made use of in designing effective antivirals against these deadly human pathogens.

  13. De novo protein structure determination using sparse NMR data

    International Nuclear Information System (INIS)

    Bowers, Peter M.; Strauss, Charlie E.M.; Baker, David

    2000-01-01

    We describe a method for generating moderate to high-resolution protein structures using limited NMR data combined with the ab initio protein structure prediction method Rosetta. Peptide fragments are selected from proteins of known structure based on sequence similarity and consistency with chemical shift and NOE data. Models are built from these fragments by minimizing an energy function that favors hydrophobic burial, strand pairing, and satisfaction of NOE constraints. Models generated using this procedure with ∼1 NOE constraint per residue are in some cases closer to the corresponding X-ray structures than the published NMR solution structures. The method requires only the sparse constraints available during initial stages of NMR structure determination, and thus holds promise for increasing the speed with which protein solution structures can be determined

  14. Calculation of forces arising from impacting projectiles upon yielding structures

    International Nuclear Information System (INIS)

    Drittler, K.; Gruner, P.; Krivy, J.

    1977-01-01

    Calculations concerning the impact of airplanes upon nuclear power plant buildings usually imply that the building [QUOTE]acts' as a rigid target. This assumption is justified for considerations concerning the structural integrity of the building being hit. However, for investigating induced vibrations of components within the structure, this approach might-in general-be too conservative. It is expected, that yielding of the structure during impact reduces the peak values of the loads and changes the temporal behaviour of the load function which is obtained for a rigid target. To calculate the changes of the load function which are due to deformations of the structure, Riera's method is extended for the case of a yielding target. The calculations are performed with a one-dimensional model for the projectile. The presented model calculations seem to verify that the motion of the target does not have much influence on the impact force for projectiles similar to the model projectile, provided the displacement of the yielding target is small in comparison with the path covered by the free-flying projectile during a time which is equivalent to the total time of impact. (Auth.)

  15. Structural adaptations of proteins to different biological membranes

    Science.gov (United States)

    Pogozheva, Irina D.; Tristram-Nagle, Stephanie; Mosberg, Henry I.; Lomize, Andrei L.

    2013-01-01

    To gain insight into adaptations of proteins to their membranes, intrinsic hydrophobic thicknesses, distributions of different chemical groups and profiles of hydrogen-bonding capacities (α and β) and the dipolarity/polarizability parameter (π*) were calculated for lipid-facing surfaces of 460 integral α-helical, β-barrel and peripheral proteins from eight types of biomembranes. For comparison, polarity profiles were also calculated for ten artificial lipid bilayers that have been previously studied by neutron and X-ray scattering. Estimated hydrophobic thicknesses are 30-31 Å for proteins from endoplasmic reticulum, thylakoid, and various bacterial plasma membranes, but differ for proteins from outer bacterial, inner mitochondrial and eukaryotic plasma membranes (23.9, 28.6 and 33.5 Å, respectively). Protein and lipid polarity parameters abruptly change in the lipid carbonyl zone that matches the calculated hydrophobic boundaries. Maxima of positively charged protein groups correspond to the location of lipid phosphates at 20-22 Å distances from the membrane center. Locations of Tyr atoms coincide with hydrophobic boundaries, while distributions maxima of Trp rings are shifted by 3-4 Å toward the membrane center. Distributions of Trp atoms indicate the presence of two 5-8 Å-wide midpolar regions with intermediate π* values within the hydrocarbon core, whose size and symmetry depend on the lipid composition of membrane leaflets. Midpolar regions are especially asymmetric in outer bacterial membranes and cell membranes of mesophilic but not hyperthermophilic archaebacteria, indicating the larger width of the central nonpolar region in the later case. In artificial lipid bilayers, midpolar regions are observed up to the level of acyl chain double bonds. PMID:23811361

  16. Lattice QCD Calculation of Nucleon Structure

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Keh-Fei [University of Kentucky, Lexington, KY (United States). Dept. of Physics and Astronomy; Draper, Terrence [University of Kentucky, Lexington, KY (United States). Dept. of Physics and Astronomy

    2016-08-30

    It is emphasized in the 2015 NSAC Long Range Plan that "understanding the structure of hadrons in terms of QCD's quarks and gluons is one of the central goals of modern nuclear physics." Over the last three decades, lattice QCD has developed into a powerful tool for ab initio calculations of strong-interaction physics. Up until now, it is the only theoretical approach to solving QCD with controlled statistical and systematic errors. Since 1985, we have proposed and carried out first-principles calculations of nucleon structure and hadron spectroscopy using lattice QCD which entails both algorithmic development and large-scale computer simulation. We started out by calculating the nucleon form factors -- electromagnetic, axial-vector, πNN, and scalar form factors, the quark spin contribution to the proton spin, the strangeness magnetic moment, the quark orbital angular momentum, the quark momentum fraction, and the quark and glue decomposition of the proton momentum and angular momentum. The first round of calculations were done with Wilson fermions in the `quenched' approximation where the dynamical effects of the quarks in the sea are not taken into account in the Monte Carlo simulation to generate the background gauge configurations. Beginning in 2000, we have started implementing the overlap fermion formulation into the spectroscopy and structure calculations. This is mainly because the overlap fermion honors chiral symmetry as in the continuum. It is going to be more and more important to take the symmetry into account as the simulations move closer to the physical point where the u and d quark masses are as light as a few MeV only. We began with lattices which have quark masses in the sea corresponding to a pion mass at ~ 300 MeV and obtained the strange form factors, charm and strange quark masses, the charmonium spectrum and the Ds meson decay constant fDs, the strangeness and charmness, the meson mass

  17. Structural studies of human glioma pathogenesis-related protein 1

    Energy Technology Data Exchange (ETDEWEB)

    Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu [College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States); Koski, Raymond A.; Bonafé, Nathalie [L2 Diagnostics LLC, 300 George Street, New Haven, CT 06511 (United States); College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States)

    2011-10-01

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn{sup 2+} complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn{sup 2+} similarly to snake-venom CRISPs, which are involved in Zn{sup 2+}-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

  18. Constraint Logic Programming approach to protein structure prediction

    Directory of Open Access Journals (Sweden)

    Fogolari Federico

    2004-11-01

    Full Text Available Abstract Background The protein structure prediction problem is one of the most challenging problems in biological sciences. Many approaches have been proposed using database information and/or simplified protein models. The protein structure prediction problem can be cast in the form of an optimization problem. Notwithstanding its importance, the problem has very seldom been tackled by Constraint Logic Programming, a declarative programming paradigm suitable for solving combinatorial optimization problems. Results Constraint Logic Programming techniques have been applied to the protein structure prediction problem on the face-centered cube lattice model. Molecular dynamics techniques, endowed with the notion of constraint, have been also exploited. Even using a very simplified model, Constraint Logic Programming on the face-centered cube lattice model allowed us to obtain acceptable results for a few small proteins. As a test implementation their (known secondary structure and the presence of disulfide bridges are used as constraints. Simplified structures obtained in this way have been converted to all atom models with plausible structure. Results have been compared with a similar approach using a well-established technique as molecular dynamics. Conclusions The results obtained on small proteins show that Constraint Logic Programming techniques can be employed for studying protein simplified models, which can be converted into realistic all atom models. The advantage of Constraint Logic Programming over other, much more explored, methodologies, resides in the rapid software prototyping, in the easy way of encoding heuristics, and in exploiting all the advances made in this research area, e.g. in constraint propagation and its use for pruning the huge search space.

  19. Constraint Logic Programming approach to protein structure prediction.

    Science.gov (United States)

    Dal Palù, Alessandro; Dovier, Agostino; Fogolari, Federico

    2004-11-30

    The protein structure prediction problem is one of the most challenging problems in biological sciences. Many approaches have been proposed using database information and/or simplified protein models. The protein structure prediction problem can be cast in the form of an optimization problem. Notwithstanding its importance, the problem has very seldom been tackled by Constraint Logic Programming, a declarative programming paradigm suitable for solving combinatorial optimization problems. Constraint Logic Programming techniques have been applied to the protein structure prediction problem on the face-centered cube lattice model. Molecular dynamics techniques, endowed with the notion of constraint, have been also exploited. Even using a very simplified model, Constraint Logic Programming on the face-centered cube lattice model allowed us to obtain acceptable results for a few small proteins. As a test implementation their (known) secondary structure and the presence of disulfide bridges are used as constraints. Simplified structures obtained in this way have been converted to all atom models with plausible structure. Results have been compared with a similar approach using a well-established technique as molecular dynamics. The results obtained on small proteins show that Constraint Logic Programming techniques can be employed for studying protein simplified models, which can be converted into realistic all atom models. The advantage of Constraint Logic Programming over other, much more explored, methodologies, resides in the rapid software prototyping, in the easy way of encoding heuristics, and in exploiting all the advances made in this research area, e.g. in constraint propagation and its use for pruning the huge search space.

  20. PSPP: a protein structure prediction pipeline for computing clusters.

    Directory of Open Access Journals (Sweden)

    Michael S Lee

    2009-07-01

    Full Text Available Protein structures are critical for understanding the mechanisms of biological systems and, subsequently, for drug and vaccine design. Unfortunately, protein sequence data exceed structural data by a factor of more than 200 to 1. This gap can be partially filled by using computational protein structure prediction. While structure prediction Web servers are a notable option, they often restrict the number of sequence queries and/or provide a limited set of prediction methodologies. Therefore, we present a standalone protein structure prediction software package suitable for high-throughput structural genomic applications that performs all three classes of prediction methodologies: comparative modeling, fold recognition, and ab initio. This software can be deployed on a user's own high-performance computing cluster.The pipeline consists of a Perl core that integrates more than 20 individual software packages and databases, most of which are freely available from other research laboratories. The query protein sequences are first divided into domains either by domain boundary recognition or Bayesian statistics. The structures of the individual domains are then predicted using template-based modeling or ab initio modeling. The predicted models are scored with a statistical potential and an all-atom force field. The top-scoring ab initio models are annotated by structural comparison against the Structural Classification of Proteins (SCOP fold database. Furthermore, secondary structure, solvent accessibility, transmembrane helices, and structural disorder are predicted. The results are generated in text, tab-delimited, and hypertext markup language (HTML formats. So far, the pipeline has been used to study viral and bacterial proteomes.The standalone pipeline that we introduce here, unlike protein structure prediction Web servers, allows users to devote their own computing assets to process a potentially unlimited number of queries as well as perform

  1. Tertiary alphabet for the observable protein structural universe.

    Science.gov (United States)

    Mackenzie, Craig O; Zhou, Jianfu; Grigoryan, Gevorg

    2016-11-22

    Here, we systematically decompose the known protein structural universe into its basic elements, which we dub tertiary structural motifs (TERMs). A TERM is a compact backbone fragment that captures the secondary, tertiary, and quaternary environments around a given residue, comprising one or more disjoint segments (three on average). We seek the set of universal TERMs that capture all structure in the Protein Data Bank (PDB), finding remarkable degeneracy. Only ∼600 TERMs are sufficient to describe 50% of the PDB at sub-Angstrom resolution. However, more rare geometries also exist, and the overall structural coverage grows logarithmically with the number of TERMs. We go on to show that universal TERMs provide an effective mapping between sequence and structure. We demonstrate that TERM-based statistics alone are sufficient to recapitulate close-to-native sequences given either NMR or X-ray backbones. Furthermore, sequence variability predicted from TERM data agrees closely with evolutionary variation. Finally, locations of TERMs in protein chains can be predicted from sequence alone based on sequence signatures emergent from TERM instances in the PDB. For multisegment motifs, this method identifies spatially adjacent fragments that are not contiguous in sequence-a major bottleneck in structure prediction. Although all TERMs recur in diverse proteins, some appear specialized for certain functions, such as interface formation, metal coordination, or even water binding. Structural biology has benefited greatly from previously observed degeneracies in structure. The decomposition of the known structural universe into a finite set of compact TERMs offers exciting opportunities toward better understanding, design, and prediction of protein structure.

  2. Annotating the protein-RNA interaction sites in proteins using evolutionary information and protein backbone structure.

    Science.gov (United States)

    Li, Tao; Li, Qian-Zhong

    2012-11-07

    RNA-protein interactions play important roles in various biological processes. The precise detection of RNA-protein interaction sites is very important for understanding essential biological processes and annotating the function of the proteins. In this study, based on various features from amino acid sequence and structure, including evolutionary information, solvent accessible surface area and torsion angles (φ, ψ) in the backbone structure of the polypeptide chain, a computational method for predicting RNA-binding sites in proteins is proposed. When the method is applied to predict RNA-binding sites in three datasets: RBP86 containing 86 protein chains, RBP107 containing 107 proteins chains and RBP109 containing 109 proteins chains, better sensitivities and specificities are obtained compared to previously published methods in five-fold cross-validation tests. In order to make further examination for the efficiency of our method, the RBP107 dataset is used as training set, RBP86 and RBP109 datasets are used as the independent test sets. In addition, as examples of our prediction, RNA-binding sites in a few proteins are presented. The annotated results are consistent with the PDB annotation. These results show that our method is useful for annotating RNA binding sites of novel proteins.

  3. Guiding exploration in conformational feature space with Lipschitz underestimation for ab-initio protein structure prediction.

    Science.gov (United States)

    Hao, Xiaohu; Zhang, Guijun; Zhou, Xiaogen

    2018-04-01

    Computing conformations which are essential to associate structural and functional information with gene sequences, is challenging due to the high dimensionality and rugged energy surface of the protein conformational space. Consequently, the dimension of the protein conformational space should be reduced to a proper level, and an effective exploring algorithm should be proposed. In this paper, a plug-in method for guiding exploration in conformational feature space with Lipschitz underestimation (LUE) for ab-initio protein structure prediction is proposed. The conformational space is converted into ultrafast shape recognition (USR) feature space firstly. Based on the USR feature space, the conformational space can be further converted into Underestimation space according to Lipschitz estimation theory for guiding exploration. As a consequence of the use of underestimation model, the tight lower bound estimate information can be used for exploration guidance, the invalid sampling areas can be eliminated in advance, and the number of energy function evaluations can be reduced. The proposed method provides a novel technique to solve the exploring problem of protein conformational space. LUE is applied to differential evolution (DE) algorithm, and metropolis Monte Carlo(MMC) algorithm which is available in the Rosetta; When LUE is applied to DE and MMC, it will be screened by the underestimation method prior to energy calculation and selection. Further, LUE is compared with DE and MMC by testing on 15 small-to-medium structurally diverse proteins. Test results show that near-native protein structures with higher accuracy can be obtained more rapidly and efficiently with the use of LUE. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Improved protein structure reconstruction using secondary structures, contacts at higher distance thresholds, and non-contacts.

    Science.gov (United States)

    Adhikari, Badri; Cheng, Jianlin

    2017-08-29

    Residue-residue contacts are key features for accurate de novo protein structure prediction. For the optimal utilization of these predicted contacts in folding proteins accurately, it is important to study the challenges of reconstructing protein structures using true contacts. Because contact-guided protein modeling approach is valuable for predicting the folds of proteins that do not have structural templates, it is necessary for reconstruction studies to focus on hard-to-predict protein structures. Using a data set consisting of 496 structural domains released in recent CASP experiments and a dataset of 150 representative protein structures, in this work, we discuss three techniques to improve the reconstruction accuracy using true contacts - adding secondary structures, increasing contact distance thresholds, and adding non-contacts. We find that reconstruction using secondary structures and contacts can deliver accuracy higher than using full contact maps. Similarly, we demonstrate that non-contacts can improve reconstruction accuracy not only when the used non-contacts are true but also when they are predicted. On the dataset consisting of 150 proteins, we find that by simply using low ranked predicted contacts as non-contacts and adding them as additional restraints, can increase the reconstruction accuracy by 5% when the reconstructed models are evaluated using TM-score. Our findings suggest that secondary structures are invaluable companions of contacts for accurate reconstruction. Confirming some earlier findings, we also find that larger distance thresholds are useful for folding many protein structures which cannot be folded using the standard definition of contacts. Our findings also suggest that for more accurate reconstruction using predicted contacts it is useful to predict contacts at higher distance thresholds (beyond 8 Å) and predict non-contacts.

  5. Fibrous Protein Structures: Hierarchy, History and Heroes.

    Science.gov (United States)

    Squire, John M; Parry, David A D

    2017-01-01

    During the 1930s and 1940s the technique of X-ray diffraction was applied widely by William Astbury and his colleagues to a number of naturally-occurring fibrous materials. On the basis of the diffraction patterns obtained, he observed that the structure of each of the fibres was dominated by one of a small number of different types of molecular conformation. One group of fibres, known as the k-m-e-f group of proteins (keratin - myosin - epidermin - fibrinogen), gave rise to diffraction characteristics that became known as the α-pattern. Others, such as those from a number of silks, gave rise to a different pattern - the β-pattern, while connective tissues yielded a third unique set of diffraction characteristics. At the time of Astbury's work, the structures of these materials were unknown, though the spacings of the main X-ray reflections gave an idea of the axial repeats and the lateral packing distances. In a breakthrough in the early 1950s, the basic structures of all of these fibrous proteins were determined. It was found that the long protein chains, composed of strings of amino acids, could be folded up in a systematic manner to generate a limited number of structures that were consistent with the X-ray data. The most important of these were known as the α-helix, the β-sheet, and the collagen triple helix. These studies provided information about the basic building blocks of all proteins, both fibrous and globular. They did not, however, provide detailed information about how these molecules packed together in three-dimensions to generate the fibres found in vivo. A number of possible packing arrangements were subsequently deduced from the X-ray diffraction and other data, but it is only in the last few years, through the continued improvements of electron microscopy, that the packing details within some fibrous proteins can now be seen directly. Here we outline briefly some of the milestones in fibrous protein structure determination, the role of the

  6. MetaGO: Predicting Gene Ontology of Non-homologous Proteins Through Low-Resolution Protein Structure Prediction and Protein-Protein Network Mapping.

    Science.gov (United States)

    Zhang, Chengxin; Zheng, Wei; Freddolino, Peter L; Zhang, Yang

    2018-03-10

    Homology-based transferal remains the major approach to computational protein function annotations, but it becomes increasingly unreliable when the sequence identity between query and template decreases below 30%. We propose a novel pipeline, MetaGO, to deduce Gene Ontology attributes of proteins by combining sequence homology-based annotation with low-resolution structure prediction and comparison, and partner's homology-based protein-protein network mapping. The pipeline was tested on a large-scale set of 1000 non-redundant proteins from the CAFA3 experiment. Under the stringent benchmark conditions where templates with >30% sequence identity to the query are excluded, MetaGO achieves average F-measures of 0.487, 0.408, and 0.598, for Molecular Function, Biological Process, and Cellular Component, respectively, which are significantly higher than those achieved by other state-of-the-art function annotations methods. Detailed data analysis shows that the major advantage of the MetaGO lies in the new functional homolog detections from partner's homology-based network mapping and structure-based local and global structure alignments, the confidence scores of which can be optimally combined through logistic regression. These data demonstrate the power of using a hybrid model incorporating protein structure and interaction networks to deduce new functional insights beyond traditional sequence homology-based referrals, especially for proteins that lack homologous function templates. The MetaGO pipeline is available at http://zhanglab.ccmb.med.umich.edu/MetaGO/. Copyright © 2018. Published by Elsevier Ltd.

  7. Continuum Electrostatics Approaches to Calculating pKas and Ems in Proteins.

    Science.gov (United States)

    Gunner, M R; Baker, N A

    2016-01-01

    Proteins change their charge state through protonation and redox reactions as well as through binding charged ligands. The free energy of these reactions is dominated by solvation and electrostatic energies and modulated by protein conformational relaxation in response to the ionization state changes. Although computational methods for calculating these interactions can provide very powerful tools for predicting protein charge states, they include several critical approximations of which users should be aware. This chapter discusses the strengths, weaknesses, and approximations of popular computational methods for predicting charge states and understanding the underlying electrostatic interactions. The goal of this chapter is to inform users about applications and potential caveats of these methods as well as outline directions for future theoretical and computational research. © 2016 Elsevier Inc. All rights reserved.

  8. Hybrid functional calculation of electronic and phonon structure of BaSnO3

    International Nuclear Information System (INIS)

    Kim, Bog G.; Jo, J.Y.; Cheong, S.W.

    2013-01-01

    Barium stannate, BaSnO 3 (BSO), with a cubic perovskite structure, has been highlighted as a promising host material for the next generation transparent oxide electrodes. This study examined theoretically the electronic structure and phonon structure of BSO using hybrid density functional theory based on the HSE06 functional. The electronic structure results of BSO were corrected by extending the phonon calculations based on the hybrid density functional. The fundamental thermal properties were also predicted based on a hybrid functional calculation. Overall, a detailed understanding of the electronic structure, phonon modes and phonon dispersion of BSO will provide a theoretical starting-point for engineering applications of this material. - Graphical Abstract: (a) Crystal structure of BaSnO 3 . The center ball is Ba and small (red) ball on edge is oxygen and SnO 6 octahedrons are plotted as polyhedron. (b) Electronic band structure along the high symmetry point in the Brillouin zone using the HSE06 hybrid functional. (c) The phonon dispersion curve calculated using the HSE06 hybrid functional (d) Zone center lowest energy F 1u phonon mode. Highlights: ► We report the full hybrid functional calculation of not only the electronic structure but also the phonon structure for BaSnO 3 . ► The band gap calculation of HSE06 revealed an indirect gap with 2.48 eV. ► The effective mass at the conduction band minimum and valence band maximum was calculated. ► In addition, the phonon structure of BSO was calculated using the HSE06 functional. ► Finally, the heat capacity was calculated and compared with the recent experimental result.

  9. Breit–Pauli atomic structure calculations for Fe XI

    International Nuclear Information System (INIS)

    Aggarwal, Sunny; Singh, Jagjit; Mohan, Man

    2013-01-01

    Energy levels, oscillator strengths, and transition probabilities are calculated for the lowest-lying 165 energy levels of Fe XI using configuration-interaction wavefunctions. The calculations include all the major correlation effects. Relativistic effects are included in the Breit–Pauli approximation by adding mass-correction, Darwin, and spin–orbit interaction terms to the non-relativistic Hamiltonian. For comparison with the calculated ab initio energy levels, we have also calculated the energy levels by using the fully relativistic multiconfiguration Dirac–Fock method. The calculated results are in close agreement with the National Institute of Standards and Technology compilation and other available results. New results are predicted for many of the levels belonging to the 3s3p 4 3d and 3s3p 3 3d 2 configurations, which are very important in astrophysics, relevant, for example, to the recent observations by the Hinode spacecraft. We expect that our extensive calculations will be useful to experimentalists in identifying the fine structure levels in their future work

  10. First-principle calculations of the structural, electronic ...

    Indian Academy of Sciences (India)

    First-principle calculations were performed to study the structural, electronic, thermodynamic and thermal properties of ... functional theory (DFT) combined with the quasi-harmonic .... is consistent with Vegard's law which assumes that the lat- tice constant varies .... reflects a charge-transfer effect which is due to the different.

  11. Protein and Peptide Gas-phase Structure Investigation Using Collision Cross Section Measurements and Hydrogen Deuterium Exchange

    Science.gov (United States)

    Khakinejad, Mahdiar

    Protein and peptide gas-phase structure analysis provides the opportunity to study these species outside of their explicit environment where the interaction network with surrounding molecules makes the analysis difficult [1]. Although gas-phase structure analysis offers a unique opportunity to study the intrinsic behavior of these biomolecules [2-4], proteins and peptides exhibit very low vapor pressures [2]. Peptide and protein ions can be rendered in the gas-phase using electrospray ionization (ESI) [5]. There is a growing body of literature that shows proteins and peptides can maintain solution structures during the process of ESI and these structures can persist for a few hundred milliseconds [6-9]. Techniques for monitoring gas-phase protein and peptide ion structures are categorized as physical probes and chemical probes. Collision cross section (CCS) measurement, being a physical probe, is a powerful method to investigate gas-phase structure size [3, 7, 10-15]; however, CCS values alone do not establish a one to one relation with structure(i.e., the CCS value is an orientationally averaged value [15-18]. Here we propose the utility of gas-phase hydrogen deuterium exchange (HDX) as a second criterion of structure elucidation. The proposed approach incudes extensive MD simulations to sample biomolecular ion conformation space with the production of numerous, random in-silico structures. Subsequently a CCS can be calculated for these structures and theoretical CCS values are compared with experimental values to produce a pool of candidate structures. Utilizing a chemical reaction model based on the gas-phase HDX mechanism, the HDX kinetics behavior of these candidate structures are predicted and compared to experimental results to nominate the best in-silico structures which match (chemically and physically) with experimental observations. For the predictive approach to succeed, an extensive technique and method development is essential. To combine CCS

  12. Structural study of surfactant-dependent interaction with protein

    Energy Technology Data Exchange (ETDEWEB)

    Mehan, Sumit; Aswal, Vinod K., E-mail: vkaswal@barc.gov.in [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Kohlbrecher, Joachim [Laboratory for Neutron Scattering, Paul Scherrer Institut, CH-5232 PSI Villigen (Switzerland)

    2015-06-24

    Small-angle neutron scattering (SANS) has been used to study the complex structure of anionic BSA protein with three different (cationic DTAB, anionic SDS and non-ionic C12E10) surfactants. These systems form very different surfactant-dependent complexes. We show that the structure of protein-surfactant complex is initiated by the site-specific electrostatic interaction between the components, followed by the hydrophobic interaction at high surfactant concentrations. It is also found that hydrophobic interaction is preferred over the electrostatic interaction in deciding the resultant structure of protein-surfactant complexes.

  13. Structural Elements Regulating AAA+ Protein Quality Control Machines.

    Science.gov (United States)

    Chang, Chiung-Wen; Lee, Sukyeong; Tsai, Francis T F

    2017-01-01

    Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins. In this mini-review, we will discuss structural elements present in AAA+ proteins involved in protein quality control, drawing similarities to their known role in substrate interaction by AAA+ proteins involved in DNA translocation. Elements to be discussed include the pore loop-1, the Inter-Subunit Signaling (ISS) motif, and the Pre-Sensor I insert (PS-I) motif. Lastly, we will summarize our current understanding on the inter-relationship of those structural elements and propose a model how ATP binding and hydrolysis might be coupled to polypeptide translocation in protein quality control machines.

  14. The structure and assembly of surface layer proteins : a combined approach of in silico and experimental methods

    International Nuclear Information System (INIS)

    Horejs, C.

    2011-01-01

    Self-assembly of matter is one of nature's most sophisticated strategies to organize molecules on a large scale and to create order from disorder. Surface (S-)layer proteins self-assemble in a highly reproducible and robust fashion in order to form crystalline layers that completely cover and protect prokaryotic cells. Long conserved during evolution, S-layers constitute a unique model system to study the molecular mechanisms of functional self-assembly, while additionally, they provide a basic matrix for the specific construction of ordered nanostructures. Due to their intrinsic capabilities to self-assemble into two-dimensional crystals, the elucidation of the three-dimensional structure of single S-layer proteins demands an approach beyond conventional structure determination methods. In this work, computer simulations were combined with experimental techniques in order to study the structure and intra- and intermolecular potentials guiding the proteins to self-assemble into lattices with different symmetries. Molecular dynamics, Monte Carlo methods, small-angle X-ray scattering involving a new theoretical description, and AFM-based single-molecule force spectroscopy yield new insights into the three-dimensional structure of S-layer proteins, the location, type and distribution of amino acids in S-layer lattices, the molecular mechanisms behind the self-assembly process, the mechanical stability and adaptive structural conformations that S-layer proteins are able to establish. In silico studies - embedded in an adequate experimental and theoretical scaffold - offer the possibility to calculate structural and thermodynamic features of proteins, while this work demonstrates the growing impact of such theoretical techniques in the fascinating field of biophysics at the nano-scale. (author) [de

  15. Structure of synaptophysin: a hexameric MARVEL-domain channel protein.

    Science.gov (United States)

    Arthur, Christopher P; Stowell, Michael H B

    2007-06-01

    Synaptophysin I (SypI) is an archetypal member of the MARVEL-domain family of integral membrane proteins and one of the first synaptic vesicle proteins to be identified and cloned. Most all MARVEL-domain proteins are involved in membrane apposition and vesicle-trafficking events, but their precise role in these processes is unclear. We have purified mammalian SypI and determined its three-dimensional (3D) structure by using electron microscopy and single-particle 3D reconstruction. The hexameric structure resembles an open basket with a large pore and tenuous interactions within the cytosolic domain. The structure suggests a model for Synaptophysin's role in fusion and recycling that is regulated by known interactions with the SNARE machinery. This 3D structure of a MARVEL-domain protein provides a structural foundation for understanding the role of these important proteins in a variety of biological processes.

  16. The structure of pyogenecin immunity protein, a novel bacteriocin-like immunity protein from streptococcus pyogenes.

    Energy Technology Data Exchange (ETDEWEB)

    Chang, C.; Coggill, P.; Bateman, A.; Finn, R.; Cymborowski, M.; Otwinowski, Z.; Minor, W.; Volkart, L.; Joachimiak, A.; Wellcome Trust Sanger Inst.; Univ. of Virginia; UT Southwestern Medical Center

    2009-12-17

    Many Gram-positive lactic acid bacteria (LAB) produce anti-bacterial peptides and small proteins called bacteriocins, which enable them to compete against other bacteria in the environment. These peptides fall structurally into three different classes, I, II, III, with class IIa being pediocin-like single entities and class IIb being two-peptide bacteriocins. Self-protective cognate immunity proteins are usually co-transcribed with these toxins. Several examples of cognates for IIa have already been solved structurally. Streptococcus pyogenes, closely related to LAB, is one of the most common human pathogens, so knowledge of how it competes against other LAB species is likely to prove invaluable. We have solved the crystal structure of the gene-product of locus Spy-2152 from S. pyogenes, (PDB: 2fu2), and found it to comprise an anti-parallel four-helix bundle that is structurally similar to other bacteriocin immunity proteins. Sequence analyses indicate this protein to be a possible immunity protein protective against class IIa or IIb bacteriocins. However, given that S. pyogenes appears to lack any IIa pediocin-like proteins but does possess class IIb bacteriocins, we suggest this protein confers immunity to IIb-like peptides. Combined structural, genomic and proteomic analyses have allowed the identification and in silico characterization of a new putative immunity protein from S. pyogenes, possibly the first structure of an immunity protein protective against potential class IIb two-peptide bacteriocins. We have named the two pairs of putative bacteriocins found in S. pyogenes pyogenecin 1, 2, 3 and 4.

  17. The contact activation proteins: a structure/function overview

    NARCIS (Netherlands)

    Meijers, J. C.; McMullen, B. A.; Bouma, B. N.

    1992-01-01

    In recent years, extensive knowledge has been obtained on the structure/function relationships of blood coagulation proteins. In this overview, we present recent developments on the structure/function relationships of the contact activation proteins: factor XII, high molecular weight kininogen,

  18. Structure Based Thermostability Prediction Models for Protein Single Point Mutations with Machine Learning Tools.

    Directory of Open Access Journals (Sweden)

    Lei Jia

    Full Text Available Thermostability issue of protein point mutations is a common occurrence in protein engineering. An application which predicts the thermostability of mutants can be helpful for guiding decision making process in protein design via mutagenesis. An in silico point mutation scanning method is frequently used to find "hot spots" in proteins for focused mutagenesis. ProTherm (http://gibk26.bio.kyutech.ac.jp/jouhou/Protherm/protherm.html is a public database that consists of thousands of protein mutants' experimentally measured thermostability. Two data sets based on two differently measured thermostability properties of protein single point mutations, namely the unfolding free energy change (ddG and melting temperature change (dTm were obtained from this database. Folding free energy change calculation from Rosetta, structural information of the point mutations as well as amino acid physical properties were obtained for building thermostability prediction models with informatics modeling tools. Five supervised machine learning methods (support vector machine, random forests, artificial neural network, naïve Bayes classifier, K nearest neighbor and partial least squares regression are used for building the prediction models. Binary and ternary classifications as well as regression models were built and evaluated. Data set redundancy and balancing, the reverse mutations technique, feature selection, and comparison to other published methods were discussed. Rosetta calculated folding free energy change ranked as the most influential features in all prediction models. Other descriptors also made significant contributions to increasing the accuracy of the prediction models.

  19. Blind Test of Physics-Based Prediction of Protein Structures

    Science.gov (United States)

    Shell, M. Scott; Ozkan, S. Banu; Voelz, Vincent; Wu, Guohong Albert; Dill, Ken A.

    2009-01-01

    We report here a multiprotein blind test of a computer method to predict native protein structures based solely on an all-atom physics-based force field. We use the AMBER 96 potential function with an implicit (GB/SA) model of solvation, combined with replica-exchange molecular-dynamics simulations. Coarse conformational sampling is performed using the zipping and assembly method (ZAM), an approach that is designed to mimic the putative physical routes of protein folding. ZAM was applied to the folding of six proteins, from 76 to 112 monomers in length, in CASP7, a community-wide blind test of protein structure prediction. Because these predictions have about the same level of accuracy as typical bioinformatics methods, and do not utilize information from databases of known native structures, this work opens up the possibility of predicting the structures of membrane proteins, synthetic peptides, or other foldable polymers, for which there is little prior knowledge of native structures. This approach may also be useful for predicting physical protein folding routes, non-native conformations, and other physical properties from amino acid sequences. PMID:19186130

  20. CASD-NMR 2: robust and accurate unsupervised analysis of raw NOESY spectra and protein structure determination with UNIO

    International Nuclear Information System (INIS)

    Guerry, Paul; Duong, Viet Dung; Herrmann, Torsten

    2015-01-01

    UNIO is a comprehensive software suite for protein NMR structure determination that enables full automation of all NMR data analysis steps involved—including signal identification in NMR spectra, sequence-specific backbone and side-chain resonance assignment, NOE assignment and structure calculation. Within the framework of the second round of the community-wide stringent blind NMR structure determination challenge (CASD-NMR 2), we participated in two categories of CASD-NMR 2, namely using either raw NMR spectra or unrefined NOE peak lists as input. A total of 15 resulting NMR structure bundles were submitted for 9 out of 10 blind protein targets. All submitted UNIO structures accurately coincided with the corresponding blind targets as documented by an average backbone root mean-square deviation to the reference proteins of only 1.2 Å. Also, the precision of the UNIO structure bundles was virtually identical to the ensemble of reference structures. By assessing the quality of all UNIO structures submitted to the two categories, we find throughout that only the UNIO–ATNOS/CANDID approach using raw NMR spectra consistently yielded structure bundles of high quality for direct deposition in the Protein Data Bank. In conclusion, the results obtained in CASD-NMR 2 are another vital proof for robust, accurate and unsupervised NMR data analysis by UNIO for real-world applications

  1. Implementation of a Parallel Protein Structure Alignment Service on Cloud

    Directory of Open Access Journals (Sweden)

    Che-Lun Hung

    2013-01-01

    Full Text Available Protein structure alignment has become an important strategy by which to identify evolutionary relationships between protein sequences. Several alignment tools are currently available for online comparison of protein structures. In this paper, we propose a parallel protein structure alignment service based on the Hadoop distribution framework. This service includes a protein structure alignment algorithm, a refinement algorithm, and a MapReduce programming model. The refinement algorithm refines the result of alignment. To process vast numbers of protein structures in parallel, the alignment and refinement algorithms are implemented using MapReduce. We analyzed and compared the structure alignments produced by different methods using a dataset randomly selected from the PDB database. The experimental results verify that the proposed algorithm refines the resulting alignments more accurately than existing algorithms. Meanwhile, the computational performance of the proposed service is proportional to the number of processors used in our cloud platform.

  2. Fast Atomic Charge Calculation for Implementation into a Polarizable Force Field and Application to an Ion Channel Protein

    Directory of Open Access Journals (Sweden)

    Raiker Witter

    2015-01-01

    Full Text Available Polarization of atoms plays a substantial role in molecular interactions. Class I and II force fields mostly calculate with fixed atomic charges which can cause inadequate descriptions for highly charged molecules, for example, ion channels or metalloproteins. Changes in charge distributions can be included into molecular mechanics calculations by various methods. Here, we present a very fast computational quantum mechanical method, the Bond Polarization Theory (BPT. Atomic charges are obtained via a charge calculation method that depend on the 3D structure of the system in a similar way as atomic charges of ab initio calculations. Different methods of population analysis and charge calculation methods and their dependence on the basis set were investigated. A refined parameterization yielded excellent correlation of R=0.9967. The method was implemented in the force field COSMOS-NMR and applied to the histidine-tryptophan-complex of the transmembrane domain of the M2 protein channel of influenza A virus. Our calculations show that moderate changes of side chain torsion angle χ1 and small variations of χ2 of Trp-41 are necessary to switch from the inactivated into the activated state; and a rough two-side jump model of His-37 is supported for proton gating in accordance with a flipping mechanism.

  3. PONDEROSA-C/S: client-server based software package for automated protein 3D structure determination.

    Science.gov (United States)

    Lee, Woonghee; Stark, Jaime L; Markley, John L

    2014-11-01

    Peak-picking Of Noe Data Enabled by Restriction Of Shift Assignments-Client Server (PONDEROSA-C/S) builds on the original PONDEROSA software (Lee et al. in Bioinformatics 27:1727-1728. doi: 10.1093/bioinformatics/btr200, 2011) and includes improved features for structure calculation and refinement. PONDEROSA-C/S consists of three programs: Ponderosa Server, Ponderosa Client, and Ponderosa Analyzer. PONDEROSA-C/S takes as input the protein sequence, a list of assigned chemical shifts, and nuclear Overhauser data sets ((13)C- and/or (15)N-NOESY). The output is a set of assigned NOEs and 3D structural models for the protein. Ponderosa Analyzer supports the visualization, validation, and refinement of the results from Ponderosa Server. These tools enable semi-automated NMR-based structure determination of proteins in a rapid and robust fashion. We present examples showing the use of PONDEROSA-C/S in solving structures of four proteins: two that enable comparison with the original PONDEROSA package, and two from the Critical Assessment of automated Structure Determination by NMR (Rosato et al. in Nat Methods 6:625-626. doi: 10.1038/nmeth0909-625 , 2009) competition. The software package can be downloaded freely in binary format from http://pine.nmrfam.wisc.edu/download_packages.html. Registered users of the National Magnetic Resonance Facility at Madison can submit jobs to the PONDEROSA-C/S server at http://ponderosa.nmrfam.wisc.edu, where instructions, tutorials, and instructions can be found. Structures are normally returned within 1-2 days.

  4. STRUCTURAL FEATURES OF PLANT CHITINASES AND CHITIN-BINDING PROTEINS

    NARCIS (Netherlands)

    BEINTEMA, JJ

    1994-01-01

    Structural features of plant chitinases and chitin-binding proteins are discussed. Many of these proteins consist of multiple domains,of which the chitin-binding hevein domain is a predominant one. X-ray and NMR structures of representatives of the major classes of these proteins are available now,

  5. Rapid and reliable protein structure determination via chemical shift threading.

    Science.gov (United States)

    Hafsa, Noor E; Berjanskii, Mark V; Arndt, David; Wishart, David S

    2018-01-01

    Protein structure determination using nuclear magnetic resonance (NMR) spectroscopy can be both time-consuming and labor intensive. Here we demonstrate how chemical shift threading can permit rapid, robust, and accurate protein structure determination using only chemical shift data. Threading is a relatively old bioinformatics technique that uses a combination of sequence information and predicted (or experimentally acquired) low-resolution structural data to generate high-resolution 3D protein structures. The key motivations behind using NMR chemical shifts for protein threading lie in the fact that they are easy to measure, they are available prior to 3D structure determination, and they contain vital structural information. The method we have developed uses not only sequence and chemical shift similarity but also chemical shift-derived secondary structure, shift-derived super-secondary structure, and shift-derived accessible surface area to generate a high quality protein structure regardless of the sequence similarity (or lack thereof) to a known structure already in the PDB. The method (called E-Thrifty) was found to be very fast (often chemical shift refinement, these results suggest that protein structure determination, using only NMR chemical shifts, is becoming increasingly practical and reliable. E-Thrifty is available as a web server at http://ethrifty.ca .

  6. Structure-based inference of molecular functions of proteins of unknown function from Berkeley Structural Genomics Center

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung-Hou; Shin, Dong Hae; Hou, Jingtong; Chandonia, John-Marc; Das, Debanu; Choi, In-Geol; Kim, Rosalind; Kim, Sung-Hou

    2007-09-02

    Advances in sequence genomics have resulted in an accumulation of a huge number of protein sequences derived from genome sequences. However, the functions of a large portion of them cannot be inferred based on the current methods of sequence homology detection to proteins of known functions. Three-dimensional structure can have an important impact in providing inference of molecular function (physical and chemical function) of a protein of unknown function. Structural genomics centers worldwide have been determining many 3-D structures of the proteins of unknown functions, and possible molecular functions of them have been inferred based on their structures. Combined with bioinformatics and enzymatic assay tools, the successful acceleration of the process of protein structure determination through high throughput pipelines enables the rapid functional annotation of a large fraction of hypothetical proteins. We present a brief summary of the process we used at the Berkeley Structural Genomics Center to infer molecular functions of proteins of unknown function.

  7. Evaluation of calculational and material models for concrete containment structures

    International Nuclear Information System (INIS)

    Dunham, R.S.; Rashid, Y.R.; Yuan, K.A.

    1984-01-01

    A computer code utilizing an appropriate finite element, material and constitutive model has been under development as a part of a comprehensive effort by the Electric Power Research Institute (EPRI) to develop and validate a realistic methodology for the ultimate load analysis of concrete containment structures. A preliminary evaluation of the reinforced and prestressed concrete modeling capabilities recently implemented in the ABAQUS-EPGEN code has been completed. This effort focuses on using a state-of-the-art calculational model to predict the behavior of large-scale reinforced concrete slabs tested under uniaxial and biaxial tension to simulate the wall of a typical concrete containment structure under internal pressure. This paper gives comparisons between calculations and experimental measurements for a uniaxially-loaded specimen. The calculated strains compare well with the measured strains in the reinforcing steel; however, the calculations gave diffused cracking patterns that do not agree with the discrete cracking observed in the experiments. Recommendations for improvement of the calculational models are given. (orig.)

  8. Molecular structures from density functional calculations with simulated annealing

    International Nuclear Information System (INIS)

    Jones, R.O.

    1991-01-01

    The geometrical structure of any aggregate of atoms is one of its basic properties and, in principle, straightforward to predict. One chooses a structure, determines the total energy E of the system of electrons and ions, and repeats the calculation for all possible geometries. The ground state structure is that with the lowest energy. A quantum mechanical calculation of the exact wave function Ψ would lead to the total energy, but this is practicable only in very small molecules. Furthermore, the number of local minima in the energy surface increases dramatically with increasing molecular size. While traditional ab initio methods have had many impressive successes, the difficulties have meant that they have focused on systems with relatively few local minima, or have used experiments or experience to limit the range of geometries studied. On the other hand, calculations for much larger molecules and extended systems are often forced to use simplifying assumptions about the interatomic forces that limit their predictive capability. The approach described here avoids both of these extremes: Total energies of predictive value are calculated without using semi-empirical force laws, and the problem of multiple minima in the energy surface is addressed. The density functional formalism, with a local density approximation for the exchange-correlation energy, allows one to calculate the total energy for a given geometry in an efficient, if approximate, manner. Calculations for heavier elements are not significantly more difficult than for those in the first row and provide an ideal way to study bonding trends. When coupled with finite-temperature molecular dynamics, this formalism can avoid many of the energetically unfavorable minima in the energy surface. We show here that the method leads to surprising and exciting results. (orig.)

  9. Predicting nucleic acid binding interfaces from structural models of proteins.

    Science.gov (United States)

    Dror, Iris; Shazman, Shula; Mukherjee, Srayanta; Zhang, Yang; Glaser, Fabian; Mandel-Gutfreund, Yael

    2012-02-01

    The function of DNA- and RNA-binding proteins can be inferred from the characterization and accurate prediction of their binding interfaces. However, the main pitfall of various structure-based methods for predicting nucleic acid binding function is that they are all limited to a relatively small number of proteins for which high-resolution three-dimensional structures are available. In this study, we developed a pipeline for extracting functional electrostatic patches from surfaces of protein structural models, obtained using the I-TASSER protein structure predictor. The largest positive patches are extracted from the protein surface using the patchfinder algorithm. We show that functional electrostatic patches extracted from an ensemble of structural models highly overlap the patches extracted from high-resolution structures. Furthermore, by testing our pipeline on a set of 55 known nucleic acid binding proteins for which I-TASSER produces high-quality models, we show that the method accurately identifies the nucleic acids binding interface on structural models of proteins. Employing a combined patch approach we show that patches extracted from an ensemble of models better predicts the real nucleic acid binding interfaces compared with patches extracted from independent models. Overall, these results suggest that combining information from a collection of low-resolution structural models could be a valuable approach for functional annotation. We suggest that our method will be further applicable for predicting other functional surfaces of proteins with unknown structure. Copyright © 2011 Wiley Periodicals, Inc.

  10. A Mesoscopic Model for Protein-Protein Interactions in Solution

    OpenAIRE

    Lund, Mikael; Jönsson, Bo

    2003-01-01

    Protein self-association may be detrimental in biological systems, but can be utilized in a controlled fashion for protein crystallization. It is hence of considerable interest to understand how factors like solution conditions prevent or promote aggregation. Here we present a computational model describing interactions between protein molecules in solution. The calculations are based on a molecular description capturing the detailed structure of the protein molecule using x-ray or nuclear ma...

  11. Using linear algebra for protein structural comparison and classification.

    Science.gov (United States)

    Gomide, Janaína; Melo-Minardi, Raquel; Dos Santos, Marcos Augusto; Neshich, Goran; Meira, Wagner; Lopes, Júlio César; Santoro, Marcelo

    2009-07-01

    In this article, we describe a novel methodology to extract semantic characteristics from protein structures using linear algebra in order to compose structural signature vectors which may be used efficiently to compare and classify protein structures into fold families. These signatures are built from the pattern of hydrophobic intrachain interactions using Singular Value Decomposition (SVD) and Latent Semantic Indexing (LSI) techniques. Considering proteins as documents and contacts as terms, we have built a retrieval system which is able to find conserved contacts in samples of myoglobin fold family and to retrieve these proteins among proteins of varied folds with precision of up to 80%. The classifier is a web tool available at our laboratory website. Users can search for similar chains from a specific PDB, view and compare their contact maps and browse their structures using a JMol plug-in.

  12. Using linear algebra for protein structural comparison and classification

    Directory of Open Access Journals (Sweden)

    Janaína Gomide

    2009-01-01

    Full Text Available In this article, we describe a novel methodology to extract semantic characteristics from protein structures using linear algebra in order to compose structural signature vectors which may be used efficiently to compare and classify protein structures into fold families. These signatures are built from the pattern of hydrophobic intrachain interactions using Singular Value Decomposition (SVD and Latent Semantic Indexing (LSI techniques. Considering proteins as documents and contacts as terms, we have built a retrieval system which is able to find conserved contacts in samples of myoglobin fold family and to retrieve these proteins among proteins of varied folds with precision of up to 80%. The classifier is a web tool available at our laboratory website. Users can search for similar chains from a specific PDB, view and compare their contact maps and browse their structures using a JMol plug-in.

  13. Protein 3D structure computed from evolutionary sequence variation.

    Directory of Open Access Journals (Sweden)

    Debora S Marks

    Full Text Available The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. Deciphering the evolutionary record held in these sequences and exploiting it for predictive and engineering purposes presents a formidable challenge. The potential benefit of solving this challenge is amplified by the advent of inexpensive high-throughput genomic sequencing.In this paper we ask whether we can infer evolutionary constraints from a set of sequence homologs of a protein. The challenge is to distinguish true co-evolution couplings from the noisy set of observed correlations. We address this challenge using a maximum entropy model of the protein sequence, constrained by the statistics of the multiple sequence alignment, to infer residue pair couplings. Surprisingly, we find that the strength of these inferred couplings is an excellent predictor of residue-residue proximity in folded structures. Indeed, the top-scoring residue couplings are sufficiently accurate and well-distributed to define the 3D protein fold with remarkable accuracy.We quantify this observation by computing, from sequence alone, all-atom 3D structures of fifteen test proteins from different fold classes, ranging in size from 50 to 260 residues, including a G-protein coupled receptor. These blinded inferences are de novo, i.e., they do not use homology modeling or sequence-similar fragments from known structures. The co-evolution signals provide sufficient information to determine accurate 3D protein structure to 2.7-4.8 Å C(α-RMSD error relative to the observed structure, over at least two-thirds of the protein (method called EVfold, details at http://EVfold.org. This discovery provides insight into essential interactions constraining protein evolution and will facilitate a comprehensive survey of the universe of

  14. Ion pairs in non-redundant protein structures

    Indian Academy of Sciences (India)

    Ion pairs contribute to several functions including the activity of catalytic triads, fusion of viral membranes, stability in thermophilic proteins and solvent–protein interactions. Furthermore, they have the ability to affect the stability of protein structures and are also a part of the forces that act to hold monomers together.

  15. Modulated structure calculated for superconducting hydrogen sulfide

    Energy Technology Data Exchange (ETDEWEB)

    Majumdar, Arnab; Tse, John S.; Yao, Yansun [Department of Physics and Engineering Physics, University of Saskatchewan, Saskatoon, SK (Canada)

    2017-09-11

    Compression of hydrogen sulfide using first principles metadynamics and molecular dynamics calculations revealed a modulated structure with high proton mobility which exhibits a diffraction pattern matching well with experiment. The structure consists of a sublattice of rectangular meandering SH{sup -} chains and molecular-like H{sub 3}S{sup +} stacked alternately in tetragonal and cubic slabs forming a long-period modulation. The novel structure offers a new perspective on the possible origin of the superconductivity at very high temperatures in which the conducting electrons in the SH chains are perturbed by the fluxional motions of the H{sub 3}S resulting in strong electron-phonon coupling. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  16. First-principle calculations of structural, electronic, optical, elastic ...

    Indian Academy of Sciences (India)

    S CHEDDADI

    2017-11-28

    Nov 28, 2017 ... First-principle calculations on the structural, electronic, optical, elastic and thermal properties of the chalcopyrite ... The Kohn–Sham equations were solved using the ... RMTKmax = 7 was used for all the investigated systems,.

  17. Dynamic calculation of structures in seismic zones. 2. ed.

    International Nuclear Information System (INIS)

    Capra, Alain; Davidovici, Victor

    1982-01-01

    The aims of this book are both didactic and practical. It is therefore addressed to both experienced engineers and students. Some general information about earthquakes and their occurrence is first given. The problem of a simple oscillator is presented. In this way, the reader is provided with an insight into undestanding the dynamic phenomena taking place and is introduced to the concept of response spectra and to an intuitive comprehension of the behavior of structures during earthquakes. The next chapter is devoted to the cases most frequently encountered with multiple oscillator structures. Theoretical studies are based on the usual modal decomposition method. The various practical methods of calculation employed are then examined, emphasis being given to the various different stages involved and to which of them is the best suited for a particular type of structure. Advise is given on how to select the model whose behavior best describes the real structure, both manual and computer methods of calculation being envisaged [fr

  18. Sampling of Stochastic Input Parameters for Rockfall Calculations and for Structural Response Calculations Under Vibratory Ground Motion

    International Nuclear Information System (INIS)

    M. Gross

    2004-01-01

    The purpose of this scientific analysis is to define the sampled values of stochastic (random) input parameters for (1) rockfall calculations in the lithophysal and nonlithophysal zones under vibratory ground motions, and (2) structural response calculations for the drip shield and waste package under vibratory ground motions. This analysis supplies: (1) Sampled values of ground motion time history and synthetic fracture pattern for analysis of rockfall in emplacement drifts in nonlithophysal rock (Section 6.3 of ''Drift Degradation Analysis'', BSC 2004 [DIRS 166107]); (2) Sampled values of ground motion time history and rock mechanical properties category for analysis of rockfall in emplacement drifts in lithophysal rock (Section 6.4 of ''Drift Degradation Analysis'', BSC 2004 [DIRS 166107]); (3) Sampled values of ground motion time history and metal to metal and metal to rock friction coefficient for analysis of waste package and drip shield damage to vibratory motion in ''Structural Calculations of Waste Package Exposed to Vibratory Ground Motion'' (BSC 2004 [DIRS 167083]) and in ''Structural Calculations of Drip Shield Exposed to Vibratory Ground Motion'' (BSC 2003 [DIRS 163425]). The sampled values are indices representing the number of ground motion time histories, number of fracture patterns and rock mass properties categories. These indices are translated into actual values within the respective analysis and model reports or calculations. This report identifies the uncertain parameters and documents the sampled values for these parameters. The sampled values are determined by GoldSim V6.04.007 [DIRS 151202] calculations using appropriate distribution types and parameter ranges. No software development or model development was required for these calculations. The calculation of the sampled values allows parameter uncertainty to be incorporated into the rockfall and structural response calculations that support development of the seismic scenario for the

  19. Calculation of forces arising from impacting projectiles upon yielding structures

    International Nuclear Information System (INIS)

    Drittler, K.; Gruner, P.; Krivy, J.

    1977-01-01

    Calculations concerning the impact of airplanes upon nuclear power plant buildings usually imply that the building 'acts' as a rigid target. This assumption is justified for considerations concerning the structural integrity of the building being hit. However, for investigating induced vibrations of components within the structure, this approach might -in general- be too conservative. It is expected, that yielding of the structure during impact reduces the peak values of the loads and changes the temporal behavior of the load function which is obtained for a rigid target. To calculate the changes of the load function which are due to deformations of the structure, Riera's method is extended for the case of a yielding target. In view of the applications of the calculations to the impact of airplanes upon buildings which are constructed to withstand loads of this kind without serious damage and without large deformations, it is possible to simplify the calculations to some extent. That is, the investigations need not take into account in detail the behavior of the target during impact. The calculations are performed with a one-dimensional model for the projectile. The direction of impact is perpendicular to the target surface; direction of impact and projectile axis coincide. The calculations were performed for several initial velocities of the projectiles simulating a fast flying military airplane. Variations of the peak values of the load functions as compared to corresponding values for a rigid target do not exceed about 10%. The overall temporal behavior of the load curves turns out to be not very sensitive to the yielding of the target, though, in some cases displacements in time of the peak positions within a single load curve do arise

  20. Host Proteins Determine MRSA Biofilm Structure and Integrity

    DEFF Research Database (Denmark)

    Dreier, Cindy; Nielsen, Astrid; Jørgensen, Nis Pedersen

    Human extracellular matrix (hECM) proteins aids the initial attachment and initiation of an infection, by specific binding to bacterial cell surface proteins. However, the importance of hECM proteins in structure, integrity and antibiotic resilience of a biofilm is unknown. This study aims...... to determine how specific hECM proteins affect S. aureus USA300 JE2 biofilms. Biofilms were grown in the presence of synovial fluid from rheumatoid arteritis patients to mimic in vivo conditions, where bacteria incorporate hECM proteins into the biofilm matrix. Difference in biofilm structure, with and without...... addition of hECM to growth media, was visualized by confocal laser scanning microscopy. Two enzymatic degradation experiments were used to study biofilm matrix composition and importance of hECM proteins: enzymatic removal of specific hECM proteins from growth media, before biofilm formation, and enzymatic...

  1. Integrating protein structures and precomputed genealogies in the Magnum database: Examples with cellular retinoid binding proteins

    Directory of Open Access Journals (Sweden)

    Bradley Michael E

    2006-02-01

    Full Text Available Abstract Background When accurate models for the divergent evolution of protein sequences are integrated with complementary biological information, such as folded protein structures, analyses of the combined data often lead to new hypotheses about molecular physiology. This represents an excellent example of how bioinformatics can be used to guide experimental research. However, progress in this direction has been slowed by the lack of a publicly available resource suitable for general use. Results The precomputed Magnum database offers a solution to this problem for ca. 1,800 full-length protein families with at least one crystal structure. The Magnum deliverables include 1 multiple sequence alignments, 2 mapping of alignment sites to crystal structure sites, 3 phylogenetic trees, 4 inferred ancestral sequences at internal tree nodes, and 5 amino acid replacements along tree branches. Comprehensive evaluations revealed that the automated procedures used to construct Magnum produced accurate models of how proteins divergently evolve, or genealogies, and correctly integrated these with the structural data. To demonstrate Magnum's capabilities, we asked for amino acid replacements requiring three nucleotide substitutions, located at internal protein structure sites, and occurring on short phylogenetic tree branches. In the cellular retinoid binding protein family a site that potentially modulates ligand binding affinity was discovered. Recruitment of cellular retinol binding protein to function as a lens crystallin in the diurnal gecko afforded another opportunity to showcase the predictive value of a browsable database containing branch replacement patterns integrated with protein structures. Conclusion We integrated two areas of protein science, evolution and structure, on a large scale and created a precomputed database, known as Magnum, which is the first freely available resource of its kind. Magnum provides evolutionary and structural

  2. Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces.

    Science.gov (United States)

    Venselaar, Hanka; Te Beek, Tim A H; Kuipers, Remko K P; Hekkelman, Maarten L; Vriend, Gert

    2010-11-08

    Many newly detected point mutations are located in protein-coding regions of the human genome. Knowledge of their effects on the protein's 3D structure provides insight into the protein's mechanism, can aid the design of further experiments, and eventually can lead to the development of new medicines and diagnostic tools. In this article we describe HOPE, a fully automatic program that analyzes the structural and functional effects of point mutations. HOPE collects information from a wide range of information sources including calculations on the 3D coordinates of the protein by using WHAT IF Web services, sequence annotations from the UniProt database, and predictions by DAS services. Homology models are built with YASARA. Data is stored in a database and used in a decision scheme to identify the effects of a mutation on the protein's 3D structure and function. HOPE builds a report with text, figures, and animations that is easy to use and understandable for (bio)medical researchers. We tested HOPE by comparing its output to the results of manually performed projects. In all straightforward cases HOPE performed similar to a trained bioinformatician. The use of 3D structures helps optimize the results in terms of reliability and details. HOPE's results are easy to understand and are presented in a way that is attractive for researchers without an extensive bioinformatics background.

  3. Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces

    Directory of Open Access Journals (Sweden)

    Hekkelman Maarten L

    2010-11-01

    Full Text Available Abstract Background Many newly detected point mutations are located in protein-coding regions of the human genome. Knowledge of their effects on the protein's 3D structure provides insight into the protein's mechanism, can aid the design of further experiments, and eventually can lead to the development of new medicines and diagnostic tools. Results In this article we describe HOPE, a fully automatic program that analyzes the structural and functional effects of point mutations. HOPE collects information from a wide range of information sources including calculations on the 3D coordinates of the protein by using WHAT IF Web services, sequence annotations from the UniProt database, and predictions by DAS services. Homology models are built with YASARA. Data is stored in a database and used in a decision scheme to identify the effects of a mutation on the protein's 3D structure and function. HOPE builds a report with text, figures, and animations that is easy to use and understandable for (biomedical researchers. Conclusions We tested HOPE by comparing its output to the results of manually performed projects. In all straightforward cases HOPE performed similar to a trained bioinformatician. The use of 3D structures helps optimize the results in terms of reliability and details. HOPE's results are easy to understand and are presented in a way that is attractive for researchers without an extensive bioinformatics background.

  4. Calculation of coupling factor for the heterogeneous accelerating structure

    International Nuclear Information System (INIS)

    Bian Xiaohao; Chen Huaibi; Zheng Shuxin

    2006-01-01

    The converging part of electron accelerator is designed to converge the phase of injecting electrons, improving the beam quality of the accelerator. It is very crucial to calculate the coupling factor between cavities and to design the geometry structure of the coupling irises. By the E module of code MAFIA, the authors calculate the frequency of every single resonant cavity and the two eigenfrequencies of two-cavitiy line. Then we get the coupling factor between the two cavities. This method can be used to design the geometry structure of the coupling isises between every two cavities. Compared to experiment, the results of the method is very accurate. (authors)

  5. PCI-SS: MISO dynamic nonlinear protein secondary structure prediction

    Directory of Open Access Journals (Sweden)

    Aboul-Magd Mohammed O

    2009-07-01

    Full Text Available Abstract Background Since the function of a protein is largely dictated by its three dimensional configuration, determining a protein's structure is of fundamental importance to biology. Here we report on a novel approach to determining the one dimensional secondary structure of proteins (distinguishing α-helices, β-strands, and non-regular structures from primary sequence data which makes use of Parallel Cascade Identification (PCI, a powerful technique from the field of nonlinear system identification. Results Using PSI-BLAST divergent evolutionary profiles as input data, dynamic nonlinear systems are built through a black-box approach to model the process of protein folding. Genetic algorithms (GAs are applied in order to optimize the architectural parameters of the PCI models. The three-state prediction problem is broken down into a combination of three binary sub-problems and protein structure classifiers are built using 2 layers of PCI classifiers. Careful construction of the optimization, training, and test datasets ensures that no homology exists between any training and testing data. A detailed comparison between PCI and 9 contemporary methods is provided over a set of 125 new protein chains guaranteed to be dissimilar to all training data. Unlike other secondary structure prediction methods, here a web service is developed to provide both human- and machine-readable interfaces to PCI-based protein secondary structure prediction. This server, called PCI-SS, is available at http://bioinf.sce.carleton.ca/PCISS. In addition to a dynamic PHP-generated web interface for humans, a Simple Object Access Protocol (SOAP interface is added to permit invocation of the PCI-SS service remotely. This machine-readable interface facilitates incorporation of PCI-SS into multi-faceted systems biology analysis pipelines requiring protein secondary structure information, and greatly simplifies high-throughput analyses. XML is used to represent the input

  6. Density-functional band-structure calculations for La-, Y-, and Sc-filled CoP3-based skutterudite structures

    International Nuclear Information System (INIS)

    Loevvik, O.M.; Prytz, O.

    2004-01-01

    The crystal structure, thermodynamic stability, and electronic structure of La-, Y-, and Sc-filled CoP 3 are predicted from density-functional band-structure calculations. The size of the cubic voids in the skutterudite structure is changed much less than the difference in size between the different filling atoms, and we expect that the larger rattling amplitude of the smaller Sc and Y atoms may decrease the lattice thermal conductivity of Sc- and Y-filled structures significantly compared to La-filled structures. The solubility of La, Y, and Sc in CoP 3 is calculated to be around 5, 3-6 %, and below 1% at 0 K, respectively. Based on similar systems, this is expected to increase considerably if Fe is substituted for Co. Fe substitution is also expected to compensate the increased charge carrier concentration of the filled structures that is seen in the calculated electron density of states. In conclusion, Sc- or Y-filled (FeCo)P 3 skutterudite structures are promising materials for thermoelectric applications

  7. Tuning structure of oppositely charged nanoparticle and protein complexes

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Sugam, E-mail: sugam@barc.gov.in; Aswal, V. K., E-mail: sugam@barc.gov.in [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai-400085 (India); Callow, P. [Institut Laue Langevin, DS/LSS, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9 (France)

    2014-04-24

    Small-angle neutron scattering (SANS) has been used to probe the structures of anionic silica nanoparticles (LS30) and cationic lyszyme protein (M.W. 14.7kD, I.P. ∼ 11.4) by tuning their interaction through the pH variation. The protein adsorption on nanoparticles is found to be increasing with pH and determined by the electrostatic attraction between two components as well as repulsion between protein molecules. We show the strong electrostatic attraction between nanoparticles and protein molecules leads to protein-mediated aggregation of nanoparticles which are characterized by fractal structures. At pH 5, the protein adsorption gives rise to nanoparticle aggregation having surface fractal morphology with close packing of nanoparticles. The surface fractals transform to open structures of mass fractal morphology at higher pH (7 and 9) on approaching isoelectric point (I.P.)

  8. Ab initio electronic band structure calculation of InP in the wurtzite phase

    Science.gov (United States)

    Dacal, Luis C. O.; Cantarero, Andrés

    2011-05-01

    We present ab initio calculations of the InP band structure in the wurtzite phase and compare it with that of the zincblende phase. In both calculations, we use the full potential linearized augmented plane wave method as implemented in the WIEN2k code and the modified Becke-Johnson exchange potential, which provides an improved value of the bandgap. The structural optimization of the wurtizte InP gives a=0.4150 nm, c=0.6912 nm, and an internal parameter u=0.371, showing the existence of a spontaneous polarization along the growth axis. As compared to the ideal wurtzite structure (that with the lattice parameter derived from the zincblende structure calculations), the actual wurtzite structure is compressed (-1.3%) in plane and expanded (0.7%) along the c-direction. The value of the calculated band gaps agrees well with recent optical experiments. The calculations are also consistent with the optical transitions found using polarized light.

  9. Relationship between Molecular Structure Characteristics of Feed Proteins and Protein In vitro Digestibility and Solubility.

    Science.gov (United States)

    Bai, Mingmei; Qin, Guixin; Sun, Zewei; Long, Guohui

    2016-08-01

    The nutritional value of feed proteins and their utilization by livestock are related not only to the chemical composition but also to the structure of feed proteins, but few studies thus far have investigated the relationship between the structure of feed proteins and their solubility as well as digestibility in monogastric animals. To address this question we analyzed soybean meal, fish meal, corn distiller's dried grains with solubles, corn gluten meal, and feather meal by Fourier transform infrared (FTIR) spectroscopy to determine the protein molecular spectral band characteristics for amides I and II as well as α-helices and β-sheets and their ratios. Protein solubility and in vitro digestibility were measured with the Kjeldahl method using 0.2% KOH solution and the pepsin-pancreatin two-step enzymatic method, respectively. We found that all measured spectral band intensities (height and area) of feed proteins were correlated with their the in vitro digestibility and solubility (p≤0.003); moreover, the relatively quantitative amounts of α-helices, random coils, and α-helix to β-sheet ratio in protein secondary structures were positively correlated with protein in vitro digestibility and solubility (p≤0.004). On the other hand, the percentage of β-sheet structures was negatively correlated with protein in vitro digestibility (pdigestibility at 28 h and solubility. Furthermore, the α-helix-to-β-sheet ratio can be used to predict the nutritional value of feed proteins.

  10. Fully local orbital-free calculation of electronic structure using pseudopotentials

    NARCIS (Netherlands)

    Pino, R.; Markvoort, Albert. J.; Santen, van R.A.; Hilbers, P.A.J.

    2003-01-01

    An exactly solvable orbital-free technique is applied to the calculation of the electronic structure of polyatomic systems. The Thomas–Fermi kinetic energy, local exchange, local electrostatic energy functionals, and pseudopotentials are used. Given the potential, the cost of the calculation of the

  11. A generative, probabilistic model of local protein structure

    DEFF Research Database (Denmark)

    Boomsma, Wouter; Mardia, Kanti V.; Taylor, Charles C.

    2008-01-01

    Despite significant progress in recent years, protein structure prediction maintains its status as one of the prime unsolved problems in computational biology. One of the key remaining challenges is an efficient probabilistic exploration of the structural space that correctly reflects the relative...... conformational stabilities. Here, we present a fully probabilistic, continuous model of local protein structure in atomic detail. The generative model makes efficient conformational sampling possible and provides a framework for the rigorous analysis of local sequence-structure correlations in the native state...

  12. 3DProIN: Protein-Protein Interaction Networks and Structure Visualization.

    Science.gov (United States)

    Li, Hui; Liu, Chunmei

    2014-06-14

    3DProIN is a computational tool to visualize protein-protein interaction networks in both two dimensional (2D) and three dimensional (3D) view. It models protein-protein interactions in a graph and explores the biologically relevant features of the tertiary structures of each protein in the network. Properties such as color, shape and name of each node (protein) of the network can be edited in either 2D or 3D views. 3DProIN is implemented using 3D Java and C programming languages. The internet crawl technique is also used to parse dynamically grasped protein interactions from protein data bank (PDB). It is a java applet component that is embedded in the web page and it can be used on different platforms including Linux, Mac and Window using web browsers such as Firefox, Internet Explorer, Chrome and Safari. It also was converted into a mac app and submitted to the App store as a free app. Mac users can also download the app from our website. 3DProIN is available for academic research at http://bicompute.appspot.com.

  13. Structure modification and functionality of whey proteins: quantitative structure-activity relationship approach.

    Science.gov (United States)

    Nakai, S; Li-Chan, E

    1985-10-01

    According to the original idea of quantitative structure-activity relationship, electric, hydrophobic, and structural parameters should be taken into consideration for elucidating functionality. Changes in these parameters are reflected in the property of protein solubility upon modification of whey proteins by heating. Although solubility is itself a functional property, it has been utilized to explain other functionalities of proteins. However, better correlations were obtained when hydrophobic parameters of the proteins were used in conjunction with solubility. Various treatments reported in the literature were applied to whey protein concentrate in an attempt to obtain whipping and gelling properties similar to those of egg white. Mapping simplex optimization was used to search for the best results. Improvement in whipping properties by pepsin hydrolysis may have been due to higher protein solubility, and good gelling properties resulting from polyphosphate treatment may have been due to an increase in exposable hydrophobicity. However, the results of angel food cake making were still unsatisfactory.

  14. Exploring protein dynamics space: the dynasome as the missing link between protein structure and function.

    Directory of Open Access Journals (Sweden)

    Ulf Hensen

    Full Text Available Proteins are usually described and classified according to amino acid sequence, structure or function. Here, we develop a minimally biased scheme to compare and classify proteins according to their internal mobility patterns. This approach is based on the notion that proteins not only fold into recurring structural motifs but might also be carrying out only a limited set of recurring mobility motifs. The complete set of these patterns, which we tentatively call the dynasome, spans a multi-dimensional space with axes, the dynasome descriptors, characterizing different aspects of protein dynamics. The unique dynamic fingerprint of each protein is represented as a vector in the dynasome space. The difference between any two vectors, consequently, gives a reliable measure of the difference between the corresponding protein dynamics. We characterize the properties of the dynasome by comparing the dynamics fingerprints obtained from molecular dynamics simulations of 112 proteins but our approach is, in principle, not restricted to any specific source of data of protein dynamics. We conclude that: 1. the dynasome consists of a continuum of proteins, rather than well separated classes. 2. For the majority of proteins we observe strong correlations between structure and dynamics. 3. Proteins with similar function carry out similar dynamics, which suggests a new method to improve protein function annotation based on protein dynamics.

  15. Chaperonin Structure - The Large Multi-Subunit Protein Complex

    Directory of Open Access Journals (Sweden)

    Irena Roterman

    2009-03-01

    Full Text Available The multi sub-unit protein structure representing the chaperonins group is analyzed with respect to its hydrophobicity distribution. The proteins of this group assist protein folding supported by ATP. The specific axial symmetry GroEL structure (two rings of seven units stacked back to back - 524 aa each and the GroES (single ring of seven units - 97 aa each polypeptide chains are analyzed using the hydrophobicity distribution expressed as excess/deficiency all over the molecule to search for structure-to-function relationships. The empirically observed distribution of hydrophobic residues is confronted with the theoretical one representing the idealized hydrophobic core with hydrophilic residues exposure on the surface. The observed discrepancy between these two distributions seems to be aim-oriented, determining the structure-to-function relation. The hydrophobic force field structure generated by the chaperonin capsule is presented. Its possible influence on substrate folding is suggested.

  16. Optimal neural networks for protein-structure prediction

    International Nuclear Information System (INIS)

    Head-Gordon, T.; Stillinger, F.H.

    1993-01-01

    The successful application of neural-network algorithms for prediction of protein structure is stymied by three problem areas: the sparsity of the database of known protein structures, poorly devised network architectures which make the input-output mapping opaque, and a global optimization problem in the multiple-minima space of the network variables. We present a simplified polypeptide model residing in two dimensions with only two amino-acid types, A and B, which allows the determination of the global energy structure for all possible sequences of pentamer, hexamer, and heptamer lengths. This model simplicity allows us to compile a complete structural database and to devise neural networks that reproduce the tertiary structure of all sequences with absolute accuracy and with the smallest number of network variables. These optimal networks reveal that the three problem areas are convoluted, but that thoughtful network designs can actually deconvolute these detrimental traits to provide network algorithms that genuinely impact on the ability of the network to generalize or learn the desired mappings. Furthermore, the two-dimensional polypeptide model shows sufficient chemical complexity so that transfer of neural-network technology to more realistic three-dimensional proteins is evident

  17. Crystal structure of Homo sapiens protein LOC79017

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Euiyoung; Bingman, Craig A.; Aceti, David J.; Phillips, Jr., George N. (UW)

    2010-02-08

    LOC79017 (MW 21.0 kDa, residues 1-188) was annotated as a hypothetical protein encoded by Homo sapiens chromosome 7 open reading frame 24. It was selected as a target by the Center for Eukaryotic Structural Genomics (CESG) because it did not share more than 30% sequence identity with any protein for which the three-dimensional structure is known. The biological function of the protein has not been established yet. Parts of LOC79017 were identified as members of uncharacterized Pfam families (residues 1-95 as PB006073 and residues 104-180 as PB031696). BLAST searches revealed homologues of LOC79017 in many eukaryotes, but none of them have been functionally characterized. Here, we report the crystal structure of H. sapiens protein LOC79017 (UniGene code Hs.530024, UniProt code O75223, CESG target number go.35223).

  18. Protein structure prediction using bee colony optimization metaheuristic

    DEFF Research Database (Denmark)

    Fonseca, Rasmus; Paluszewski, Martin; Winter, Pawel

    2010-01-01

    of the proteins structure, an energy potential and some optimization algorithm that ¿nds the structure with minimal energy. Bee Colony Optimization (BCO) is a relatively new approach to solving opti- mization problems based on the foraging behaviour of bees. Several variants of BCO have been suggested......Predicting the native structure of proteins is one of the most challenging problems in molecular biology. The goal is to determine the three-dimensional struc- ture from the one-dimensional amino acid sequence. De novo prediction algorithms seek to do this by developing a representation...... our BCO method to generate good solutions to the protein structure prediction problem. The results show that BCO generally ¿nds better solutions than simulated annealing which so far has been the metaheuristic of choice for this problem....

  19. Nonlinear deterministic structures and the randomness of protein sequences

    CERN Document Server

    Huang Yan Zhao

    2003-01-01

    To clarify the randomness of protein sequences, we make a detailed analysis of a set of typical protein sequences representing each structural classes by using nonlinear prediction method. No deterministic structures are found in these protein sequences and this implies that they behave as random sequences. We also give an explanation to the controversial results obtained in previous investigations.

  20. Integrated Structural Biology for α-Helical Membrane Protein Structure Determination.

    Science.gov (United States)

    Xia, Yan; Fischer, Axel W; Teixeira, Pedro; Weiner, Brian; Meiler, Jens

    2018-04-03

    While great progress has been made, only 10% of the nearly 1,000 integral, α-helical, multi-span membrane protein families are represented by at least one experimentally determined structure in the PDB. Previously, we developed the algorithm BCL::MP-Fold, which samples the large conformational space of membrane proteins de novo by assembling predicted secondary structure elements guided by knowledge-based potentials. Here, we present a case study of rhodopsin fold determination by integrating sparse and/or low-resolution restraints from multiple experimental techniques including electron microscopy, electron paramagnetic resonance spectroscopy, and nuclear magnetic resonance spectroscopy. Simultaneous incorporation of orthogonal experimental restraints not only significantly improved the sampling accuracy but also allowed identification of the correct fold, which is demonstrated by a protein size-normalized transmembrane root-mean-square deviation as low as 1.2 Å. The protocol developed in this case study can be used for the determination of unknown membrane protein folds when limited experimental restraints are available. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Fast protein tertiary structure retrieval based on global surface shape similarity.

    Science.gov (United States)

    Sael, Lee; Li, Bin; La, David; Fang, Yi; Ramani, Karthik; Rustamov, Raif; Kihara, Daisuke

    2008-09-01

    Characterization and identification of similar tertiary structure of proteins provides rich information for investigating function and evolution. The importance of structure similarity searches is increasing as structure databases continue to expand, partly due to the structural genomics projects. A crucial drawback of conventional protein structure comparison methods, which compare structures by their main-chain orientation or the spatial arrangement of secondary structure, is that a database search is too slow to be done in real-time. Here we introduce a global surface shape representation by three-dimensional (3D) Zernike descriptors, which represent a protein structure compactly as a series expansion of 3D functions. With this simplified representation, the search speed against a few thousand structures takes less than a minute. To investigate the agreement between surface representation defined by 3D Zernike descriptor and conventional main-chain based representation, a benchmark was performed against a protein classification generated by the combinatorial extension algorithm. Despite the different representation, 3D Zernike descriptor retrieved proteins of the same conformation defined by combinatorial extension in 89.6% of the cases within the top five closest structures. The real-time protein structure search by 3D Zernike descriptor will open up new possibility of large-scale global and local protein surface shape comparison. 2008 Wiley-Liss, Inc.

  2. Bayesian comparison of protein structures using partial Procrustes distance.

    Science.gov (United States)

    Ejlali, Nasim; Faghihi, Mohammad Reza; Sadeghi, Mehdi

    2017-09-26

    An important topic in bioinformatics is the protein structure alignment. Some statistical methods have been proposed for this problem, but most of them align two protein structures based on the global geometric information without considering the effect of neighbourhood in the structures. In this paper, we provide a Bayesian model to align protein structures, by considering the effect of both local and global geometric information of protein structures. Local geometric information is incorporated to the model through the partial Procrustes distance of small substructures. These substructures are composed of β-carbon atoms from the side chains. Parameters are estimated using a Markov chain Monte Carlo (MCMC) approach. We evaluate the performance of our model through some simulation studies. Furthermore, we apply our model to a real dataset and assess the accuracy and convergence rate. Results show that our model is much more efficient than previous approaches.

  3. The Three-Dimensional Solution Structure of the Src Homology Domain-2 of the Growth Factor Receptor-Bound Protein-2

    International Nuclear Information System (INIS)

    Senior, Mary M.; Frederick, Anne F.; Black, Stuart; Murgolo, Nicholas J.; Perkins, Louise M.; Wilson, Oswald; Snow, Mark E.; Wang Yusen

    1998-01-01

    A set of high-resolution three-dimensional solution structures of the Src homology region-2 (SH2) domain of the growth factor receptor-bound protein-2 was determined using heteronuclear NMR spectroscopy. The NMR data used in this study were collected on a stable monomeric protein solution that was free of protein aggregates and proteolysis. The solution structure was determined based upon a total of 1439 constraints, which included 1326 nuclear Overhauser effect distance constraints, 70 hydrogen bond constraints, and 43 dihedral angle constraints. Distance geometry-simulated annealing calculations followed by energy minimization yielded a family of 18 structures that converged to a root-mean-square deviation of 1.09 A for all backbone atoms and 0.40 A for the backbone atoms of the central β-sheet. The core structure of the SH2 domain contains an antiparallel β-sheet flanked by two parallel α-helices displaying an overall architecture that is similar to other known SH2 domain structures. This family of NMR structures is compared to the X-ray structure and to another family of NMR solution structures determined under different solution conditions

  4. Structural analysis of recombinant human protein QM

    International Nuclear Information System (INIS)

    Gualberto, D.C.H.; Fernandes, J.L.; Silva, F.S.; Saraiva, K.W.; Affonso, R.; Pereira, L.M.; Silva, I.D.C.G.

    2012-01-01

    Full text: The ribosomal protein QM belongs to a family of ribosomal proteins, which is highly conserved from yeast to humans. The presence of the QM protein is necessary for joining the 60S and 40S subunits in a late step of the initiation of mRNA translation. Although the exact extra-ribosomal functions of QM are not yet fully understood, it has been identified as a putative tumor suppressor. This protein was reported to interact with the transcription factor c-Jun and thereby prevent c-Jun actives genes of the cellular growth. In this study, the human QM protein was expressed in bacterial system, in the soluble form and this structure was analyzed by Circular Dichroism and Fluorescence. The results of Circular Dichroism showed that this protein has less alpha helix than beta sheet, as described in the literature. QM protein does not contain a leucine zipper region; however the ion zinc is necessary for binding of QM to c-Jun. Then we analyzed the relationship between the removal of zinc ions and folding of protein. Preliminary results obtained by the technique Fluorescence showed a gradual increase in fluorescence with the addition of increasing concentration of EDTA. This suggests that the zinc is important in the tertiary structure of the protein. More studies are being made for better understand these results. (author)

  5. Microscopic calculations of nuclear structure and nuclear correlations

    International Nuclear Information System (INIS)

    Wiringa, R.B.

    1992-01-01

    A major goal in nuclear physics is to understand how nuclear structure comes about from the underlying interactions between nucleons. This requires modelling nuclei as collections of strongly interacting particles. Using realistic nucleon-nucleon potentials, supplemented with consistent three-nucleon potentials and two-body electroweak current operators, variational Monte Carlo methods are used to calculate nuclear ground-state properties, such as the binding energy, electromagnetic form factors, and momentum distributions. Other properties such as excited states and low-energy reactions are also calculable with these methods

  6. Utilizing knowledge base of amino acids structural neighborhoods to predict protein-protein interaction sites.

    Science.gov (United States)

    Jelínek, Jan; Škoda, Petr; Hoksza, David

    2017-12-06

    Protein-protein interactions (PPI) play a key role in an investigation of various biochemical processes, and their identification is thus of great importance. Although computational prediction of which amino acids take part in a PPI has been an active field of research for some time, the quality of in-silico methods is still far from perfect. We have developed a novel prediction method called INSPiRE which benefits from a knowledge base built from data available in Protein Data Bank. All proteins involved in PPIs were converted into labeled graphs with nodes corresponding to amino acids and edges to pairs of neighboring amino acids. A structural neighborhood of each node was then encoded into a bit string and stored in the knowledge base. When predicting PPIs, INSPiRE labels amino acids of unknown proteins as interface or non-interface based on how often their structural neighborhood appears as interface or non-interface in the knowledge base. We evaluated INSPiRE's behavior with respect to different types and sizes of the structural neighborhood. Furthermore, we examined the suitability of several different features for labeling the nodes. Our evaluations showed that INSPiRE clearly outperforms existing methods with respect to Matthews correlation coefficient. In this paper we introduce a new knowledge-based method for identification of protein-protein interaction sites called INSPiRE. Its knowledge base utilizes structural patterns of known interaction sites in the Protein Data Bank which are then used for PPI prediction. Extensive experiments on several well-established datasets show that INSPiRE significantly surpasses existing PPI approaches.

  7. Mining protein loops using a structural alphabet and statistical exceptionality

    Directory of Open Access Journals (Sweden)

    Martin Juliette

    2010-02-01

    Full Text Available Abstract Background Protein loops encompass 50% of protein residues in available three-dimensional structures. These regions are often involved in protein functions, e.g. binding site, catalytic pocket... However, the description of protein loops with conventional tools is an uneasy task. Regular secondary structures, helices and strands, have been widely studied whereas loops, because they are highly variable in terms of sequence and structure, are difficult to analyze. Due to data sparsity, long loops have rarely been systematically studied. Results We developed a simple and accurate method that allows the description and analysis of the structures of short and long loops using structural motifs without restriction on loop length. This method is based on the structural alphabet HMM-SA. HMM-SA allows the simplification of a three-dimensional protein structure into a one-dimensional string of states, where each state is a four-residue prototype fragment, called structural letter. The difficult task of the structural grouping of huge data sets is thus easily accomplished by handling structural letter strings as in conventional protein sequence analysis. We systematically extracted all seven-residue fragments in a bank of 93000 protein loops and grouped them according to the structural-letter sequence, named structural word. This approach permits a systematic analysis of loops of all sizes since we consider the structural motifs of seven residues rather than complete loops. We focused the analysis on highly recurrent words of loops (observed more than 30 times. Our study reveals that 73% of loop-lengths are covered by only 3310 highly recurrent structural words out of 28274 observed words. These structural words have low structural variability (mean RMSd of 0.85 Å. As expected, half of these motifs display a flanking-region preference but interestingly, two thirds are shared by short (less than 12 residues and long loops. Moreover, half of

  8. Mining protein loops using a structural alphabet and statistical exceptionality.

    Science.gov (United States)

    Regad, Leslie; Martin, Juliette; Nuel, Gregory; Camproux, Anne-Claude

    2010-02-04

    Protein loops encompass 50% of protein residues in available three-dimensional structures. These regions are often involved in protein functions, e.g. binding site, catalytic pocket... However, the description of protein loops with conventional tools is an uneasy task. Regular secondary structures, helices and strands, have been widely studied whereas loops, because they are highly variable in terms of sequence and structure, are difficult to analyze. Due to data sparsity, long loops have rarely been systematically studied. We developed a simple and accurate method that allows the description and analysis of the structures of short and long loops using structural motifs without restriction on loop length. This method is based on the structural alphabet HMM-SA. HMM-SA allows the simplification of a three-dimensional protein structure into a one-dimensional string of states, where each state is a four-residue prototype fragment, called structural letter. The difficult task of the structural grouping of huge data sets is thus easily accomplished by handling structural letter strings as in conventional protein sequence analysis. We systematically extracted all seven-residue fragments in a bank of 93000 protein loops and grouped them according to the structural-letter sequence, named structural word. This approach permits a systematic analysis of loops of all sizes since we consider the structural motifs of seven residues rather than complete loops. We focused the analysis on highly recurrent words of loops (observed more than 30 times). Our study reveals that 73% of loop-lengths are covered by only 3310 highly recurrent structural words out of 28274 observed words). These structural words have low structural variability (mean RMSd of 0.85 A). As expected, half of these motifs display a flanking-region preference but interestingly, two thirds are shared by short (less than 12 residues) and long loops. Moreover, half of recurrent motifs exhibit a significant level of

  9. HDAPD: a web tool for searching the disease-associated protein structures

    Science.gov (United States)

    2010-01-01

    Background The protein structures of the disease-associated proteins are important for proceeding with the structure-based drug design to against a particular disease. Up until now, proteins structures are usually searched through a PDB id or some sequence information. However, in the HDAPD database presented here the protein structure of a disease-associated protein can be directly searched through the associated disease name keyed in. Description The search in HDAPD can be easily initiated by keying some key words of a disease, protein name, protein type, or PDB id. The protein sequence can be presented in FASTA format and directly copied for a BLAST search. HDAPD is also interfaced with Jmol so that users can observe and operate a protein structure with Jmol. The gene ontological data such as cellular components, molecular functions, and biological processes are provided once a hyperlink to Gene Ontology (GO) is clicked. Further, HDAPD provides a link to the KEGG map such that where the protein is placed and its relationship with other proteins in a metabolic pathway can be found from the map. The latest literatures namely titles, journals, authors, and abstracts searched from PubMed for the protein are also presented as a length controllable list. Conclusions Since the HDAPD data content can be routinely updated through a PHP-MySQL web page built, the new database presented is useful for searching the structures for some disease-associated proteins that may play important roles in the disease developing process for performing the structure-based drug design to against the diseases. PMID:20158919

  10. Affinity and specificity of serine endopeptidase-protein inhibitor interactions. Empirical free energy calculations based on X-ray crystallographic structures.

    Science.gov (United States)

    Krystek, S; Stouch, T; Novotny, J

    1993-12-05

    An empirical function was used to calculate free energy change (delta G) of complex formation between the following inhibitors and enzymes: Kunitz inhibitor (BPTI) with trypsin, trypsinogen and kallikrein; turkey ovomucoid 3rd domain (OMTKY3) with alpha-chymotrypsin and the Streptomyces griseus protease B; the potato chymotrypsin inhibitor with the protease B; and the barely chymotrypsin inhibitor and eglin-c with subtilisin and thermitase. Using X-ray coordinates of the nine complexes, we estimated the contributions that hydrophobic effect, electrostatic interactions and side-chain conformational entropy make towards the stability of the complexes. The calculated delta G values showed good agreement with the experimentally measured ones, the only exception being the kallikrein/BPTI complex whose X-ray structure was solved at an exceptionally low pH. In complexes with different enzymes, the same inhibitor residues contributed identically towards complex formation (delta G(residue) Spearman rank correlation coefficient 0.7 to 1.0). The most productive enzyme-contacting residues in OMTKY3, eglin-c, and the chymotrypsin inhibitors were found in analogous positions on their respective binding loops; thus, our calculations identified a functional (energetic) motif that parallels the well-known structural similarity of the binding loops. The delta G values calculated for BPTI complexed with trypsin (-21.7 kcal) and trypsinogen (-23.4 kcal) were similar and close to the experimental delta G value of the trypsin/BPTI complex (-18.1 kcal), lending support to the suggestion that the 10(7) difference in the observed stabilities (KA) of these two complexes reflects the energetic cost of conformational changes induced in trypsinogen during the pre-equilibrium stages of complex formation. In almost all of the complexes studied, the stabilization free energy contributed by the inhibitors was larger than that donated by the enzymes. In the trypsin-BPTI complex, the calculated

  11. Combining neural networks for protein secondary structure prediction

    DEFF Research Database (Denmark)

    Riis, Søren Kamaric

    1995-01-01

    In this paper structured neural networks are applied to the problem of predicting the secondary structure of proteins. A hierarchical approach is used where specialized neural networks are designed for each structural class and then combined using another neural network. The submodels are designed...... by using a priori knowledge of the mapping between protein building blocks and the secondary structure and by using weight sharing. Since none of the individual networks have more than 600 adjustable weights over-fitting is avoided. When ensembles of specialized experts are combined the performance...

  12. Protein Structure Determination Using Chemical Shifts

    DEFF Research Database (Denmark)

    Christensen, Anders Steen

    is determined using only chemical shifts recorded and assigned through automated processes. The CARMSD to the experimental X-ray for this structure is 1.1. Å. Additionally, the method is combined with very sparse NOE-restraints and evolutionary distance restraints and tested on several protein structures >100...

  13. Inductance calculation of 3D superconducting structures with ground plane

    International Nuclear Information System (INIS)

    Teh, C.H.; Kitagawa, M.; Okabe, Y.

    1999-01-01

    An inductance calculation method, which is based on calculating the current distribution of a fluxoid-trapped superconducting loop by using the expression of momentum and the Maxwell equations, is reconstructed to enable calculation of arbitrary 3D structures which have a ground plane (GP). Calculation of the mutual inductances of the superconductor system is also incorporated into the algorithm. The method of images is used to save computational resources, and the mirror plane is demonstrated to be just at the effective penetration depth below the upper boundary of the GP. The algorithm offers accurate results with reasonable calculation time. (author)

  14. An Algebro-Topological Description of Protein Domain Structure

    Science.gov (United States)

    Penner, Robert Clark; Knudsen, Michael; Wiuf, Carsten; Andersen, Jørgen Ellegaard

    2011-01-01

    The space of possible protein structures appears vast and continuous, and the relationship between primary, secondary and tertiary structure levels is complex. Protein structure comparison and classification is therefore a difficult but important task since structure is a determinant for molecular interaction and function. We introduce a novel mathematical abstraction based on geometric topology to describe protein domain structure. Using the locations of the backbone atoms and the hydrogen bonds, we build a combinatorial object – a so-called fatgraph. The description is discrete yet gives rise to a 2-dimensional mathematical surface. Thus, each protein domain corresponds to a particular mathematical surface with characteristic topological invariants, such as the genus (number of holes) and the number of boundary components. Both invariants are global fatgraph features reflecting the interconnectivity of the domain by hydrogen bonds. We introduce the notion of robust variables, that is variables that are robust towards minor changes in the structure/fatgraph, and show that the genus and the number of boundary components are robust. Further, we invesigate the distribution of different fatgraph variables and show how only four variables are capable of distinguishing different folds. We use local (secondary) and global (tertiary) fatgraph features to describe domain structures and illustrate that they are useful for classification of domains in CATH. In addition, we combine our method with two other methods thereby using primary, secondary, and tertiary structure information, and show that we can identify a large percentage of new and unclassified structures in CATH. PMID:21629687

  15. Protein Structure Classification and Loop Modeling Using Multiple Ramachandran Distributions

    KAUST Repository

    Najibi, Seyed Morteza; Maadooliat, Mehdi; Zhou, Lan; Huang, Jianhua Z.; Gao, Xin

    2017-01-01

    Recently, the study of protein structures using angular representations has attracted much attention among structural biologists. The main challenge is how to efficiently model the continuous conformational space of the protein structures based on the differences and similarities between different Ramachandran plots. Despite the presence of statistical methods for modeling angular data of proteins, there is still a substantial need for more sophisticated and faster statistical tools to model the large-scale circular datasets. To address this need, we have developed a nonparametric method for collective estimation of multiple bivariate density functions for a collection of populations of protein backbone angles. The proposed method takes into account the circular nature of the angular data using trigonometric spline which is more efficient compared to existing methods. This collective density estimation approach is widely applicable when there is a need to estimate multiple density functions from different populations with common features. Moreover, the coefficients of adaptive basis expansion for the fitted densities provide a low-dimensional representation that is useful for visualization, clustering, and classification of the densities. The proposed method provides a novel and unique perspective to two important and challenging problems in protein structure research: structure-based protein classification and angular-sampling-based protein loop structure prediction.

  16. Protein Structure Classification and Loop Modeling Using Multiple Ramachandran Distributions

    KAUST Repository

    Najibi, Seyed Morteza

    2017-02-08

    Recently, the study of protein structures using angular representations has attracted much attention among structural biologists. The main challenge is how to efficiently model the continuous conformational space of the protein structures based on the differences and similarities between different Ramachandran plots. Despite the presence of statistical methods for modeling angular data of proteins, there is still a substantial need for more sophisticated and faster statistical tools to model the large-scale circular datasets. To address this need, we have developed a nonparametric method for collective estimation of multiple bivariate density functions for a collection of populations of protein backbone angles. The proposed method takes into account the circular nature of the angular data using trigonometric spline which is more efficient compared to existing methods. This collective density estimation approach is widely applicable when there is a need to estimate multiple density functions from different populations with common features. Moreover, the coefficients of adaptive basis expansion for the fitted densities provide a low-dimensional representation that is useful for visualization, clustering, and classification of the densities. The proposed method provides a novel and unique perspective to two important and challenging problems in protein structure research: structure-based protein classification and angular-sampling-based protein loop structure prediction.

  17. Density functional study of molecular interactions in secondary structures of proteins.

    Science.gov (United States)

    Takano, Yu; Kusaka, Ayumi; Nakamura, Haruki

    2016-01-01

    Proteins play diverse and vital roles in biology, which are dominated by their three-dimensional structures. The three-dimensional structure of a protein determines its functions and chemical properties. Protein secondary structures, including α-helices and β-sheets, are key components of the protein architecture. Molecular interactions, in particular hydrogen bonds, play significant roles in the formation of protein secondary structures. Precise and quantitative estimations of these interactions are required to understand the principles underlying the formation of three-dimensional protein structures. In the present study, we have investigated the molecular interactions in α-helices and β-sheets, using ab initio wave function-based methods, the Hartree-Fock method (HF) and the second-order Møller-Plesset perturbation theory (MP2), density functional theory, and molecular mechanics. The characteristic interactions essential for forming the secondary structures are discussed quantitatively.

  18. Protein crystal structure analysis using synchrotron radiation at atomic resolution

    International Nuclear Information System (INIS)

    Nonaka, Takamasa

    1999-01-01

    We can now obtain a detailed picture of protein, allowing the identification of individual atoms, by interpreting the diffraction of X-rays from a protein crystal at atomic resolution, 1.2 A or better. As of this writing, about 45 unique protein structures beyond 1.2 A resolution have been deposited in the Protein Data Bank. This review provides a simplified overview of how protein crystallographers use such diffraction data to solve, refine, and validate protein structures. (author)

  19. Structure and Calcium Binding Properties of a Neuronal Calcium-Myristoyl Switch Protein, Visinin-Like Protein 3.

    Science.gov (United States)

    Li, Congmin; Lim, Sunghyuk; Braunewell, Karl H; Ames, James B

    2016-01-01

    Visinin-like protein 3 (VILIP-3) belongs to a family of Ca2+-myristoyl switch proteins that regulate signal transduction in the brain and retina. Here we analyze Ca2+ binding, characterize Ca2+-induced conformational changes, and determine the NMR structure of myristoylated VILIP-3. Three Ca2+ bind cooperatively to VILIP-3 at EF2, EF3 and EF4 (KD = 0.52 μM and Hill slope of 1.8). NMR assignments, mutagenesis and structural analysis indicate that the covalently attached myristoyl group is solvent exposed in Ca2+-bound VILIP-3, whereas Ca2+-free VILIP-3 contains a sequestered myristoyl group that interacts with protein residues (E26, Y64, V68), which are distinct from myristate contacts seen in other Ca2+-myristoyl switch proteins. The myristoyl group in VILIP-3 forms an unusual L-shaped structure that places the C14 methyl group inside a shallow protein groove, in contrast to the much deeper myristoyl binding pockets observed for recoverin, NCS-1 and GCAP1. Thus, the myristoylated VILIP-3 protein structure determined in this study is quite different from those of other known myristoyl switch proteins (recoverin, NCS-1, and GCAP1). We propose that myristoylation serves to fine tune the three-dimensional structures of neuronal calcium sensor proteins as a means of generating functional diversity.

  20. Chemical cross-linking and mass spectrometry for protein structural modeling

    NARCIS (Netherlands)

    Back, Jaap Willem; de Jong, Luitzen; Muijsers, Anton O.; de Koster, Chris G.

    2003-01-01

    The growth of gene and protein sequence information is currently so rapid that three-dimensional structural information is lacking for the overwhelming majority of known proteins. In this review, efforts towards rapid and sensitive methods for protein structural characterization are described,

  1. Analyzing the simplicial decomposition of spatial protein structures

    Directory of Open Access Journals (Sweden)

    Szabadka Zoltán

    2008-02-01

    Full Text Available Abstract Background The fast growing Protein Data Bank contains the three-dimensional description of more than 45000 protein- and nucleic-acid structures today. The large majority of the data in the PDB are measured by X-ray crystallography by thousands of researchers in millions of work-hours. Unfortunately, lots of structural errors, bad labels, missing atoms, falsely identified chains and groups make dificult the automated processing of this treasury of structural biological data. Results After we performed a rigorous re-structuring of the whole PDB on graph-theoretical basis, we created the RS-PDB (Rich-Structure PDB database. Using this cleaned and repaired database, we defined simplicial complexes on the heavy-atoms of the PDB, and analyzed the tetrahedra for geometric properties. Conclusion We have found surprisingly characteristic differences between simplices with atomic vertices of different types, and between the atomic neighborhoods – described also by simplices – of different ligand atoms in proteins.

  2. A Structural Perspective on the Modulation of Protein-Protein Interactions with Small Molecules.

    Science.gov (United States)

    Demirel, Habibe Cansu; Dogan, Tunca; Tuncbag, Nurcan

    2018-05-31

    Protein-protein interactions (PPIs) are the key components in many cellular processes including signaling pathways, enzymatic reactions and epigenetic regulation. Abnormal interactions of some proteins may be pathogenic and cause various disorders including cancer and neurodegenerative diseases. Although inhibiting PPIs with small molecules is a challenging task, it gained an increasing interest because of its strong potential for drug discovery and design. The knowledge of the interface as well as the structural and chemical characteristics of the PPIs and their roles in the cellular pathways are necessary for a rational design of small molecules to modulate PPIs. In this study, we review the recent progress in the field and detail the physicochemical properties of PPIs including binding hot spots with a focus on structural methods. Then, we review recent approaches for structural prediction of PPIs. Finally, we revisit the concept of targeting PPIs in a systems biology perspective and we refer to the non-structural approaches, usually employed when the structural information is not present. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. On the atomic shell structure calculation (1)

    International Nuclear Information System (INIS)

    Choe Sun Chol

    1986-01-01

    We have considered the problem of atomic shell structure calculation using operator technique. We introduce reduced matrix elements of annihilation operators according to eg. (4). The normalized basis function is denoted as || ...>. The reduced matrix elements of the pair annihilation operators are expressed throw one-electron matrix elements. Some numerical results are represented and the problem of sign assignment is discussed. (author)

  4. Sequential Release of Proteins from Structured Multishell Microcapsules.

    Science.gov (United States)

    Shimanovich, Ulyana; Michaels, Thomas C T; De Genst, Erwin; Matak-Vinkovic, Dijana; Dobson, Christopher M; Knowles, Tuomas P J

    2017-10-09

    In nature, a wide range of functional materials is based on proteins. Increasing attention is also turning to the use of proteins as artificial biomaterials in the form of films, gels, particles, and fibrils that offer great potential for applications in areas ranging from molecular medicine to materials science. To date, however, most such applications have been limited to single component materials despite the fact that their natural analogues are composed of multiple types of proteins with a variety of functionalities that are coassembled in a highly organized manner on the micrometer scale, a process that is currently challenging to achieve in the laboratory. Here, we demonstrate the fabrication of multicomponent protein microcapsules where the different components are positioned in a controlled manner. We use molecular self-assembly to generate multicomponent structures on the nanometer scale and droplet microfluidics to bring together the different components on the micrometer scale. Using this approach, we synthesize a wide range of multiprotein microcapsules containing three well-characterized proteins: glucagon, insulin, and lysozyme. The localization of each protein component in multishell microcapsules has been detected by labeling protein molecules with different fluorophores, and the final three-dimensional microcapsule structure has been resolved by using confocal microscopy together with image analysis techniques. In addition, we show that these structures can be used to tailor the release of such functional proteins in a sequential manner. Moreover, our observations demonstrate that the protein release mechanism from multishell capsules is driven by the kinetic control of mass transport of the cargo and by the dissolution of the shells. The ability to generate artificial materials that incorporate a variety of different proteins with distinct functionalities increases the breadth of the potential applications of artificial protein-based materials

  5. EVA: continuous automatic evaluation of protein structure prediction servers.

    Science.gov (United States)

    Eyrich, V A; Martí-Renom, M A; Przybylski, D; Madhusudhan, M S; Fiser, A; Pazos, F; Valencia, A; Sali, A; Rost, B

    2001-12-01

    Evaluation of protein structure prediction methods is difficult and time-consuming. Here, we describe EVA, a web server for assessing protein structure prediction methods, in an automated, continuous and large-scale fashion. Currently, EVA evaluates the performance of a variety of prediction methods available through the internet. Every week, the sequences of the latest experimentally determined protein structures are sent to prediction servers, results are collected, performance is evaluated, and a summary is published on the web. EVA has so far collected data for more than 3000 protein chains. These results may provide valuable insight to both developers and users of prediction methods. http://cubic.bioc.columbia.edu/eva. eva@cubic.bioc.columbia.edu

  6. Positively-charged semi-tunnel is a structural and surface characteristic of polyphosphate-binding proteins: an in-silico study.

    Directory of Open Access Journals (Sweden)

    Zheng Zachory Wei

    Full Text Available Phosphate is essential for all major life processes, especially energy metabolism and signal transduction. A linear phosphate polymer, polyphosphate (polyP, linked by high-energy phosphoanhydride bonds, can interact with various proteins, playing important roles as an energy source and regulatory factor. However, polyP-binding structures are largely unknown. Here we proposed a putative polyP binding site, a positively-charged semi-tunnel (PCST, identified by surface electrostatics analyses in polyP kinases (PPKs and many other polyP-related proteins. We found that the PCSTs in varied proteins were folded in different secondary structure compositions. Molecular docking calculations revealed a significant value for binding affinity to polyP in PCST-containing proteins. Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3. The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities. This should greatly enhance the understanding of the many physiological functions of protein-bound polyP and the involvement of polyP and polyP-binding proteins in various human diseases.

  7. Semi-empirical calculations on the structure of the uronium ion

    NARCIS (Netherlands)

    Harkema, Sybolt

    1972-01-01

    Semi-empirical calculations (CNDO/2) on the structure of the uronium ion are presented. Assuming a planar ion with fixed bond lengths, the bond angles involving the heavy atoms can be calculated with fair accuracy. Changes in bond length and angles, which occur upon protonation of the urea molecule,

  8. G-LoSA for Prediction of Protein-Ligand Binding Sites and Structures.

    Science.gov (United States)

    Lee, Hui Sun; Im, Wonpil

    2017-01-01

    Recent advances in high-throughput structure determination and computational protein structure prediction have significantly enriched the universe of protein structure. However, there is still a large gap between the number of available protein structures and that of proteins with annotated function in high accuracy. Computational structure-based protein function prediction has emerged to reduce this knowledge gap. The identification of a ligand binding site and its structure is critical to the determination of a protein's molecular function. We present a computational methodology for predicting small molecule ligand binding site and ligand structure using G-LoSA, our protein local structure alignment and similarity measurement tool. All the computational procedures described here can be easily implemented using G-LoSA Toolkit, a package of standalone software programs and preprocessed PDB structure libraries. G-LoSA and G-LoSA Toolkit are freely available to academic users at http://compbio.lehigh.edu/GLoSA . We also illustrate a case study to show the potential of our template-based approach harnessing G-LoSA for protein function prediction.

  9. SIRAH: a structurally unbiased coarse-grained force field for proteins with aqueous solvation and long-range electrostatics.

    Science.gov (United States)

    Darré, Leonardo; Machado, Matías Rodrigo; Brandner, Astrid Febe; González, Humberto Carlos; Ferreira, Sebastián; Pantano, Sergio

    2015-02-10

    Modeling of macromolecular structures and interactions represents an important challenge for computational biology, involving different time and length scales. However, this task can be facilitated through the use of coarse-grained (CG) models, which reduce the number of degrees of freedom and allow efficient exploration of complex conformational spaces. This article presents a new CG protein model named SIRAH, developed to work with explicit solvent and to capture sequence, temperature, and ionic strength effects in a topologically unbiased manner. SIRAH is implemented in GROMACS, and interactions are calculated using a standard pairwise Hamiltonian for classical molecular dynamics simulations. We present a set of simulations that test the capability of SIRAH to produce a qualitatively correct solvation on different amino acids, hydrophilic/hydrophobic interactions, and long-range electrostatic recognition leading to spontaneous association of unstructured peptides and stable structures of single polypeptides and protein-protein complexes.

  10. Overcoming barriers to membrane protein structure determination

    NARCIS (Netherlands)

    Bill, Roslyn M.; Henderson, Peter J. F.; Iwata, So; Kunji, Edmund R. S.; Michel, Hartmut; Neutze, Richard; Newstead, Simon; Poolman, Bert; Tate, Christopher G.; Vogel, Horst

    After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new

  11. De novo protein structure generation from incomplete chemical shift assignments

    Energy Technology Data Exchange (ETDEWEB)

    Shen Yang [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Vernon, Robert; Baker, David [University of Washington, Department of Biochemistry and Howard Hughes Medical Institute (United States); Bax, Ad [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)], E-mail: bax@nih.gov

    2009-02-15

    NMR chemical shifts provide important local structural information for proteins. Consistent structure generation from NMR chemical shift data has recently become feasible for proteins with sizes of up to 130 residues, and such structures are of a quality comparable to those obtained with the standard NMR protocol. This study investigates the influence of the completeness of chemical shift assignments on structures generated from chemical shifts. The Chemical-Shift-Rosetta (CS-Rosetta) protocol was used for de novo protein structure generation with various degrees of completeness of the chemical shift assignment, simulated by omission of entries in the experimental chemical shift data previously used for the initial demonstration of the CS-Rosetta approach. In addition, a new CS-Rosetta protocol is described that improves robustness of the method for proteins with missing or erroneous NMR chemical shift input data. This strategy, which uses traditional Rosetta for pre-filtering of the fragment selection process, is demonstrated for two paramagnetic proteins and also for two proteins with solid-state NMR chemical shift assignments.

  12. Soliton concepts and protein structure

    Science.gov (United States)

    Krokhotin, Andrei; Niemi, Antti J.; Peng, Xubiao

    2012-03-01

    Structural classification shows that the number of different protein folds is surprisingly small. It also appears that proteins are built in a modular fashion from a relatively small number of components. Here we propose that the modular building blocks are made of the dark soliton solution of a generalized discrete nonlinear Schrödinger equation. We find that practically all protein loops can be obtained simply by scaling the size and by joining together a number of copies of the soliton, one after another. The soliton has only two loop-specific parameters, and we compute their statistical distribution in the Protein Data Bank (PDB). We explicitly construct a collection of 200 sets of parameters, each determining a soliton profile that describes a different short loop. The ensuing profiles cover practically all those proteins in PDB that have a resolution which is better than 2.0 Å, with a precision such that the average root-mean-square distance between the loop and its soliton is less than the experimental B-factor fluctuation distance. We also present two examples that describe how the loop library can be employed both to model and to analyze folded proteins.

  13. NMR structure of the protein NP-247299.1: comparison with the crystal structure

    International Nuclear Information System (INIS)

    Jaudzems, Kristaps; Geralt, Michael; Serrano, Pedro; Mohanty, Biswaranjan; Horst, Reto; Pedrini, Bill; Elsliger, Marc-André; Wilson, Ian A.; Wüthrich, Kurt

    2010-01-01

    Comparison of the NMR and crystal structures of a protein determined using largely automated methods has enabled the interpretation of local differences in the highly similar structures. These differences are found in segments of higher B values in the crystal and correlate with dynamic processes on the NMR chemical shift timescale observed in solution. The NMR structure of the protein NP-247299.1 in solution at 313 K has been determined and is compared with the X-ray crystal structure, which was also solved in the Joint Center for Structural Genomics (JCSG) at 100 K and at 1.7 Å resolution. Both structures were obtained using the current largely automated crystallographic and solution NMR methods used by the JCSG. This paper assesses the accuracy and precision of the results from these recently established automated approaches, aiming for quantitative statements about the location of structure variations that may arise from either one of the methods used or from the different environments in solution and in the crystal. To evaluate the possible impact of the different software used for the crystallographic and the NMR structure determinations and analysis, the concept is introduced of reference structures, which are computed using the NMR software with input of upper-limit distance constraints derived from the molecular models representing the results of the two structure determinations. The use of this new approach is explored to quantify global differences that arise from the different methods of structure determination and analysis versus those that represent interesting local variations or dynamics. The near-identity of the protein core in the NMR and crystal structures thus provided a basis for the identification of complementary information from the two different methods. It was thus observed that locally increased crystallographic B values correlate with dynamic structural polymorphisms in solution, including that the solution state of the protein involves

  14. Structural entanglements in protein complexes

    Science.gov (United States)

    Zhao, Yani; Chwastyk, Mateusz; Cieplak, Marek

    2017-06-01

    We consider multi-chain protein native structures and propose a criterion that determines whether two chains in the system are entangled or not. The criterion is based on the behavior observed by pulling at both termini of each chain simultaneously in the two chains. We have identified about 900 entangled systems in the Protein Data Bank and provided a more detailed analysis for several of them. We argue that entanglement enhances the thermodynamic stability of the system but it may have other functions: burying the hydrophobic residues at the interface and increasing the DNA or RNA binding area. We also study the folding and stretching properties of the knotted dimeric proteins MJ0366, YibK, and bacteriophytochrome. These proteins have been studied theoretically in their monomeric versions so far. The dimers are seen to separate on stretching through the tensile mechanism and the characteristic unraveling force depends on the pulling direction.

  15. Diameter structure modeling and the calculation of plantation volume of black poplar clones

    Directory of Open Access Journals (Sweden)

    Andrašev Siniša

    2004-01-01

    Full Text Available A method of diameter structure modeling was applied in the calculation of plantation (stand volume of two black poplar clones in the section Aigeiros (Duby: 618 (Lux and S1-8. Diameter structure modeling by Weibull function makes it possible to calculate the plantation volume by volume line. Based on the comparison of the proposed method with the existing methods, the obtained error of plantation volume was less than 2%. Diameter structure modeling and the calculation of plantation volume by diameter structure model, by the regularity of diameter distribution, enables a better analysis of the production level and assortment structure and it can be used in the construction of yield and increment tables.

  16. Yellow fluorescent protein phiYFPv (Phialidium): structure and structure-based mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Pletneva, Nadya V.; Pletnev, Vladimir Z., E-mail: vzpletnev@gmail.com; Souslova, Ekaterina; Chudakov, Dmitry M. [Russian Academy of Sciences, Moscow (Russian Federation); Lukyanov, Sergey [Russian Academy of Sciences, Moscow (Russian Federation); Nizhny Novgorod State Medical Academy, Nizhny Novgorod (Russian Federation); Martynov, Vladimir I.; Arhipova, Svetlena; Artemyev, Igor [Russian Academy of Sciences, Moscow (Russian Federation); Wlodawer, Alexander [National Cancer Institute, Frederick, MD 21702 (United States); Dauter, Zbigniew [National Cancer Institute, Argonne, IL 60439 (United States); Pletnev, Sergei [National Cancer Institute, Argonne, IL 60439 (United States); SAIC-Frederick, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Russian Academy of Sciences, Moscow (Russian Federation)

    2013-06-01

    The yellow fluorescent protein phiYFPv with improved folding has been developed from the spectrally identical wild-type phiYFP found in the marine jellyfish Phialidium. The yellow fluorescent protein phiYFPv (λ{sub em}{sup max} ≃ 537 nm) with improved folding has been developed from the spectrally identical wild-type phiYFP found in the marine jellyfish Phialidium. The latter fluorescent protein is one of only two known cases of naturally occurring proteins that exhibit emission spectra in the yellow–orange range (535–555 nm). Here, the crystal structure of phiYFPv has been determined at 2.05 Å resolution. The ‘yellow’ chromophore formed from the sequence triad Thr65-Tyr66-Gly67 adopts the bicyclic structure typical of fluorophores emitting in the green spectral range. It was demonstrated that perfect antiparallel π-stacking of chromophore Tyr66 and the proximal Tyr203, as well as Val205, facing the chromophore phenolic ring are chiefly responsible for the observed yellow emission of phiYFPv at 537 nm. Structure-based site-directed mutagenesis has been used to identify the key functional residues in the chromophore environment. The obtained results have been utilized to improve the properties of phiYFPv and its homologous monomeric biomarker tagYFP.

  17. Photonic band structure calculations using nonlinear eigenvalue techniques

    International Nuclear Information System (INIS)

    Spence, Alastair; Poulton, Chris

    2005-01-01

    This paper considers the numerical computation of the photonic band structure of periodic materials such as photonic crystals. This calculation involves the solution of a Hermitian nonlinear eigenvalue problem. Numerical methods for nonlinear eigenvalue problems are usually based on Newton's method or are extensions of techniques for the standard eigenvalue problem. We present a new variation on existing methods which has its derivation in methods for bifurcation problems, where bordered matrices are used to compute critical points in singular systems. This new approach has several advantages over the current methods. First, in our numerical calculations the new variation is more robust than existing techniques, having a larger domain of convergence. Second, the linear systems remain Hermitian and are nonsingular as the method converges. Third, the approach provides an elegant and efficient way of both thinking about the problem and organising the computer solution so that only one linear system needs to be factorised at each stage in the solution process. Finally, first- and higher-order derivatives are calculated as a natural extension of the basic method, and this has advantages in the electromagnetic problem discussed here, where the band structure is plotted as a set of paths in the (ω,k) plane

  18. Structure-sequence based analysis for identification of conserved regions in proteins

    Science.gov (United States)

    Zemla, Adam T; Zhou, Carol E; Lam, Marisa W; Smith, Jason R; Pardes, Elizabeth

    2013-05-28

    Disclosed are computational methods, and associated hardware and software products for scoring conservation in a protein structure based on a computationally identified family or cluster of protein structures. A method of computationally identifying a family or cluster of protein structures in also disclosed herein.

  19. Protein Secondary Structure Prediction Using Deep Convolutional Neural Fields.

    Science.gov (United States)

    Wang, Sheng; Peng, Jian; Ma, Jianzhu; Xu, Jinbo

    2016-01-11

    Protein secondary structure (SS) prediction is important for studying protein structure and function. When only the sequence (profile) information is used as input feature, currently the best predictors can obtain ~80% Q3 accuracy, which has not been improved in the past decade. Here we present DeepCNF (Deep Convolutional Neural Fields) for protein SS prediction. DeepCNF is a Deep Learning extension of Conditional Neural Fields (CNF), which is an integration of Conditional Random Fields (CRF) and shallow neural networks. DeepCNF can model not only complex sequence-structure relationship by a deep hierarchical architecture, but also interdependency between adjacent SS labels, so it is much more powerful than CNF. Experimental results show that DeepCNF can obtain ~84% Q3 accuracy, ~85% SOV score, and ~72% Q8 accuracy, respectively, on the CASP and CAMEO test proteins, greatly outperforming currently popular predictors. As a general framework, DeepCNF can be used to predict other protein structure properties such as contact number, disorder regions, and solvent accessibility.

  20. Global nuclear-structure calculations

    International Nuclear Information System (INIS)

    Moeller, P.; Nix, J.R.

    1990-01-01

    The revival of interest in nuclear ground-state octupole deformations that occurred in the 1980's was stimulated by observations in 1980 of particularly large deviations between calculated and experimental masses in the Ra region, in a global calculation of nuclear ground-state masses. By minimizing the total potential energy with respect to octupole shape degrees of freedom in addition to ε 2 and ε 4 used originally, a vastly improved agreement between calculated and experimental masses was obtained. To study the global behavior and interrelationships between other nuclear properties, we calculate nuclear ground-state masses, spins, pairing gaps and Β-decay and half-lives and compare the results to experimental qualities. The calculations are based on the macroscopic-microscopic approach, with the microscopic contributions calculated in a folded-Yukawa single-particle potential

  1. G-protein-coupled receptor structures were not built in a day.

    Science.gov (United States)

    Blois, Tracy M; Bowie, James U

    2009-07-01

    Among the most exciting recent developments in structural biology is the structure determination of G-protein-coupled receptors (GPCRs), which comprise the largest class of membrane proteins in mammalian cells and have enormous importance for disease and drug development. The GPCR structures are perhaps the most visible examples of a nascent revolution in membrane protein structure determination. Like other major milestones in science, however, such as the sequencing of the human genome, these achievements were built on a hidden foundation of technological developments. Here, we describe some of the methods that are fueling the membrane protein structure revolution and have enabled the determination of the current GPCR structures, along with new techniques that may lead to future structures.

  2. Secondary Structure Prediction of Protein using Resilient Back Propagation Learning Algorithm

    Directory of Open Access Journals (Sweden)

    Jyotshna Dongardive

    2015-12-01

    Full Text Available The paper proposes a neural network based approach to predict secondary structure of protein. It uses Multilayer Feed Forward Network (MLFN with resilient back propagation as the learning algorithm. Point Accepted Mutation (PAM is adopted as the encoding scheme and CB396 data set is used for the training and testing of the network. Overall accuracy of the network has been experimentally calculated with different window sizes for the sliding window scheme and by varying the number of units in the hidden layer. The best results were obtained with eleven as the window size and seven as the number of units in the hidden layer.

  3. Structure and assembly of scalable porous protein cages

    Science.gov (United States)

    Sasaki, Eita; Böhringer, Daniel; van de Waterbeemd, Michiel; Leibundgut, Marc; Zschoche, Reinhard; Heck, Albert J. R.; Ban, Nenad; Hilvert, Donald

    2017-03-01

    Proteins that self-assemble into regular shell-like polyhedra are useful, both in nature and in the laboratory, as molecular containers. Here we describe cryo-electron microscopy (EM) structures of two versatile encapsulation systems that exploit engineered electrostatic interactions for cargo loading. We show that increasing the number of negative charges on the lumenal surface of lumazine synthase, a protein that naturally assembles into a ~1-MDa dodecahedron composed of 12 pentamers, induces stepwise expansion of the native protein shell, giving rise to thermostable ~3-MDa and ~6-MDa assemblies containing 180 and 360 subunits, respectively. Remarkably, these expanded particles assume unprecedented tetrahedrally and icosahedrally symmetric structures constructed entirely from pentameric units. Large keyhole-shaped pores in the shell, not present in the wild-type capsid, enable diffusion-limited encapsulation of complementarily charged guests. The structures of these supercharged assemblies demonstrate how programmed electrostatic effects can be effectively harnessed to tailor the architecture and properties of protein cages.

  4. Ab initio protein structure assembly using continuous structure fragments and optimized knowledge-based force field.

    Science.gov (United States)

    Xu, Dong; Zhang, Yang

    2012-07-01

    Ab initio protein folding is one of the major unsolved problems in computational biology owing to the difficulties in force field design and conformational search. We developed a novel program, QUARK, for template-free protein structure prediction. Query sequences are first broken into fragments of 1-20 residues where multiple fragment structures are retrieved at each position from unrelated experimental structures. Full-length structure models are then assembled from fragments using replica-exchange Monte Carlo simulations, which are guided by a composite knowledge-based force field. A number of novel energy terms and Monte Carlo movements are introduced and the particular contributions to enhancing the efficiency of both force field and search engine are analyzed in detail. QUARK prediction procedure is depicted and tested on the structure modeling of 145 nonhomologous proteins. Although no global templates are used and all fragments from experimental structures with template modeling score >0.5 are excluded, QUARK can successfully construct 3D models of correct folds in one-third cases of short proteins up to 100 residues. In the ninth community-wide Critical Assessment of protein Structure Prediction experiment, QUARK server outperformed the second and third best servers by 18 and 47% based on the cumulative Z-score of global distance test-total scores in the FM category. Although ab initio protein folding remains a significant challenge, these data demonstrate new progress toward the solution of the most important problem in the field. Copyright © 2012 Wiley Periodicals, Inc.

  5. Status and prospects for the calculation of hadron structure from lattice QCD

    International Nuclear Information System (INIS)

    Renner, Dru B.

    2010-02-01

    Lattice QCD calculations of hadron structure are a valuable complement to many experimental programs as well as an indispensable tool to understand the dynamics of QCD. I present a focused review of a few representative topics chosen to illustrate both the challenges and advances of our community: the momentum fraction, axial charge and charge radius of the nucleon. I will discuss the current status of these calculations and speculate on the prospects for accurate calculations of hadron structure from lattice QCD. (orig.)

  6. VoroMQA: Assessment of protein structure quality using interatomic contact areas.

    Science.gov (United States)

    Olechnovič, Kliment; Venclovas, Česlovas

    2017-06-01

    In the absence of experimentally determined protein structure many biological questions can be addressed using computational structural models. However, the utility of protein structural models depends on their quality. Therefore, the estimation of the quality of predicted structures is an important problem. One of the approaches to this problem is the use of knowledge-based statistical potentials. Such methods typically rely on the statistics of distances and angles of residue-residue or atom-atom interactions collected from experimentally determined structures. Here, we present VoroMQA (Voronoi tessellation-based Model Quality Assessment), a new method for the estimation of protein structure quality. Our method combines the idea of statistical potentials with the use of interatomic contact areas instead of distances. Contact areas, derived using Voronoi tessellation of protein structure, are used to describe and seamlessly integrate both explicit interactions between protein atoms and implicit interactions of protein atoms with solvent. VoroMQA produces scores at atomic, residue, and global levels, all in the fixed range from 0 to 1. The method was tested on the CASP data and compared to several other single-model quality assessment methods. VoroMQA showed strong performance in the recognition of the native structure and in the structural model selection tests, thus demonstrating the efficacy of interatomic contact areas in estimating protein structure quality. The software implementation of VoroMQA is freely available as a standalone application and as a web server at http://bioinformatics.lt/software/voromqa. Proteins 2017; 85:1131-1145. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Computational Calculation Of The Ionization Energies Of The Human Prion Protein By The Coarse-grain Method

    Science.gov (United States)

    Lyu, Justin; Andrianarijaona, V. M.

    2016-05-01

    The causes of the misfolding of prion protein -i.e. the transformation of PrPC to PrPSc - have not been clearly elucidated. Many studies have focused on identifying possible chemical conditions, such as pH, temperature and chemical denaturation, that may trigger the pathological transformation of prion proteins (Weiwei Tao, Gwonchan Yoon, Penghui Cao, `` β-sheet-like formation during the mechanical unfolding of prion protein'', The Journal of Chemical Physics, 2015, 143, 125101). Here, we attempt to calculate the ionization energies of the prion protein, which will be able to shed light onto the possible causes of the misfolding. We plan on using the coarse-grain method which allows for a more feasible calculation time by means of approximation. We believe that by being able to approximate the ionization potential, particularly that of the regions known to form stable β-strands of the PrPSc form, the possible sources of denaturation, be it chemical or mechanical, may be narrowed down.

  8. Inverse boundary element calculations based on structural modes

    DEFF Research Database (Denmark)

    Juhl, Peter Møller

    2007-01-01

    The inverse problem of calculating the flexural velocity of a radiating structure of a general shape from measurements in the field is often solved by combining a Boundary Element Method with the Singular Value Decomposition and a regularization technique. In their standard form these methods sol...

  9. Phylogenetic continuum indicates "galaxies" in the protein universe: preliminary results on the natural group structures of proteins.

    Science.gov (United States)

    Ladunga, I

    1992-04-01

    The markedly nonuniform, even systematic distribution of sequences in the protein "universe" has been analyzed by methods of protein taxonomy. Mapping of the natural hierarchical system of proteins has revealed some dense cores, i.e., well-defined clusterings of proteins that seem to be natural structural groupings, possibly seeds for a future protein taxonomy. The aim was not to force proteins into more or less man-made categories by discriminant analysis, but to find structurally similar groups, possibly of common evolutionary origin. Single-valued distance measures between pairs of superfamilies from the Protein Identification Resource were defined by two chi 2-like methods on tripeptide frequencies and the variable-length subsequence identity method derived from dot-matrix comparisons. Distance matrices were processed by several methods of cluster analysis to detect phylogenetic continuum between highly divergent proteins. Only well-defined clusters characterized by relatively unique structural, intracellular environmental, organismal, and functional attribute states were selected as major protein groups, including subsets of viral and Escherichia coli proteins, hormones, inhibitors, plant, ribosomal, serum and structural proteins, amino acid synthases, and clusters dominated by certain oxidoreductases and apolar and DNA-associated enzymes. The limited repertoire of functional patterns due to small genome size, the high rate of recombination, specific features of the bacterial membranes, or of the virus cycle canalize certain proteins of viruses and Gram-negative bacteria, respectively, to organismal groups.

  10. Structural basis of protein oxidation resistance: a lysozyme study.

    Directory of Open Access Journals (Sweden)

    Marion Girod

    Full Text Available Accumulation of oxidative damage in proteins correlates with aging since it can cause irreversible and progressive degeneration of almost all cellular functions. Apparently, native protein structures have evolved intrinsic resistance to oxidation since perfectly folded proteins are, by large most robust. Here we explore the structural basis of protein resistance to radiation-induced oxidation using chicken egg white lysozyme in the native and misfolded form. We study the differential resistance to oxidative damage of six different parts of native and misfolded lysozyme by a targeted tandem/mass spectrometry approach of its tryptic fragments. The decay of the amount of each lysozyme fragment with increasing radiation dose is found to be a two steps process, characterized by a double exponential evolution of their amounts: the first one can be largely attributed to oxidation of specific amino acids, while the second one corresponds to further degradation of the protein. By correlating these results to the structural parameters computed from molecular dynamics (MD simulations, we find the protein parts with increased root-mean-square deviation (RMSD to be more susceptible to modifications. In addition, involvement of amino acid side-chains in hydrogen bonds has a protective effect against oxidation Increased exposure to solvent of individual amino acid side chains correlates with high susceptibility to oxidative and other modifications like side chain fragmentation. Generally, while none of the structural parameters alone can account for the fate of peptides during radiation, together they provide an insight into the relationship between protein structure and susceptibility to oxidation.

  11. Crystal structure of human protein kinase CK2

    DEFF Research Database (Denmark)

    Niefind, K; Guerra, B; Ermakowa, I

    2001-01-01

    The crystal structure of a fully active form of human protein kinase CK2 (casein kinase 2) consisting of two C-terminally truncated catalytic and two regulatory subunits has been determined at 3.1 A resolution. In the CK2 complex the regulatory subunits form a stable dimer linking the two catalyt...... as a docking partner for various protein kinases. Furthermore it shows an inter-domain mobility in the catalytic subunit known to be functionally important in protein kinases and detected here for the first time directly within one crystal structure.......The crystal structure of a fully active form of human protein kinase CK2 (casein kinase 2) consisting of two C-terminally truncated catalytic and two regulatory subunits has been determined at 3.1 A resolution. In the CK2 complex the regulatory subunits form a stable dimer linking the two catalytic...... subunits, which make no direct contact with one another. Each catalytic subunit interacts with both regulatory chains, predominantly via an extended C-terminal tail of the regulatory subunit. The CK2 structure is consistent with its constitutive activity and with a flexible role of the regulatory subunit...

  12. Insulin as a model to teach three-dimensional structure of proteins

    Directory of Open Access Journals (Sweden)

    João Batista Teixeira da Rocha

    2018-02-01

    Proteins are the most ubiquitous macromolecules found in the living cells and have innumerous physiological functions. Therefore, it is fundamental to build a solid knowledge about the proteins three dimensional structure to better understand the living state. The hierarchical structure of proteins is usually studied in the undergraduate discipline of Biochemistry. Here we described pedagogical interventions designed to increase the preservice teacher chemistry students’ knowledge about protein structure. The activities were made using alternative and cheap materials to encourage the application of these simple methodologies by the future teachers in the secondary school. From the primary structure of insulin chains, students had to construct a three-dimensional structure of insulin. After the activities, the students highlighted an improvement of their previous knowledge about proteins structure. The construction of a tridimensional model together with other activities seems to be an efficient way to promote the learning about the structure of proteins to undergraduate students. The methodology used was inexpensiveness and simple and it can be used both in the university and in the high-school.

  13. Crystal structures of MW1337R and lin2004: Representatives of a novel protein family that adopt a four-helical bundle fold

    Energy Technology Data Exchange (ETDEWEB)

    Kozbial, Piotr; Xu, Qingping; Chiu, Hsiu-Ju; McMullan, Daniel; Krishna, S. Sri; Miller, Mitchell D.; Abdubek, Polat; Acosta, Claire; Astakhova, Tamara; Axelrod, Herbert L.; Carlton, Dennis; Clayton, Thomas; Deller, Marc; Duan, Lian; Elias, Ylva; Elsliger, Marc-André; Feuerhelm, Julie; Grzechnik, Slawomir K.; Hale, Joanna; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Koesema, Eric; Kumar, Abhinav; Marciano, David; Morse, Andrew T.; Murphy, Kevin D.; Nigoghossian, Edward; Okach, Linda; Oommachen, Silvya; Reyes, Ron; Rife, Christopher L.; Spraggon, Glen; Trout, Christina V.; ban den Bedem, Henry; Weekes, Dana; White, Aprilfawn; Wolf, Guenter; Zubieta, Chloe; Hodgson, Keith O.; Wooley, John; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A. (Scripps); (SSRL); (JCSG); (UCSD); (Burnham)

    2009-08-28

    To extend the structural coverage of proteins with unknown functions, we targeted a novel protein family (Pfam accession number PF08807, DUF1798) for which we proposed and determined the structures of two representative members. The MW1337R gene of Staphylococcus aureus subsp. aureus Rosenbach (Wood 46) encodes a protein with a molecular weight of 13.8 kDa (residues 1-116) and a calculated isoelectric point of 5.15. The lin2004 gene of the nonspore-forming bacterium Listeria innocua Clip11262 encodes a protein with a molecular weight of 14.6 kDa (residues 1-121) and a calculated isoelectric point of 5.45. MW1337R and lin2004, as well as their homologs, which, so far, have been found only in Bacillus, Staphylococcus, Listeria, and related genera (Geobacillus, Exiguobacterium, and Oceanobacillus), have unknown functions and are annotated as hypothetical proteins. The genomic contexts of MW1337R and lin2004 are similar and conserved in related species. In prokaryotic genomes, most often, functionally interacting proteins are coded by genes, which are colocated in conserved operons. Proteins from the same operon as MW1337R and lin2004 either have unknown functions (i.e., belong to DUF1273, Pfam accession number PF06908) or are similar to ypsB from Bacillus subtilis. The function of ypsB is unclear, although it has a strong similarity to the N-terminal region of DivIVA, which was characterized as a bifunctional protein with distinct roles during vegetative growth and sporulation. In addition, members of the DUF1273 family display distant sequence similarity with the DprA/Smf protein, which acts downstream of the DNA uptake machinery, possibly in conjunction with RecA. The RecA activities in Bacillus subtilis are modulated by RecU Holliday-junction resolvase. In all analyzed cases, the gene coding for RecU is in the vicinity of MW1337R, lin2004, or their orthologs, but on a different operon located in the complementary DNA strand. Here, we report the crystal structures

  14. Systematic comparison of crystal and NMR protein structures deposited in the protein data bank.

    Science.gov (United States)

    Sikic, Kresimir; Tomic, Sanja; Carugo, Oliviero

    2010-09-03

    Nearly all the macromolecular three-dimensional structures deposited in Protein Data Bank were determined by either crystallographic (X-ray) or Nuclear Magnetic Resonance (NMR) spectroscopic methods. This paper reports a systematic comparison of the crystallographic and NMR results deposited in the files of the Protein Data Bank, in order to find out to which extent these information can be aggregated in bioinformatics. A non-redundant data set containing 109 NMR - X-ray structure pairs of nearly identical proteins was derived from the Protein Data Bank. A series of comparisons were performed by focusing the attention towards both global features and local details. It was observed that: (1) the RMDS values between NMR and crystal structures range from about 1.5 Å to about 2.5 Å; (2) the correlation between conformational deviations and residue type reveals that hydrophobic amino acids are more similar in crystal and NMR structures than hydrophilic amino acids; (3) the correlation between solvent accessibility of the residues and their conformational variability in solid state and in solution is relatively modest (correlation coefficient = 0.462); (4) beta strands on average match better between NMR and crystal structures than helices and loops; (5) conformational differences between loops are independent of crystal packing interactions in the solid state; (6) very seldom, side chains buried in the protein interior are observed to adopt different orientations in the solid state and in solution.

  15. A computational tool to predict the evolutionarily conserved protein-protein interaction hot-spot residues from the structure of the unbound protein.

    Science.gov (United States)

    Agrawal, Neeraj J; Helk, Bernhard; Trout, Bernhardt L

    2014-01-21

    Identifying hot-spot residues - residues that are critical to protein-protein binding - can help to elucidate a protein's function and assist in designing therapeutic molecules to target those residues. We present a novel computational tool, termed spatial-interaction-map (SIM), to predict the hot-spot residues of an evolutionarily conserved protein-protein interaction from the structure of an unbound protein alone. SIM can predict the protein hot-spot residues with an accuracy of 36-57%. Thus, the SIM tool can be used to predict the yet unknown hot-spot residues for many proteins for which the structure of the protein-protein complexes are not available, thereby providing a clue to their functions and an opportunity to design therapeutic molecules to target these proteins. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  16. Pressure induced structural phase transition of OsB2: First-principles calculations

    International Nuclear Information System (INIS)

    Ren Fengzhu; Wang Yuanxu; Lo, V.C.

    2010-01-01

    Orthorhombic OsB 2 was synthesized at 1000 deg. C and its compressibility was measured by using the high-pressure X-ray diffraction in a Diacell diamond anvil cell from ambient pressure to 32 GPa [R.W. Cumberland, et al. (2005)]. First-principles calculations were performed to study the possibility of the phase transition of OsB 2 . An analysis of the calculated enthalpy shows that orthorhombic OsB 2 can transfer to the hexagonal phase at 10.8 GPa. The calculated results with the quasi-harmonic approximation indicate that this phase transition pressure is little affected by the thermal effect. The calculated phonon band structure shows that the hexagonal P 6 3 /mmc structure (high-pressure phase) is stable for OsB 2 . We expect the phase transition can be further confirmed by the experimental work. - Abstract: Graphical Abstract Legend (TOC Figure): Table of Contents Figure Pressure induced structural phase transition from the orthorhombic structure to the hexagonal one for OsB 2 takes place under 10.8 GPa (0 K), 10.35 GPa (300, 1000 K) by the first-principles predictions.

  17. Heterochiral Knottin Protein: Folding and Solution Structure.

    Science.gov (United States)

    Mong, Surin K; Cochran, Frank V; Yu, Hongtao; Graziano, Zachary; Lin, Yu-Shan; Cochran, Jennifer R; Pentelute, Bradley L

    2017-10-31

    Homochirality is a general feature of biological macromolecules, and Nature includes few examples of heterochiral proteins. Herein, we report on the design, chemical synthesis, and structural characterization of heterochiral proteins possessing loops of amino acids of chirality opposite to that of the rest of a protein scaffold. Using the protein Ecballium elaterium trypsin inhibitor II, we discover that selective β-alanine substitution favors the efficient folding of our heterochiral constructs. Solution nuclear magnetic resonance spectroscopy of one such heterochiral protein reveals a homogeneous global fold. Additionally, steered molecular dynamics simulation indicate β-alanine reduces the free energy required to fold the protein. We also find these heterochiral proteins to be more resistant to proteolysis than homochiral l-proteins. This work informs the design of heterochiral protein architectures containing stretches of both d- and l-amino acids.

  18. Structural features that predict real-value fluctuations of globular proteins.

    Science.gov (United States)

    Jamroz, Michal; Kolinski, Andrzej; Kihara, Daisuke

    2012-05-01

    It is crucial to consider dynamics for understanding the biological function of proteins. We used a large number of molecular dynamics (MD) trajectories of nonhomologous proteins as references and examined static structural features of proteins that are most relevant to fluctuations. We examined correlation of individual structural features with fluctuations and further investigated effective combinations of features for predicting the real value of residue fluctuations using the support vector regression (SVR). It was found that some structural features have higher correlation than crystallographic B-factors with fluctuations observed in MD trajectories. Moreover, SVR that uses combinations of static structural features showed accurate prediction of fluctuations with an average Pearson's correlation coefficient of 0.669 and a root mean square error of 1.04 Å. This correlation coefficient is higher than the one observed in predictions by the Gaussian network model (GNM). An advantage of the developed method over the GNMs is that the former predicts the real value of fluctuation. The results help improve our understanding of relationships between protein structure and fluctuation. Furthermore, the developed method provides a convienient practial way to predict fluctuations of proteins using easily computed static structural features of proteins. Copyright © 2012 Wiley Periodicals, Inc.

  19. Chiral nucleon-nucleon forces in nuclear structure calculations

    Directory of Open Access Journals (Sweden)

    Coraggio L.

    2016-01-01

    Full Text Available Realistic nuclear potentials, derived within chiral perturbation theory, are a major breakthrough in modern nuclear structure theory, since they provide a direct link between nuclear physics and its underlying theory, namely the QCD. As a matter of fact, chiral potentials are tailored on the low-energy regime of nuclear structure physics, and chiral perturbation theory provides on the same footing two-nucleon forces as well as many-body ones. This feature fits well with modern advances in ab-initio methods and realistic shell-model. Here, we will review recent nuclear structure calculations, based on realistic chiral potentials, for both finite nuclei and infinite nuclear matter.

  20. Human cancer protein-protein interaction network: a structural perspective.

    Directory of Open Access Journals (Sweden)

    Gozde Kar

    2009-12-01

    Full Text Available Protein-protein interaction networks provide a global picture of cellular function and biological processes. Some proteins act as hub proteins, highly connected to others, whereas some others have few interactions. The dysfunction of some interactions causes many diseases, including cancer. Proteins interact through their interfaces. Therefore, studying the interface properties of cancer-related proteins will help explain their role in the interaction networks. Similar or overlapping binding sites should be used repeatedly in single interface hub proteins, making them promiscuous. Alternatively, multi-interface hub proteins make use of several distinct binding sites to bind to different partners. We propose a methodology to integrate protein interfaces into cancer interaction networks (ciSPIN, cancer structural protein interface network. The interactions in the human protein interaction network are replaced by interfaces, coming from either known or predicted complexes. We provide a detailed analysis of cancer related human protein-protein interfaces and the topological properties of the cancer network. The results reveal that cancer-related proteins have smaller, more planar, more charged and less hydrophobic binding sites than non-cancer proteins, which may indicate low affinity and high specificity of the cancer-related interactions. We also classified the genes in ciSPIN according to phenotypes. Within phenotypes, for breast cancer, colorectal cancer and leukemia, interface properties were found to be discriminating from non-cancer interfaces with an accuracy of 71%, 67%, 61%, respectively. In addition, cancer-related proteins tend to interact with their partners through distinct interfaces, corresponding mostly to multi-interface hubs, which comprise 56% of cancer-related proteins, and constituting the nodes with higher essentiality in the network (76%. We illustrate the interface related affinity properties of two cancer-related hub

  1. BioJava-ModFinder: identification of protein modifications in 3D structures from the Protein Data Bank.

    Science.gov (United States)

    Gao, Jianjiong; Prlic, Andreas; Bi, Chunxiao; Bluhm, Wolfgang F; Dimitropoulos, Dimitris; Xu, Dong; Bourne, Philip E; Rose, Peter W

    2017-07-01

    We developed a new software tool, BioJava-ModFinder, for identifying protein modifications observed in 3D structures archived in the Protein Data Bank (PDB). Information on more than 400 types of protein modifications were collected and curated from annotations in PDB, RESID, and PSI-MOD. We divided these modifications into three categories: modified residues, attachment modifications, and cross-links. We have developed a systematic method to identify these modifications in 3D protein structures. We have integrated this package with the RCSB PDB web application and added protein modification annotations to the sequence diagram and structure display. By scanning all 3D structures in the PDB using BioJava-ModFinder, we identified more than 30 000 structures with protein modifications, which can be searched, browsed, and visualized on the RCSB PDB website. BioJava-ModFinder is available as open source (LGPL license) at ( https://github.com/biojava/biojava/tree/master/biojava-modfinder ). The RCSB PDB can be accessed at http://www.rcsb.org . pwrose@ucsd.edu. © The Author 2017. Published by Oxford University Press.

  2. Exact calculation of loop formation probability identifies folding motifs in RNA secondary structures

    Science.gov (United States)

    Sloma, Michael F.; Mathews, David H.

    2016-01-01

    RNA secondary structure prediction is widely used to analyze RNA sequences. In an RNA partition function calculation, free energy nearest neighbor parameters are used in a dynamic programming algorithm to estimate statistical properties of the secondary structure ensemble. Previously, partition functions have largely been used to estimate the probability that a given pair of nucleotides form a base pair, the conditional stacking probability, the accessibility to binding of a continuous stretch of nucleotides, or a representative sample of RNA structures. Here it is demonstrated that an RNA partition function can also be used to calculate the exact probability of formation of hairpin loops, internal loops, bulge loops, or multibranch loops at a given position. This calculation can also be used to estimate the probability of formation of specific helices. Benchmarking on a set of RNA sequences with known secondary structures indicated that loops that were calculated to be more probable were more likely to be present in the known structure than less probable loops. Furthermore, highly probable loops are more likely to be in the known structure than the set of loops predicted in the lowest free energy structures. PMID:27852924

  3. Structure of the ordered hydration of amino acids in proteins: analysis of crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Biedermannová, Lada, E-mail: lada.biedermannova@ibt.cas.cz; Schneider, Bohdan [Institute of Biotechnology CAS, Videnska 1083, 142 20 Prague (Czech Republic)

    2015-10-27

    The hydration of protein crystal structures was studied at the level of individual amino acids. The dependence of the number of water molecules and their preferred spatial localization on various parameters, such as solvent accessibility, secondary structure and side-chain conformation, was determined. Crystallography provides unique information about the arrangement of water molecules near protein surfaces. Using a nonredundant set of 2818 protein crystal structures with a resolution of better than 1.8 Å, the extent and structure of the hydration shell of all 20 standard amino-acid residues were analyzed as function of the residue conformation, secondary structure and solvent accessibility. The results show how hydration depends on the amino-acid conformation and the environment in which it occurs. After conformational clustering of individual residues, the density distribution of water molecules was compiled and the preferred hydration sites were determined as maxima in the pseudo-electron-density representation of water distributions. Many hydration sites interact with both main-chain and side-chain amino-acid atoms, and several occurrences of hydration sites with less canonical contacts, such as carbon–donor hydrogen bonds, OH–π interactions and off-plane interactions with aromatic heteroatoms, are also reported. Information about the location and relative importance of the empirically determined preferred hydration sites in proteins has applications in improving the current methods of hydration-site prediction in molecular replacement, ab initio protein structure prediction and the set-up of molecular-dynamics simulations.

  4. The Expanded FindCore Method for Identification of a Core Atom Set for Assessment of Protein Structure Prediction

    Science.gov (United States)

    Snyder, David A.; Grullon, Jennifer; Huang, Yuanpeng J.; Tejero, Roberto; Montelione, Gaetano T.

    2014-01-01

    Maximizing the scientific impact of NMR-based structure determination requires robust and statistically sound methods for assessing the precision of NMR-derived structures. In particular, a method to define a core atom set for calculating superimpositions and validating structure predictions is critical to the use of NMR-derived structures as targets in the CASP competition. FindCore (D.A. Snyder and G.T. Montelione PROTEINS 2005;59:673–686) is a superimposition independent method for identifying a core atom set, and partitioning that set into domains. However, as FindCore optimizes superimposition by sensitively excluding not-well-defined atoms, the FindCore core may not comprise all atoms suitable for use in certain applications of NMR structures, including the CASP assessment process. Adapting the FindCore approach to assess predicted models against experimental NMR structures in CASP10 required modification of the FindCore method. This paper describes conventions and a standard protocol to calculate an “Expanded FindCore” atom set suitable for validation and application in biological and biophysical contexts. A key application of the Expanded FindCore method is to identify a core set of atoms in the experimental NMR structure for which it makes sense to validate predicted protein structure models. We demonstrate the application of this Expanded FindCore method in characterizing well-defined regions of 18 NMR-derived CASP10 target structures. The Expanded FindCore protocol defines “expanded core atom sets” that match an expert’s intuition of which parts of the structure are sufficiently well-defined to use in assessing CASP model predictions. We also illustrate the impact of this analysis on the CASP GDT assessment scores. PMID:24327305

  5. Structure and Dynamic Properties of Membrane Proteins using NMR

    DEFF Research Database (Denmark)

    Rösner, Heike; Kragelund, Birthe

    2012-01-01

    conformational changes. Their structural and functional decoding is challenging and has imposed demanding experimental development. Solution nuclear magnetic resonance (NMR) spectroscopy is one of the techniques providing the capacity to make a significant difference in the deciphering of the membrane protein...... structure-function paradigm. The method has evolved dramatically during the last decade resulting in a plethora of new experiments leading to a significant increase in the scientific repertoire for studying membrane proteins. Besides solving the three-dimensional structures using state-of-the-art approaches......-populated states, this review seeks to introduce the vast possibilities solution NMR can offer to the study of membrane protein structure-function analyses with special focus on applicability. © 2012 American Physiological Society. Compr Physiol 2:1491-1539, 2012....

  6. Thermal green protein, an extremely stable, nonaggregating fluorescent protein created by structure-guided surface engineering.

    Science.gov (United States)

    Close, Devin W; Paul, Craig Don; Langan, Patricia S; Wilce, Matthew C J; Traore, Daouda A K; Halfmann, Randal; Rocha, Reginaldo C; Waldo, Geoffery S; Payne, Riley J; Rucker, Joseph B; Prescott, Mark; Bradbury, Andrew R M

    2015-07-01

    In this article, we describe the engineering and X-ray crystal structure of Thermal Green Protein (TGP), an extremely stable, highly soluble, non-aggregating green fluorescent protein. TGP is a soluble variant of the fluorescent protein eCGP123, which despite being highly stable, has proven to be aggregation-prone. The X-ray crystal structure of eCGP123, also determined within the context of this paper, was used to carry out rational surface engineering to improve its solubility, leading to TGP. The approach involved simultaneously eliminating crystal lattice contacts while increasing the overall negative charge of the protein. Despite intentional disruption of lattice contacts and introduction of high entropy glutamate side chains, TGP crystallized readily in a number of different conditions and the X-ray crystal structure of TGP was determined to 1.9 Å resolution. The structural reasons for the enhanced stability of TGP and eCGP123 are discussed. We demonstrate the utility of using TGP as a fusion partner in various assays and significantly, in amyloid assays in which the standard fluorescent protein, EGFP, is undesirable because of aberrant oligomerization. © 2014 Wiley Periodicals, Inc.

  7. Structure of haze forming proteins in white wines: Vitis vinifera thaumatin-like proteins.

    Science.gov (United States)

    Marangon, Matteo; Van Sluyter, Steven C; Waters, Elizabeth J; Menz, Robert I

    2014-01-01

    Grape thaumatin-like proteins (TLPs) play roles in plant-pathogen interactions and can cause protein haze in white wine unless removed prior to bottling. Different isoforms of TLPs have different hazing potential and aggregation behavior. Here we present the elucidation of the molecular structures of three grape TLPs that display different hazing potential. The three TLPs have very similar structures despite belonging to two different classes (F2/4JRU is a thaumatin-like protein while I/4L5H and H2/4MBT are VVTL1), and having different unfolding temperatures (56 vs. 62°C), with protein F2/4JRU being heat unstable and forming haze, while I/4L5H does not. These differences in properties are attributable to the conformation of a single loop and the amino acid composition of its flanking regions.

  8. Structural Conservation of the Myoviridae Phage Tail Sheath Protein Fold

    Energy Technology Data Exchange (ETDEWEB)

    Aksyuk, Anastasia A.; Kurochkina, Lidia P.; Fokine, Andrei; Forouhar, Farhad; Mesyanzhinov, Vadim V.; Tong, Liang; Rossmann, Michael G. (SOIBC); (Purdue); (Columbia)

    2012-02-21

    Bacteriophage phiKZ is a giant phage that infects Pseudomonas aeruginosa, a human pathogen. The phiKZ virion consists of a 1450 {angstrom} diameter icosahedral head and a 2000 {angstrom}-long contractile tail. The structure of the whole virus was previously reported, showing that its tail organization in the extended state is similar to the well-studied Myovirus bacteriophage T4 tail. The crystal structure of a tail sheath protein fragment of phiKZ was determined to 2.4 {angstrom} resolution. Furthermore, crystal structures of two prophage tail sheath proteins were determined to 1.9 and 3.3 {angstrom} resolution. Despite low sequence identity between these proteins, all of these structures have a similar fold. The crystal structure of the phiKZ tail sheath protein has been fitted into cryo-electron-microscopy reconstructions of the extended tail sheath and of a polysheath. The structural rearrangement of the phiKZ tail sheath contraction was found to be similar to that of phage T4.

  9. Multilevel domain decomposition for electronic structure calculations

    International Nuclear Information System (INIS)

    Barrault, M.; Cances, E.; Hager, W.W.; Le Bris, C.

    2007-01-01

    We introduce a new multilevel domain decomposition method (MDD) for electronic structure calculations within semi-empirical and density functional theory (DFT) frameworks. This method iterates between local fine solvers and global coarse solvers, in the spirit of domain decomposition methods. Using this approach, calculations have been successfully performed on several linear polymer chains containing up to 40,000 atoms and 200,000 atomic orbitals. Both the computational cost and the memory requirement scale linearly with the number of atoms. Additional speed-up can easily be obtained by parallelization. We show that this domain decomposition method outperforms the density matrix minimization (DMM) method for poor initial guesses. Our method provides an efficient preconditioner for DMM and other linear scaling methods, variational in nature, such as the orbital minimization (OM) procedure

  10. Calculation of atom displacement cross section for structure material

    International Nuclear Information System (INIS)

    Liu Ping; Xu Yiping

    2015-01-01

    The neutron radiation damage in material is an important consideration of the reactor design. The radiation damage of materials mainly comes from atom displacements of crystal structure materials. The reaction cross sections of charged particles, cross sections of displacements per atom (DPA) and KERMA are the basis of radiation damage calculation. In order to study the differences of DPA cross sections with different codes and different evaluated nuclear data libraries, the DPA cross sections for structure materials were calculated with UNF and NJOY codes, and the comparisons of results were given. The DPA cross sections from different evaluated nuclear data libraries were compared. And the comparison of DPA cross sections between NJOY and Monte Carlo codes was also done. The results show that the differences among these evaluated nuclear data libraries exist. (authors)

  11. Constraining cyclic peptides to mimic protein structure motifs

    DEFF Research Database (Denmark)

    Hill, Timothy A.; Shepherd, Nicholas E.; Diness, Frederik

    2014-01-01

    peptides can have protein-like biological activities and potencies, enabling their uses as biological probes and leads to therapeutics, diagnostics and vaccines. This Review highlights examples of cyclic peptides that mimic three-dimensional structures of strand, turn or helical segments of peptides...... and proteins, and identifies some additional restraints incorporated into natural product cyclic peptides and synthetic macrocyclic pepti-domimetics that refine peptide structure and confer biological properties....

  12. Project W-320, 241-C-106 sluicing: Civil/structural calculations. Volume 6

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, J.W.

    1998-07-24

    This supporting document has been prepared to make the FDNW calculations for Project W-320 readily retrievable. The purpose of this calculation is to conservatively estimate the weight of equipment and structures being added over Tank 241-C-106 as a result of Project W-320 and combine these weights with the estimated weights of existing structures and equipment as calculated in Attachment 1. The combined weights will be compared to the allowable live load limit to provide a preliminary assessment of loading conditions above Tank 241-C-106.

  13. Structure of PIN-domain protein PH0500 from Pyrococcus horikoshii

    International Nuclear Information System (INIS)

    Jeyakanthan, Jeyaraman; Inagaki, Eiji; Kuroishi, Chizu; Tahirov, Tahir H.

    2005-01-01

    The structure of P. horikoshii OT3 protein PH0500 was determined by the multiple anomalous dispersion method and refined in two crystal forms. The protein is a dimer and has a PIN-domain fold. The Pyrococcus horikoshii OT3 protein PH0500 is highly conserved within the Pyrococcus genus of hyperthermophilic archaea and shows low amino-acid sequence similarity with a family of PIN-domain proteins. The protein has been expressed, purified and crystallized in two crystal forms: PH0500-I and PH0500-II. The structure was determined at 2.0 Å by the multiple anomalous dispersion method using a selenomethionyl derivative of crystal form PH0500-I (PH0500-I-Se). The structure of PH0500-I has been refined at 1.75 Å resolution to an R factor of 20.9% and the structure of PH0500-II has been refined at 2.0 Å resolution to an R factor of 23.4%. In both crystal forms as well as in solution the molecule appears to be a dimer. Searches of the databases for protein-fold similarities confirmed that the PH0500 protein is a PIN-domain protein with possible exonuclease activity and involvement in DNA or RNA editing

  14. Overcoming bottlenecks in the membrane protein structural biology pipeline.

    Science.gov (United States)

    Hardy, David; Bill, Roslyn M; Jawhari, Anass; Rothnie, Alice J

    2016-06-15

    Membrane proteins account for a third of the eukaryotic proteome, but are greatly under-represented in the Protein Data Bank. Unfortunately, recent technological advances in X-ray crystallography and EM cannot account for the poor solubility and stability of membrane protein samples. A limitation of conventional detergent-based methods is that detergent molecules destabilize membrane proteins, leading to their aggregation. The use of orthologues, mutants and fusion tags has helped improve protein stability, but at the expense of not working with the sequence of interest. Novel detergents such as glucose neopentyl glycol (GNG), maltose neopentyl glycol (MNG) and calixarene-based detergents can improve protein stability without compromising their solubilizing properties. Styrene maleic acid lipid particles (SMALPs) focus on retaining the native lipid bilayer of a membrane protein during purification and biophysical analysis. Overcoming bottlenecks in the membrane protein structural biology pipeline, primarily by maintaining protein stability, will facilitate the elucidation of many more membrane protein structures in the near future. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  15. Automated assignment and 3D structure calculations using combinations of 2D homonuclear and 3D heteronuclear NOESY spectra

    International Nuclear Information System (INIS)

    Oezguen, Numan; Adamian, Larisa; Xu Yuan; Rajarathnam, Krishna; Braun, Werner

    2002-01-01

    The NOAH/DIAMOD suite uses feedback filtering and self-correcting distance geometry to generate 3D structures from unassigned NOESY spectra. In this study we determined the minimum set of experiments needed to generate a high quality structure bundle. Different combinations of 3D 15 N-edited, 13 C-edited HSQC-NOESY and 2D homonuclear 1 H- 1 H NOESY spectra of the 77 amino acid protein, myeloid progenitor inhibitory factor-1 (MPIF-1) were used as input for NOAH/DIAMOD calculations. The quality of the assignments of NOESY cross peaks and the accuracy of the automatically generated 3D structures were compared to those obtained with a conventional manual procedure. Combining data from two types of experiments synergistically increased the number of peaks assigned unambiguously in both individual spectra. As a general trend for the accuracy of the structures we observed structural variations in the backbone fold of the final structures of about 2 A for single spectral data, of 1 A to 1.5 A for double spectral data, and of 0.6 A for triple spectral data sets. The quality of the assignments and 3D structures from the optimal data using all three spectra were similar to those obtained from traditional assignment methods with structural variations within the bundle of 0.6 A and 1.3 A for backbone and heavy atoms, respectively. Almost all constraints (97%) of the automatic NOESY cross peak assignments were cross compatible with the structures from the conventional manual assignment procedure, and an even larger proportion (99%) of the manually derived constraints were compatible with the automatically determined 3D structures. The two mean structures determined by both methods differed only by 1.3 A rmsd for the backbone atoms in the well-defined regions of the protein. Thus NOAD/DIAMOD analysis of spectra from labeled proteins provides a reliable method for high throughput analysis of genomic targets

  16. Protein Structural Change Data - PSCDB | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available List Contact us PSCDB Protein Structural Change Data Data detail Data name Protein Structural Change Data DO...History of This Database Site Policy | Contact Us Protein Structural Change Data - PSCDB | LSDB Archive ...

  17. Using an alignment of fragment strings for comparing protein structures

    DEFF Research Database (Denmark)

    Friedberg, Iddo; Harder, Tim; Kolodny, Rachel

    2007-01-01

    . RESULTS: Here we describe the use of a particular structure fragment library, denoted here as KL-strings, for the 1D representation of protein structure. Using KL-strings, we develop an infrastructure for comparing protein structures with a 1D representation. This study focuses on the added value gained...

  18. Crystal structure of secretory protein Hcp3 from Pseudomonas aeruginosa.

    Science.gov (United States)

    Osipiuk, Jerzy; Xu, Xiaohui; Cui, Hong; Savchenko, Alexei; Edwards, Aled; Joachimiak, Andrzej

    2011-03-01

    The Type VI secretion pathway transports proteins across the cell envelope of Gram-negative bacteria. Pseudomonas aeruginosa, an opportunistic Gram-negative bacterial pathogen infecting humans, uses the type VI secretion pathway to export specific effector proteins crucial for its pathogenesis. The HSI-I virulence locus encodes for several proteins that has been proposed to participate in protein transport including the Hcp1 protein, which forms hexameric rings that assemble into nanotubes in vitro. Two Hcp1 paralogues have been identified in the P. aeruginosa genome, Hsp2 and Hcp3. Here, we present the structure of the Hcp3 protein from P. aeruginosa. The overall structure of the monomer resembles Hcp1 despite the lack of amino-acid sequence similarity between the two proteins. The monomers assemble into hexamers similar to Hcp1. However, instead of forming nanotubes in head-to-tail mode like Hcp1, Hcp3 stacks its rings in head-to-head mode forming double-ring structures.

  19. The synthesis of recombinant membrane proteins in yeast for structural studies.

    Science.gov (United States)

    Routledge, Sarah J; Mikaliunaite, Lina; Patel, Anjana; Clare, Michelle; Cartwright, Stephanie P; Bawa, Zharain; Wilks, Martin D B; Low, Floren; Hardy, David; Rothnie, Alice J; Bill, Roslyn M

    2016-02-15

    Historically, recombinant membrane protein production has been a major challenge meaning that many fewer membrane protein structures have been published than those of soluble proteins. However, there has been a recent, almost exponential increase in the number of membrane protein structures being deposited in the Protein Data Bank. This suggests that empirical methods are now available that can ensure the required protein supply for these difficult targets. This review focuses on methods that are available for protein production in yeast, which is an important source of recombinant eukaryotic membrane proteins. We provide an overview of approaches to optimize the expression plasmid, host cell and culture conditions, as well as the extraction and purification of functional protein for crystallization trials in preparation for structural studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Mass Spectrometry Coupled Experiments and Protein Structure Modeling Methods

    Directory of Open Access Journals (Sweden)

    Lee Sael

    2013-10-01

    Full Text Available With the accumulation of next generation sequencing data, there is increasing interest in the study of intra-species difference in molecular biology, especially in relation to disease analysis. Furthermore, the dynamics of the protein is being identified as a critical factor in its function. Although accuracy of protein structure prediction methods is high, provided there are structural templates, most methods are still insensitive to amino-acid differences at critical points that may change the overall structure. Also, predicted structures are inherently static and do not provide information about structural change over time. It is challenging to address the sensitivity and the dynamics by computational structure predictions alone. However, with the fast development of diverse mass spectrometry coupled experiments, low-resolution but fast and sensitive structural information can be obtained. This information can then be integrated into the structure prediction process to further improve the sensitivity and address the dynamics of the protein structures. For this purpose, this article focuses on reviewing two aspects: the types of mass spectrometry coupled experiments and structural data that are obtainable through those experiments; and the structure prediction methods that can utilize these data as constraints. Also, short review of current efforts in integrating experimental data in the structural modeling is provided.

  1. Structure and Sequence Search on Aptamer-Protein Docking

    Science.gov (United States)

    Xiao, Jiajie; Bonin, Keith; Guthold, Martin; Salsbury, Freddie

    2015-03-01

    Interactions between proteins and deoxyribonucleic acid (DNA) play a significant role in the living systems, especially through gene regulation. However, short nucleic acids sequences (aptamers) with specific binding affinity to specific proteins exhibit clinical potential as therapeutics. Our capillary and gel electrophoresis selection experiments show that specific sequences of aptamers can be selected that bind specific proteins. Computationally, given the experimentally-determined structure and sequence of a thrombin-binding aptamer, we can successfully dock the aptamer onto thrombin in agreement with experimental structures of the complex. In order to further study the conformational flexibility of this thrombin-binding aptamer and to potentially develop a predictive computational model of aptamer-binding, we use GPU-enabled molecular dynamics simulations to both examine the conformational flexibility of the aptamer in the absence of binding to thrombin, and to determine our ability to fold an aptamer. This study should help further de-novo predictions of aptamer sequences by enabling the study of structural and sequence-dependent effects on aptamer-protein docking specificity.

  2. Protein Secondary Structures (α-helix and β-sheet) at a Cellular Level and Protein Fractions in Relation to Rumen Degradation Behaviours of Protein: A New Approach

    International Nuclear Information System (INIS)

    Yu, P.

    2007-01-01

    Studying the secondary structure of proteins leads to an understanding of the components that make up a whole protein, and such an understanding of the structure of the whole protein is often vital to understanding its digestive behaviour and nutritive value in animals. The main protein secondary structures are the α-helix and β-sheet. The percentage of these two structures in protein secondary structures influences protein nutritive value, quality and digestive behaviour. A high percentage of β-sheet structure may partly cause a low access to gastrointestinal digestive enzymes, which results in a low protein value. The objectives of the present study were to use advanced synchrotron-based Fourier transform IR (S-FTIR) microspectroscopy as a new approach to reveal the molecular chemistry of the protein secondary structures of feed tissues affected by heat-processing within intact tissue at a cellular level, and to quantify protein secondary structures using multicomponent peak modelling Gaussian and Lorentzian methods, in relation to protein digestive behaviours and nutritive value in the rumen, which was determined using the Cornell Net Carbohydrate Protein System. The synchrotron-based molecular chemistry research experiment was performed at the National Synchrotron Light Source at Brookhaven National Laboratory, US Department of Energy. The results showed that, with S-FTIR microspectroscopy, the molecular chemistry, ultrastructural chemical make-up and nutritive characteristics could be revealed at a high ultraspatial resolution (∼10 μm). S-FTIR microspectroscopy revealed that the secondary structure of protein differed between raw and roasted golden flaxseeds in terms of the percentages and ratio of α-helixes and β-sheets in the mid-IR range at the cellular level. By using multicomponent peak modelling, the results show that the roasting reduced (P <0.05) the percentage of α-helixes (from 47.1% to 36.1%: S-FTIR absorption intensity), increased the

  3. Protein Secondary Structures (alpha-helix and beta-sheet) at a Cellular Levle and Protein Fractions in Relation to Rumen Degradation Behaviours of Protein: A New Approach

    Energy Technology Data Exchange (ETDEWEB)

    Yu,P.

    2007-01-01

    Studying the secondary structure of proteins leads to an understanding of the components that make up a whole protein, and such an understanding of the structure of the whole protein is often vital to understanding its digestive behaviour and nutritive value in animals. The main protein secondary structures are the {alpha}-helix and {beta}-sheet. The percentage of these two structures in protein secondary structures influences protein nutritive value, quality and digestive behaviour. A high percentage of {beta}-sheet structure may partly cause a low access to gastrointestinal digestive enzymes, which results in a low protein value. The objectives of the present study were to use advanced synchrotron-based Fourier transform IR (S-FTIR) microspectroscopy as a new approach to reveal the molecular chemistry of the protein secondary structures of feed tissues affected by heat-processing within intact tissue at a cellular level, and to quantify protein secondary structures using multicomponent peak modelling Gaussian and Lorentzian methods, in relation to protein digestive behaviours and nutritive value in the rumen, which was determined using the Cornell Net Carbohydrate Protein System. The synchrotron-based molecular chemistry research experiment was performed at the National Synchrotron Light Source at Brookhaven National Laboratory, US Department of Energy. The results showed that, with S-FTIR microspectroscopy, the molecular chemistry, ultrastructural chemical make-up and nutritive characteristics could be revealed at a high ultraspatial resolution ({approx}10 {mu}m). S-FTIR microspectroscopy revealed that the secondary structure of protein differed between raw and roasted golden flaxseeds in terms of the percentages and ratio of {alpha}-helixes and {beta}-sheets in the mid-IR range at the cellular level. By using multicomponent peak modelling, the results show that the roasting reduced (P <0.05) the percentage of {alpha}-helixes (from 47.1% to 36.1%: S

  4. Improvement of hydrogen bond geometry in protein NMR structures by residual dipolar couplings - an assessment of the interrelation of NMR restraints

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Pernille Rose; Axelsen, Jacob Bock [University of Copenhagen, Institute of Molecular Biology (Denmark); Lerche, Mathilde Hauge [Amersham Health (Sweden); Poulsen, Flemming M. [University of Copenhagen, Institute of Molecular Biology (Denmark)], E-mail: fmp@apk.molbio.ku.dk

    2004-01-15

    We have examined how the hydrogen bond geometry in three different proteins is affected when structural restraints based on measurements of residual dipolar couplings are included in the structure calculations. The study shows, that including restraints based solely on {sup 1}H{sup N}-{sup 15}N residual dipolar couplings has pronounced impact on the backbone rmsd and Ramachandran plot but does not improve the hydrogen bond geometry. In the case of chymotrypsin inhibitor 2 the addition of {sup 13}CO-{sup 13}C{sup {alpha}} and {sup 15}N-{sup 13}CO one bond dipolar couplings as restraints in the structure calculations improved the hydrogen bond geometry to a quality comparable to that obtained in the 1.8 A resolution X-ray structure of this protein. A systematic restraint study was performed, in which four types of restraints, residual dipolar couplings, hydrogen bonds, TALOS angles and NOEs, were allowed in two states. This study revealed the importance of using several types of residual dipolar couplings to get good hydrogen bond geometry. The study also showed that using a small set of NOEs derived only from the amide protons, together with a full set of residual dipolar couplings resulted in structures of very high quality. When reducing the NOE set, it is mainly the side-chain to side-chain NOEs that are removed. Despite of this the effect on the side-chain packing is very small when a reduced NOE set is used, which implies that the over all fold of a protein structure is mainly determined by correct folding of the backbone.

  5. Structural fragment clustering reveals novel structural and functional motifs in α-helical transmembrane proteins

    Directory of Open Access Journals (Sweden)

    Vassilev Boris

    2010-04-01

    Full Text Available Abstract Background A large proportion of an organism's genome encodes for membrane proteins. Membrane proteins are important for many cellular processes, and several diseases can be linked to mutations in them. With the tremendous growth of sequence data, there is an increasing need to reliably identify membrane proteins from sequence, to functionally annotate them, and to correctly predict their topology. Results We introduce a technique called structural fragment clustering, which learns sequential motifs from 3D structural fragments. From over 500,000 fragments, we obtain 213 statistically significant, non-redundant, and novel motifs that are highly specific to α-helical transmembrane proteins. From these 213 motifs, 58 of them were assigned to function and checked in the scientific literature for a biological assessment. Seventy percent of the motifs are found in co-factor, ligand, and ion binding sites, 30% at protein interaction interfaces, and 12% bind specific lipids such as glycerol or cardiolipins. The vast majority of motifs (94% appear across evolutionarily unrelated families, highlighting the modularity of functional design in membrane proteins. We describe three novel motifs in detail: (1 a dimer interface motif found in voltage-gated chloride channels, (2 a proton transfer motif found in heme-copper oxidases, and (3 a convergently evolved interface helix motif found in an aspartate symporter, a serine protease, and cytochrome b. Conclusions Our findings suggest that functional modules exist in membrane proteins, and that they occur in completely different evolutionary contexts and cover different binding sites. Structural fragment clustering allows us to link sequence motifs to function through clusters of structural fragments. The sequence motifs can be applied to identify and characterize membrane proteins in novel genomes.

  6. Co-operative intra-protein structural response due to protein-protein complexation revealed through thermodynamic quantification: study of MDM2-p53 binding.

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2017-10-01

    The p53 protein activation protects the organism from propagation of cells with damaged DNA having oncogenic mutations. In normal cells, activity of p53 is controlled by interaction with MDM2. The well understood p53-MDM2 interaction facilitates design of ligands that could potentially disrupt or prevent the complexation owing to its emergence as an important objective for cancer therapy. However, thermodynamic quantification of the p53-peptide induced structural changes of the MDM2-protein remains an area to be explored. This study attempts to understand the conformational free energy and entropy costs due to this complex formation from the histograms of dihedral angles generated from molecular dynamics simulations. Residue-specific quantification illustrates that, hydrophobic residues of the protein contribute maximum to the conformational thermodynamic changes. Thermodynamic quantification of structural changes of the protein unfold the fact that, p53 binding provides a source of inter-element cooperativity among the protein secondary structural elements, where the highest affected structural elements (α2 and α4) found at the binding site of the protein affects faraway structural elements (β1 and Loop1) of the protein. The communication perhaps involves water mediated hydrogen bonded network formation. Further, we infer that in inhibitory F19A mutation of P53, though Phe19 is important in the recognition process, it has less prominent contribution in the stability of the complex. Collectively, this study provides vivid microscopic understanding of the interaction within the protein complex along with exploring mutation sites, which will contribute further to engineer the protein function and binding affinity.

  7. Co-operative intra-protein structural response due to protein-protein complexation revealed through thermodynamic quantification: study of MDM2-p53 binding

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2017-10-01

    The p53 protein activation protects the organism from propagation of cells with damaged DNA having oncogenic mutations. In normal cells, activity of p53 is controlled by interaction with MDM2. The well understood p53-MDM2 interaction facilitates design of ligands that could potentially disrupt or prevent the complexation owing to its emergence as an important objective for cancer therapy. However, thermodynamic quantification of the p53-peptide induced structural changes of the MDM2-protein remains an area to be explored. This study attempts to understand the conformational free energy and entropy costs due to this complex formation from the histograms of dihedral angles generated from molecular dynamics simulations. Residue-specific quantification illustrates that, hydrophobic residues of the protein contribute maximum to the conformational thermodynamic changes. Thermodynamic quantification of structural changes of the protein unfold the fact that, p53 binding provides a source of inter-element cooperativity among the protein secondary structural elements, where the highest affected structural elements (α2 and α4) found at the binding site of the protein affects faraway structural elements (β1 and Loop1) of the protein. The communication perhaps involves water mediated hydrogen bonded network formation. Further, we infer that in inhibitory F19A mutation of P53, though Phe19 is important in the recognition process, it has less prominent contribution in the stability of the complex. Collectively, this study provides vivid microscopic understanding of the interaction within the protein complex along with exploring mutation sites, which will contribute further to engineer the protein function and binding affinity.

  8. Characterization of structural proteins of hirame rhabdovirus, HRV

    Science.gov (United States)

    Nishizawa, Toyohiko; Yoshimizu, Mamoru; Winton, James; Ahne, Winfried; Kimura, Takahisa

    1991-01-01

    Structural proteins of hirame rhabdovirus (HRV) were analyzed by SDS-polyacrylarnide gel electrophoresis, western blotting, 2-dimensional gel electrophoresis, and Triton X-100 treatment. Purified HRV virions were composed of: polymerase (L), glycoprotein (G), nucleoprotein (N), and 2 matrix proteins (M1 and M2). Based upon their relative mobilities, the estimated molecular weights of the proteins were: L, 156 KDa; G, 68 KDa; N, 46.4 KDa; M1, 26.4 KDa; and M2, 19.9 KDa. The electrophorehc pattern formed by the structural proteins of HRV was clearly different from that formed by pike fry rhabdovirus, spring viremia of carp virus, eel virus of America, and eel virus European X which belong to the Vesiculovirus genus; however, it resembled the pattern formed by structural proteins of viral hemorrhagic septicemia virus (VHSV) and infectious hematopoietic necrosis virus (IHNV) which are members of the Lyssavirus genus. Among HRV, IHNV, and VHSV, differences were observed in the relative mobilities of the G, N, M1, and M2 proteins. Western blot analysis revealed that the G. N, and M2 proteins of HRV shared antigenic determinants with IHNV and VHSV, but not with any of the 4 fish vesiculoviruses tested. Cross-reactions between the M1 proteins of HRV, IHNV, or VHSV were not detected in this assay. Two-dimensional gel electrophoresis was used to show that HRV differed from IHNV or VHSV in the isoelectric point (PI) of the M1 and M2 proteins. In this system, 2 forms of the M1 protein of HRV and IHNV were observed.These subspecies of M1 had the same relative mobility but different p1 values. Treatment of purified virions with 2% Triton X-100 in Tris buffer containing NaCl removed the G, M1, and M2 proteins of IHNV, but HRV virions were more stable under these conditions.

  9. (PS)2: protein structure prediction server version 3.0.

    Science.gov (United States)

    Huang, Tsun-Tsao; Hwang, Jenn-Kang; Chen, Chu-Huang; Chu, Chih-Sheng; Lee, Chi-Wen; Chen, Chih-Chieh

    2015-07-01

    Protein complexes are involved in many biological processes. Examining coupling between subunits of a complex would be useful to understand the molecular basis of protein function. Here, our updated (PS)(2) web server predicts the three-dimensional structures of protein complexes based on comparative modeling; furthermore, this server examines the coupling between subunits of the predicted complex by combining structural and evolutionary considerations. The predicted complex structure could be indicated and visualized by Java-based 3D graphics viewers and the structural and evolutionary profiles are shown and compared chain-by-chain. For each subunit, considerations with or without the packing contribution of other subunits cause the differences in similarities between structural and evolutionary profiles, and these differences imply which form, complex or monomeric, is preferred in the biological condition for the subunit. We believe that the (PS)(2) server would be a useful tool for biologists who are interested not only in the structures of protein complexes but also in the coupling between subunits of the complexes. The (PS)(2) is freely available at http://ps2v3.life.nctu.edu.tw/. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Cloud prediction of protein structure and function with PredictProtein for Debian.

    Science.gov (United States)

    Kaján, László; Yachdav, Guy; Vicedo, Esmeralda; Steinegger, Martin; Mirdita, Milot; Angermüller, Christof; Böhm, Ariane; Domke, Simon; Ertl, Julia; Mertes, Christian; Reisinger, Eva; Staniewski, Cedric; Rost, Burkhard

    2013-01-01

    We report the release of PredictProtein for the Debian operating system and derivatives, such as Ubuntu, Bio-Linux, and Cloud BioLinux. The PredictProtein suite is available as a standard set of open source Debian packages. The release covers the most popular prediction methods from the Rost Lab, including methods for the prediction of secondary structure and solvent accessibility (profphd), nuclear localization signals (predictnls), and intrinsically disordered regions (norsnet). We also present two case studies that successfully utilize PredictProtein packages for high performance computing in the cloud: the first analyzes protein disorder for whole organisms, and the second analyzes the effect of all possible single sequence variants in protein coding regions of the human genome.

  11. Motion Tree Delineates Hierarchical Structure of Protein Dynamics Observed in Molecular Dynamics Simulation.

    Directory of Open Access Journals (Sweden)

    Kei Moritsugu

    Full Text Available Molecular dynamics (MD simulations of proteins provide important information to understand their functional mechanisms, which are, however, likely to be hidden behind their complicated motions with a wide range of spatial and temporal scales. A straightforward and intuitive analysis of protein dynamics observed in MD simulation trajectories is therefore of growing significance with the large increase in both the simulation time and system size. In this study, we propose a novel description of protein motions based on the hierarchical clustering of fluctuations in the inter-atomic distances calculated from an MD trajectory, which constructs a single tree diagram, named a "Motion Tree", to determine a set of rigid-domain pairs hierarchically along with associated inter-domain fluctuations. The method was first applied to the MD trajectory of substrate-free adenylate kinase to clarify the usefulness of the Motion Tree, which illustrated a clear-cut dynamics picture of the inter-domain motions involving the ATP/AMP lid and the core domain together with the associated amplitudes and correlations. The comparison of two Motion Trees calculated from MD simulations of ligand-free and -bound glutamine binding proteins clarified changes in inherent dynamics upon ligand binding appeared in both large domains and a small loop that stabilized ligand molecule. Another application to a huge protein, a multidrug ATP binding cassette (ABC transporter, captured significant increases of fluctuations upon binding a drug molecule observed in both large scale inter-subunit motions and a motion localized at a transmembrane helix, which may be a trigger to the subsequent structural change from inward-open to outward-open states to transport the drug molecule. These applications demonstrated the capabilities of Motion Trees to provide an at-a-glance view of various sizes of functional motions inherent in the complicated MD trajectory.

  12. The role of ab initio electronic structure calculations in studies of the strength of materials

    International Nuclear Information System (INIS)

    Sob, M.; Friak, M.; Legut, D.; Fiala, J.; Vitek, V.

    2004-01-01

    In this paper we give an account of applications of quantum-mechanical (first-principles) electronic structure calculations to the problem of theoretical tensile strength in metals and intermetallics. First, we review previous as well as ongoing research on this subject. We then describe briefly the electronic structure calculational methods and simulation of the tensile test. This approach is then illustrated by calculations of theoretical tensile strength in iron and in the intermetallic compound Ni 3 Al. The anisotropy of calculated tensile strength is explained in terms of higher-symmetry structures encountered along the deformation paths studied. The table summarizing values of theoretical tensile strengths calculated up to now is presented and the role of ab initio electronic structure calculations in contemporary studies of the strength of material is discussed

  13. Segmental isotope labeling of proteins for NMR structural study using a protein S tag for higher expression and solubility

    International Nuclear Information System (INIS)

    Kobayashi, Hiroshi; Swapna, G. V. T.; Wu, Kuen-Phon; Afinogenova, Yuliya; Conover, Kenith; Mao, Binchen; Montelione, Gaetano T.; Inouye, Masayori

    2012-01-01

    A common obstacle to NMR studies of proteins is sample preparation. In many cases, proteins targeted for NMR studies are poorly expressed and/or expressed in insoluble forms. Here, we describe a novel approach to overcome these problems. In the protein S tag-intein (PSTI) technology, two tandem 92-residue N-terminal domains of protein S (PrS 2 ) from Myxococcus xanthus is fused at the N-terminal end of a protein to enhance its expression and solubility. Using intein technology, the isotope-labeled PrS 2 -tag is replaced with non-isotope labeled PrS 2 -tag, silencing the NMR signals from PrS 2 -tag in isotope-filtered 1 H-detected NMR experiments. This method was applied to the E. coli ribosome binding factor A (RbfA), which aggregates and precipitates in the absence of a solubilization tag unless the C-terminal 25-residue segment is deleted (RbfAΔ25). Using the PrS 2 -tag, full-length well-behaved RbfA samples could be successfully prepared for NMR studies. PrS 2 (non-labeled)-tagged RbfA (isotope-labeled) was produced with the use of the intein approach. The well-resolved TROSY-HSQC spectrum of full-length PrS 2 -tagged RbfA superimposes with the TROSY-HSQC spectrum of RbfAΔ25, indicating that PrS 2 -tag does not affect the structure of the protein to which it is fused. Using a smaller PrS-tag, consisting of a single N-terminal domain of protein S, triple resonance experiments were performed, and most of the backbone 1 H, 15 N and 13 C resonance assignments for full-length E. coli RbfA were determined. Analysis of these chemical shift data with the Chemical Shift Index and heteronuclear 1 H– 15 N NOE measurements reveal the dynamic nature of the C-terminal segment of the full-length RbfA protein, which could not be inferred using the truncated RbfAΔ25 construct. CS-Rosetta calculations also demonstrate that the core structure of full-length RbfA is similar to that of the RbfAΔ25 construct.

  14. Solution structure of the cold-shock-like protein from Rickettsia rickettsii

    International Nuclear Information System (INIS)

    Gerarden, Kyle P.; Fuchs, Andrew M.; Koch, Jonathan M.; Mueller, Melissa M.; Graupner, David R.; O’Rorke, Justin T.; Frost, Caleb D.; Heinen, Heather A.; Lackner, Emily R.; Schoeller, Scott J.; House, Paul G.; Peterson, Francis C.; Veldkamp, Christopher T.

    2012-01-01

    The solution structure of the cold-shock-like protein from R. rickettsii, the causative agent of Rocky Mountain spotted fever, is reported. Rocky Mountain spotted fever is caused by Rickettsia rickettsii infection. R. rickettsii can be transmitted to mammals, including humans, through the bite of an infected hard-bodied tick of the family Ixodidae. Since the R. rickettsii genome contains only one cold-shock-like protein and given the essential nature of cold-shock proteins in other bacteria, the structure of the cold-shock-like protein from R. rickettsii was investigated. With the exception of a short α-helix found between β-strands 3 and 4, the solution structure of the R. rickettsii cold-shock-like protein has the typical Greek-key five-stranded β-barrel structure found in most cold-shock domains. Additionally, the R. rickettsii cold-shock-like protein, with a ΔG of unfolding of 18.4 kJ mol −1 , has a similar stability when compared with other bacterial cold-shock proteins

  15. Structure of haze forming proteins in white wines: Vitis vinifera thaumatin-like proteins.

    Directory of Open Access Journals (Sweden)

    Matteo Marangon

    Full Text Available Grape thaumatin-like proteins (TLPs play roles in plant-pathogen interactions and can cause protein haze in white wine unless removed prior to bottling. Different isoforms of TLPs have different hazing potential and aggregation behavior. Here we present the elucidation of the molecular structures of three grape TLPs that display different hazing potential. The three TLPs have very similar structures despite belonging to two different classes (F2/4JRU is a thaumatin-like protein while I/4L5H and H2/4MBT are VVTL1, and having different unfolding temperatures (56 vs. 62°C, with protein F2/4JRU being heat unstable and forming haze, while I/4L5H does not. These differences in properties are attributable to the conformation of a single loop and the amino acid composition of its flanking regions.

  16. PONDEROSA-C/S: client–server based software package for automated protein 3D structure determination

    OpenAIRE

    Lee, Woonghee; Stark, Jaime L.; Markley, John L.

    2014-01-01

    Peak-picking Of Noe Data Enabled by Restriction Of Shift Assignments-Client Server (PONDEROSA-C/S) builds on the original PONDEROSA software (Lee et al. in Bioinformatics 27:1727–1728. doi:10.1093/bioinformatics/btr200, 2011) and includes improved features for structure calculation and refinement. PONDEROSA-C/S consists of three programs: Ponderosa Server, Ponderosa Client, and Ponderosa Analyzer. PONDEROSA-C/S takes as input the protein sequence, a list of assigned chemical shifts, and nucle...

  17. Characterization of dry globular proteins and protein fibrils by synchrotron radiation vacuum UV circular dichroism

    DEFF Research Database (Denmark)

    Nesgaard, Lise W.; Hoffmann, Søren Vrønning; Andersen, Christian Beyschau

    2008-01-01

    Circular dichroism using synchrotron radiation (SRCD) can extend the spectral range down to approximately 130 nm for dry proteins, potentially providing new structural information. Using a selection of dried model proteins, including alpha-helical, beta-sheet, and mixed-structure proteins, we...... with previously published theoretical calculations related to pi-orbital transitions. We also show that drying does not lead to large changes in the secondary structure and does not induce orientational artifacts. In combination with principal component analysis, our SRCD data allow us to distinguish between two...... different types of protein fibrils, highlighting that bona fide fibrils formed by lysozyme are structurally more similar to the nonclassical fibrillar aggregates formed by the SerADan peptide than with the amyloid formed by alpha-synuclein. Thus, despite the lack of direct structural conclusions...

  18. The structure of myristoylated Mason-Pfizer monkey virus matrix protein and the role of phosphatidylinositol-(4,5)-bisphosphate in its membrane binding.

    Science.gov (United States)

    Prchal, Jan; Srb, Pavel; Hunter, Eric; Ruml, Tomáš; Hrabal, Richard

    2012-10-26

    We determined the solution structure of myristoylated Mason-Pfizer monkey virus matrix protein by NMR spectroscopy. The myristoyl group is buried inside the protein and causes a slight reorientation of the helices. This reorientation leads to the creation of a binding site for phosphatidylinositols. The interaction between the matrix protein and phosphatidylinositols carrying C(8) fatty acid chains was monitored by observation of concentration-dependent chemical shift changes of the affected amino acid residues, a saturation transfer difference experiment and changes in (31)P chemical shifts. No differences in the binding mode or affinity were observed with differently phosphorylated phosphatidylinositols. The structure of the matrix protein-phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)] complex was then calculated with HADDOCK software based on the intermolecular nuclear Overhauser enhancement contacts between the ligand and the matrix protein obtained from a (13)C-filtered/(13)C-edited nuclear Overhauser enhancement spectroscopy experiment. PI(4,5)P(2) binding was not strong enough for triggering of the myristoyl-switch. The structural changes of the myristoylated matrix protein were also found to result in a drop in the oligomerization capacity of the protein. Copyright © 2012. Published by Elsevier Ltd.

  19. Water polygons in high-resolution protein crystal structures.

    Science.gov (United States)

    Lee, Jonas; Kim, Sung-Hou

    2009-07-01

    We have analyzed the interstitial water (ISW) structures in 1500 protein crystal structures deposited in the Protein Data Bank that have greater than 1.5 A resolution with less than 90% sequence similarity with each other. We observed varieties of polygonal water structures composed of three to eight water molecules. These polygons may represent the time- and space-averaged structures of "stable" water oligomers present in liquid water, and their presence as well as relative population may be relevant in understanding physical properties of liquid water at a given temperature. On an average, 13% of ISWs are localized enough to be visible by X-ray diffraction. Of those, averages of 78% are water molecules in the first water layer on the protein surface. Of the localized ISWs beyond the first layer, almost half of them form water polygons such as trigons, tetragons, as well as expected pentagons, hexagons, higher polygons, partial dodecahedrons, and disordered networks. Most of the octagons and nanogons are formed by fusion of smaller polygons. The trigons are most commonly observed. We suggest that our observation provides an experimental basis for including these water polygon structures in correlating and predicting various water properties in liquid state.

  20. First principles calculations of structural, electronic and thermal ...

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science; Volume 37; Issue 5. First principles calculations of structural, electronic and thermal properties of lead chalcogenides PbS, PbSe and PbTe compounds. N Boukhris H Meradji S Amara Korba S Drablia S Ghemid F El Haj Hassan. Volume 37 Issue 5 August 2014 pp 1159-1166 ...

  1. Pythoscape: a framework for generation of large protein similarity networks.

    Science.gov (United States)

    Barber, Alan E; Babbitt, Patricia C

    2012-11-01

    Pythoscape is a framework implemented in Python for processing large protein similarity networks for visualization in other software packages. Protein similarity networks are graphical representations of sequence, structural and other similarities among proteins for which pairwise all-by-all similarity connections have been calculated. Mapping of biological and other information to network nodes or edges enables hypothesis creation about sequence-structure-function relationships across sets of related proteins. Pythoscape provides several options to calculate pairwise similarities for input sequences or structures, applies filters to network edges and defines sets of similar nodes and their associated data as single nodes (termed representative nodes) for compression of network information and output data or formatted files for visualization.

  2. SA-Search: a web tool for protein structure mining based on a Structural Alphabet

    OpenAIRE

    Guyon, Frédéric; Camproux, Anne-Claude; Hochez, Joëlle; Tufféry, Pierre

    2004-01-01

    SA-Search is a web tool that can be used to mine for protein structures and extract structural similarities. It is based on a hidden Markov model derived Structural Alphabet (SA) that allows the compression of three-dimensional (3D) protein conformations into a one-dimensional (1D) representation using a limited number of prototype conformations. Using such a representation, classical methods developed for amino acid sequences can be employed. Currently, SA-Search permits the performance of f...

  3. CONFOLD2: improved contact-driven ab initio protein structure modeling.

    Science.gov (United States)

    Adhikari, Badri; Cheng, Jianlin

    2018-01-25

    Contact-guided protein structure prediction methods are becoming more and more successful because of the latest advances in residue-residue contact prediction. To support contact-driven structure prediction, effective tools that can quickly build tertiary structural models of good quality from predicted contacts need to be developed. We develop an improved contact-driven protein modelling method, CONFOLD2, and study how it may be effectively used for ab initio protein structure prediction with predicted contacts as input. It builds models using various subsets of input contacts to explore the fold space under the guidance of a soft square energy function, and then clusters the models to obtain the top five models. CONFOLD2 obtains an average reconstruction accuracy of 0.57 TM-score for the 150 proteins in the PSICOV contact prediction dataset. When benchmarked on the CASP11 contacts predicted using CONSIP2 and CASP12 contacts predicted using Raptor-X, CONFOLD2 achieves a mean TM-score of 0.41 on both datasets. CONFOLD2 allows to quickly generate top five structural models for a protein sequence when its secondary structures and contacts predictions at hand. The source code of CONFOLD2 is publicly available at https://github.com/multicom-toolbox/CONFOLD2/ .

  4. Accelerating large-scale protein structure alignments with graphics processing units

    Directory of Open Access Journals (Sweden)

    Pang Bin

    2012-02-01

    Full Text Available Abstract Background Large-scale protein structure alignment, an indispensable tool to structural bioinformatics, poses a tremendous challenge on computational resources. To ensure structure alignment accuracy and efficiency, efforts have been made to parallelize traditional alignment algorithms in grid environments. However, these solutions are costly and of limited accessibility. Others trade alignment quality for speedup by using high-level characteristics of structure fragments for structure comparisons. Findings We present ppsAlign, a parallel protein structure Alignment framework designed and optimized to exploit the parallelism of Graphics Processing Units (GPUs. As a general-purpose GPU platform, ppsAlign could take many concurrent methods, such as TM-align and Fr-TM-align, into the parallelized algorithm design. We evaluated ppsAlign on an NVIDIA Tesla C2050 GPU card, and compared it with existing software solutions running on an AMD dual-core CPU. We observed a 36-fold speedup over TM-align, a 65-fold speedup over Fr-TM-align, and a 40-fold speedup over MAMMOTH. Conclusions ppsAlign is a high-performance protein structure alignment tool designed to tackle the computational complexity issues from protein structural data. The solution presented in this paper allows large-scale structure comparisons to be performed using massive parallel computing power of GPU.

  5. MOLECULAR DESIGNER: an interactive program for the display of protein structure on the IBM-PC.

    Science.gov (United States)

    Hannon, G J; Jentoft, J E

    1985-09-01

    A BASIC interactive graphics program has been developed for the IBM-PC which utilizes the graphics capabilities of that computer to display and manipulate protein structure from coordinates. Structures may be generated from typed files, or from Brookhaven National Laboratories' Protein Data Bank data tapes. Once displayed, images may be rotated, translated and expanded to any desired size. Figures may be viewed as ball-and-stick or space-filling models. Calculated multiple-point perspective may also be added to the display. Docking manipulations are possible since more than a single figure may be displayed and manipulated simultaneously. Further, stereo images and red/blue three-dimensional images may be generated using the accompanying DESIPLOT program and an HP-7475A plotter. A version of the program is also currently available for the Apple Macintosh. Full implementation on the Macintosh requires 512 K and at least one disk drive. Otherwise this version is essentially identical to the IBM-PC version described herein.

  6. Structural and Functional Annotation of Hypothetical Proteins of O139

    Directory of Open Access Journals (Sweden)

    Md. Saiful Islam

    2015-06-01

    Full Text Available In developing countries threat of cholera is a significant health concern whenever water purification and sewage disposal systems are inadequate. Vibrio cholerae is one of the responsible bacteria involved in cholera disease. The complete genome sequence of V. cholerae deciphers the presence of various genes and hypothetical proteins whose function are not yet understood. Hence analyzing and annotating the structure and function of hypothetical proteins is important for understanding the V. cholerae. V. cholerae O139 is the most common and pathogenic bacterial strain among various V. cholerae strains. In this study sequence of six hypothetical proteins of V. cholerae O139 has been annotated from NCBI. Various computational tools and databases have been used to determine domain family, protein-protein interaction, solubility of protein, ligand binding sites etc. The three dimensional structure of two proteins were modeled and their ligand binding sites were identified. We have found domains and families of only one protein. The analysis revealed that these proteins might have antibiotic resistance activity, DNA breaking-rejoining activity, integrase enzyme activity, restriction endonuclease, etc. Structural prediction of these proteins and detection of binding sites from this study would indicate a potential target aiding docking studies for therapeutic designing against cholera.

  7. Features of the Calculation Deployment Large Transformable Structures of Different Configurations

    Directory of Open Access Journals (Sweden)

    V. N. Zimin

    2014-01-01

    Full Text Available Despite the significant progress achieved in the design of space transformable structures to ensure a smooth and reliable deployment remains an important task. This type of construction can consist of dozens, hundreds or even thousands of interconnected elements. Deployment transformable space structures in orbit to test their performance in orbital conditions are associated with high material costs. Full deploy: experimental development process transformable structures involve a number of fundamental difficulties: It is impossible to eliminate the influence of gravity and resistance forces conditions. Thus, to calculate deploy of large transformable structures of various configurations is an important stage of their creation. Simulation provides an opportunity to analyze various schemes of deploy, to reveal their advantages and possible disadvantages. For numerical analysis of deploy of such structures is necessary to use modern software modeling of the dynamics of multi-component of mechanical systems such as EULER and Adams. Simulation of deployment space transformable structures was performed taking as example folding flat antenna contours diameter of 5 m and 20 m, foldable spatial calibration reflector diameter of 3 m, deployable antenna reflector truss-type aperture 3×6 m.The results of the calculations represent following characteristics: the time of adoption of the working position structures; form intermediate positions structures during deployment; dependence of opening angles and angular velocities of the design links on the time. The parameters of these calculations can be used as input in the development of structural elements providing deployment. They can also be used to prepare stands for experimental testing of disclosure designs in ground conditions. It should be noted that the theoretical models are the only way to analyze the deployment of such structures for possible emergency situations.

  8. Protein Function Prediction Based on Sequence and Structure Information

    KAUST Repository

    Smaili, Fatima Z.

    2016-05-25

    The number of available protein sequences in public databases is increasing exponentially. However, a significant fraction of these sequences lack functional annotation which is essential to our understanding of how biological systems and processes operate. In this master thesis project, we worked on inferring protein functions based on the primary protein sequence. In the approach we follow, 3D models are first constructed using I-TASSER. Functions are then deduced by structurally matching these predicted models, using global and local similarities, through three independent enzyme commission (EC) and gene ontology (GO) function libraries. The method was tested on 250 “hard” proteins, which lack homologous templates in both structure and function libraries. The results show that this method outperforms the conventional prediction methods based on sequence similarity or threading. Additionally, our method could be improved even further by incorporating protein-protein interaction information. Overall, the method we use provides an efficient approach for automated functional annotation of non-homologous proteins, starting from their sequence.

  9. Structural Basis for Target Protein Regcognition by Thiredoxin

    DEFF Research Database (Denmark)

    Maeda, Kenji

    2007-01-01

    Ser) and a mutant of an in vitro substrate alpha-amylase/subtilisin inhibitor (BASI) (Cys144Ser), as a reaction intermediate-mimic of Trx-catalyzed disulfide reduction. The resultant structure showed a sequence of BASI residues along a conserved hydrophobic groove constituted of three loop segments...... of Trx-fold proteins glutaredoxin and glutathione transferase. This study suggests that the features of main chain conformation as well as charge property around disulfide bonds in protein substrates are important factors for interaction with Trx. Moreover, this study describes a detailed structural......Thioredoxin (Trx) is an ubiquitous protein disulfide reductase that possesses two redox active cysteines in the conserved active site sequence motif, Trp-CysN-Gly/Pro-Pro-CysC situated in the so called Trx-fold. The lack of insight into the protein substrate recognition mechanism of Trx has to date...

  10. The Structure and Function of Non-Collagenous Bone Proteins

    Science.gov (United States)

    Hook, Magnus

    1997-01-01

    The long-term goal for this program is to determine the structural and functional relationships of bone proteins and proteins that interact with bone. This information will used to design useful pharmacological compounds that will have a beneficial effect in osteoporotic patients and in the osteoporotic-like effects experienced on long duration space missions. The first phase of this program, funded under a cooperative research agreement with NASA through the Texas Medical Center, aimed to develop powerful recombinant expression systems and purification methods for production of large amounts of target proteins. Proteins expressed in sufficient'amount and purity would be characterized by a variety of structural methods, and made available for crystallization studies. In order to increase the likelihood of crystallization and subsequent high resolution solution of structures, we undertook to develop expression of normal and mutant forms of proteins by bacterial and mammalian cells. In addition to the main goals of this program, we would also be able to provide reagents for other related studies, including development of anti-fibrotic and anti-metastatic therapeutics.

  11. Dissociative recombination of interstellar ions: electronic structure calculations for HCO+

    International Nuclear Information System (INIS)

    Kraemer, W.P.; Hazi, A.U.

    1985-01-01

    The present study of the interstellar formyl ion HCO + is the first attempt to investigate dissociative recombination for a triatomic molecular ion using an entirely theoretical approach. We describe a number of fairly extensive electronic structure calculations that were performed to determine the reaction mechanism of the e-HCO + process. Similar calculations for the isoelectronic ions HOC + and HN 2 + are in progress. 60 refs

  12. A sub-structure method for multidimensional integral transport calculations

    International Nuclear Information System (INIS)

    Kavenoky, A.; Stankovski, Z.

    1983-03-01

    A new method has been developed for fine structure burn-up calculations of very heterogeneous large size media. It is a generalization of the well-known surface-source method, allowing coupling actual two-dimensional heterogeneous assemblies, called sub-structures. The method has been applied to a rectangular medium, divided into sub-structures, containing rectangular and/or cylindrical fuel, moderator and structure elements. The sub-structures are divided into homogeneous zones. A zone-wise flux expansion is used to formulate a direct collision probability problem within it (linear or flat flux expansion in the rectangular zones, flat flux in the others). The coupling of the sub-structures is performed by making extra assumptions on the currents entering and leaving the interfaces. The accuracies and computing times achieved are illustrated by numerical results on two benchmark problems

  13. Atomic Reference Data for Electronic Structure Calculations

    CERN Document Server

    Kotochigova, S; Shirley, E L

    We have generated data for atomic electronic structure calculations, to provide a standard reference for results of specified accuracy under commonly used approximations. Results are presented here for total energies and orbital energy eigenvalues for all atoms from H to U, at microHartree accuracy in the total energy, as computed in the local-density approximation (LDA) the local-spin-density approximation (LSD); the relativistic local-density approximation (RLDA); and scalar-relativistic local-density approximation (ScRLDA).

  14. Structural determinants for protein adsorption/non-adsorption to silica surface

    International Nuclear Information System (INIS)

    Mathe, Christelle; Devineau, Stephanie; Aude, Jean-Christophe; Lagniel, Gilles; Chedin, Stephane; Legros, Veronique; Mathon, Marie-Helene; Renault, Jean-Philippe; Pin, Serge; Boulard, Yves; Labarre, Jean

    2013-01-01

    The understanding of the mechanisms involved in the interaction of proteins with inorganic surfaces is of major interest in both fundamental research and applications such as nano-technology. However, despite intense research, the mechanisms and the structural determinants of protein/surface interactions are still unclear. We developed a strategy consisting in identifying, in a mixture of hundreds of soluble proteins, those proteins that are adsorbed on the surface and those that are not. If the two protein subsets are large enough, their statistical comparative analysis must reveal the physicochemical determinants relevant for adsorption versus non-adsorption. This methodology was tested with silica nanoparticles. We found that the adsorbed proteins contain a higher number of charged amino acids, particularly arginine, which is consistent with involvement of this basic amino acid in electrostatic interactions with silica. The analysis also identified a marked bias toward low aromatic amino acid content (phenylalanine, tryptophan, tyrosine and histidine) in adsorbed proteins. Structural analyses and molecular dynamics simulations of proteins from the two groups indicate that non-adsorbed proteins have twice as many p-p interactions and higher structural rigidity. The data are consistent with the notion that adsorption is correlated with the flexibility of the protein and with its ability to spread on the surface. Our findings led us to propose a refined model of protein adsorption. (authors)

  15. Structural determinants for protein adsorption/non-adsorption to silica surface.

    Directory of Open Access Journals (Sweden)

    Christelle Mathé

    Full Text Available The understanding of the mechanisms involved in the interaction of proteins with inorganic surfaces is of major interest in both fundamental research and applications such as nanotechnology. However, despite intense research, the mechanisms and the structural determinants of protein/surface interactions are still unclear. We developed a strategy consisting in identifying, in a mixture of hundreds of soluble proteins, those proteins that are adsorbed on the surface and those that are not. If the two protein subsets are large enough, their statistical comparative analysis must reveal the physicochemical determinants relevant for adsorption versus non-adsorption. This methodology was tested with silica nanoparticles. We found that the adsorbed proteins contain a higher number of charged amino acids, particularly arginine, which is consistent with involvement of this basic amino acid in electrostatic interactions with silica. The analysis also identified a marked bias toward low aromatic amino acid content (phenylalanine, tryptophan, tyrosine and histidine in adsorbed proteins. Structural analyses and molecular dynamics simulations of proteins from the two groups indicate that non-adsorbed proteins have twice as many π-π interactions and higher structural rigidity. The data are consistent with the notion that adsorption is correlated with the flexibility of the protein and with its ability to spread on the surface. Our findings led us to propose a refined model of protein adsorption.

  16. Structural and Function Prediction of Musa acuminata subsp. Malaccensis Protein

    Directory of Open Access Journals (Sweden)

    Anum Munir

    2016-03-01

    Full Text Available Hypothetical proteins (HPs are the proteins whose presence has been anticipated, yet in vivo function has not been built up. Illustrating the structural and functional privileged insights of these HPs might likewise prompt a superior comprehension of the protein-protein associations or networks in diverse types of life. Bananas (Musa acuminata spp., including sweet and cooking types, are giant perennial monocotyledonous herbs of the order Zingiberales, a sister grouped to the all-around considered Poales, which incorporate oats. Bananas are crucial for nourishment security in numerous tropical and subtropical nations and the most prominent organic product in industrialized nations. In the present study, the hypothetical protein of M. acuminata (Banana was chosen for analysis and modeling by distinctive bioinformatics apparatuses and databases. As indicated by primary and secondary structure analysis, XP_009393594.1 is a stable hydrophobic protein containing a noteworthy extent of α-helices; Homology modeling was done utilizing SWISS-MODEL server where the templates identity with XP_009393594.1 protein was less which demonstrated novelty of our protein. Ab initio strategy was conducted to produce its 3D structure. A few evaluations of quality assessment and validation parameters determined the generated protein model as stable with genuinely great quality. Functional analysis was completed by ProtFun 2.2, and KEGG (KAAS, recommended that the hypothetical protein is a transcription factor with cytoplasmic domain as zinc finger. The protein was observed to be vital for translation process, involved in metabolism, signaling and cellular processes, genetic information processing and Zinc ion binding. It is suggested that further test approval would help to anticipate the structures and functions of other uncharacterized proteins of different plants and living being.

  17. Neutron structure of the hydrophobic plant protein crambin

    International Nuclear Information System (INIS)

    Teeter, M.M.; Kossiakoff, A.A.

    1982-01-01

    Crystals of the small hydrophobic protein crambin have been shown to diffract to a resolution of at least 0.88 A. This means that crambin presents a rare opportunity to study a protein structure at virtually atomic resolution. The high resolution of the diffraction pattern coupled with the assets of neutron diffraction present the distinct possibility that crambin's analysis may surpass that of any other protein system in degree and accuracy of detail. The neutron crambin structure is currently being refined at 1.50 A (44.9% of the data to 1.2 A has also been included). It is expected that a nominal resolution of 1.0 A can be achieved. 15 references, 6 figures, 2 tables

  18. On the calculation of {sup 3}J{sub {alpha}{beta}}-coupling constants for side chains in proteins

    Energy Technology Data Exchange (ETDEWEB)

    Steiner, Denise [Swiss Federal Institute of Technology, Laboratory of Physical Chemistry, ETH (Switzerland); Allison, Jane R. [Massey University Albany, Centre for Theoretical Chemistry and Physics, Institute for Natural Sciences (New Zealand); Eichenberger, Andreas P.; Gunsteren, Wilfred F. van, E-mail: wfvgn@igc.phys.chem.ethz.ch [Swiss Federal Institute of Technology, Laboratory of Physical Chemistry, ETH (Switzerland)

    2012-07-15

    Structural knowledge about proteins is mainly derived from values of observables, measurable in NMR spectroscopic or X-ray diffraction experiments, i.e. absorbed or scattered intensities, through theoretically derived relationships between structural quantities such as atom positions or torsional angles on the one hand and observable quantities such as squared structure factor amplitudes, NOE intensities or {sup 3}J-coupling constants on the other. The standardly used relation connecting {sup 3}J-couplings to torsional angles is the Karplus relation, which is used in protein structure refinement as well as in the evaluation of simulated properties of proteins. The accuracy of the simple and generalised Karplus relations is investigated using side-chain structural and {sup 3}J{sub {alpha}{beta}}-coupling data for three different proteins, Plastocyanin, Lysozyme, and FKBP, for which such data are available. The results show that the widely used Karplus relations are only a rough estimate for the relation between {sup 3}J{sub {alpha}{beta}}-couplings and the corresponding {chi}{sub 1}-angle in proteins.

  19. DNA nanotubes for NMR structure determination of membrane proteins.

    Science.gov (United States)

    Bellot, Gaëtan; McClintock, Mark A; Chou, James J; Shih, William M

    2013-04-01

    Finding a way to determine the structures of integral membrane proteins using solution nuclear magnetic resonance (NMR) spectroscopy has proved to be challenging. A residual-dipolar-coupling-based refinement approach can be used to resolve the structure of membrane proteins up to 40 kDa in size, but to do this you need a weak-alignment medium that is detergent-resistant and it has thus far been difficult to obtain such a medium suitable for weak alignment of membrane proteins. We describe here a protocol for robust, large-scale synthesis of detergent-resistant DNA nanotubes that can be assembled into dilute liquid crystals for application as weak-alignment media in solution NMR structure determination of membrane proteins in detergent micelles. The DNA nanotubes are heterodimers of 400-nm-long six-helix bundles, each self-assembled from a M13-based p7308 scaffold strand and >170 short oligonucleotide staple strands. Compatibility with proteins bearing considerable positive charge as well as modulation of molecular alignment, toward collection of linearly independent restraints, can be introduced by reducing the negative charge of DNA nanotubes using counter ions and small DNA-binding molecules. This detergent-resistant liquid-crystal medium offers a number of properties conducive for membrane protein alignment, including high-yield production, thermal stability, buffer compatibility and structural programmability. Production of sufficient nanotubes for four or five NMR experiments can be completed in 1 week by a single individual.

  20. How to calculate clearance of highly protein-bound drugs during continuous venovenous hemofiltration demonstrated with flucloxacillin.

    Science.gov (United States)

    Meyer, Brigitte; Ahmed el Gendy, Salwa; Delle Karth, Georg; Locker, Gottfried J; Heinz, Gottfried; Jaeger, Walter; Thalhammer, Florian

    2003-01-01

    Flucloxacillin is an important antimicrobial drug in the treatment of infections with Staphylococcus aureus and therefore is often used in staphylococcal infections. Furthermore, flucloxacillin has a high protein binding rate as for example ceftriaxone or teicoplanin--drugs which have formerly been characterized as not being dialyzable. The pharmacokinetic parameters of 4.0 g flucloxacillin every 8 h were examined in 10 intensive care patients during continuous venovenous hemofiltration (CVVH) using a polyamide capillary hemofilter. In addition, the difficulty of calculating the hemofiltration clearance of a highly protein-bound drug is described. Flucloxacillin serum levels were significantly lowered (56.9 +/- 24.0%) even though only 15% of the drug was detected in the ultrafiltrate. Elimination half-life, total body clearance and sieving coefficient were 4.9 +/- 0.7 h, 117.2 +/- 79.1 ml/min and 0.21 +/- 0.09, respectively. These discrepancies can be explained by the high protein binding of flucloxacillin, the adsorbing property of polyamide and the equation in order to calculate hemofiltration clearance. The unbound fraction of a 4.0 g flucloxacillin dosage facilitates time above the minimum inhibitory concentration (T > MIC) of 60% only for strains up to a minimum inhibitory concentration (MIC) of 0.5 mg/l. Based on the data of this study, we conclude that intensive care patients with staphylococcal infections on CVVH should be treated with 4.0 g flucloxacillin every 8 h which was safe and well tolerated. Moreover, further studies with highly protein-bound drugs are recommended to check the classical 'hemodialysis' equation as the standard equation in calculating the CVVH clearance of highly protein-bound drugs. Copyright 2003 S. Karger AG, Basel

  1. An approach to large scale identification of non-obvious structural similarities between proteins

    Science.gov (United States)

    Cherkasov, Artem; Jones, Steven JM

    2004-01-01

    Background A new sequence independent bioinformatics approach allowing genome-wide search for proteins with similar three dimensional structures has been developed. By utilizing the numerical output of the sequence threading it establishes putative non-obvious structural similarities between proteins. When applied to the testing set of proteins with known three dimensional structures the developed approach was able to recognize structurally similar proteins with high accuracy. Results The method has been developed to identify pathogenic proteins with low sequence identity and high structural similarity to host analogues. Such protein structure relationships would be hypothesized to arise through convergent evolution or through ancient horizontal gene transfer events, now undetectable using current sequence alignment techniques. The pathogen proteins, which could mimic or interfere with host activities, would represent candidate virulence factors. The developed approach utilizes the numerical outputs from the sequence-structure threading. It identifies the potential structural similarity between a pair of proteins by correlating the threading scores of the corresponding two primary sequences against the library of the standard folds. This approach allowed up to 64% sensitivity and 99.9% specificity in distinguishing protein pairs with high structural similarity. Conclusion Preliminary results obtained by comparison of the genomes of Homo sapiens and several strains of Chlamydia trachomatis have demonstrated the potential usefulness of the method in the identification of bacterial proteins with known or potential roles in virulence. PMID:15147578

  2. An approach to large scale identification of non-obvious structural similarities between proteins

    Directory of Open Access Journals (Sweden)

    Cherkasov Artem

    2004-05-01

    Full Text Available Abstract Background A new sequence independent bioinformatics approach allowing genome-wide search for proteins with similar three dimensional structures has been developed. By utilizing the numerical output of the sequence threading it establishes putative non-obvious structural similarities between proteins. When applied to the testing set of proteins with known three dimensional structures the developed approach was able to recognize structurally similar proteins with high accuracy. Results The method has been developed to identify pathogenic proteins with low sequence identity and high structural similarity to host analogues. Such protein structure relationships would be hypothesized to arise through convergent evolution or through ancient horizontal gene transfer events, now undetectable using current sequence alignment techniques. The pathogen proteins, which could mimic or interfere with host activities, would represent candidate virulence factors. The developed approach utilizes the numerical outputs from the sequence-structure threading. It identifies the potential structural similarity between a pair of proteins by correlating the threading scores of the corresponding two primary sequences against the library of the standard folds. This approach allowed up to 64% sensitivity and 99.9% specificity in distinguishing protein pairs with high structural similarity. Conclusion Preliminary results obtained by comparison of the genomes of Homo sapiens and several strains of Chlamydia trachomatis have demonstrated the potential usefulness of the method in the identification of bacterial proteins with known or potential roles in virulence.

  3. ELECTRONIC-STRUCTURE OF THE MISFIT-LAYER COMPOUND (SNS)(1.17)NBS2 DEDUCED FROM BAND-STRUCTURE CALCULATIONS AND PHOTOELECTRON-SPECTRA

    NARCIS (Netherlands)

    FANG, CM; ETTEMA, ARHF; HAAS, C; WIEGERS, GA; VANLEUKEN, H; DEGROOT, RA

    1995-01-01

    In order to understand the electronic structure of the misfit-layer compound (SnS)(1.17)NbS2 we carried out an ab initio band-structure calculation of the closely related commensurate compound (SnS)(1.20)NbS2. The band structure is compared with calculations for NbS2 and for hypothetical SnS with

  4. Formatt: Correcting protein multiple structural alignments by incorporating sequence alignment

    Directory of Open Access Journals (Sweden)

    Daniels Noah M

    2012-10-01

    Full Text Available Abstract Background The quality of multiple protein structure alignments are usually computed and assessed based on geometric functions of the coordinates of the backbone atoms from the protein chains. These purely geometric methods do not utilize directly protein sequence similarity, and in fact, determining the proper way to incorporate sequence similarity measures into the construction and assessment of protein multiple structure alignments has proved surprisingly difficult. Results We present Formatt, a multiple structure alignment based on the Matt purely geometric multiple structure alignment program, that also takes into account sequence similarity when constructing alignments. We show that Formatt outperforms Matt and other popular structure alignment programs on the popular HOMSTRAD benchmark. For the SABMark twilight zone benchmark set that captures more remote homology, Formatt and Matt outperform other programs; depending on choice of embedded sequence aligner, Formatt produces either better sequence and structural alignments with a smaller core size than Matt, or similarly sized alignments with better sequence similarity, for a small cost in average RMSD. Conclusions Considering sequence information as well as purely geometric information seems to improve quality of multiple structure alignments, though defining what constitutes the best alignment when sequence and structural measures would suggest different alignments remains a difficult open question.

  5. Energetically Unfavorable Amide Conformations for N6-Acetyllysine Side Chains in Refined Protein Structures

    Science.gov (United States)

    Genshaft, Alexander; Moser, Joe-Ann S.; D'Antonio, Edward L.; Bowman, Christine M.; Christianson, David W.

    2013-01-01

    The reversible acetylation of lysine to form N6-acetyllysine in the regulation of protein function is a hallmark of epigenetics. Acetylation of the positively charged amino group of the lysine side chain generates a neutral N-alkylacetamide moiety that serves as a molecular “switch” for the modulation of protein function and protein-protein interactions. We now report the analysis of 381 N6-acetyllysine side chain amide conformations as found in 79 protein crystal structures and 11 protein NMR structures deposited in the Protein Data Bank (PDB) of the Research Collaboratory for Structural Bioinformatics. We find that only 74.3% of N6-acetyllysine residues in protein crystal structures and 46.5% in protein NMR structures contain amide groups with energetically preferred trans or generously trans conformations. Surprisingly, 17.6% of N6-acetyllysine residues in protein crystal structures and 5.3% in protein NMR structures contain amide groups with energetically unfavorable cis or generously cis conformations. Even more surprisingly, 8.1% of N6-acetyllysine residues in protein crystal structures and 48.2% in NMR structures contain amide groups with energetically prohibitive twisted conformations that approach the transition state structure for cis-trans isomerization. In contrast, 109 unique N-alkylacetamide groups contained in 84 highly-accurate small molecule crystal structures retrieved from the Cambridge Structural Database exclusively adopt energetically preferred trans conformations. Therefore, we conclude that cis and twisted N6-acetyllysine amides in protein structures deposited in the PDB are erroneously modeled due to their energetically unfavorable or prohibitive conformations. PMID:23401043

  6. Quantification of Protein Hydration, Glass Transitions, and Structural Relaxations of Aqueous Protein and Carbohydrate-Protein Systems.

    Science.gov (United States)

    Roos, Yrjö H; Potes, Naritchaya

    2015-06-11

    Water distribution and miscibility of carbohydrate and protein components in biological materials and their structural contributions in concentrated solids are poorly understood. In the present study, structural relaxations and a glass transition of protein hydration water and antiplasticization of the hydration water at low temperatures were measured using dynamic mechanical analysis (DMA) and differential scanning calorimetry (DSC) for bovine whey protein (BWP), aqueous glucose-fructose (GF), and their mixture. Thermal transitions of α-lactalbumin and β-lactoglobulin components of BWP included water-content-dependent endothermic but reversible dehydration and denaturation, and exothermic and irreversible aggregation. An α-relaxation assigned to hydration water in BWP appeared at water-content-dependent temperatures and increased to over the range of 150-200 K at decreasing water content and in the presence of GF. Two separate glass transitions and individual fractions of unfrozen water of ternary GF-BWP-water systems contributed to uncoupled α-relaxations, suggesting different roles of protein hydration water and carbohydrate vitrification in concentrated solids during freezing and dehydration. Hydration water in the BWP fraction of GF-BWP systems was derived from equilibrium water sorption and glass transition data of the GF fraction, which gave a significant universal method to quantify (i) protein hydration water and (ii) the unfrozen water in protein-carbohydrate systems for such applications as cryopreservation, freezing, lyophilization, and dehydration of biological materials. A ternary supplemented phase diagram (state diagram) established for the GF-BWP-water system can be used for the analysis of the water distribution across carbohydrate and protein components in such applications.

  7. Reflections on protein splicing: structures, functions and mechanisms

    Science.gov (United States)

    Anraku, Yasuhiro; Satow, Yoshinori

    2009-01-01

    Twenty years ago, evidence that one gene produces two enzymes via protein splicing emerged from structural and expression studies of the VMA1 gene in Saccharomyces cerevisiae. VMA1 consists of a single open reading frame and contains two independent genetic information for Vma1p (a catalytic 70-kDa subunit of the vacuolar H+-ATPase) and VDE (a 50-kDa DNA endonuclease) as an in-frame spliced insert in the gene. Protein splicing is a posttranslational cellular process, in which an intervening polypeptide termed as the VMA1 intein is self-catalytically excised out from a nascent 120-kDa VMA1 precursor and two flanking polypeptides of the N- and C-exteins are ligated to produce the mature Vma1p. Subsequent studies have demonstrated that protein splicing is not unique to the VMA1 precursor and there are many operons in nature, which implement genetic information editing at protein level. To elucidate its structure-directed chemical mechanisms, a series of biochemical and crystal structural studies has been carried out with the use of various VMA1 recombinants. This article summarizes a VDE-mediated self-catalytic mechanism for protein splicing that is triggered and terminated solely via thiazolidine intermediates with tetrahedral configurations formed within the splicing sites where proton ingress and egress are driven by balanced protonation and deprotonation. PMID:19907126

  8. Fundamental Characteristics of AAA+ Protein Family Structure and Function.

    Science.gov (United States)

    Miller, Justin M; Enemark, Eric J

    2016-01-01

    Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

  9. Calculation of electrodynamical characteristics and choice of accelerating structure for storage ring

    International Nuclear Information System (INIS)

    Karnaukhov, I.M.; Popkov, Yu.P.; Telegin, Yu.N.; Trushkin, N.A.; Dajkovskij, A.G.; Zakamskaya, L.T.; Ryabov, A.D.

    1989-01-01

    Comparative analysis of several types of accelerating structures at standing E 010 wave is conducted on the basis of numerical calculations performed with the use of the PRUD-0 and PRUD programs. Dispersion dependences of electromagnetic field distribution, quality and coupling impedance are calculated both for axially symmetric and axially asymmetric modes of oscillations in structures with 699.3 MHz operating frequency. It is shown that structure with a cell the form of which is optimized with respect to shunt resistance on the main mode possesses the numerical spurious impedance in higher modes. This is the main factor when choosing accelerating structure for storage ring with multi-bunch operation conditions. 12 refs.; 3 figs.; 3 tabs

  10. Efficient identification of critical residues based only on protein structure by network analysis.

    Directory of Open Access Journals (Sweden)

    Michael P Cusack

    2007-05-01

    Full Text Available Despite the increasing number of published protein structures, and the fact that each protein's function relies on its three-dimensional structure, there is limited access to automatic programs used for the identification of critical residues from the protein structure, compared with those based on protein sequence. Here we present a new algorithm based on network analysis applied exclusively on protein structures to identify critical residues. Our results show that this method identifies critical residues for protein function with high reliability and improves automatic sequence-based approaches and previous network-based approaches. The reliability of the method depends on the conformational diversity screened for the protein of interest. We have designed a web site to give access to this software at http://bis.ifc.unam.mx/jamming/. In summary, a new method is presented that relates critical residues for protein function with the most traversed residues in networks derived from protein structures. A unique feature of the method is the inclusion of the conformational diversity of proteins in the prediction, thus reproducing a basic feature of the structure/function relationship of proteins.

  11. Association of protein structure, protein and carbohydrate subfractions with bioenergy profiles and biodegradation functions in modeled forage

    Science.gov (United States)

    Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

    2016-03-01

    The objectives of this study were to detect unique aspects and association of forage protein inherent structure, biological compounds, protein and carbohydrate subfractions, bioenergy profiles, and biodegradation features. In this study, common available alfalfa hay from two different sourced-origins (FSO vs. CSO) was used as a modeled forage for inherent structure profile, bioenergy, biodegradation and their association between their structure and bio-functions. The molecular spectral profiles were determined using non-invasive molecular spectroscopy. The parameters included: protein structure amide I group, amide II group and their ratios; protein subfractions (PA1, PA2, PB1, PB2, PC); carbohydrate fractions (CA1, CA2, CA3, CA4, CB1, CB2, CC); biodegradable and undegradable fractions of protein (RDPA2, RDPB1, RDPB2, RDP; RUPA2 RUPB1, RUPB2, RUPC, RUP); biodegradable and undegradable fractions of carbohydrate (RDCA4, RDCB1, RDCB2, RDCB3, RDCHO; RUCA4, RUCB1; RUCB2; RUCB3 RUCC, RUCHO) and bioenergy profiles (tdNDF, tdFA, tdCP, tdNFC, TDN1 ×, DE3 ×, ME3 ×, NEL3 ×; NEm, NEg). The results show differences in protein and carbohydrate (CHO) subfractions in the moderately degradable true protein fraction (PB1: 502 vs. 420 g/kg CP, P = 0.09), slowly degraded true protein fraction (PB2: 45 vs. 96 g/kg CP, P = 0.02), moderately degradable CHO fraction (CB2: 283 vs. 223 g/kg CHO, P = 0.06) and slowly degraded CHO fraction (CB3: 369 vs. 408 g/kg CHO) between the two sourced origins. As to biodegradable (RD) fractions of protein and CHO in rumen, there were differences in RD of PB1 (417 vs. 349 g/kg CP, P = 0.09), RD of PB2 (29 vs. 62 g/kg CP, P = 0.02), RD of CB2 (251 vs. 198 g/kg DM, P = 0.06), RD of CB3 (236 vs. 261 g/kg CHO, P = 0.08). As to bioenergy profile, there were differences in total digestible nutrient (TDN: 551 vs. 537 g/kg DM, P = 0.06), and metabolic bioenergy (P = 0.095). As to protein molecular structure, there were differences in protein structure 1st

  12. Perspective: Structural fluctuation of protein and Anfinsen's thermodynamic hypothesis

    Science.gov (United States)

    Hirata, Fumio; Sugita, Masatake; Yoshida, Masasuke; Akasaka, Kazuyuki

    2018-01-01

    The thermodynamics hypothesis, casually referred to as "Anfinsen's dogma," is described theoretically in terms of a concept of the structural fluctuation of protein or the first moment (average structure) and the second moment (variance and covariance) of the structural distribution. The new theoretical concept views the unfolding and refolding processes of protein as a shift of the structural distribution induced by a thermodynamic perturbation, with the variance-covariance matrix varying. Based on the theoretical concept, a method to characterize the mechanism of folding (or unfolding) is proposed. The transition state, if any, between two stable states is interpreted as a gap in the distribution, which is created due to an extensive reorganization of hydrogen bonds among back-bone atoms of protein and with water molecules in the course of conformational change. Further perspective to applying the theory to the computer-aided drug design, and to the material science, is briefly discussed.

  13. Structural protein relationships among eastern equine encephalitis viruses.

    Science.gov (United States)

    Strizki, J M; Repik, P M

    1994-11-01

    We have re-evaluated the relationships among the polypeptides of eastern equine encephalitis (EEE) viruses using SDS-PAGE and peptide mapping of individual virion proteins. Four to five distinct polypeptide bands were detected upon SDS-PAGE analysis of viruses: the E1, E2 and C proteins normally associated with alphavirus virions, as well as an additional more rapidly-migrating E2-associated protein and a high M(r) (HMW) protein. In contrast with previous findings by others, the electrophoretic profiles of the virion proteins of EEE viruses displayed a marked correlation with serotype. The protein profiles of the 33 North American (NA)-serotype viruses examined were remarkably homogeneous, with variation detected only in the E1 protein of two isolates. In contrast, considerable heterogeneity was observed in the migration profiles of both the E1 and E2 glycoproteins of the 13 South American (SA)-type viruses examined. Peptide mapping of individual virion proteins using limited proteolysis with Staphylococcus aureus V8 protease confirmed that, in addition to the homogeneity evident among NA-type viruses and relative heterogeneity among SA-type viruses, the E1 and E2 proteins of NA- and SA-serotype viruses exhibited serotype-specific structural variation. The C protein was highly conserved among isolates of both virus serotypes. Endoglycosidase analyses of intact virions did not reveal substantial glycosylation differences between the glycoproteins of NA- and SA-serotype viruses. Both the HMW protein and the E2 protein (doublet) of EEE virus appeared to contain, at least in part, high-mannose type N-linked oligosaccharides. No evidence of O-linked glycans was found on either the E1 or the E2 glycoprotein. Despite the observed structural differences between proteins of NA- and SA-type viruses, Western blot analyses utilizing polyclonal antibodies indicated that immunoreactive epitopes appeared to be conserved.

  14. Cross-over between discrete and continuous protein structure space: insights into automatic classification and networks of protein structures.

    Directory of Open Access Journals (Sweden)

    Alberto Pascual-García

    2009-03-01

    Full Text Available Structural classifications of proteins assume the existence of the fold, which is an intrinsic equivalence class of protein domains. Here, we test in which conditions such an equivalence class is compatible with objective similarity measures. We base our analysis on the transitive property of the equivalence relationship, requiring that similarity of A with B and B with C implies that A and C are also similar. Divergent gene evolution leads us to expect that the transitive property should approximately hold. However, if protein domains are a combination of recurrent short polypeptide fragments, as proposed by several authors, then similarity of partial fragments may violate the transitive property, favouring the continuous view of the protein structure space. We propose a measure to quantify the violations of the transitive property when a clustering algorithm joins elements into clusters, and we find out that such violations present a well defined and detectable cross-over point, from an approximately transitive regime at high structure similarity to a regime with large transitivity violations and large differences in length at low similarity. We argue that protein structure space is discrete and hierarchic classification is justified up to this cross-over point, whereas at lower similarities the structure space is continuous and it should be represented as a network. We have tested the qualitative behaviour of this measure, varying all the choices involved in the automatic classification procedure, i.e., domain decomposition, alignment algorithm, similarity score, and clustering algorithm, and we have found out that this behaviour is quite robust. The final classification depends on the chosen algorithms. We used the values of the clustering coefficient and the transitivity violations to select the optimal choices among those that we tested. Interestingly, this criterion also favours the agreement between automatic and expert classifications

  15. Building a better fragment library for de novo protein structure prediction.

    Directory of Open Access Journals (Sweden)

    Saulo H P de Oliveira

    Full Text Available Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10. We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. "Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources".

  16. Building a Better Fragment Library for De Novo Protein Structure Prediction

    Science.gov (United States)

    de Oliveira, Saulo H. P.; Shi, Jiye; Deane, Charlotte M.

    2015-01-01

    Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10). We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. “Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources”. PMID:25901595

  17. Cell-free protein synthesis for structure determination by X-ray crystallography.

    Science.gov (United States)

    Watanabe, Miki; Miyazono, Ken-ichi; Tanokura, Masaru; Sawasaki, Tatsuya; Endo, Yaeta; Kobayashi, Ichizo

    2010-01-01

    Structure determination has been difficult for those proteins that are toxic to the cells and cannot be prepared in a large amount in vivo. These proteins, even when biologically very interesting, tend to be left uncharacterized in the structural genomics projects. Their cell-free synthesis can bypass the toxicity problem. Among the various cell-free systems, the wheat-germ-based system is of special interest due to the following points: (1) Because the gene is placed under a plant translational signal, its toxic expression in a bacterial host is reduced. (2) It has only little codon preference and, especially, little discrimination between methionine and selenomethionine (SeMet), which allows easy preparation of selenomethionylated proteins for crystal structure determination by SAD and MAD methods. (3) Translation is uncoupled from transcription, so that the toxicity of the translation product on DNA and its transcription, if any, can be bypassed. We have shown that the wheat-germ-based cell-free protein synthesis is useful for X-ray crystallography of one of the 4-bp cutter restriction enzymes, which are expected to be very toxic to all forms of cells retaining the genome. Our report on its structure represents the first report of structure determination by X-ray crystallography using protein overexpressed with the wheat-germ-based cell-free protein expression system. This will be a method of choice for cytotoxic proteins when its cost is not a problem. Its use will become popular when the crystal structure determination technology has evolved to require only a tiny amount of protein.

  18. The shell structure effects in neutron cross section calculation by a ...

    African Journals Online (AJOL)

    The role of the shell structure properties of the nucleus in the calculation of neutron-induced reaction cross-section data based on nuclear reaction theory has been investigated. In this investigation, measured, evaluated and calculated (n.p) reaction cross-section data on la spherical nucleus (i.e. 112Sn) and a deformed ...

  19. Hill-Climbing search and diversification within an evolutionary approach to protein structure prediction.

    Science.gov (United States)

    Chira, Camelia; Horvath, Dragos; Dumitrescu, D

    2011-07-30

    Proteins are complex structures made of amino acids having a fundamental role in the correct functioning of living cells. The structure of a protein is the result of the protein folding process. However, the general principles that govern the folding of natural proteins into a native structure are unknown. The problem of predicting a protein structure with minimum-energy starting from the unfolded amino acid sequence is a highly complex and important task in molecular and computational biology. Protein structure prediction has important applications in fields such as drug design and disease prediction. The protein structure prediction problem is NP-hard even in simplified lattice protein models. An evolutionary model based on hill-climbing genetic operators is proposed for protein structure prediction in the hydrophobic - polar (HP) model. Problem-specific search operators are implemented and applied using a steepest-ascent hill-climbing approach. Furthermore, the proposed model enforces an explicit diversification stage during the evolution in order to avoid local optimum. The main features of the resulting evolutionary algorithm - hill-climbing mechanism and diversification strategy - are evaluated in a set of numerical experiments for the protein structure prediction problem to assess their impact to the efficiency of the search process. Furthermore, the emerging consolidated model is compared to relevant algorithms from the literature for a set of difficult bidimensional instances from lattice protein models. The results obtained by the proposed algorithm are promising and competitive with those of related methods.

  20. Hill-Climbing search and diversification within an evolutionary approach to protein structure prediction

    Directory of Open Access Journals (Sweden)

    Chira Camelia

    2011-07-01

    Full Text Available Abstract Proteins are complex structures made of amino acids having a fundamental role in the correct functioning of living cells. The structure of a protein is the result of the protein folding process. However, the general principles that govern the folding of natural proteins into a native structure are unknown. The problem of predicting a protein structure with minimum-energy starting from the unfolded amino acid sequence is a highly complex and important task in molecular and computational biology. Protein structure prediction has important applications in fields such as drug design and disease prediction. The protein structure prediction problem is NP-hard even in simplified lattice protein models. An evolutionary model based on hill-climbing genetic operators is proposed for protein structure prediction in the hydrophobic - polar (HP model. Problem-specific search operators are implemented and applied using a steepest-ascent hill-climbing approach. Furthermore, the proposed model enforces an explicit diversification stage during the evolution in order to avoid local optimum. The main features of the resulting evolutionary algorithm - hill-climbing mechanism and diversification strategy - are evaluated in a set of numerical experiments for the protein structure prediction problem to assess their impact to the efficiency of the search process. Furthermore, the emerging consolidated model is compared to relevant algorithms from the literature for a set of difficult bidimensional instances from lattice protein models. The results obtained by the proposed algorithm are promising and competitive with those of related methods.

  1. Functional diversification of structurally alike NLR proteins in plants.

    Science.gov (United States)

    Chakraborty, Joydeep; Jain, Akansha; Mukherjee, Dibya; Ghosh, Suchismita; Das, Sampa

    2018-04-01

    In due course of evolution many pathogens alter their effector molecules to modulate the host plants' metabolism and immune responses triggered upon proper recognition by the intracellular nucleotide-binding oligomerization domain containing leucine-rich repeat (NLR) proteins. Likewise, host plants have also evolved with diversified NLR proteins as a survival strategy to win the battle against pathogen invasion. NLR protein indeed detects pathogen derived effector proteins leading to the activation of defense responses associated with programmed cell death (PCD). In this interactive process, genome structure and plasticity play pivotal role in the development of innate immunity. Despite being quite conserved with similar biological functions in all eukaryotes, the intracellular NLR immune receptor proteins happen to be structurally distinct. Recent studies have made progress in identifying transcriptional regulatory complexes activated by NLR proteins. In this review, we attempt to decipher the intracellular NLR proteins mediated surveillance across the evolutionarily diverse taxa, highlighting some of the recent updates on NLR protein compartmentalization, molecular interactions before and after activation along with insights into the finer role of these receptor proteins to combat invading pathogens upon their recognition. Latest information on NLR sensors, helpers and NLR proteins with integrated domains in the context of plant pathogen interactions are also discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Illuminating structural proteins in viral "dark matter" with metaproteomics.

    Science.gov (United States)

    Brum, Jennifer R; Ignacio-Espinoza, J Cesar; Kim, Eun-Hae; Trubl, Gareth; Jones, Robert M; Roux, Simon; VerBerkmoes, Nathan C; Rich, Virginia I; Sullivan, Matthew B

    2016-03-01

    Viruses are ecologically important, yet environmental virology is limited by dominance of unannotated genomic sequences representing taxonomic and functional "viral dark matter." Although recent analytical advances are rapidly improving taxonomic annotations, identifying functional dark matter remains problematic. Here, we apply paired metaproteomics and dsDNA-targeted metagenomics to identify 1,875 virion-associated proteins from the ocean. Over one-half of these proteins were newly functionally annotated and represent abundant and widespread viral metagenome-derived protein clusters (PCs). One primarily unannotated PC dominated the dataset, but structural modeling and genomic context identified this PC as a previously unidentified capsid protein from multiple uncultivated tailed virus families. Furthermore, four of the five most abundant PCs in the metaproteome represent capsid proteins containing the HK97-like protein fold previously found in many viruses that infect all three domains of life. The dominance of these proteins within our dataset, as well as their global distribution throughout the world's oceans and seas, supports prior hypotheses that this HK97-like protein fold is the most abundant biological structure on Earth. Together, these culture-independent analyses improve virion-associated protein annotations, facilitate the investigation of proteins within natural viral communities, and offer a high-throughput means of illuminating functional viral dark matter.

  3. PCNA Structure and Interactions with Partner Proteins

    KAUST Repository

    Oke, Muse; Zaher, Manal S.; Hamdan, Samir

    2018-01-01

    Proliferating cell nuclear antigen (PCNA) consists of three identical monomers that topologically encircle double-stranded DNA. PCNA stimulates the processivity of DNA polymerase δ and, to a less extent, the intrinsically highly processive DNA polymerase ε. It also functions as a platform that recruits and coordinates the activities of a large number of DNA processing proteins. Emerging structural and biochemical studies suggest that the nature of PCNA-partner proteins interactions is complex. A hydrophobic groove at the front side of PCNA serves as a primary docking site for the consensus PIP box motifs present in many PCNA-binding partners. Sequences that immediately flank the