WorldWideScience

Sample records for model molecular system

  1. A Molecular Communication System Model for Particulate Drug Delivery Systems.

    Science.gov (United States)

    Chahibi, Youssef; Pierobon, Massimiliano; Song, Sang Ok; Akyildiz, Ian F

    2013-12-01

    The goal of a drug delivery system (DDS) is to convey a drug where the medication is needed, while, at the same time, preventing the drug from affecting other healthy parts of the body. Drugs composed of micro- or nano-sized particles (particulate DDS) that are able to cross barriers which prevent large particles from escaping the bloodstream are used in the most advanced solutions. Molecular communication (MC) is used as an abstraction of the propagation of drug particles in the body. MC is a new paradigm in communication research where the exchange of information is achieved through the propagation of molecules. Here, the transmitter is the drug injection, the receiver is the drug delivery, and the channel is realized by the transport of drug particles, thus enabling the analysis and design of a particulate DDS using communication tools. This is achieved by modeling the MC channel as two separate contributions, namely, the cardiovascular network model and the drug propagation network. The cardiovascular network model allows to analytically compute the blood velocity profile in every location of the cardiovascular system given the flow input by the heart. The drug propagation network model allows the analytical expression of the drug delivery rate at the targeted site given the drug injection rate. Numerical results are also presented to assess the flexibility and accuracy of the developed model. The study of novel optimization techniques for a more effective and less invasive drug delivery will be aided by this model, while paving the way for novel communication techniques for Intrabody communication networks.

  2. Computer modeling of properties of complex molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Kulkova, E.Yu. [Moscow State University of Technology “STANKIN”, Vadkovsky per., 1, Moscow 101472 (Russian Federation); Khrenova, M.G.; Polyakov, I.V. [Lomonosov Moscow State University, Chemistry Department, Leninskie Gory 1/3, Moscow 119991 (Russian Federation); Nemukhin, A.V. [Lomonosov Moscow State University, Chemistry Department, Leninskie Gory 1/3, Moscow 119991 (Russian Federation); N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina 4, Moscow 119334 (Russian Federation)

    2015-03-10

    Large molecular aggregates present important examples of strongly nonhomogeneous systems. We apply combined quantum mechanics / molecular mechanics approaches that assume treatment of a part of the system by quantum-based methods and the rest of the system with conventional force fields. Herein we illustrate these computational approaches by two different examples: (1) large-scale molecular systems mimicking natural photosynthetic centers, and (2) components of prospective solar cells containing titan dioxide and organic dye molecules. We demonstrate that modern computational tools are capable to predict structures and spectra of such complex molecular aggregates.

  3. Molecular modeling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-01-01

    Full Text Available The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and the exponential growth of the knowledge of protein structures have made it possible for organic compounds to be tailored to decrease the harmful side effects and increase the potency. This article provides a detailed description of the techniques employed in molecular modeling. Molecular modeling is a rapidly developing discipline, and has been supported by the dramatic improvements in computer hardware and software in recent years.

  4. Modeling molecular hydrogen emission in M dwarf exoplanetary systems

    Science.gov (United States)

    Evonosky, William; France, Kevin; Kruczek, Nick E.; Youngblood, Allison; Measurements of the Ultraviolet Spectral Characteristics of Low-mass Exoplanet host Stars (MUSCLES)

    2017-01-01

    Exoplanets orbiting low-mass stars are prime candidates for atmospheric characterization due to their astronomical abundance and short orbital periods. These planets orbit stars that are often more active than main sequence solar-type stars. They are exposed to differing levels of ultraviolet radiation which can cause traditional “biosignature” gases to be generated abiotically, potentially causing false-positive identifications of life. We modeled the recently discovered molecular hydrogen emission in the ultraviolet spectra (1350 - 1650 Å) as arising from the stellar surface, excited by radiation generated in the upper chromosphere. The model was compared with observed hydrogen emission from the “Measurements of the Ultraviolet Spectral Characteristics of Low-mass Exoplanet host Stars” (MUSCLES) survey by conducting a grid search and implementing a chi-squared minimization routine. We considered only progressions from the [1, 4] and [1, 7] first excited electronic levels. Our modeling procedure varied the atomic hydrogen column density (in the chromosphere) as well as the photospheric molecular hydrogen column density and temperature. The model required as an input a reconstructed intrinsic Lyman α profile which served as the pumping radiation for the molecular hydrogen. We found that an atomic hydrogen column density of log10N(H I) = 14.13 ± 0.16 cm-2 represents a breaking point above which there is not enough Lyman α flux available to excite a significant molecular hydrogen population into the [1, 7] state. We also present H2 temperatures which may suggest that star spots on low mass stars persist longer, and encompass more area than star spots on solar-type stars.

  5. Molecular Modelling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-12-01

    Full Text Available

    The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important
    tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and
    the exponential growth of the knowledge of protein structures have made it possible for organic compounds to tailored to
    decrease harmful side effects and increase the potency. This article provides a detailed description of the techniques
    employed in molecular modeling. Molecular modelling is a rapidly developing discipline, and has been supported from
    the dramatic improvements in computer hardware and software in recent years.

  6. Parametrizing coarse grained models for molecular systems at equilibrium

    KAUST Repository

    Kalligiannaki, E.

    2016-10-18

    Hierarchical coarse graining of atomistic molecular systems at equilibrium has been an intensive research topic over the last few decades. In this work we (a) review theoretical and numerical aspects of different parametrization methods (structural-based, force matching and relative entropy) to derive the effective interaction potential between coarse-grained particles. All methods approximate the many body potential of mean force; resulting, however, in different optimization problems. (b) We also use a reformulation of the force matching method by introducing a generalized force matching condition for the local mean force in the sense that allows the approximation of the potential of mean force under both linear and non-linear coarse graining mappings (E. Kalligiannaki, et al., J. Chem. Phys. 2015). We apply and compare these methods to: (a) a benchmark system of two isolated methane molecules; (b) methane liquid; (c) water; and (d) an alkane fluid. Differences between the effective interactions, derived from the various methods, are found that depend on the actual system under study. The results further reveal the relation of the various methods and the sensitivities that may arise in the implementation of numerical methods used in each case.

  7. Parametrizing coarse grained models for molecular systems at equilibrium

    Science.gov (United States)

    Kalligiannaki, E.; Chazirakis, A.; Tsourtis, A.; Katsoulakis, M. A.; Plecháč, P.; Harmandaris, V.

    2016-10-01

    Hierarchical coarse graining of atomistic molecular systems at equilibrium has been an intensive research topic over the last few decades. In this work we (a) review theoretical and numerical aspects of different parametrization methods (structural-based, force matching and relative entropy) to derive the effective interaction potential between coarse-grained particles. All methods approximate the many body potential of mean force; resulting, however, in different optimization problems. (b) We also use a reformulation of the force matching method by introducing a generalized force matching condition for the local mean force in the sense that allows the approximation of the potential of mean force under both linear and non-linear coarse graining mappings (E. Kalligiannaki, et al., J. Chem. Phys. 2015). We apply and compare these methods to: (a) a benchmark system of two isolated methane molecules; (b) methane liquid; (c) water; and (d) an alkane fluid. Differences between the effective interactions, derived from the various methods, are found that depend on the actual system under study. The results further reveal the relation of the various methods and the sensitivities that may arise in the implementation of numerical methods used in each case.

  8. A Comparative Study of Successful Central Nervous System Drugs Using Molecular Modeling

    Science.gov (United States)

    Kim, Hyosub; Sulaimon, Segun; Menezes, Sandra; Son, Anne; Menezes, Warren J. C.

    2011-01-01

    Molecular modeling is a powerful tool used for three-dimensional visualization and for exploring electrostatic forces involved in drug transport. This tool enhances student understanding of structure-property relationships, as well as actively engaging them in class. Molecular modeling of several central nervous system (CNS) drugs is used to…

  9. A Comparative Study of Successful Central Nervous System Drugs Using Molecular Modeling

    Science.gov (United States)

    Kim, Hyosub; Sulaimon, Segun; Menezes, Sandra; Son, Anne; Menezes, Warren J. C.

    2011-01-01

    Molecular modeling is a powerful tool used for three-dimensional visualization and for exploring electrostatic forces involved in drug transport. This tool enhances student understanding of structure-property relationships, as well as actively engaging them in class. Molecular modeling of several central nervous system (CNS) drugs is used to…

  10. Parameter estimation method for improper fractional models and its application to molecular biological systems.

    Science.gov (United States)

    Tian, Li-Ping; Liu, Lizhi; Wu, Fang-Xiang

    2010-01-01

    Derived from biochemical principles, molecular biological systems can be described by a group of differential equations. Generally these differential equations contain fractional functions plus polynomials (which we call improper fractional model) as reaction rates. As a result, molecular biological systems are nonlinear in both parameters and states. It is well known that it is challenging to estimate parameters nonlinear in a model. However, in fractional functions both the denominator and numerator are linear in the parameters while polynomials are also linear in parameters. Based on this observation, we develop an iterative linear least squares method for estimating parameters in biological systems modeled by improper fractional functions. The basic idea is to transfer optimizing a nonlinear least squares objective function into iteratively solving a sequence of linear least squares problems. The developed method is applied to the estimation of parameters in a metabolism system. The simulation results show the superior performance of the proposed method for estimating parameters in such molecular biological systems.

  11. Modeling of molecular photocells: Application to two-level photovoltaic system with electron-hole interaction.

    Science.gov (United States)

    Nemati Aram, Tahereh; Anghel-Vasilescu, Petrutza; Asgari, Asghar; Ernzerhof, Matthias; Mayou, Didier

    2016-09-28

    We present a novel simple model to describe molecular photocells where the energy conversion process takes place by a single molecular donor-acceptor complex attached to electrodes. By applying quantum scattering theory, an open quantum system method, the coherent molecular photocell is described by a wave function. We analyze photon absorption, energy conversion, and quantum yield of a molecular photocell by considering the effects of electron-hole interaction and non-radiative recombination. We model the exciton creation, dissociation, and subsequent effects on quantum yield in the energy domain. We find that depending on the photocell structure, the electron-hole interaction can normally decrease or abnormally increase the cell efficiency. The proposed model helps to understand the mechanisms of molecular photocells, and it can be used to optimize their yield.

  12. Origami: A Versatile Modeling System for Visualising Chemical Structure and Exploring Molecular Function

    Science.gov (United States)

    Davis, James; Leslie, Ray; Billington, Susan; Slater, Peter R.

    2010-01-01

    The use of "Origami" is presented as an accessible and transferable modeling system through which to convey the intricacies of molecular shape and highlight structure-function relationships. The implementation of origami has been found to be a versatile alternative to conventional ball-and-stick models, possessing the key advantages of being both…

  13. Molecular modeling in confined polymer and biomembrane systems

    Directory of Open Access Journals (Sweden)

    Jayeeta Ghosh

    2009-07-01

    Full Text Available The computational study of soft materials under confinement for bio- and nanotechnology still poses significantchallenges but has come a long way in the last decade. It is possible to realistically model and understand the fundamentalmechanisms which are at play if soft materials are confined to nanometer dimensions. Here, we present several recentexamples of such studies. Thin polymer films are abundantly used as friction modifiers or steric stabilizers. We show howsystematic modeling can shed light on the interplay between entropic and energetic interactions. Thin glassy films arecritical for the success of nanolithography. For that we have to understand the effect of confinement on the glass transitionbehavior in order to guarantee the stability and integrity of the lithographic masks. Simulations aim to understand the fundamental differences in the densities of states of glass formers in bulk and under confinement. With the advent of bionanotechnology the structure and phase behavior of lipid membranes as models for cellular membranes at the nano scale length is of importance due to implications in understanding the role of the lipids in biochemical membrane processes.

  14. Systems level circuit model of C. elegans undulatory locomotion: mathematical modeling and molecular genetics.

    Science.gov (United States)

    Karbowski, Jan; Schindelman, Gary; Cronin, Christopher J; Seah, Adeline; Sternberg, Paul W

    2008-06-01

    To establish the relationship between locomotory behavior and dynamics of neural circuits in the nematode C. elegans we combined molecular and theoretical approaches. In particular, we quantitatively analyzed the motion of C. elegans with defective synaptic GABA and acetylcholine transmission, defective muscle calcium signaling, and defective muscles and cuticle structures, and compared the data with our systems level circuit model. The major experimental findings are: (1) anterior-to-posterior gradients of body bending flex for almost all strains both for forward and backward motion, and for neuronal mutants, also analogous weak gradients of undulatory frequency, (2) existence of some form of neuromuscular (stretch receptor) feedback, (3) invariance of neuromuscular wavelength, (4) biphasic dependence of frequency on synaptic signaling, and (5) decrease of frequency with increase of the muscle time constant. Based on (1) we hypothesize that the Central Pattern Generator (CPG) is located in the head both for forward and backward motion. Points (1) and (2) are the starting assumptions for our theoretical model, whose dynamical patterns are qualitatively insensitive to the details of the CPG design if stretch receptor feedback is sufficiently strong and slow. The model reveals that stretch receptor coupling in the body wall is critical for generation of the neuromuscular wave. Our model agrees with our behavioral data (3), (4), and (5), and with other pertinent published data, e.g., that frequency is an increasing function of muscle gap-junction coupling.

  15. How molecular should your molecular model be? On the level of molecular detail required to simulate biological networks in systems and synthetic biology.

    Science.gov (United States)

    Gonze, Didier; Abou-Jaoudé, Wassim; Ouattara, Djomangan Adama; Halloy, José

    2011-01-01

    The recent advance of genetic studies and the rapid accumulation of molecular data, together with the increasing performance of computers, led researchers to design more and more detailed mathematical models of biological systems. Many modeling approaches rely on ordinary differential equations (ODE) which are based on standard enzyme kinetics. Michaelis-Menten and Hill functions are indeed commonly used in dynamical models in systems and synthetic biology because they provide the necessary nonlinearity to make the dynamics nontrivial (i.e., limit-cycle oscillations or multistability). For most of the systems modeled, the actual molecular mechanism is unknown, and the enzyme equations should be regarded as phenomenological. In this chapter, we discuss the validity and accuracy of these approximations. In particular, we focus on the validity of the Michaelis-Menten function for open systems and on the use of Hill kinetics to describe transcription rates of regulated genes. Our discussion is illustrated by numerical simulations of prototype systems, including the Repressilator (a genetic oscillator) and the Toggle Switch model (a bistable system). We systematically compare the results obtained with the compact version (based on Michaelis-Menten and Hill functions) with its corresponding developed versions (based on "elementary" reaction steps and mass action laws). We also discuss the use of compact approaches to perform stochastic simulations (Gillespie algorithm). On the basis of these results, we argue that using compact models is suitable to model qualitatively biological systems.

  16. Quantitative computational models of molecular self-assembly in systems biology

    Science.gov (United States)

    Thomas, Marcus; Schwartz, Russell

    2017-06-01

    Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally.

  17. Theory of quantum and classical connections in modeling atomic, molecular and electrodynamical systems

    CERN Document Server

    Popa, Alexandru

    2013-01-01

    Quantum and Classical Connections in Modeling Atomic, Molecular and Electrodynamic Systems is intended for scientists and graduate students interested in the foundations of quantum mechanics and applied scientists interested in accurate atomic and molecular models. This is a reference to those working in the new field of relativistic optics, in topics related to relativistic interactions between very intense laser beams and particles, and is based on 30 years of research. The novelty of this work consists of accurate connections between the properties of quantum equations and correspon

  18. Applications of quantum and classical connections in modeling atomic, molecular and electrodynamic systems

    CERN Document Server

    Popa, Alexandru

    2013-01-01

    Applications of Quantum and Classical Connections in Modeling Atomic, Molecular and Electrodynamical Systems is a reference on the new field of relativistic optics, examining topics related to relativistic interactions between very intense laser beams and particles. Based on 30 years of research, this unique book connects the properties of quantum equations to corresponding classical equations used to calculate the energetic values and the symmetry properties of atomic, molecular and electrodynamical systems. In addition, it examines applications for these methods, and for the calculation of

  19. Development of models and methods for the molecular simulation of large systems and molecules

    CERN Document Server

    Walter, Jonathan; Horsch, Martin; Vrabec, Jadran; Hasse, Hans

    2010-01-01

    The most important factor for quantitative results in molecular dynamics simulation are well developed force fields and models. In the present work, the development of new models and the usage of force fields from the literature in large systems are presented. Both tasks lead to time consuming simulations that require massively parallel high performance computing. In the present work, new models for carbon dioxide and cyclohexanolare discussed and a new method for the model development is introduced. Force fields and models for the simulation of PNIPAAm hydrogel in pure water and sodium chloride solution are tested and verified and applied to the simulation of nucleation processes.

  20. A Molecular Thermodynamic Model for Interfacial Tension in Surfactant-Oil-Water System

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    An interfacial equation of state based on perturbation theory for surfactant-oil-water system has been developed. By combining the interfacial equation of state with Boudh-Hir and Mansoori's model, a molecular ther- modynamic model has been proposed. The interfacial tension of surfactant-oil-water systems can be calculated from the surface tensions of pure oil and water by this model. The inteffacial tension data for sodium dodecyl sulphate- heptane-water system, polyoxyethylene n-octylphenol-heptane-water system and hexadecyl trimethyl ammonium bromide-heptane-water system have been correlated. By using the adjustable parameters obtained, the interfacial tensions of these systems at other temperatures have been predicted. Both the correlated and the predicted values are satisfactory.

  1. Synergetics of molecular systems

    CERN Document Server

    Lupichev, Lev N; Kadantsev, Vasiliy N

    2014-01-01

    Synergetics is the quantitative study of multicomponent systems that exhibit nonlinear dynamics and cooperativity. This book specifically considers basic models of the nonlinear dynamics of molecular systems and discusses relevant applications in biological physics and the polymer sciences.Emphasis is placed on specific solutions to the dynamical equations that correspond to the coherent formation of spatial-temporal structures, such as solitons, kinks and breathers, in particular. The emergence of these patterns in molecular structures provides a variety of information on their structural pro

  2. Coarse-Grained Molecular Dynamics for Computer Modeling of Nanomechanical Systems

    Energy Technology Data Exchange (ETDEWEB)

    Rudd, R E

    2003-11-02

    Unique challenges for computer modeling and simulation arise in the course of the development and design of nanoscale mechanical systems. Materials often exhibit unconventional behavior at the nanoscale that can affect device operation and failure. This uncertainty poses a problem because of the limited experimental characterization at these ultra-small length scales. In this Article we give an overview of how we have used concurrent multiscale modeling techniques to address some of these issues. Of particular interest are the dynamic and temperature-dependent processes found in nanomechanical systems. We focus on the behavior of sub-micron mechanical components of Micro-Electro-Mechanical Systems (MEMS) and Nano-Electro-Mechanical Systems (NEMS), especially flexural-mode resonators. The concurrent multiscale methodology we have developed for NEMS employs an atomistic description of millions of atoms in relatively small but key regions of the system, coupled to, and run concurrently with, a generalized finite element model of the periphery. We describe two such techniques. The more precise model, Coarse-Grained Molecular Dynamics (CGMD), describes the dynamics on a mesh of elements, but the equations of motion are built up from the underlying atomistic physics to ensure a smooth coupling between regions governed by different length scales. In many cases the degrees of smoothness of the coupling provided by CGMD is not necessary. The hybrid Coupling of Length Scales (CLS) methodology, combining molecular dynamics with conventional finite element modeling, provides a suitable technique for these cases at a greatly reduced computation expense. We review these models and some of the results we have obtained regarding size effects in the elasticity and dissipation of nanomechanical systems.

  3. Mathematical models of non-linear phenomena, processes and systems: from molecular scale to planetary atmosphere

    CERN Document Server

    2013-01-01

    This book consists of twenty seven chapters, which can be divided into three large categories: articles with the focus on the mathematical treatment of non-linear problems, including the methodologies, algorithms and properties of analytical and numerical solutions to particular non-linear problems; theoretical and computational studies dedicated to the physics and chemistry of non-linear micro-and nano-scale systems, including molecular clusters, nano-particles and nano-composites; and, papers focused on non-linear processes in medico-biological systems, including mathematical models of ferments, amino acids, blood fluids and polynucleic chains.

  4. Study of system- size effects in multi- fragmentation using Quantum Molecular Dynamics model

    CERN Document Server

    Singh, J; Aichelin, Jörg; Singh, Jaivir; Puri, Rajeev K.

    2001-01-01

    We report, for the first time, the dependence of the multiplicity of different fragments on the system size employing a quantum molecular dynamics model. This dependence is extracted from the simulations of symmetric collisions of Ca+Ca, Ni+Ni, Nb+Nb, Xe+Xe, Er+Er, Au+Au and U+U at incident energies between 50 A MeV and 1 A GeV. We find that the multiplicity of different fragments scales with the size of the system which can be parameterized by a simple power law.

  5. Experiments and simulation models of a basic computation element of an autonomous molecular computing system.

    Science.gov (United States)

    Takinoue, Masahiro; Kiga, Daisuke; Shohda, Koh-Ichiroh; Suyama, Akira

    2008-10-01

    Autonomous DNA computers have been attracting much attention because of their ability to integrate into living cells. Autonomous DNA computers can process information through DNA molecules and their molecular reactions. We have already proposed an idea of an autonomous molecular computer with high computational ability, which is now named Reverse-transcription-and-TRanscription-based Autonomous Computing System (RTRACS). In this study, we first report an experimental demonstration of a basic computation element of RTRACS and a mathematical modeling method for RTRACS. We focus on an AND gate, which produces an output RNA molecule only when two input RNA molecules exist, because it is one of the most basic computation elements in RTRACS. Experimental results demonstrated that the basic computation element worked as designed. In addition, its behaviors were analyzed using a mathematical model describing the molecular reactions of the RTRACS computation elements. A comparison between experiments and simulations confirmed the validity of the mathematical modeling method. This study will accelerate construction of various kinds of computation elements and computational circuits of RTRACS, and thus advance the research on autonomous DNA computers.

  6. Thermodynamic Modeling of Ag-Ni System Combining Experiments and Molecular Dynamic Simulation

    Science.gov (United States)

    Rajkumar, V. B.; Chen, Sinn-wen

    2017-04-01

    Ag-Ni is a simple and important system with immiscible liquids and (Ag,Ni) phases. Previously, this system has been thermodynamically modeled utilizing certain thermochemical and phase equilibria information based on conjecture. An attempt is made in this study to determine the missing information which are difficult to measure experimentally. The boundaries of the liquid miscibility gap at high temperatures are determined using a pyrometer. The temperature of the liquid ⇌ (Ag) + (Ni) eutectic reaction is measured using differential thermal analysis. Tie-lines of the Ag-Ni system at 1023 K and 1473 K are measured using a conventional metallurgical method. The enthalpy of mixing of the liquid at 1773 K and the (Ag,Ni) at 973 K is calculated by molecular dynamics simulation using a large-scale atomic/molecular massively parallel simulator. These results along with literature information are used to model the Gibbs energy of the liquid and (Ag,Ni) by a calculation of phase diagrams approach, and the Ag-Ni phase diagram is then calculated.

  7. Model systems to unravel the molecular mechanisms of heavy metal tolerance in the ericoid mycorrhizal symbiosis.

    Science.gov (United States)

    Daghino, Stefania; Martino, Elena; Perotto, Silvia

    2016-05-01

    Ericoid mycorrhizal plants dominate in harsh environments where nutrient-poor, acidic soil conditions result in a higher availability of potentially toxic metals. Although metal-tolerant plant species and ecotypes are known in the Ericaceae, metal tolerance in these plants has been mainly attributed to their association with ericoid mycorrhizal fungi. The mechanisms underlying plant protection by the fungal symbiont are poorly understood, whereas some insights have been achieved regarding the molecular mechanisms of heavy metal tolerance in the fungal symbiont. This review will briefly introduce the general features of heavy metal tolerance in mycorrhizal fungi and will then focus on the use of "omics" approaches and heterologous expression in model organisms to reveal the molecular bases of fungal response to heavy metals. Functional complementation in Saccharomyces cerevisiae has allowed the identification of several ericoid mycorrhizal fungi genes (i.e., antioxidant enzymes, metal transporters, and DNA damage repair proteins) that may contribute to metal tolerance in a metal-tolerant ericoid Oidiodendron maius isolate. Although a powerful system, the use of the yeast complementation assay to study metal tolerance in mycorrhizal symbioses has limitations. Thus, O. maius has been developed as a model system to study heavy metal tolerance mechanisms in mycorrhizal fungi, thanks to its high metal tolerance, easy handling and in vitro mycorrhization, stable genetic transformation, genomics, transcriptomic and proteomic resources.

  8. Open source molecular modeling.

    Science.gov (United States)

    Pirhadi, Somayeh; Sunseri, Jocelyn; Koes, David Ryan

    2016-09-01

    The success of molecular modeling and computational chemistry efforts are, by definition, dependent on quality software applications. Open source software development provides many advantages to users of modeling applications, not the least of which is that the software is free and completely extendable. In this review we categorize, enumerate, and describe available open source software packages for molecular modeling and computational chemistry. An updated online version of this catalog can be found at https://opensourcemolecularmodeling.github.io.

  9. Modeling of molecular properties

    CERN Document Server

    Comba, Peter

    2011-01-01

    Molecular modeling encompasses applied theoretical approaches and computational techniques to model structures and properties of molecular compounds and materials in order to predict and / or interpret their properties. The modeling covered in this book ranges from methods for small chemical to large biological molecules and materials. With its comprehensive coverage of important research fields in molecular and materials science, this is a must-have for all organic, inorganic and biochemists as well as materials scientists interested in applied theoretical and computational chemistry. The 28

  10. Two-dimensional spectroscopy of molecular excitons in a model dimer system

    Science.gov (United States)

    Halpin, Alexei

    The physics of molecular excitons has been the subject of many recent studies using electronic two-dimensional photon-echo spectroscopy (2DPE), particularly in the context of light harvesting in photosynthesis. Since the spectra for multichromophoric aggregates are congested, particularly so at room temperature, we present a study of a model dimer comprised of identical chromophores with a well defined electronic coupling strength, to provide clear signatures for coherences between vibronic excitons in 2D spectra. We begin by describing the design of a broadband passively phase-stabilized interferometer for collection of 2D spectra, which also allows for the investigation of state preparation in 2D spectroscopy by using shaped excitation pulses. In experiments on the model dimer we observe strong oscillating off-diagonal features in the 2D spectra which are present only before the onset of dephasing, which occurs in less than 100 fs due to strong system-bath coupling. This is in contrast with the parent dye, where low amplitude oscillations associated with Raman active vibrations persist for several ps following excitation. The results of this comparative study indicate that the signals observed earlier in photosynthetic proteins likely reflect vibrational motion in isolated pigments, and not delocalized quantum coherence. While long-lived vibrational coherences are of questionable biological relevance at face value, we conclude with a discussion on initial findings using coherently controlled 2D spectroscopy, where we observe long-lived signatures associated to vibronic coherences at room temperature. These results point to new directions of study using multidimensional spectroscopy to unravel the role of coherence in excitation energy transfer in molecular aggregates in an experimentally direct fashion.

  11. Respectful Modeling: Addressing Uncertainty in Dynamic System Models for Molecular Biology.

    Science.gov (United States)

    Tsigkinopoulou, Areti; Baker, Syed Murtuza; Breitling, Rainer

    2017-06-01

    Although there is still some skepticism in the biological community regarding the value and significance of quantitative computational modeling, important steps are continually being taken to enhance its accessibility and predictive power. We view these developments as essential components of an emerging 'respectful modeling' framework which has two key aims: (i) respecting the models themselves and facilitating the reproduction and update of modeling results by other scientists, and (ii) respecting the predictions of the models and rigorously quantifying the confidence associated with the modeling results. This respectful attitude will guide the design of higher-quality models and facilitate the use of models in modern applications such as engineering and manipulating microbial metabolism by synthetic biology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Diffusion Monte Carlo applied to weak interactions - hydrogen bonding and aromatic stacking in (bio-)molecular model systems

    Science.gov (United States)

    Fuchs, M.; Ireta, J.; Scheffler, M.; Filippi, C.

    2006-03-01

    Dispersion (Van der Waals) forces are important in many molecular phenomena such as self-assembly of molecular crystals or peptide folding. Calculating this nonlocal correlation effect requires accurate electronic structure methods. Usual density-functional theory with generalized gradient functionals (GGA-DFT) fails unless empirical corrections are added that still need extensive validation. Quantum chemical methods like MP2 and coupled cluster are more accurate, yet limited to rather small systems by their unfavorable computational scaling. Diffusion Monte Carlo (DMC) can provide accurate molecular total energies and remains feasible also for larger systems. Here we apply the fixed-node DMC method to (bio-)molecular model systems where dispersion forces are significant: (dimethyl-) formamide and benzene dimers, and adenine-thymine DNA base pairs. Our DMC binding energies agree well with data from coupled cluster (CCSD(T)), in particular for stacked geometries where GGA-DFT fails qualitatively and MP2 predicts too strong binding.

  13. Molecular systems biology of Sic1 in yeast cell cycle regulation through multiscale modeling.

    Science.gov (United States)

    Barberis, Matteo

    2012-01-01

    Cell cycle control is highly regulated to guarantee the precise timing of events essential for cell growth, i.e., DNA replication onset and cell division. Failure of this control plays a role in cancer and molecules called cyclin-dependent kinase (Cdk) inhibitors (Ckis) exploit a critical function in cell cycle timing. Here we present a multiscale modeling where experimental and computational studies have been employed to investigate structure, function and temporal dynamics of the Cki Sic1 that regulates cell cycle progression in Saccharomyces cerevisiae. Structural analyses reveal molecular details of the interaction between Sic1 and Cdk/cyclin complexes, and biochemical investigation reveals Sic1 function in analogy to its human counterpart p27(Kip1), whose deregulation leads to failure in timing of kinase activation and, therefore, to cancer. Following these findings, a bottom-up systems biology approach has been developed to characterize modular networks addressing Sic1 regulatory function. Through complementary experimentation and modeling, we suggest a mechanism that underlies Sic1 function in controlling temporal waves of cyclins to ensure correct timing of the phase-specific Cdk activities.

  14. Ab-initio molecular modeling of interfaces in tantalum-carbon system

    Energy Technology Data Exchange (ETDEWEB)

    Balani, Kantesh; Mungole, Tarang [Materials Science and Engineering, Indian Institute of Technology, Kanpur-208016 (India); Bakshi, Srinivasa Rao [Mechanical and Materials Engineering, Florida International University, Miami, Florida 33174 (United States); Metallurgical and Materials Engineering, Indian Institute of Technology Madras, Chennai 600036 (India); Agarwal, Arvind [Mechanical and Materials Engineering, Florida International University, Miami, Florida 33174 (United States)

    2012-03-15

    Processing of ultrahigh temperature TaC ceramic material with sintering additives of B{sub 4}C and reinforcement of carbon nanotubes (CNTs) gives rise to possible formation of several interfaces (Ta{sub 2}C-TaC, TaC-CNT, Ta{sub 2}C-CNT, TaB{sub 2}-TaC, and TaB{sub 2}-CNT) that could influence the resultant properties. Current work focuses on interfaces developed during spark plasma sintering of TaC-system and performing ab initio molecular modeling of the interfaces generated during processing of TaC-B{sub 4}C and TaC-CNT composites. The energy of the various interfaces has been evaluated and compared with TaC-Ta{sub 2}C interface. The iso-surface electronic contours are extracted from the calculations eliciting the enhanced stability of TaC-CNT interface by 72.2%. CNTs form stable interfaces with Ta{sub 2}C and TaB{sub 2} phases with a reduction in the energy by 35.8% and 40.4%, respectively. The computed Ta-C-B interfaces are also compared with experimentally observed interfaces in high resolution TEM images.

  15. Molecular tools and bumble bees: revealing hidden details of ecology and evolution in a model system.

    Science.gov (United States)

    Woodard, S Hollis; Lozier, Jeffrey D; Goulson, David; Williams, Paul H; Strange, James P; Jha, Shalene

    2015-06-01

    Bumble bees are a longstanding model system for studies on behaviour, ecology and evolution, due to their well-studied social lifestyle, invaluable role as wild and managed pollinators, and ubiquity and diversity across temperate ecosystems. Yet despite their importance, many aspects of bumble bee biology have remained enigmatic until the rise of the genetic and, more recently, genomic eras. Here, we review and synthesize new insights into the ecology, evolution and behaviour of bumble bees that have been gained using modern genetic and genomic techniques. Special emphasis is placed on four areas of bumble bee biology: the evolution of eusociality in this group, population-level processes, large-scale evolutionary relationships and patterns, and immunity and resistance to pesticides. We close with a prospective on the future of bumble bee genomics research, as this rapidly advancing field has the potential to further revolutionize our understanding of bumble bees, particularly in regard to adaptation and resilience. Worldwide, many bumble bee populations are in decline. As such, throughout the review, connections are drawn between new molecular insights into bumble bees and our understanding of the causal factors involved in their decline. Ongoing and potential applications to bumble bee management and conservation are also included to demonstrate how genetics- and genomics-enabled research aids in the preservation of this threatened group. © 2015 John Wiley & Sons Ltd.

  16. Synthetic molecular systems based on porphyrins as models for the study of energy transfer in photosynthesis

    Science.gov (United States)

    Konovalova, Nadezhda V.; Evstigneeva, Rima P.; Luzgina, Valentina N.

    2001-11-01

    The published data on the synthesis and photochemical properties of porphyrin-based molecular ensembles which represent models of natural photosynthetic light-harvesting complexes are generalised and systematised. The dependence of the transfer of excitation energy on the distance between donor and acceptor components, their mutual arrangement, electronic and environmental factors are discussed. Two mechanisms of energy transfer reactions, viz., 'through space' and 'through bond', are considered. The bibliography includes 96 references.

  17. The Renormalization Group and Its Applications to Generating Coarse-Grained Models of Large Biological Molecular Systems.

    Science.gov (United States)

    Koehl, Patrice; Poitevin, Frédéric; Navaza, Rafael; Delarue, Marc

    2017-03-14

    Understanding the dynamics of biomolecules is the key to understanding their biological activities. Computational methods ranging from all-atom molecular dynamics simulations to coarse-grained normal-mode analyses based on simplified elastic networks provide a general framework to studying these dynamics. Despite recent successes in studying very large systems with up to a 100,000,000 atoms, those methods are currently limited to studying small- to medium-sized molecular systems due to computational limitations. One solution to circumvent these limitations is to reduce the size of the system under study. In this paper, we argue that coarse-graining, the standard approach to such size reduction, must define a hierarchy of models of decreasing sizes that are consistent with each other, i.e., that each model contains the information of the dynamics of its predecessor. We propose a new method, Decimate, for generating such a hierarchy within the context of elastic networks for normal-mode analysis. This method is based on the concept of the renormalization group developed in statistical physics. We highlight the details of its implementation, with a special focus on its scalability to large systems of up to millions of atoms. We illustrate its application on two large systems, the capsid of a virus and the ribosome translation complex. We show that highly decimated representations of those systems, containing down to 1% of their original number of atoms, still capture qualitatively and quantitatively their dynamics. Decimate is available as an OpenSource resource.

  18. Modeling of Nanoparticular Magnetoresistive Systems and the Impact on Molecular Recognition

    Directory of Open Access Journals (Sweden)

    Lisa Teich

    2015-04-01

    Full Text Available The formation of magnetic bead or nanoparticle superstructures due to magnetic dipole dipole interactions can be used as configurable matter in order to realize low-cost magnetoresistive sensors with very high GMR-effect amplitudes. Experimentally, this can be realized by immersing magnetic beads or nanoparticles in conductive liquid gels and rearranging them by applying suitable external magnetic fields. After gelatinization of the gel matrix the bead or nanoparticle positions are fixed and the resulting system can be used as a magnetoresistive sensor. In order to optimize such sensor structures we have developed a simulation tool chain that allows us not only to study the structuring process in the liquid state but also to rigorously calculate the magnetoresistive characteristic curves for arbitrary nanoparticle arrangements. As an application, we discuss the role of magnetoresistive sensors in finding answers to molecular recognition.

  19. Molecular tools and bumble bees: revealing hidden details of ecology and evolution in a model system

    Science.gov (United States)

    Bumble bees are a longstanding model system for studies on behavior, ecology, and evolution, due to their well-studied social lifestyle, invaluable roles as both wild and managed pollinators, and their ubiquity and diversity across temperate ecosystems. Yet despite their importance, many aspects of ...

  20. WI-38 cell long-term quiescence model system: a valuable tool to study molecular events that regulate growth.

    Science.gov (United States)

    Soprano, K J

    1994-04-01

    A number of cell culture model systems have been used to study the regulation of cell cycle progression at the molecular level. In this paper we describe the WI-38 cell long-term quiescence model system. By modulating the length of time that WI-38 cells are density arrested, it is possible to proportionately alter the length of the prereplicative or G-1 phase which the cell traverses after growth factor stimulation in preparation for entry into DNA synthesis. Through studies aimed at understanding the cause and molecular nature of the prolongation of the prereplicative phase, we have determined that gene expression plays an important role in establishing growth factor "competence" and that once the cell becomes "competent" there is a defined order to the molecular events that follow during the remainder of G-1. More specifically, we have determined that the prolongation represents a delay in the ability of long term quiescent cells to become fully "competent" to respond to growth factors which regulate progression through G-1 into S. This prolongation appears to occur as a result of changes during long term quiescence in the ability of immediate early G-1 specific genes (such as c-myc) to activate the expression of early G-1 specific genes (such as ornithine decarboxylase). While ODC is the first and thus far only growth associated gene identified as a target of c-myc (and the Myc/Max protein complex), it is likely that further studies in this model system will reveal other early G-1 growth regulatory genes. We anticipate that future follow-up studies in this model system will provide additional valuable information about the function of growth-regulatory genes in controlling growth factor responsiveness and cell cycle progression.

  1. Molecular model for chirality phenomena.

    Science.gov (United States)

    Latinwo, Folarin; Stillinger, Frank H; Debenedetti, Pablo G

    2016-10-21

    Chirality is a hallmark feature for molecular recognition in biology and chemical physics. We present a three-dimensional continuum model for studying chirality phenomena in condensed phases using molecular simulations. Our model system is based upon a simple four-site molecule and incorporates non-trivial kinetic behavior, including the ability to switch chirality or racemize, as well as thermodynamics arising from an energetic preference for specific chiral interactions. In particular, we introduce a chiral renormalization parameter that can locally favor either homochiral or heterochiral configurations. Using this model, we explore a range of chirality-specific phenomena, including the kinetics of chiral inversion, the mechanism of spontaneous chiral symmetry breaking in the liquid, chirally driven liquid-liquid phase separation, and chiral crystal structures.

  2. Theoretical modeling of large molecular systems. Advances in the local self consistent field method for mixed quantum mechanics/molecular mechanics calculations.

    Science.gov (United States)

    Monari, Antonio; Rivail, Jean-Louis; Assfeld, Xavier

    2013-02-19

    Molecular mechanics methods can efficiently compute the macroscopic properties of a large molecular system but cannot represent the electronic changes that occur during a chemical reaction or an electronic transition. Quantum mechanical methods can accurately simulate these processes, but they require considerably greater computational resources. Because electronic changes typically occur in a limited part of the system, such as the solute in a molecular solution or the substrate within the active site of enzymatic reactions, researchers can limit the quantum computation to this part of the system. Researchers take into account the influence of the surroundings by embedding this quantum computation into a calculation of the whole system described at the molecular mechanical level, a strategy known as the mixed quantum mechanics/molecular mechanics (QM/MM) approach. The accuracy of this embedding varies according to the types of interactions included, whether they are purely mechanical or classically electrostatic. This embedding can also introduce the induced polarization of the surroundings. The difficulty in QM/MM calculations comes from the splitting of the system into two parts, which requires severing the chemical bonds that link the quantum mechanical subsystem to the classical subsystem. Typically, researchers replace the quantoclassical atoms, those at the boundary between the subsystems, with a monovalent link atom. For example, researchers might add a hydrogen atom when a C-C bond is cut. This Account describes another approach, the Local Self Consistent Field (LSCF), which was developed in our laboratory. LSCF links the quantum mechanical portion of the molecule to the classical portion using a strictly localized bond orbital extracted from a small model molecule for each bond. In this scenario, the quantoclassical atom has an apparent nuclear charge of +1. To achieve correct bond lengths and force constants, we must take into account the inner shell of

  3. Comprehensive Reactive Receiver Modeling for Diffusive Molecular Communication Systems: Reversible Binding, Molecule Degradation, and Finite Number of Receptors

    CERN Document Server

    Ahmadzadeh, Arman; Burkovski, Andreas; Schober, Robert

    2016-01-01

    This paper studies the problem of receiver modeling in molecular communication systems. We consider the diffusive molecular communication channel between a transmitter nano-machine and a receiver nano-machine in a fluid environment. The information molecules released by the transmitter nano-machine into the environment can degrade in the channel via a first-order degradation reaction and those that reach the receiver nano-machine can participate in a reversible bimolecular reaction with receiver receptor proteins. Thereby, we distinguish between two scenarios. In the first scenario, we assume that the entire surface of the receiver is covered by receptor molecules. We derive a closed-form analytical expression for the expected received signal at the receiver, i.e., the expected number of activated receptors on the surface of the receiver. Then, in the second scenario, we consider the case where the number of receptor molecules is finite and the uniformly distributed receptor molecules cover the receiver surfa...

  4. Top-down models in biology: explanation and control of complex living systems above the molecular level.

    Science.gov (United States)

    Pezzulo, Giovanni; Levin, Michael

    2016-11-01

    It is widely assumed in developmental biology and bioengineering that optimal understanding and control of complex living systems follows from models of molecular events. The success of reductionism has overshadowed attempts at top-down models and control policies in biological systems. However, other fields, including physics, engineering and neuroscience, have successfully used the explanations and models at higher levels of organization, including least-action principles in physics and control-theoretic models in computational neuroscience. Exploiting the dynamic regulation of pattern formation in embryogenesis and regeneration requires new approaches to understand how cells cooperate towards large-scale anatomical goal states. Here, we argue that top-down models of pattern homeostasis serve as proof of principle for extending the current paradigm beyond emergence and molecule-level rules. We define top-down control in a biological context, discuss the examples of how cognitive neuroscience and physics exploit these strategies, and illustrate areas in which they may offer significant advantages as complements to the mainstream paradigm. By targeting system controls at multiple levels of organization and demystifying goal-directed (cybernetic) processes, top-down strategies represent a roadmap for using the deep insights of other fields for transformative advances in regenerative medicine and systems bioengineering.

  5. Top-down models in biology: explanation and control of complex living systems above the molecular level

    Science.gov (United States)

    2016-01-01

    It is widely assumed in developmental biology and bioengineering that optimal understanding and control of complex living systems follows from models of molecular events. The success of reductionism has overshadowed attempts at top-down models and control policies in biological systems. However, other fields, including physics, engineering and neuroscience, have successfully used the explanations and models at higher levels of organization, including least-action principles in physics and control-theoretic models in computational neuroscience. Exploiting the dynamic regulation of pattern formation in embryogenesis and regeneration requires new approaches to understand how cells cooperate towards large-scale anatomical goal states. Here, we argue that top-down models of pattern homeostasis serve as proof of principle for extending the current paradigm beyond emergence and molecule-level rules. We define top-down control in a biological context, discuss the examples of how cognitive neuroscience and physics exploit these strategies, and illustrate areas in which they may offer significant advantages as complements to the mainstream paradigm. By targeting system controls at multiple levels of organization and demystifying goal-directed (cybernetic) processes, top-down strategies represent a roadmap for using the deep insights of other fields for transformative advances in regenerative medicine and systems bioengineering. PMID:27807271

  6. The quantum-chemical modeling of structure and spectral characteristics for molecular complexes in system «penton-terlon»

    Directory of Open Access Journals (Sweden)

    Andrey V. Tokar

    2014-03-01

    Full Text Available The structure and spectral properties for molecular complexes, which formed by added monomer form of pentaplast as well as N-phenylbenzamide with some species of intermolecular interaction in system «penton-terlon» have been investigated at ab initio level of theory. It is shown, that the main contribution in total energy of molecules have included by dispersion forces, which realized between Chlorine atom of CH2Cl-group and Hydrogen atoms of benzene rings with amide fragment. The proposed theoretical models are validated in reflection of spectral and energetic characteristics of investigating system. Finally, the results of calculations are in good agreement with that data, which have been obtained for such type modeling previously.

  7. Assessment of Molecular Modeling & Simulation

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-01-03

    This report reviews the development and applications of molecular and materials modeling in Europe and Japan in comparison to those in the United States. Topics covered include computational quantum chemistry, molecular simulations by molecular dynamics and Monte Carlo methods, mesoscale modeling of material domains, molecular-structure/macroscale property correlations like QSARs and QSPRs, and related information technologies like informatics and special-purpose molecular-modeling computers. The panel's findings include the following: The United States leads this field in many scientific areas. However, Canada has particular strengths in DFT methods and homogeneous catalysis; Europe in heterogeneous catalysis, mesoscale, and materials modeling; and Japan in materials modeling and special-purpose computing. Major government-industry initiatives are underway in Europe and Japan, notably in multi-scale materials modeling and in development of chemistry-capable ab-initio molecular dynamics codes.

  8. Molecular modelling and molecular dynamics of CFTR.

    Science.gov (United States)

    Callebaut, Isabelle; Hoffmann, Brice; Lehn, Pierre; Mornon, Jean-Paul

    2017-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a member of the ATP-binding cassette (ABC) transporter superfamily that functions as an ATP-gated channel. Considerable progress has been made over the last years in the understanding of the molecular basis of the CFTR functions, as well as dysfunctions causing the common genetic disease cystic fibrosis (CF). This review provides a global overview of the theoretical studies that have been performed so far, especially molecular modelling and molecular dynamics (MD) simulations. A special emphasis is placed on the CFTR-specific evolution of an ABC transporter framework towards a channel function, as well as on the understanding of the effects of disease-causing mutations and their specific modulation. This in silico work should help structure-based drug discovery and design, with a view to develop CFTR-specific pharmacotherapeutic approaches for the treatment of CF in the context of precision medicine.

  9. Molecular Thermodynamic Modeling and Design of Microencapsulation Systems for Drug Delivery

    DEFF Research Database (Denmark)

    Abildskov, Jens; O’Connell, John P.

    2011-01-01

    is based on fundamental thermodynamic relations and group contributions to properties of pure species (solvent, active ingredient and polymer) and their mixtures. The method is intended for pharmaceuticals with complex molecular structures, for which limited experimental information is known. Case studies...

  10. Modeling complex and multi-component food systems in molecular dynamics simulations on the example of chocolate conching.

    Science.gov (United States)

    Greiner, Maximilian; Sonnleitner, Bettina; Mailänder, Markus; Briesen, Heiko

    2014-02-01

    Additional benefits of foods are an increasing factor in the consumer's purchase. To produce foods with the properties the consumer demands, understanding the micro- and nanostructure is becoming more important in food research today. We present molecular dynamics (MD) simulations as a tool to study complex and multi-component food systems on the example of chocolate conching. The process of conching is chosen because of the interesting challenges it provides: the components (fats, emulsifiers and carbohydrates) contain diverse functional groups, are naturally fluctuating in their chemical composition, and have a high number of internal degrees of freedom. Further, slow diffusion in the non-aqueous medium is expected. All of these challenges are typical to food systems in general. Simulation results show the suitability of present force fields to correctly model the liquid and crystal density of cocoa butter and sucrose, respectively. Amphiphilic properties of emulsifiers are observed by micelle formation in water. For non-aqueous media, pulling simulations reveal high energy barriers for motion in the viscous cocoa butter. The work for detachment of an emulsifier from the sucrose crystal is calculated and matched with detachment of the head and tail groups separately. Hydrogen bonding is shown to be the dominant interaction between the emulsifier and the crystal surface. Thus, MD simulations are suited to model the interaction between the emulsifier and sugar crystal interface in non-aqueous media, revealing detailed information about the structuring and interactions on a molecular level. With interaction parameters being available for a wide variety of chemical groups, MD simulations are a valuable tool to understand complex and multi-component food systems in general. MD simulations provide a substantial benefit to researchers to verify their hypothesis in dynamic simulations with an atomistic resolution. Rapid rise of computational resources successively

  11. Variational methods in molecular modeling

    CERN Document Server

    2017-01-01

    This book presents tutorial overviews for many applications of variational methods to molecular modeling. Topics discussed include the Gibbs-Bogoliubov-Feynman variational principle, square-gradient models, classical density functional theories, self-consistent-field theories, phase-field methods, Ginzburg-Landau and Helfrich-type phenomenological models, dynamical density functional theory, and variational Monte Carlo methods. Illustrative examples are given to facilitate understanding of the basic concepts and quantitative prediction of the properties and rich behavior of diverse many-body systems ranging from inhomogeneous fluids, electrolytes and ionic liquids in micropores, colloidal dispersions, liquid crystals, polymer blends, lipid membranes, microemulsions, magnetic materials and high-temperature superconductors. All chapters are written by leading experts in the field and illustrated with tutorial examples for their practical applications to specific subjects. With emphasis placed on physical unders...

  12. Molecular modelling and multisimplex optimization of tocotrienol-rich self emulsified drug delivery systems.

    Science.gov (United States)

    Alayoubi, Alaadin; Satyanarayanajois, Seetharama D; Sylvester, Paul W; Nazzal, Sami

    2012-04-15

    The objective of this study was to optimize a novel tocotrienol (TRF)-rich self emulsified drug delivery system (SEDDS). In the first part, an unusual phenomenon was investigated. It was observed that by substituting Tween 80 with Cremophor EL in the SEDDS it was possible to emulsify>55% TRF (by weight of the formulation) into submicron (emulsified into crude emulsion. The superiority of Cremophor was attributed to the special arrangement of the surfactant at the oil/water interface, which was confirmed by modelling and docking studies. In the second part of this study, the composition of the secondary ingredients in the TRF-rich SEDDS were optimized by the modified Multisimplex approach. SEDDS were manufactured at pre-defined step-size and tested for their dissolution behavior. Testing was performed sequentially until the optimum composition that can emulsify 50% of the loaded TRF into a stable<150 nm submicron emulsion was obtained. Optimization end-point was identified when the "membership value" approached 1, which was confirmed by a second Multisimplex run. Overall, this study demonstrated the utility of docking studies and the Multisimplex approach in product development when little is known about the experimental "design space".

  13. Systems biology in molecular psychiatry.

    Science.gov (United States)

    Gebicke-Haerter, P J

    2008-09-01

    The last ten to fifteen years have seen a remarkable shift of research strategies from hypothesis-driven, reductionistic to data driven, hypothesis-free approaches. This tendency has become evident after completion of the sequencing of the human genome, when publications under the label systems biology have been skyrocketing. This shift marks a gradual revision of scientific understanding of biological systems. Whilst the former has been component-oriented, precluding elements that do not belong to the hypothesis, the latter try to extract information from the whole system in the first place. Only with this information at hand, data driven strategies develop hypotheses. Data driven strategies unearth the immense complexity of biological systems and, hence, necessitate computer-aided support. Mathematical tools derived from chaos theory appear to be applicable in biological systems, but require significant improvements. The combination of high throughput data collection with in silico modelling of molecular or higher order systems can markedly extend our understanding of onset and progression of diseases. Undoubtedly, systems thinking in brain research is the greatest challenge for the years to come.

  14. Molecular Dynamics Modeling of Hydrated Calcium-Silicate-Hydrate (CSH) Cement Molecular Structure

    Science.gov (United States)

    2014-08-30

    properties of key hydrated cement constituent calcium-silicate-hydrate (CSH) at the molecular, nanometer scale level. Due to complexity, still unknown...public release; distribution is unlimited. Molecular Dynamics Modeling of Hydrated Calcium-Silicate- Hydrate (CSH) Cement Molecular Structure The views... Cement Molecular Structure Report Title Multi-scale modeling of complex material systems requires starting from fundamental building blocks to

  15. Magnetohydrodynamic Models of Molecular Tornadoes

    Science.gov (United States)

    Au, Kelvin; Fiege, Jason D.

    2017-07-01

    Recent observations near the Galactic Center (GC) have found several molecular filaments displaying striking helically wound morphology that are collectively known as molecular tornadoes. We investigate the equilibrium structure of these molecular tornadoes by formulating a magnetohydrodynamic model of a rotating, helically magnetized filament. A special analytical solution is derived where centrifugal forces balance exactly with toroidal magnetic stress. From the physics of torsional Alfvén waves we derive a constraint that links the toroidal flux-to-mass ratio and the pitch angle of the helical field to the rotation laws, which we find to be an important component in describing the molecular tornado structure. The models are compared to the Ostriker solution for isothermal, nonmagnetic, nonrotating filaments. We find that neither the analytic model nor the Alfvén wave model suffer from the unphysical density inversions noted by other authors. A Monte Carlo exploration of our parameter space is constrained by observational measurements of the Pigtail Molecular Cloud, the Double Helix Nebula, and the GC Molecular Tornado. Observable properties such as the velocity dispersion, filament radius, linear mass, and surface pressure can be used to derive three dimensionless constraints for our dimensionless models of these three objects. A virial analysis of these constrained models is studied for these three molecular tornadoes. We find that self-gravity is relatively unimportant, whereas magnetic fields and external pressure play a dominant role in the confinement and equilibrium radial structure of these objects.

  16. Pendulum as a model system for driven rotation in molecular nanoscale machines

    DEFF Research Database (Denmark)

    Christiansen, Peter Leth; Nordén, B.; Savin, A. V.;

    2000-01-01

    and periodically. A pendulum driven by short impulses at its stable equilibrium point is shown to be a simple mechanical model which can be constructed easily and used for visual observation of the ratchet rotation. A possible application of this mechanism in nanotechnology is briefly discussed....

  17. Utilization of Lymphoblastoid Cell Lines as a System for the Molecular Modeling of Autism

    Science.gov (United States)

    Baron, Colin A.; Liu, Stephenie Y.; Hicks, Chindo; Gregg, Jeffrey P.

    2006-01-01

    In order to provide an alternative approach for understanding the biology and genetics of autism, we performed statistical analysis of gene expression profiles of lymphoblastoid cell lines derived from children with autism and their families. The goal was to assess the feasibility of using this model in identifying autism-associated genes.…

  18. Optimal drug cocktail design: methods for targeting molecular ensembles and insights from theoretical model systems.

    Science.gov (United States)

    Radhakrishnan, Mala L; Tidor, Bruce

    2008-05-01

    Drug resistance is a significant obstacle in the effective treatment of diseases with rapidly mutating targets, such as AIDS, malaria, and certain forms of cancer. Such targets are remarkably efficient at exploring the space of functional mutants and at evolving to evade drug binding while still maintaining their biological role. To overcome this challenge, drug regimens must be active against potential target variants. Such a goal may be accomplished by one drug molecule that recognizes multiple variants or by a drug "cocktail"--a small collection of drug molecules that collectively binds all desired variants. Ideally, one wants the smallest cocktail possible due to the potential for increased toxicity with each additional drug. Therefore, the task of designing a regimen for multiple target variants can be framed as an optimization problem--find the smallest collection of molecules that together "covers" the relevant target variants. In this work, we formulate and apply this optimization framework to theoretical model target ensembles. These results are analyzed to develop an understanding of how the physical properties of a target ensemble relate to the properties of the optimal cocktail. We focus on electrostatic variation within target ensembles, as it is one important mechanism by which drug resistance is achieved. Using integer programming, we systematically designed optimal cocktails to cover model target ensembles. We found that certain drug molecules covered much larger regions of target space than others, a phenomenon explained by theory grounded in continuum electrostatics. Molecules within optimal cocktails were often dissimilar, such that each drug was responsible for binding variants with a certain electrostatic property in common. On average, the number of molecules in the optimal cocktails correlated with the number of variants, the differences in the variants' electrostatic properties at the binding interface, and the level of binding affinity

  19. Hybrid Quantum Mechanics/Molecular Mechanics/Coarse Grained Modeling: A Triple-Resolution Approach for Biomolecular Systems.

    Science.gov (United States)

    Sokkar, Pandian; Boulanger, Eliot; Thiel, Walter; Sanchez-Garcia, Elsa

    2015-04-14

    We present a hybrid quantum mechanics/molecular mechanics/coarse-grained (QM/MM/CG) multiresolution approach for solvated biomolecular systems. The chemically important active-site region is treated at the QM level. The biomolecular environment is described by an atomistic MM force field, and the solvent is modeled with the CG Martini force field using standard or polarizable (pol-CG) water. Interactions within the QM, MM, and CG regions, and between the QM and MM regions, are treated in the usual manner, whereas the CG-MM and CG-QM interactions are evaluated using the virtual sites approach. The accuracy and efficiency of our implementation is tested for two enzymes, chorismate mutase (CM) and p-hydroxybenzoate hydroxylase (PHBH). In CM, the QM/MM/CG potential energy scans along the reaction coordinate yield reaction energies that are too large, both for the standard and polarizable Martini CG water models, which can be attributed to adverse effects of using large CG water beads. The inclusion of an atomistic MM water layer (10 Å for uncharged CG water and 5 Å for polarizable CG water) around the QM region improves the energy profiles compared to the reference QM/MM calculations. In analogous QM/MM/CG calculations on PHBH, the use of the pol-CG description for the outer water does not affect the stabilization of the highly charged FADHOOH-pOHB transition state compared to the fully atomistic QM/MM calculations. Detailed performance analysis in a glycine-water model system indicates that computation times for QM energy and gradient evaluations at the density functional level are typically reduced by 40-70% for QM/MM/CG relative to fully atomistic QM/MM calculations.

  20. A Molecular Survey of the Diversity of Microbial Communities in Different Amazonian Agricultural Model Systems

    Directory of Open Access Journals (Sweden)

    Acácio A. Navarrete

    2010-05-01

    Full Text Available The processes of land conversion and agricultural intensification are a significant cause of biodiversity loss, with consequent negative effects both on the environment and the sustainability of food production.The anthrosols associated with pre-Colombian settlements in the Amazonian region are examples of how anthropogenic activities may sustain the native populations against harsh tropical environments for human establishment, even without a previous intentionality of anthropic soil formation. In a case study (Model I—“Slash-and-Burn” the community structures detected by automated ribosomal intergenic spacer analysis (ARISA revealed that soil archaeal, bacterial and fungal communities are heterogeneous and each capable of responding differently to environmental characteristics. ARISA data evidenced considerable difference in structure existing between microbial communities in forest and agricultural soils. In a second study (Model II—“Anthropogenic Soil”, the bacterial community structures revealed by terminal restriction fragment length polymorphism (T-RFLP differed among an Amazonian Dark Earth (ADE, black carbon (BC and its adjacent non-anthropogenic oxisoil. The bacterial 16S rRNA gene (OTU richness estimated by pyrosequencing was higher in ADE than BC. The most abundant bacterial phyla in ADE soils and BC were Proteobacteria—24% ADE, 15% BC; Acidobacteria—10% ADE, 21% BC; Actinobacteria—7% ADE, 12% BC; Verrucomicrobia, 8% ADE; 9% BC; Firmicutes—3% ADE, 8% BC. Overall, unclassified bacteria corresponded to 36% ADE, and 26% BC. Regardless of current land uses, our data suggest that soil microbial community structures may be strongly influenced by the historical soil management and that anthrosols in Amazonia, of anthropogenic origins, in addition to their capacity of enhancing crop yields, may also improve microbial diversity, with the support of the black carbon, which may sustain a particular and unique habitat for the

  1. Theoretical modelling of photoactive molecular systems: insights using the Density Functional Theory

    Energy Technology Data Exchange (ETDEWEB)

    Ciofini, I.; Adamo, C. [Ecole Nationale Superieure de Chimie de Paris, Lab. d' Electrochimie et Chimie Analytique, CNRS UMR 7575, 75 - Paris (France); Laine, Ph.P. [Universite Rene-Descartes, Lab. de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS UMR 8601, 75 - Paris (France); Bedioui, F. [Ecole Nationale Superieure de Chimie de Paris, Lab. de Pharmacologie Chimique et Genetique, CNRS FRE 2463 and INSERM U 640, 75 - Paris (France); Daul, C.A. [Fribourg Univ., Dept. de Chimie (Switzerland)

    2006-02-15

    An account of the performance of a modern and efficient approach to Density Functional Theory (DFT) for the prediction of the photophysical behavior of a series of Ru(II) and Os(II) complexes is given. The time-dependent-DFT method was used to interpret their electronic spectra. Two different types of compounds have been analyzed: (1) a complex undergoing a light induced isomerization of one of its coordination bonds; (2) an inorganic dyads expected to undergo intramolecular photoinduced electron transfer to form a charge separated (CS) sate. Besides the noticeable quantitative agreement between computed and experimental absorption spectra, our results allow to clarify, by first principles, both the nature of the excited states and the photochemical behavior of these complex systems, thus underlying the predictive character of the theoretical approach. (authors)

  2. Reaction dynamics in polyatomic molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Miller, W.H. [Lawrence Berkeley Laboratory, CA (United States)

    1993-12-01

    The goal of this program is the development of theoretical methods and models for describing the dynamics of chemical reactions, with specific interest for application to polyatomic molecular systems of special interest and relevance. There is interest in developing the most rigorous possible theoretical approaches and also in more approximate treatments that are more readily applicable to complex systems.

  3. Molecular Thermodynamic Model for Associated Polymers

    Institute of Scientific and Technical Information of China (English)

    PENG,Chang-Jun(彭昌军); LIU,Hong-Lai(刘洪来); HU,Ying(胡英)

    2001-01-01

    A molecular thermedynmnic model for homopolyrner and copolymer systems with association segments was establishedby adopting the molecular thermodynamic model for hard-sphere-chain fluid as a reference,a perturbation term contributed by the square-well potential and a contribution of as sociation terms.The latter considers the multi-associated-seg-ments in a chain-like molecule based on the shield-sticky model of chemical association.The model can be used to correlate the pVT of melten homopolymer and copolymer.Good agree-ments with experimental data have been obtained.

  4. Molecular modeling of inelastic electron transport in molecular junctions

    Science.gov (United States)

    Jiang, Jun; Kula, Mathias; Luo, Yi

    2008-09-01

    A quantum chemical approach for the modeling of inelastic electron tunneling spectroscopy of molecular junctions based on scattering theory is presented. Within a harmonic approximation, the proposed method allows us to calculate the electron-vibration coupling strength analytically, which makes it applicable to many different systems. The calculated inelastic electron transport spectra are often in very good agreement with their experimental counterparts, allowing the revelation of detailed information about molecular conformations inside the junction, molecule-metal contact structures, and intermolecular interaction that is largely inaccessible experimentally.

  5. Molecular modeling of inelastic electron transport in molecular junctions

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Jun; Kula, Mathias; Luo Yi [Department of Theoretical Chemistry, School of Biotechnology, Royal Institute of Technology, S-106 91 Stockholm (Sweden)], E-mail: luo@kth.se

    2008-09-17

    A quantum chemical approach for the modeling of inelastic electron tunneling spectroscopy of molecular junctions based on scattering theory is presented. Within a harmonic approximation, the proposed method allows us to calculate the electron-vibration coupling strength analytically, which makes it applicable to many different systems. The calculated inelastic electron transport spectra are often in very good agreement with their experimental counterparts, allowing the revelation of detailed information about molecular conformations inside the junction, molecule-metal contact structures, and intermolecular interaction that is largely inaccessible experimentally.

  6. Molecular thermodynamic model for copolymer systems%共聚物系统的分子热力学模型

    Institute of Scientific and Technical Information of China (English)

    彭昌军; 刘洪来; 胡英

    2001-01-01

    在非均核硬球链流体的基础上,通过引入方阱势能的贡献,导出了实际共聚物系统的分子热力学模型,并建立了相应的状态方程.建立的方程同计算机模拟结果比较,可发现方程能预测共聚物在不同条件下的压缩因子.%Using a model of heteronuclear hardsphere chain fluids as the basic principles, a molecular thermodynamic model for copolymers and theirs mixtures has been derived by introducing the Squarewell potential contribution. The corresponding equation of state has been established. The established model is tested against molecular simulation data from the literature.It is shown that proposed model could predict compressibility factors of copolymers at different conditions.

  7. Combination of capillary electrophoresis, molecular modeling and NMR to study the enantioselective complexation of sulpiride with double cyclodextrin systems.

    Science.gov (United States)

    Melani, Fabrizio; Pasquini, Benedetta; Caprini, Claudia; Gotti, Roberto; Orlandini, Serena; Furlanetto, Sandra

    2015-10-10

    The enantioselective complexation of sulpiride by a number of cyclodextrins (CDs) was deeply investigated by different techniques with the aim of evaluating the role of the used chiral selectors involved in the enantioseparation of the eutomer levosulpiride (S-SUL) and its dextro-isomer by capillary electrophoresis (CE). A CE method was previously developed with the aim of determining the optical purity of S-SUL and was based on the use of a dual cyclodextrin system, made by sulfated-β-cyclodextrin (SβCD) and methyl-β-cyclodextrin (MβCD). In this paper, a molecular modeling study made it possible to explain the different affinity of sulpiride enantiomers for several CDs, which had been tested during the early phase of CE method development. The potential and the gain energy of the inclusion complexes between the enantiomers and neutral and charged CDs were calculated on the minimized conformations. The calculated docking energies indicated that the most stable complexes were effectively obtained with SβCD and MβCD. A correlation between CE migration time of the last migrating enantiomer S-SUL and the stability of analyte-neutral CDs complexes was postulated. Furthermore, two-dimensional rotating-frame Overhauser effect spectroscopy NMR (2-D ROESY) experiments were carried out, which clearly indicated the formation of complexes and suggested the inclusion of the benzene sulfonamide moiety of S-SUL inside the hydrophobic cavity of the CDs.

  8. Energy Dissipation in Molecular Systems

    CERN Document Server

    Tramer, André; Lahmani, Fran oise

    2005-01-01

    Energy Dissipation in Molecular Systems analyzes experimental data on the redistribution and dissipation of energy injected into molecular systems by radiation or charged particles. These processes, competing with such practically important relaxation channels as chemical reaction or stimulated emission (laser action), are the primary focus in this monograph. Among other topics, the book treats vibrational redistribution and electronic relaxation in isolated molecules and the effects of inter-molecular interactions (collisions, complex formation, solvent effects) on the relaxation paths. Primary photo-chemical processes (such as isomerization, proton or hydrogen-atom transfer, electron transfer and ionization) are also treated as particular cases of vibrational or electronic relaxation. Only a basic knowledge of quantum mechanics and spectroscopy is assumed and calculations are kept to a strict minimum, making the book more accessible to students.

  9. Molecular modelling and drug design.

    Science.gov (United States)

    Meyer, E F; Swanson, S M; Williams, J A

    2000-03-01

    Drug design is a creative act of the same magnitude as composing, sculpting, or writing. The results can touch the lives of millions, but the creator is rarely one scientist and the rewards are distributed differently in the arts than in the sciences. The mechanisms of creativity are the same, i.e., incremental (plodding from darkness to dawn) or sudden (the "Eureka" effect) realization, but both are poorly understood. Creativity remains a human characteristic, but it is directly related to the tools available, especially computer software and hardware. While modelling software continues to mature, very little new has evolved in terms of hardware. Here, we discuss the history of molecular modelling and describe two novel modelling tools, a haptic device and a program, SCULPT, to generate solid molecular models at atomic resolution.

  10. Applying Virtual Realitzy to Molecular Graphics System

    Institute of Scientific and Technical Information of China (English)

    ChangNoYoon; MyungHwanChi; 等

    1996-01-01

    Mlecular graphics can be thought of as a window to the computer through which the chemist expresses ideas for computational evaluation and receives results in an understandable form.Furthermore,with beautiful graphic images it can give out the realistic molecular model like a real thing in real world.Molecule has various properties including volume,electronic,van der waals forces,etc.These properties are very important to understand the molecular world.So if the virtual reality tools are used,then the imaginary world can be studied intuitively by touching and feeling a tremendous amount of data.Computational chemistry generates such amount of molecular property data through supercomputing with molecular simulation experiment.One of the objects to investigate the molecular world is to understand the intermolecular interaction such as drug-receptor interaction.Another thing is to measure the geometrical data in molecular architecture.Virtual reality system provides the easiest way to meet these objects.This kind of simple system changes a numerical data set,which is very difficults to deal with,into a visible and understandable data set.Recently two functions of such a system were improved to get an insight into biomolecular interaction.The first one is a real time force generation during navigation in macromolecular environment.An cylindrical arrow shows the magnitude and direction of molecular force.The second one is to see a molecular vibration such as a concerted motion of the binding site in protein molecule.So one can understand th molecular shape change for drugreceptor docking procedure.But some problems which are difficult to solve still remain.

  11. Modelling the molecular mechanisms of aging

    Science.gov (United States)

    Mc Auley, Mark T.; Guimera, Alvaro Martinez; Hodgson, David; Mcdonald, Neil; Mooney, Kathleen M.; Morgan, Amy E.

    2017-01-01

    The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field. PMID:28096317

  12. Modelling the molecular mechanisms of aging.

    Science.gov (United States)

    Mc Auley, Mark T; Guimera, Alvaro Martinez; Hodgson, David; Mcdonald, Neil; Mooney, Kathleen M; Morgan, Amy E; Proctor, Carole J

    2017-02-28

    The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field.

  13. Propagation Modeling and Analysis of Molecular Motors in Molecular Communication.

    Science.gov (United States)

    Chahibi, Youssef; Akyildiz, Ian F; Balasingham, Ilangko

    2016-12-01

    Molecular motor networks (MMNs) are networks constructed from molecular motors to enable nanomachines to perform coordinated tasks of sensing, computing, and actuation at the nano- and micro- scales. Living cells are naturally enabled with this same mechanism to establish point-to-point communication between different locations inside the cell. Similar to a railway system, the cytoplasm contains an intricate infrastructure of tracks, named microtubules, interconnecting different internal components of the cell. Motor proteins, such as kinesin and dynein, are able to travel along these tracks directionally, carrying with them large molecules that would otherwise be unreliably transported across the cytoplasm using free diffusion. Molecular communication has been previously proposed for the design and study of MMNs. However, the topological aspects of MMNs, including the effects of branches, have been ignored in the existing studies. In this paper, a physical end-to-end model for MMNs is developed, considering the location of the transmitter node, the network topology, and the receiver nodes. The end-to-end gain and group delay are considered as the performance measures, and analytical expressions for them are derived. The analytical model is validated by Monte-Carlo simulations and the performance of MMNs is analyzed numerically. It is shown that, depending on their nature and position, MMN nodes create impedance effects that are critical for the overall performance. This model could be applied to assist the design of artificial MMNs and to study cargo transport in neurofilaments to elucidate brain diseases related to microtubule jamming.

  14. Molecular modeling of heterogeneous catalysis

    Science.gov (United States)

    Gislason, Jason Joseph

    A novel method for modeling heterogeneous catalysis was developed to further facilitate the understanding of catalytic reactor mechanisms. The method employs molecular dynamics simulations, statistical mechanical, and Unity Bond Index - Quadratic Exponential Potential (UBI-QEP) calculations to calculate the rate constants for reactions on metal surfaces. The primary difficulty of molecular dynamics simulations on metal surfaces has been the lack of reliable reactive potential energy surfaces. We have overcome this through the development of the Normalized Bond Index - Reactive Potential Function (NBI-RPF), which can accurately describe the reaction of adsorbates on metal surfaces. The first calculations of rate constants for a reaction on a metal surface using molecular dynamics simulations are presented. This method is applied to the determination of the mechanism for selective hydrogenation of acetylene in an ethylene rich flow. It was determined that the selectivity for acetylene hydrogenation is attributable to the higher reactivity of acetylene versus ethylene with respect to hydrogenation by molecular hydrogen. It was shown that hydrogen transfer from the carbonaceous layer to acetylene or ethylene is insignificant in the hydrogenation process. Molecular dynamics simulations and molecular mechanics calculations were used to determine the diffusion rate constants for dimethylnaphthalene isomers is mordenite. 2,6-dimethylnaphthalene and 2,7-dimethylnaphthalene were found to have similar diffusion rate constants. Grand canonical Monte Carlo calculations were performed on the competitive adsorption of 2,6-dimethylnaphthalene and 2,7-dimethylnaphthalene in type X zeolites exchanged individually with barium, calcium, potassium, and rubidium ions, calcium exchanged MCM-22, and hydrogen form mordenite (MOR), X zeolite, Y zeolite, hypBEB, ZSM- 12, and MCM-22. These calculations showed that barium exchanged X zeolite was the most selective toward 2

  15. Relaxation time in disordered molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Rodrigo P. [Departamento de Física, Universidade Federal de Santa Catarina, 88040-900 Florianópolis-SC (Brazil); Freire, José A., E-mail: jfreire@fisica.ufpr.br [Departamento de Física, Universidade Federal do Paraná, 81531-990 Curitiba-PR (Brazil)

    2015-05-28

    Relaxation time is the typical time it takes for a closed physical system to attain thermal equilibrium. The equilibrium is brought about by the action of a thermal reservoir inducing changes in the system micro-states. The relaxation time is intuitively expected to increase with system disorder. We derive a simple analytical expression for this dependence in the context of electronic equilibration in an amorphous molecular system model. We find that the disorder dramatically enhances the relaxation time but does not affect its independence of the nature of the initial state.

  16. A Systems Biology Approach to Understanding Alcoholic Liver Disease Molecular Mechanism: The Development of Static and Dynamic Models.

    Science.gov (United States)

    Shafaghati, Leila; Razaghi-Moghadam, Zahra; Mohammadnejad, Javad

    2017-08-28

    Alcoholic liver disease (ALD) is a complex disease characterized by damages to the liver and is the consequence of excessive alcohol consumption over years. Since this disease is associated with several pathway failures, pathway reconstruction and network analysis are likely to explicit the molecular basis of the disease. To this aim, in this paper, a network medicine approach was employed to integrate interactome (protein-protein interaction and signaling pathways) and transcriptome data to reconstruct both a static network of ALD and a dynamic model for it. Several data sources were exploited to assemble a set of ALD-associated genes which further was used for network reconstruction. Moreover, a comprehensive literature mining reveals that there are four signaling pathways with crosstalk (TLR4, NF- [Formula: see text]B, MAPK and Apoptosis) which play a major role in ALD. These four pathways were exploited to reconstruct a dynamic model of ALD. The results assure that these two models are consistent with a number of experimental observations. The static network of ALD and its dynamic model are the first models provided for ALD which offer potentially valuable information for researchers in this field.

  17. Information theory of molecular systems

    CERN Document Server

    Nalewajski, Roman F

    2006-01-01

    As well as providing a unified outlook on physics, Information Theory (IT) has numerous applications in chemistry and biology owing to its ability to provide a measure of the entropy/information contained within probability distributions and criteria of their information ""distance"" (similarity) and independence. Information Theory of Molecular Systems applies standard IT to classical problems in the theory of electronic structure and chemical reactivity. The book starts by introducing the basic concepts of modern electronic structure/reactivity theory based upon the Density Functional Theory

  18. Molecular modeling of fentanyl analogs

    Directory of Open Access Journals (Sweden)

    LJILJANA DOSEN-MICOVIC

    2004-11-01

    Full Text Available Fentanyl is a highly potent and clinically widely used narcotic analgesic. A large number of its analogs have been synthesized, some of which (sufentanil and alfentanyl are also in clinical use. Theoretical studies, in recent years, afforded a better understanding of the structure-activity relationships of this class of opiates and allowed insight into the molecular mechanism of the interactions of fentanyl analogs with their receptors. An overview of the current computational techniques for modeling fentanyl analogs, their receptors and ligand-receptor interactions is presented in this paper.

  19. Optical models of the molecular atmosphere

    Science.gov (United States)

    Zuev, V. E.; Makushkin, Y. S.; Mitsel, A. A.; Ponomarev, Y. N.; Rudenko, V. P.; Firsov, K. M.

    1986-01-01

    The use of optical and laser methods for performing atmospheric investigations has stimulated the development of the optical models of the atmosphere. The principles of constructing the optical models of molecular atmosphere for radiation with different spectral composition (wideband, narrowband, and monochromatic) are considered in the case of linear and nonlinear absorptions. The example of the development of a system which provides for the modeling of the processes of optical-wave energy transfer in the atmosphere is presented. Its physical foundations, structure, programming software, and functioning were considered.

  20. Interactive Modelling of Molecular Structures

    Science.gov (United States)

    Rustad, J. R.; Kreylos, O.; Hamann, B.

    2004-12-01

    The "Nanotech Construction Kit" (NCK) [1] is a new project aimed at improving the understanding of molecular structures at a nanometer-scale level by visualization and interactive manipulation. Our very first prototype is a virtual-reality program allowing the construction of silica and carbon structures from scratch by assembling them one atom at a time. In silica crystals or glasses, the basic building block is an SiO4 unit, with the four oxygen atoms arranged around the central silicon atom in the shape of a regular tetrahedron. Two silicate units can connect to each other by their silicon atoms covalently bonding to one shared oxygen atom. Geometrically, this means that two tetrahedra can link at their vertices. Our program is based on geometric representations and uses simple force fields to simulate the interaction of building blocks, such as forming/breaking of bonds and repulsion. Together with stereoscopic visualization and direct manipulation of building blocks using wands or data gloves, this enables users to create realistic and complex molecular models in short amounts of time. The NCK can either be used as a standalone tool, to analyze or experiment with molecular structures, or it can be used in combination with "traditional" molecular dynamics (MD) simulations. In a first step, the NCK can create initial configurations for subsequent MD simulation. In a more evolved setup, the NCK can serve as a visual front-end for an ongoing MD simulation, visualizing changes in simulation state in real time. Additionally, the NCK can be used to change simulation state on-the-fly, to experiment with different simulation conditions, or force certain events, e.g., the forming of a bond, and observe the simulation's reaction. [1] http://graphics.cs.ucdavis.edu/~okreylos/ResDev/NanoTech

  1. In-cell protease assay systems based on trans-localizing molecular beacon proteins using HCV protease as a model system.

    Directory of Open Access Journals (Sweden)

    Jeong Hee Kim

    Full Text Available This study describes a sensitive in-cell protease detection system that enables direct fluorescence detection of a target protease and its inhibition inside living cells. This live-cell imaging system provides a fluorescent molecular beacon protein comprised of an intracellular translocation signal sequence, a protease-specific cleavage sequence, and a fluorescent tag sequence(s. The molecular beacon protein is designed to change its intracellular localization upon cleavage by a target protease, i.e., from the cytosol to a subcellular organelle or from a subcellular organelle to the cytosol. Protease activity can be monitored at the single cell level, and accordingly the entire cell population expressing the protease can be accurately enumerated. The clear cellular change in fluorescence pattern makes this system an ideal tool for various life science and drug discovery research, including high throughput and high content screening applications.

  2. Molecular contamination modeling with CTSP

    Science.gov (United States)

    Brieda, Lubos

    2016-11-01

    Spacecraft instruments and thermal control surfaces are generally highly sensitive to molecular and particulate contamination. Despite best efforts taken during assembly, integration, and test, it is impossible to completely eliminate all sources of contaminants. Contamination transport analysis then becomes of critical importance. It can be used to predict the end of life accumulation on critical surfaces from prescribed source rates. Conversely, given allowable deposition levels, contamination modeling can be used to determine the cleanliness requirements to be met prior to launch. This paper describes a recently developed code for modeling contamination transport. Unlike other tools used by the community, CTSP concurrently traces many simulation particles through small time steps. This allows the code to visualize contaminant partial pressures, and to also include aerodynamic, gravitation, or electrostatic forces. The code is demonstrated by simulating an outgassing characterization test in a bell jar.

  3. Accounting for intra-molecular vibrational modes in open quantum system description of molecular systems.

    Science.gov (United States)

    Roden, Jan; Strunz, Walter T; Whaley, K Birgitta; Eisfeld, Alexander

    2012-11-28

    Electronic-vibrational dynamics in molecular systems that interact with an environment involve a large number of degrees of freedom and are therefore often described by means of open quantum system approaches. A popular approach is to include only the electronic degrees of freedom into the system part and to couple these to a non-Markovian bath of harmonic vibrational modes that is characterized by a spectral density. Since this bath represents both intra-molecular and external vibrations, it is important to understand how to construct a spectral density that accounts for intra-molecular vibrational modes that couple further to other modes. Here, we address this problem by explicitly incorporating an intra-molecular vibrational mode together with the electronic degrees of freedom into the system part and using the Fano theory for a resonance coupled to a continuum to derive an "effective" bath spectral density, which describes the contribution of intra-molecular modes. We compare this effective model for the intra-molecular mode with the method of pseudomodes, a widely used approach in simulation of non-Markovian dynamics. We clarify the difference between these two approaches and demonstrate that the respective resulting dynamics and optical spectra can be very different.

  4. Interaction between ropinirole hydrochloride and aspirin with human serum albumin as binary and ternary systems by multi-spectroscopic, molecular modeling and zeta potential

    Energy Technology Data Exchange (ETDEWEB)

    Mahaki, Hanie, E-mail: hanieh.mahaki@gmail.com [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Memarpoor-Yazdi, Mina; Chamani, Jamshidkhan [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Reza Saberi, Mohammad [Medical Chemistry Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

    2013-02-15

    The aim of the present study was to describe the competition of ropinirole hydrochloride (RP) and aspirin (ASA) in binding to human serum albumin (HSA) in physiological buffer (pH=7.4) using multi-spectroscopic, molecular modeling and zeta-potential measurements. Fluorescence analysis was used to define the binding and quenching properties of drug-HSA complexes in binary and ternary systems. Fluorescence spectroscopy showed that in the presence of RP, the binding constant of HSA-ASA was increased. Static quenching was confirmed to result in the fluorescence quenching and FRET. The effect of drugs on the conformation of HSA was analyzed using synchronous fluorescence spectroscopy, three-dimensional fluorescence spectra and circular dichroism (CD). The RLS method determined the critical aggregation concentration of drugs on HSA in binary and ternary systems that confirmed the zeta potential results. Structural modeling showed that the affinity of each of the drugs to HSA in binary and ternary systems confirms the spectroscopic results. - Highlights: Black-Right-Pointing-Pointer We studied the interaction of ropinirole hydrochloride and aspirin with HSA. Black-Right-Pointing-Pointer Molecular modeling and zeta-potential used to describe competitive interaction. Black-Right-Pointing-Pointer We determined the critical induced aggregation concentration of both drugs on HSA. Black-Right-Pointing-Pointer The binding mechanism of drugs as separate and simultaneous to HSA has been compared. Black-Right-Pointing-Pointer The binding site of both drugs as simultaneous effects on HSA has been determined.

  5. Informing mechanistic toxicology with computational molecular models.

    Science.gov (United States)

    Goldsmith, Michael R; Peterson, Shane D; Chang, Daniel T; Transue, Thomas R; Tornero-Velez, Rogelio; Tan, Yu-Mei; Dary, Curtis C

    2012-01-01

    Computational molecular models of chemicals interacting with biomolecular targets provides toxicologists a valuable, affordable, and sustainable source of in silico molecular level information that augments, enriches, and complements in vitro and in vivo efforts. From a molecular biophysical ansatz, we describe how 3D molecular modeling methods used to numerically evaluate the classical pair-wise potential at the chemical/biological interface can inform mechanism of action and the dose-response paradigm of modern toxicology. With an emphasis on molecular docking, 3D-QSAR and pharmacophore/toxicophore approaches, we demonstrate how these methods can be integrated with chemoinformatic and toxicogenomic efforts into a tiered computational toxicology workflow. We describe generalized protocols in which 3D computational molecular modeling is used to enhance our ability to predict and model the most relevant toxicokinetic, metabolic, and molecular toxicological endpoints, thereby accelerating the computational toxicology-driven basis of modern risk assessment while providing a starting point for rational sustainable molecular design.

  6. Molecular Spectroscopy of Living Systems

    Science.gov (United States)

    Cheng, Ji-Xin

    2016-06-01

    Molecular spectroscopy has been a powerful tool in the study of molecules in gas phase, condensed phase, and at interfaces. The transition from in vitro spectroscopy to spectroscopic imaging of living systems is opening new opportunities to reveal cellular machinery and to enable molecule-based diagnosis (Science 2015, 350: 1054). Such a transition involves more than a simple combination of spectrometry and microscopy. In this presentation, I will discuss the most recent efforts that have pushed the physical limits of spectroscopic imaging in terms of spectral acquisition speed, detection sensitivity, spatial resolution and imaging depth. I will further highlight significant applications in functional analysis of single cells and in label-free detection of diseases.

  7. Molecular modeling of fluoropropene refrigerants.

    Science.gov (United States)

    Raabe, Gabriele

    2012-05-17

    Different fluoropropenes are currently considered as refrigerants, either as pure compounds or as components in low GWP (global warming potential) refrigerant mixtures. Due to their limited commercial production, experimental data for the thermophysical properties of fluoropropenes and their mixtures are in general rare, which hampers the exploration of their performance in technical applications. In principle, molecular simulation can be used to predict the relevant properties of refrigerants and refrigerant blends, provided that adequate intermolecular potential functions ("force fields") are available. In our earlier work (Raabe, G.; Maginn, E. J., J. Phys. Chem. B2010, 114, 10133-10142), we introduced a transferable force field for fluoropropenes comprising the compounds 3,3,3-trifluoro-1-propene (HFO-1243zf), 2,3,3,3-tetrafluoro-1-propene (HFO-1234yf), and hexafluoro-1-propene (HFO-1216). In this paper, we provide an extension of the force field model to the trans- and cis-1,3,3,3-tetrafluoro-1-propene (HFO-1234ze(E), HFO-1234ze) and the cis-1,2,3,3,3-pentafluoro-1-propene (HFO-1225ye(Z)) as well as revised simulation results for HFO-1216. We present Gibbs ensemble simulation results on the vapor pressures, saturated densities, and heats of vaporization of these compounds in comparison with experimental results. The simulation results show that the force field model enables reliable predictions of the properties of the different fluoropropenes and also reproduces well the differing vapor-liquid coexistence and vapor pressure curve of the cis- and trans-isomers of 1,3,3,3-tetrafluoro-1-propene, HFO-1234ze and HFO-1234ze(E). For these two isomers, we also present molecular dynamics simulation studies on their local structure.

  8. Reactions of small molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Wittig, C. [Univ. of Southern California, Los Angeles, CA (United States)

    1993-12-01

    This DOE program remains focused on small molecular systems relevant to combustion. Though a number of experimental approaches and machines are available for this research, the authors` activities are centered around the high-n Rydberg time-of-flight (HRTOF) apparatus in this laboratory. One student and one postdoc carry out experiments with this machine and also engage in small intra-group collaborations involving shared equipment. This past year was more productive than the previous two, due to the uninterrupted operation of the HRTOF apparatus. Results were obtained with CH{sub 3}OH, CH{sub 3}SH, Rg-HX complexes, HCOOH, and their deuterated analogs where appropriate. One paper is in print, three have been accepted for publication, and one is under review. Many preliminary results that augur well for the future were obtained with other systems such as HNO{sub 3}, HBr-HI complexes, toluene, etc. Highlights from the past year are presented below that display some of the features of this program.

  9. Modeling off-resonant nonlinear-optical cascading in mesoscopic thin films and guest-host molecular systems

    CERN Document Server

    Dawson, Nathan J; Crescimanno, Michael

    2013-01-01

    We develop a model for off-resonant microscopic cascading of scalar polarizabilities using a self-consistent field approach, and use it to study the effects of boundaries on mesoscopic systems of nonlinear polarizable atoms and molecules. We find that higher-ordered susceptibilities can be enhanced by increasing the surface-to-volume ratio through reducing the distance between boundaries perpendicular to the linear polarization. We also show lattice scaling effects on the effective nonlinear refractive indices for Gaussian beams, and illustrate finite size effects on dipole field distributions in films subject to long-wavelength propagating fields. We derive simplified expressions for the microscopic cascading of the nonlinear optical response in guest-host systems.

  10. 3D Printing of Molecular Models

    Science.gov (United States)

    Gardner, Adam; Olson, Arthur

    2016-01-01

    Physical molecular models have played a valuable role in our understanding of the invisible nano-scale world. We discuss 3D printing and its use in producing models of the molecules of life. Complex biomolecular models, produced from 3D printed parts, can demonstrate characteristics of molecular structure and function, such as viral self-assembly,…

  11. 3D Printing of Molecular Models

    Science.gov (United States)

    Gardner, Adam; Olson, Arthur

    2016-01-01

    Physical molecular models have played a valuable role in our understanding of the invisible nano-scale world. We discuss 3D printing and its use in producing models of the molecules of life. Complex biomolecular models, produced from 3D printed parts, can demonstrate characteristics of molecular structure and function, such as viral self-assembly,…

  12. Airy-like pulses in models of large molecular chains, and conservative numerical methods for quasi-linear Hamiltonian systems

    CERN Document Server

    LeMesurier, Brenton

    2013-01-01

    The phenomenon of coherent energetic pulse propagation in macromolecular chains such as $\\alpha$-helix protein is studied using the Davydov-Scott model, with both numerical studies using a new unconditionally stable fourth order accurate energy-momentum conserving time discretization, and with analysis based on ideas of center manifold theory. It is shown that for physically natural impulsive initial data, the coherent traveling pulses seen have a form related to the Airy function, but with rapid variation of phase along the chain. This can be explained in terms of a new continuum limit approximation by the third derivative nonlinear Schr\\"odinger equation, which differs from the previous continuum limit approximations related to the standard NLS equation. A theorem is given describing the construction of such conservative time discretizations for a large class of Hamiltonian systems.

  13. Molecular Imaging System for Monitoring Tumor Angiogenesis

    Science.gov (United States)

    Aytac, Esra; Burcin Unlu, Mehmet

    2012-02-01

    In cancer, non-invasive imaging techniques that monitor molecular processes associated with the tumor angiogenesis could have a central role in the evaluation of novel antiangiogenic and proangiogenic therapies as well as early detection of the disease. Matrix metalloproteinases (MMP) can serve as specific biological targets for imaging of angiogenesis since expression of MMPs is required for angiogenesis and has been found to be upregulated in every type of human cancer and correlates with stage, invasive, metastatic properties and poor prognosis. However, for most cancers it is still unknown when, where and how MMPs are involved in the tumor angiogenesis [1]. Development of high-resolution, high sensitivity imaging techniques in parallel with the tumor models could prove invaluable for assessing the physical location and the time frame of MMP enzymatic acitivity. The goal of this study is to understand where, when and how MMPs are involved in the tumor angiogenesis. We will accomplish this goal by following two objectives: to develop a high sensitivity, high resolution molecular imaging system, to develop a virtual tumor simulator that can predict the physical location and the time frame of the MMP activity. In order to achieve our objectives, we will first develop a PAM system and develop a mathematical tumor model in which the quantitative data obtained from the PAM can be integrated. So, this work will develop a virtual tumor simulator and a molecular imaging system for monitoring tumor angiogenesis. 1.Kessenbrock, K., V. Plaks, and Z. Werb, MMP:regulators of the tumor microenvironment. Cell, 2010. 141(1)

  14. Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patients

    DEFF Research Database (Denmark)

    Anvar, Seyed Yahya; hoen, Peter Ac; Venema, Andrea

    2011-01-01

    Oculopharyngeal muscular dystrophy (OPMD) is a late-onset progressive muscle disorder caused by a poly-alanine expansion mutation in the Poly(A) Binding Protein Nuclear 1 (PABPN1). The molecular mechanisms that regulate disease onset and progression are largely unknown. In order to identify molec...

  15. Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patients

    DEFF Research Database (Denmark)

    Anvar, Seyed Yahya; hoen, Peter Ac; Venema, Andrea;

    2011-01-01

    Oculopharyngeal muscular dystrophy (OPMD) is a late-onset progressive muscle disorder caused by a poly-alanine expansion mutation in the Poly(A) Binding Protein Nuclear 1 (PABPN1). The molecular mechanisms that regulate disease onset and progression are largely unknown. In order to identify molec...

  16. Molecular Modeling of Cardiac Troponin

    Science.gov (United States)

    Manning, Edward P.

    The cardiac thin filament regulates interactions of actin and myosin, the force-generating elements of muscular contraction. Over the past several decades many details have been discovered regarding the structure and function of the cardiac thin filament and its components, including cardiac troponin (cTn). My hypothesis is that signal propagation occurs between distant ends of the cardiac troponin complex through calcium-dependent alterations in the dynamics of cTn and tropomyosin (Tm). I propose a model of the thin filament that encompasses known structures of cTn, Tm and actin to gain insight into cardiac troponin's allosteric regulation of thin filament dynamics. By performing molecular dynamics simulations of cTn in conjunction with overlapping Tm in two conditions, with and without calcium bound to site II of cardiac troponin C (cTnC), I found a combination of calcium-dependent changes in secondary structure and dynamics throughout the cTn-Tm complex. I then applied this model to investigate familial hypertrophic cardiomyopathy (FHC), a disease of the sarcomere that is one of the most commonly occurring genetic causes of heart disease. Approximately 15% of known FHC-related mutations are found in cardiac troponin T (cTnT), most of which are in or flank the alpha-helical N-tail domain TNT1. TNT1 directly interacts with overlapping Tm coiled coils. Using this model I identified effects of TNT1 mutations that propagate to the cTn core where site II of cTnC, the regulatory site of calcium binding in the thin filament, is located. Specifically, I found that mutations in TNT1 alter the flexibility of TNT1 and that the flexibility of TNT1 is inversely proportional to the cooperativity of calcium activation of the thin filament. Further, I identified a pathway of propagation of structural and dynamic changes linking TNT1 to site II of cTnC. Mutation-induced changes at site II cTnC alter calcium coordination which corresponds to biophysical measurements of calcium

  17. [Novel bioconversion systems using a yeast molecular display system].

    Science.gov (United States)

    Shibasaki, Seiji

    2010-11-01

    The budding yeast Saccharomyces cerevisiae has been used for the process of fermentation as well as for studies in biochemistry and molecular biology as a eukaryotic model cell or tool for the analysis of gene functions. Thus, yeast is essential in industries and researches. Yeast cells have a cell wall, which is one characteristic that helps distinguish yeast cells from other eukaryotic cells such as mammalian cells. We have developed a molecular display system using the protein of the yeast cell wall as an anchor for foreign proteins. Yeast cells have been designed for use in sensing and metal adsorption, and have been used in vaccines and for screening novel proteins. Currently, yeast is used not only as a tool for analyzing gene or protein function but also in molecular display technology. The phage display system, which is at the forefront of molecular display technologies, is a powerful tool for screening ligands bound to a target molecule and for analyzing protein-protein interactions; however, in some cases, eukaryotic proteins are not easily expressed by this system. On the other hand, yeast cells have the ability to express eukaryotic proteins and proliferate; thus, these cells display various proteins. Yeast cells are more appropriate for white biotechnology. In this review, displays of enzymes that are important in bioconversion, such as lipases and β-glucosidases, are going to be introduced.

  18. Modeling molecular mechanisms in the axon

    Science.gov (United States)

    de Rooij, R.; Miller, K. E.; Kuhl, E.

    2017-03-01

    Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena—both in isolation and in interaction—to explore emergent cellular-level features under physiological and pathological conditions.

  19. Validation of systems biology models

    NARCIS (Netherlands)

    Hasdemir, D.

    2015-01-01

    The paradigm shift from qualitative to quantitative analysis of biological systems brought a substantial number of modeling approaches to the stage of molecular biology research. These include but certainly are not limited to nonlinear kinetic models, static network models and models obtained by the

  20. A computational systems biology software platform for multiscale modeling and simulation: integrating whole-body physiology, disease biology, and molecular reaction networks.

    Science.gov (United States)

    Eissing, Thomas; Kuepfer, Lars; Becker, Corina; Block, Michael; Coboeken, Katrin; Gaub, Thomas; Goerlitz, Linus; Jaeger, Juergen; Loosen, Roland; Ludewig, Bernd; Meyer, Michaela; Niederalt, Christoph; Sevestre, Michael; Siegmund, Hans-Ulrich; Solodenko, Juri; Thelen, Kirstin; Telle, Ulrich; Weiss, Wolfgang; Wendl, Thomas; Willmann, Stefan; Lippert, Joerg

    2011-01-01

    Today, in silico studies and trial simulations already complement experimental approaches in pharmaceutical R&D and have become indispensable tools for decision making and communication with regulatory agencies. While biology is multiscale by nature, project work, and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. We present a modeling and simulation software platform consisting of PK-Sim(®) and MoBi(®) capable of building and simulating models that integrate across biological scales. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization. Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression. In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials. The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drug-drug, or drug-metabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach.

  1. A computational systems biology software platform for multiscale modeling and simulation: Integrating whole-body physiology, disease biology, and molecular reaction networks

    Directory of Open Access Journals (Sweden)

    Thomas eEissing

    2011-02-01

    Full Text Available Today, in silico studies and trial simulations already complement experimental approaches in pharmaceutical R&D and have become indispensable tools for decision making and communication with regulatory agencies. While biology is multi-scale by nature, project work and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. We present a modeling and simulation software platform consisting of PK-Sim® and MoBi® capable of building and simulating models that integrate across biological scales. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization. Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression. In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials. The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drug-drug or drug-metabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach.

  2. Computerized molecular modeling of carbohydrates

    Science.gov (United States)

    Computerized molecular modleing continues to increase in capability and applicability to carbohydrates. This chapter covers nomenclature and conformational aspects of carbohydrates, perhaps of greater use to carbohydrate-inexperienced computational chemists. Its comments on various methods and studi...

  3. A Molecular Model for Chiral Symmetry Breaking

    Science.gov (United States)

    Latinwo, Folarin; Stillinger, Frank; Debenedetti, Pablo

    In this work, we present a new class of molecular models for chiral phenomena in condensed matter systems. A key feature of these models is the ability of the four-site (tetramer) ``molecules'' to inter-convert between two distinct chiral forms (enantiomers). Given this feature, we use analytical theory and computer simulations to investigate the emergent chiral properties (including symmetry breaking) over a range of conditions. In particular, we consider the single-molecule level and condensed-phase behavior of our model system. Interestingly, we find that our liquid-phase predictions are in excellent agreement with recent experimental reports on chiral self-sorting in isotropic liquids. From this perspective, our model demonstrates accurate predictive capabilities, as well as a platform for understanding the microscopic origins of a variety of chiral phenomena. In a broader context, we anticipate that this class of models will be relevant to chirality-dominated areas such as the pharmaceutical industry and pre-biotic geochemistry.

  4. Molecular Modeling of Estrogen Receptor Using Molecular Operating Environment

    Science.gov (United States)

    Roy, Urmi; Luck, Linda A.

    2007-01-01

    Molecular modeling is pervasive in the pharmaceutical industry that employs many of our students from Biology, Chemistry and the interdisciplinary majors. To expose our students to this important aspect of their education we have incorporated a set of tutorials in our Biochemistry class. The present article describes one of our tutorials where…

  5. The cognitive life of mechanical molecular models.

    Science.gov (United States)

    Charbonneau, Mathieu

    2013-12-01

    The use of physical models of molecular structures as research tools has been central to the development of biochemistry and molecular biology. Intriguingly, it has received little attention from scholars of science. In this paper, I argue that these physical models are not mere three-dimensional representations but that they are in fact very special research tools: they are cognitive augmentations. Despite the fact that they are external props, these models serve as cognitive tools that augment and extend the modeler's cognitive capacities and performance in molecular modeling tasks. This cognitive enhancement is obtained because of the way the modeler interacts with these models, the models' materiality contributing to the solving of the molecule's structure. Furthermore, I argue that these material models and their component parts were designed, built and used specifically to serve as cognitive facilitators and cognitive augmentations.

  6. Asphaltenes molecular modeling of Boscan crude oil

    Energy Technology Data Exchange (ETDEWEB)

    Kowalewski, I.; Vandenbroucke, M.; Behar, F.; Huc, A.Y. [Institut Francais du Petrole (IFP), 92 - Rueil-Malmaison (France); Faulon, J.L. [Sandia National Labs., Albuquerque, NM (United States); Taylor, M.J.

    1996-01-01

    The asphaltenes presence in the petrochemical feedstocks can disturb a lot some refining processes. In this context, some molecular models have been carried out to better understand the chemical structures of these asphaltenes molecules. The aim of this work is to estimate for the asphaltenes molecules the molecular models potentialities by the use of crystal structure elucidation programs (XMOL and SIGNATURE softwares) and by molecular simulation (INSIGHT II/DISCOVER softwares). In particular, two models of Boscan asphaltenes covalent molecules with intense reticulation degrees are discussed. (O.L.). 29 refs., 6 figs., 6 tabs.

  7. Molecular assembly in natural and engineered systems

    CERN Document Server

    Howorka, Stefan

    2011-01-01

    This volume explores some of the most exciting recent advances in basic research on molecular assembly in natural and engineered systems and how this knowledge is leading to advances in the various fields.* This series provides a forum for discussion of new discoveries, approaches, and ideas * Contributions from leading scholars and industry experts * Reference guide for researchers involved in molecular biology and related fields

  8. pysimm: A python package for simulation of molecular systems

    Science.gov (United States)

    Fortunato, Michael E.; Colina, Coray M.

    In this work, we present pysimm, a python package designed to facilitate structure generation, simulation, and modification of molecular systems. pysimm provides a collection of simulation tools and smooth integration with highly optimized third party software. Abstraction layers enable a standardized methodology to assign various force field models to molecular systems and perform simple simulations. These features have allowed pysimm to aid the rapid development of new applications specifically in the area of amorphous polymer simulations.

  9. Theoretical Modeling and Computer Simulations for the Origins and Evolution of Reproducing Molecular Systems and Complex Systems with Many Interactive Parts

    Science.gov (United States)

    Liang, Shoudan

    2000-01-01

    Our research effort has produced nine publications in peer-reviewed journals listed at the end of this report. The work reported here are in the following areas: (1) genetic network modeling; (2) autocatalytic model of pre-biotic evolution; (3) theoretical and computational studies of strongly correlated electron systems; (4) reducing thermal oscillations in atomic force microscope; (5) transcription termination mechanism in prokaryotic cells; and (6) the low glutamine usage in thennophiles obtained by studying completely sequenced genomes. We discuss the main accomplishments of these publications.

  10. Modeling the Hydrogen Bond within Molecular Dynamics

    Science.gov (United States)

    Lykos, Peter

    2004-01-01

    The structure of a hydrogen bond is elucidated within the framework of molecular dynamics based on the model of Rahman and Stillinger (R-S) liquid water treatment. Thus, undergraduates are exposed to the powerful but simple use of classical mechanics to solid objects from a molecular viewpoint.

  11. General theory for multiple input-output perturbations in complex molecular systems. 1. Linear QSPR electronegativity models in physical, organic, and medicinal chemistry.

    Science.gov (United States)

    González-Díaz, Humberto; Arrasate, Sonia; Gómez-SanJuan, Asier; Sotomayor, Nuria; Lete, Esther; Besada-Porto, Lina; Ruso, Juan M

    2013-01-01

    In general perturbation methods starts with a known exact solution of a problem and add "small" variation terms in order to approach to a solution for a related problem without known exact solution. Perturbation theory has been widely used in almost all areas of science. Bhor's quantum model, Heisenberg's matrix mechanincs, Feyman diagrams, and Poincare's chaos model or "butterfly effect" in complex systems are examples of perturbation theories. On the other hand, the study of Quantitative Structure-Property Relationships (QSPR) in molecular complex systems is an ideal area for the application of perturbation theory. There are several problems with exact experimental solutions (new chemical reactions, physicochemical properties, drug activity and distribution, metabolic networks, etc.) in public databases like CHEMBL. However, in all these cases, we have an even larger list of related problems without known solutions. We need to know the change in all these properties after a perturbation of initial boundary conditions. It means, when we test large sets of similar, but different, compounds and/or chemical reactions under the slightly different conditions (temperature, time, solvents, enzymes, assays, protein targets, tissues, partition systems, organisms, etc.). However, to the best of our knowledge, there is no QSPR general-purpose perturbation theory to solve this problem. In this work, firstly we review general aspects and applications of both perturbation theory and QSPR models. Secondly, we formulate a general-purpose perturbation theory for multiple-boundary QSPR problems. Last, we develop three new QSPR-Perturbation theory models. The first model classify correctly >100,000 pairs of intra-molecular carbolithiations with 75-95% of Accuracy (Ac), Sensitivity (Sn), and Specificity (Sp). The model predicts probabilities of variations in the yield and enantiomeric excess of reactions due to at least one perturbation in boundary conditions (solvent, temperature

  12. Molecular motor assembly of a biomimetic system

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Active biological molecules and functional structures can be fabricated into a bio-mimetic system by using molecular assembly method. Such materials can be used for the drug delivery, disease diagnosis and therapy, and new nanodevice construction.

  13. Orthogonal photoswitching in a multifunctional molecular system

    NARCIS (Netherlands)

    Lerch, Michael M.; Hansen, Mickel J.; Velema, Willem A.; Szymanski, Wiktor; Feringa, Ben L.

    2016-01-01

    The wavelength-selective, reversible photocontrol over various molecular processes in parallel remains an unsolved challenge. Overlapping ultraviolet-visible spectra of frequently employed photoswitches have prevented the development of orthogonally responsive systems, analogous to those that rely o

  14. Theoretical investigation of two model systems for molecular photoswitch functionality. I. 2-(4-nitropyrimidin-2-yl)ethenol

    Science.gov (United States)

    Woywod, Clemens; Csehi, András; Halász, Gábor J.; Ruud, Kenneth; Vibók, Ágnes

    2014-03-01

    The ground and five lowest-lying electronically excited singlet states of 2-(4-nitropyrimidin-2-yl)ethenol (NPE) have been studied theoretically using the complete active space self-consistent-field (CASSCF), Møller-Plesset second-order perturbation theory (MP2) and second-order multi-configurational perturbation theory (CASPT2) methods. The molecule can be regarded as being composed of a frame and a crane component and is characterised by the existence of two planar minima of similar energy on the ground-state potential energy (PE) surface. This work explores the possibility of an excited-state intramolecular hydrogen transfer (ESIHT) process in NPE. A hypothetical reaction coordinate has been constructed for NPE. State-averaged CASSCF and CASPT2 calculations of the six lowest-lying singlet states have been performed for the isomerisation. Adiabatic and simplified quasi-diabatic PE and transition dipole moment functions have been constructed. The computations indicate that there exist substantial barriers for the rotation process on the adiabatic PE surfaces of all the five excited states investigated. The six quasi-diabatic electronic states considered here decompose into two classes based on whether the electronic wave functions depend weakly or strongly on the nuclear displacement, subject to the effect of the torsion on relevant molecular orbitals.

  15. Molecular System Bioenergics of the Heart: Experimental Studies of Metabolic Compartmentation and Energy Fluxes versus Computer Modeling

    Directory of Open Access Journals (Sweden)

    Valdur Saks

    2011-12-01

    Full Text Available In this review we analyze the recent important and remarkable advancements in studies of compartmentation of adenine nucleotides in muscle cells due to their binding to macromolecular complexes and cellular structures, which results in non-equilibrium steady state of the creatine kinase reaction. We discuss the problems of measuring the energy fluxes between different cellular compartments and their simulation by using different computer models. Energy flux determinations by 18O transfer method have shown that in heart about 80% of energy is carried out of mitochondrial intermembrane space into cytoplasm by phosphocreatine fluxes generated by mitochondrial creatine kinase from adenosine triphosphate (ATP, produced by ATP Synthasome. We have applied the mathematical model of compartmentalized energy transfer for analysis of experimental data on the dependence of oxygen consumption rate on heart workload in isolated working heart reported by Williamson et al. The analysis of these data show that even at the maximal workloads and respiration rates, equal to 174 µmol O2 per min per g dry weight, phosphocreatine flux, and not ATP, carries about 80–85% percent of energy needed out of mitochondria into the cytosol. We analyze also the reasons of failures of several computer models published in the literature to correctly describe the experimental data.

  16. Modeling hybrid perovskites by molecular dynamics.

    Science.gov (United States)

    Mattoni, Alessandro; Filippetti, Alessio; Caddeo, Claudia

    2017-02-01

    The topical review describes the recent progress in the modeling of hybrid perovskites by molecular dynamics simulations. Hybrid perovskites and in particular methylammonium lead halide (MAPI) have a tremendous technological relevance representing the fastest-advancing solar material to date. They also represent the paradigm of an organic-inorganic crystalline material with some conceptual peculiarities: an inorganic semiconductor for what concerns the electronic and absorption properties with a hybrid and solution processable organic-inorganic body. After briefly explaining the basic concepts of ab initio and classical molecular dynamics, the model potential recently developed for hybrid perovskites is described together with its physical motivation as a simple ionic model able to reproduce the main dynamical properties of the material. Advantages and limits of the two strategies (either ab initio or classical) are discussed in comparison with the time and length scales (from pico to microsecond scale) necessary to comprehensively study the relevant properties of hybrid perovskites from molecular reorientations to electrocaloric effects. The state-of-the-art of the molecular dynamics modeling of hybrid perovskites is reviewed by focusing on a selection of showcase applications of methylammonium lead halide: molecular cations disorder; temperature evolution of vibrations; thermally activated defects diffusion; thermal transport. We finally discuss the perspectives in the modeling of hybrid perovskites by molecular dynamics.

  17. Modeling hybrid perovskites by molecular dynamics

    Science.gov (United States)

    Mattoni, Alessandro; Filippetti, Alessio; Caddeo, Claudia

    2017-02-01

    The topical review describes the recent progress in the modeling of hybrid perovskites by molecular dynamics simulations. Hybrid perovskites and in particular methylammonium lead halide (MAPI) have a tremendous technological relevance representing the fastest-advancing solar material to date. They also represent the paradigm of an organic-inorganic crystalline material with some conceptual peculiarities: an inorganic semiconductor for what concerns the electronic and absorption properties with a hybrid and solution processable organic-inorganic body. After briefly explaining the basic concepts of ab initio and classical molecular dynamics, the model potential recently developed for hybrid perovskites is described together with its physical motivation as a simple ionic model able to reproduce the main dynamical properties of the material. Advantages and limits of the two strategies (either ab initio or classical) are discussed in comparison with the time and length scales (from pico to microsecond scale) necessary to comprehensively study the relevant properties of hybrid perovskites from molecular reorientations to electrocaloric effects. The state-of-the-art of the molecular dynamics modeling of hybrid perovskites is reviewed by focusing on a selection of showcase applications of methylammonium lead halide: molecular cations disorder; temperature evolution of vibrations; thermally activated defects diffusion; thermal transport. We finally discuss the perspectives in the modeling of hybrid perovskites by molecular dynamics.

  18. Structures in Molecular Clouds: Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kane, J O; Mizuta, A; Pound, M W; Remington, B A; Ryutov, D D

    2006-04-20

    We attempt to predict the observed morphology, column density and velocity gradient of Pillar II of the Eagle Nebula, using Rayleigh Taylor (RT) models in which growth is seeded by an initial perturbation in density or in shape of the illuminated surface, and cometary models in which structure is arises from a initially spherical cloud with a dense core. Attempting to mitigate suppression of RT growth by recombination, we use a large cylindrical model volume containing the illuminating source and the self-consistently evolving ablated outflow and the photon flux field, and use initial clouds with finite lateral extent. An RT model shows no growth, while a cometary model appears to be more successful at reproducing observations.

  19. Characterizing Molecular Interactions in Chemical Systems.

    Science.gov (United States)

    Günther, David; Boto, Roberto A; Contreras-Garcia, Juila; Piquemal, Jean-Philip; Tierny, Julien

    2014-12-01

    Interactions between atoms have a major influence on the chemical properties of molecular systems. While covalent interactions impose the structural integrity of molecules, noncovalent interactions govern more subtle phenomena such as protein folding, bonding or self assembly. The understanding of these types of interactions is necessary for the interpretation of many biological processes and chemical design tasks. While traditionally the electron density is analyzed to interpret the quantum chemistry of a molecular system, noncovalent interactions are characterized by low electron densities and only slight variations of them--challenging their extraction and characterization. Recently, the signed electron density and the reduced gradient, two scalar fields derived from the electron density, have drawn much attention in quantum chemistry since they enable a qualitative visualization of these interactions even in complex molecular systems and experimental measurements. In this work, we present the first combinatorial algorithm for the automated extraction and characterization of covalent and noncovalent interactions in molecular systems. The proposed algorithm is based on a joint topological analysis of the signed electron density and the reduced gradient. Combining the connectivity information of the critical points of these two scalar fields enables to visualize, enumerate, classify and investigate molecular interactions in a robust manner. Experiments on a variety of molecular systems, from simple dimers to proteins or DNA, demonstrate the ability of our technique to robustly extract these interactions and to reveal their structural relations to the atoms and bonds forming the molecules. For simple systems, our analysis corroborates the observations made by the chemists while it provides new visual and quantitative insights on chemical interactions for larger molecular systems.

  20. Model Systems

    Directory of Open Access Journals (Sweden)

    Francisco Rodríguez-Trelles

    1998-12-01

    Full Text Available Current efforts to study the biological effects of global change have focused on ecological responses, particularly shifts in species ranges. Mostly ignored are microevolutionary changes. Genetic changes may be at least as important as ecological ones in determining species' responses. In addition, such changes may be a sensitive indicator of global changes that will provide different information than that provided by range shifts. We discuss potential candidate systems to use in such monitoring programs. Studies of Drosophila subobscura suggest that its chromosomal inversion polymorphisms are responding to global warming. Drosophila inversion polymorphisms can be useful indicators of the effects of climate change on populations and ecosystems. Other species also hold the potential to become important indicators of global change. Such studies might significantly influence ecosystem conservation policies and research priorities.

  1. Theoretical study on O$\\cdots$Br and O$\\cdots$Cl halogen bonds in some small model molecular systems

    Indian Academy of Sciences (India)

    Damanjit Kaur; Rajinder Kaur

    2014-11-01

    Halogen bonding interactions of type X$\\cdots$O=C are important in various fields including biological systems. In this work, theoretical calculations were carried out using B3LYP/6-31++G∗∗, MP2/6-31++G∗∗ and MP2/aug-cc-pVDZ methods on a series of O$\\cdots$X halogen bonds between CH2O andCH3CHO as halogen bond acceptor with X-Y (X = Cl, Br; Y = CF3, CF2 H, CFH2, CN, CCH, CCCN) as halogen bond donors. The strength of interaction energy for O$\\cdots$Br halogen-bonded complexes varies from −2.16 to −5.26 kcal/mol while for O$\\cdots$Cl complexes, it is between −1.65 to −3.67 kcal/mol, which indicate the O$\\cdots$Br bond to be stronger in comparison to O$\\cdots$Cl bond. SAPT analysis suggests that the strength of halogen bonding arises from the electrostatic and induction forces while dispersion is playing a comparatively smaller role. The halogen-bonded interaction energies were found to correlate well with positive electrostatic potential VS,max, halogen bonded distances, and the change in s-character of C-X bond. The halogen-bonded interaction energies were also evaluated for O$\\cdots$I bonded complexes and thus these complexes were found to be stronger than O$\\cdots$Br and O$\\cdots$Cl bonded complexes.

  2. Reactive molecular dynamics models from ab initio molecular dynamics data using relative entropy minimization

    Science.gov (United States)

    Arntsen, Christopher; Chen, Chen; Voth, Gregory A.

    2017-09-01

    We present two new multiscale molecular dynamics (MS-RMD) models for the hydrated excess proton in water developed directly from ab initio molecular dynamics (AIMD) simulation data of the same system. The potential of mean force along the proton transfer reaction coordinate and radial distribution functions for the MS-RMD models are shown to faithfully reproduce those of AIMD. The models are developed using an algorithm based on relative entropy minimization, thus demonstrating the ability of the method to rapidly generate accurate and highly efficient reactive MD force fields.

  3. Limiting assumptions in molecular modeling: electrostatics.

    Science.gov (United States)

    Marshall, Garland R

    2013-02-01

    Molecular mechanics attempts to represent intermolecular interactions in terms of classical physics. Initial efforts assumed a point charge located at the atom center and coulombic interactions. It is been recognized over multiple decades that simply representing electrostatics with a charge on each atom failed to reproduce the electrostatic potential surrounding a molecule as estimated by quantum mechanics. Molecular orbitals are not spherically symmetrical, an implicit assumption of monopole electrostatics. This perspective reviews recent evidence that requires use of multipole electrostatics and polarizability in molecular modeling.

  4. Exploring Organic Mechanistic Puzzles with Molecular Modeling

    Science.gov (United States)

    Horowitz, Gail; Schwartz, Gary

    2004-01-01

    The molecular modeling was used to reinforce more general skills such as deducing and drawing reaction mechanisms, analyzing reaction kinetics and thermodynamics and drawing reaction coordinate energy diagrams. This modeling was done through the design of mechanistic puzzles, involving reactions not familiar to the students.

  5. Learning generative models of molecular dynamics.

    Science.gov (United States)

    Razavian, Narges Sharif; Kamisetty, Hetunandan; Langmead, Christopher J

    2012-01-01

    We introduce three algorithms for learning generative models of molecular structures from molecular dynamics simulations. The first algorithm learns a Bayesian-optimal undirected probabilistic model over user-specified covariates (e.g., fluctuations, distances, angles, etc). L1 regularization is used to ensure sparse models and thus reduce the risk of over-fitting the data. The topology of the resulting model reveals important couplings between different parts of the protein, thus aiding in the analysis of molecular motions. The generative nature of the model makes it well-suited to making predictions about the global effects of local structural changes (e.g., the binding of an allosteric regulator). Additionally, the model can be used to sample new conformations. The second algorithm learns a time-varying graphical model where the topology and parameters change smoothly along the trajectory, revealing the conformational sub-states. The last algorithm learns a Markov Chain over undirected graphical models which can be used to study and simulate kinetics. We demonstrate our algorithms on multiple molecular dynamics trajectories.

  6. Modeling molecular hyperfine line emission

    CERN Document Server

    Keto, Eric

    2010-01-01

    In this paper we discuss two approximate methods previously suggested for modeling hyperfine spectral line emission for molecules whose collisional transitions rates between hyperfine levels are unknown. Hyperfine structure is seen in the rotational spectra of many commonly observed molecules such as HCN, HNC, NH3, N2H+, and C17O. The intensities of these spectral lines can be modeled by numerical techniques such as Lambda-iteration that alternately solve the equations of statistical equilibrium and the equation of radiative transfer. However, these calculations require knowledge of both the radiative and collisional rates for all transitions. For most commonly observed radio frequency spectral lines, only the net collisional rates between rotational levels are known. For such cases, two approximate methods have been suggested. The first method, hyperfine statistical equilibrium (HSE), distributes the hyperfine level populations according to their statistical weight, but allows the population of the rotationa...

  7. Medulloblastoma: Molecular Genetics and Animal Models

    Directory of Open Access Journals (Sweden)

    Corey Raffel

    2004-07-01

    Full Text Available Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.

  8. A molecular dynamics study of polymer/graphene interfacial systems

    Energy Technology Data Exchange (ETDEWEB)

    Rissanou, Anastassia N.; Harmandaris, Vagelis [Department of Mathematics and Applied Mathematics, University of Crete, GR-71409, Heraklion, Crete, Greece and Institute of Applied and Computational Mathematics (IACM), Foundation for Research and Technology Hellas (FORTH), GR-71110, Heraklion, Cret (Greece)

    2014-05-15

    Graphene based polymer nanocomposites are hybrid materials with a very broad range of technological applications. In this work, we study three hybrid polymer/graphene interfacial systems (polystyrene/graphene, poly(methyl methacrylate)/graphene and polyethylene/graphene) through detailed atomistic molecular dynamics (MD) simulations. Density profiles, structural characteristics and mobility aspects are being examined at the molecular level for all model systems. In addition, we compare the properties of the hybrid systems to the properties of the corresponding bulk ones, as well as to theoretical predictions.

  9. Molecular Models for Conductance in Junctions and Electrochemical Electron Transfer

    Science.gov (United States)

    Mazinani, Shobeir Khezr Seddigh

    This thesis develops molecular models for electron transport in molecular junctions and intra-molecular electron transfer. The goal is to identify molecular descriptors that afford a substantial simplification of these electronic processes. First, the connection between static molecular polarizability and the molecular conductance is examined. A correlation emerges whereby the measured conductance of a tunneling junction decreases as a function of the calculated molecular polarizability for several systems, a result consistent with the idea of a molecule as a polarizable dielectric. A model based on a macroscopic extension of the Clausius-Mossotti equation to the molecular domain and Simmon's tunneling model is developed to explain this correlation. Despite the simplicity of the theory, it paves the way for further experimental, conceptual and theoretical developments in the use of molecular descriptors to describe both conductance and electron transfer. Second, the conductance of several biologically relevant, weakly bonded, hydrogen-bonded systems is systematically investigated. While there is no correlation between hydrogen bond strength and conductance, the results indicate a relation between the conductance and atomic polarizability of the hydrogen bond acceptor atom. The relevance of these results to electron transfer in biological systems is discussed. Hydrogen production and oxidation using catalysts inspired by hydrogenases provides a more sustainable alternative to the use of precious metals. To understand electrochemical and spectroscopic properties of a collection of Fe and Ni mimics of hydrogenases, high-level density functional theory calculations are described. The results, based on a detailed analysis of the energies, charges and molecular orbitals of these metal complexes, indicate the importance of geometric constraints imposed by the ligand on molecular properties such as acidity and electrocatalytic activity. Based on model calculations of

  10. Logic circuits based on molecular spider systems.

    Science.gov (United States)

    Mo, Dandan; Lakin, Matthew R; Stefanovic, Darko

    2016-08-01

    Spatial locality brings the advantages of computation speed-up and sequence reuse to molecular computing. In particular, molecular walkers that undergo localized reactions are of interest for implementing logic computations at the nanoscale. We use molecular spider walkers to implement logic circuits. We develop an extended multi-spider model with a dynamic environment wherein signal transmission is triggered via localized reactions, and use this model to implement three basic gates (AND, OR, NOT) and a cascading mechanism. We develop an algorithm to automatically generate the layout of the circuit. We use a kinetic Monte Carlo algorithm to simulate circuit computations, and we analyze circuit complexity: our design scales linearly with formula size and has a logarithmic time complexity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Stokes Efficiency of Molecular Motor-Cargo Systems

    Directory of Open Access Journals (Sweden)

    Hongyun Wang

    2008-01-01

    Full Text Available A molecular motor utilizes chemical free energy to generate a unidirectional motion through the viscous fluid. In many experimental settings and biological settings, a molecular motor is elastically linked to a cargo. The stochastic motion of a molecular motor-cargo system is governed by a set of Langevin equations, each corresponding to an individual chemical occupancy state. The change of chemical occupancy state is modeled by a continuous time discrete space Markov process. The probability density of a motor-cargo system is governed by a two-dimensional Fokker-Planck equation. The operation of a molecular motor is dominated by high viscous friction and large thermal fluctuations from surrounding fluid. The instantaneous velocity of a molecular motor is highly stochastic: the past velocity is quickly damped by the viscous friction and the new velocity is quickly excited by bombardments of surrounding fluid molecules. Thus, the theory for macroscopic motors should not be applied directly to molecular motors without close examination. In particular, a molecular motor behaves differently working against a viscous drag than working against a conservative force. The Stokes efficiency was introduced to measure how efficiently a motor uses chemical free energy to drive against viscous drag. For a motor without cargo, it was proved that the Stokes efficiency is bounded by 100% [H. Wang and G. Oster, (2002]. Here, we present a proof for the general motor-cargo system.

  12. Modelling spin Hamiltonian parameters of molecular nanomagnets.

    Science.gov (United States)

    Gupta, Tulika; Rajaraman, Gopalan

    2016-07-12

    Molecular nanomagnets encompass a wide range of coordination complexes possessing several potential applications. A formidable challenge in realizing these potential applications lies in controlling the magnetic properties of these clusters. Microscopic spin Hamiltonian (SH) parameters describe the magnetic properties of these clusters, and viable ways to control these SH parameters are highly desirable. Computational tools play a proactive role in this area, where SH parameters such as isotropic exchange interaction (J), anisotropic exchange interaction (Jx, Jy, Jz), double exchange interaction (B), zero-field splitting parameters (D, E) and g-tensors can be computed reliably using X-ray structures. In this feature article, we have attempted to provide a holistic view of the modelling of these SH parameters of molecular magnets. The determination of J includes various class of molecules, from di- and polynuclear Mn complexes to the {3d-Gd}, {Gd-Gd} and {Gd-2p} class of complexes. The estimation of anisotropic exchange coupling includes the exchange between an isotropic metal ion and an orbitally degenerate 3d/4d/5d metal ion. The double-exchange section contains some illustrative examples of mixed valance systems, and the section on the estimation of zfs parameters covers some mononuclear transition metal complexes possessing very large axial zfs parameters. The section on the computation of g-anisotropy exclusively covers studies on mononuclear Dy(III) and Er(III) single-ion magnets. The examples depicted in this article clearly illustrate that computational tools not only aid in interpreting and rationalizing the observed magnetic properties but possess the potential to predict new generation MNMs.

  13. Integrated Multiscale Modeling of Molecular Computing Devices

    Energy Technology Data Exchange (ETDEWEB)

    Jerzy Bernholc

    2011-02-03

    photolithography will some day reach a miniaturization limit, forcing designers of Si-based electronics to pursue increased performance by other means. Any other alternative approach would have the unenviable task of matching the ability of Si technology to pack more than a billion interconnected and addressable devices on a chip the size of a thumbnail. Nevertheless, the prospects of developing alternative approaches to fabricate electronic devices have spurred an ever-increasing pace of fundamental research. One of the promising possibilities is molecular electronics (ME), self-assembled molecular-based electronic systems composed of single-molecule devices in ultra dense, ultra fast molecular-sized components. This project focused on developing accurate, reliable theoretical modeling capabilities for describing molecular electronics devices. The participants in the project are given in Table 1. The primary outcomes of this fundamental computational science grant are publications in the open scientific literature. As listed below, 62 papers have been published from this project. In addition, the research has also been the subject of more than 100 invited talks at conferences, including several plenary or keynote lectures. Many of the goals of the original proposal were completed. Specifically, the multi-disciplinary group developed a unique set of capabilities and tools for investigating electron transport in fabricated and self-assembled nanostructures at multiple length and time scales.

  14. Models and algorithms for biomolecules and molecular networks

    CERN Document Server

    DasGupta, Bhaskar

    2016-01-01

    By providing expositions to modeling principles, theories, computational solutions, and open problems, this reference presents a full scope on relevant biological phenomena, modeling frameworks, technical challenges, and algorithms. * Up-to-date developments of structures of biomolecules, systems biology, advanced models, and algorithms * Sampling techniques for estimating evolutionary rates and generating molecular structures * Accurate computation of probability landscape of stochastic networks, solving discrete chemical master equations * End-of-chapter exercises

  15. Probing Interactions in Complex Molecular Systems through Ordered Assembly

    Energy Technology Data Exchange (ETDEWEB)

    De Yoreo, J J; Bartelt, M C; Orme, C A; Villacampa, A; Weeks, B L; Miller, A E

    2002-01-31

    Emerging from the machinery of epitaxial science and chemical synthesis, is a growing emphasis on development of self-organized systems of complex molecular species. The nature of self-organization in these systems spans the continuum from simple crystallization of large molecules such as dendrimers and proteins, to assembly into large organized networks of nanometer-scale structures such as quantum dots or nanoparticles. In truth, self-organization in complex molecular systems has always been a central feature of many scientific disciplines including fields as diverse as structural biology, polymer science and geochemistry. But over the past decade, changes in those fields have often been marked by the degree to which researchers are using molecular-scale approaches to understand the hierarchy of structures and processes driven by this ordered assembly. At the same time, physical scientists have begun to use their knowledge of simple atomic and molecular systems to fabricate synthetic self-organized systems. This increasing activity in the field of self-organization is testament to the success of the physical and chemical sciences in building a detailed understanding of crystallization and epitaxy in simple atomic and molecular systems, one that is soundly rooted in thermodynamics and chemical kinetics. One of the fundamental challenges of chemistry and materials science in the coming decades is to develop a similarly well-founded physical understanding of assembly processes in complex molecular systems. Over the past five years, we have successfully used in situ atomic force microscopy (AFM) to investigate the physical controls on single crystal epitaxy from solutions for a wide range of molecular species. More recently, we have combined this method with grazing incidence X-ray diffraction and kinetic Monte Carlo modeling in order to relate morphology to surface atomic structure and processes. The purpose of this proposal was to extend this approach to assemblies

  16. Trends in Substitution Models of Molecular Evolution

    Directory of Open Access Journals (Sweden)

    Miguel eArenas

    2015-10-01

    Full Text Available Substitution models of evolution describe the process of genetic variation through fixed mutations and constitute the basis of the evolutionary analysis at the molecular level. Almost forty years after the development of first substitution models, highly sophisticated and data-specific substitution models continue emerging with the aim of better mimicking real evolutionary processes. Here I describe current trends in substitution models of DNA, codon and amino acid sequence evolution, including advantages and pitfalls of the most popular models. The perspective concludes that despite the large number of currently available substitution models, further research is required for more realistic modeling, especially for DNA coding and amino acid data. Additionally, the development of more accurate complex models should be coupled with new implementations and improvements of methods and frameworks for substitution model selection and downstream evolutionary analysis.

  17. Molecular Modeling of Interfacial Behaviors of Nanomaterials

    Science.gov (United States)

    2007-05-01

    15 L. Huang, and J. Kieffer, ’Molecular Dynamics Study of Cristobalite Silica Using a Charge Transfer Three- Body Potential Model,’ J. Chem. Phys...8217 Nano Letters in preparation (2006). 20 J. Zhou, and J. Kieffer, ’Simulation of Hexane-Functionalized Polyhedral Oligomeric Silses- quioxanes,’ J

  18. Molecular simulation and modeling of complex I.

    Science.gov (United States)

    Hummer, Gerhard; Wikström, Mårten

    2016-07-01

    Molecular modeling and molecular dynamics simulations play an important role in the functional characterization of complex I. With its large size and complicated function, linking quinone reduction to proton pumping across a membrane, complex I poses unique modeling challenges. Nonetheless, simulations have already helped in the identification of possible proton transfer pathways. Simulations have also shed light on the coupling between electron and proton transfer, thus pointing the way in the search for the mechanistic principles underlying the proton pump. In addition to reviewing what has already been achieved in complex I modeling, we aim here to identify pressing issues and to provide guidance for future research to harness the power of modeling in the functional characterization of complex I. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Molecular dynamics model of dimethyl ether

    Energy Technology Data Exchange (ETDEWEB)

    Lin, B.; Halley, W.J. [Univ. of Minnesota, Minneapolis, MN (United States)

    1995-11-02

    We report a molecular dynamics model of the monomeric liquid dimethyl ether. The united atom approach is used to treat CH{sub 3} groups as point source centers. Partial charges are derived from the experimental dipole moment. Harmonic force constants are used for intramolecular interactions, and their values are so chosen that the model`s fundamental frequencies agree with experimental results. Because we are interested in solvation properties, the model contains flexible molecules, allowing molecular distortion and internal dynamical quantities. We report radial distribution functions and the static structure factors as well as some dynamical quantities such as the dynamical structure factor, infrared absorption, and Raman scattering spectra. Calculated results agree reasonably well with experimental and other simulation results. 25 refs., 8 figs., 1 tab.

  20. Exploring RNA structure by integrative molecular modelling

    DEFF Research Database (Denmark)

    Masquida, Benoît; Beckert, Bertrand; Jossinet, Fabrice

    2010-01-01

    RNA molecular modelling is adequate to rapidly tackle the structure of RNA molecules. With new structured RNAs constituting a central class of cellular regulators discovered every year, the need for swift and reliable modelling methods is more crucial than ever. The pragmatic method based...... on interactive all-atom molecular modelling relies on the observation that specific structural motifs are recurrently found in RNA sequences. Once identified by a combination of comparative sequence analysis and biochemical data, the motifs composing the secondary structure of a given RNA can be extruded...... in three dimensions (3D) and used as building blocks assembled manually during a bioinformatic interactive process. Comparing the models to the corresponding crystal structures has validated the method as being powerful to predict the RNA topology and architecture while being less accurate regarding...

  1. Active Versus Passive: Receiver Model Transforms for Diffusive Molecular Communication

    CERN Document Server

    Noel, Adam; Makrakis, Dimitrios; Hafid, Abdelhakim

    2016-01-01

    This paper presents an analytical comparison of the active and passive receiver models in diffusive molecular communication. In the active model, molecules are absorbed when they collide with the receiver surface. In the passive model, the receiver is a virtual boundary that does not affect molecule behavior. Two approaches are presented to derive transforms between the active and passive receiver signals. As an example, we unify the two models for an unbounded diffusion-only molecular communication system with a spherical receiver. As time increases in the three-dimensional system, the transform functions have constant scaling factors, such that the receiver models are effectively equivalent. Methods are presented to enable the transformation of stochastic simulations, which are used to verify the transforms and demonstrate that transforming the simulation of a passive receiver can be more efficient and more accurate than the direct simulation of an absorbing receiver.

  2. Metal cluster fission: jellium model and Molecular dynamics simulations

    DEFF Research Database (Denmark)

    Lyalin, Andrey G.; Obolensky, Oleg I.; Solov'yov, Ilia;

    2004-01-01

    Fission of doubly charged sodium clusters is studied using the open-shell two-center deformed jellium model approximation and it ab initio molecular dynamic approach accounting for all electrons in the system. Results of calculations of fission reactions Na_10^2+ --> Na_7^+ + Na_3^+ and Na_18^2+ ...

  3. Scalable Molecular Dynamics for Large Biomolecular Systems

    Directory of Open Access Journals (Sweden)

    Robert K. Brunner

    2000-01-01

    Full Text Available We present an optimized parallelization scheme for molecular dynamics simulations of large biomolecular systems, implemented in the production-quality molecular dynamics program NAMD. With an object-based hybrid force and spatial decomposition scheme, and an aggressive measurement-based predictive load balancing framework, we have attained speeds and speedups that are much higher than any reported in literature so far. The paper first summarizes the broad methodology we are pursuing, and the basic parallelization scheme we used. It then describes the optimizations that were instrumental in increasing performance, and presents performance results on benchmark simulations.

  4. Molecular Modeling of Solid Fluid Phase Behavior

    Energy Technology Data Exchange (ETDEWEB)

    Peter A. Monson

    2007-12-20

    This report gives a summary of the achievements under DOE contract No. DOE/ER/14150 during the period September 1, 1990 to December 31, 2007. This project was concerned with the molecular modeling of solid-fluid equilibrium. The focus was on understanding how solid-fluid and solid-solid phase behavior are related to molecular structure, and the research program made a seminal contribution in this area. The project led to 34 journal articles, including a comprehensive review article published in Advances in Chemical Physics. The DOE funding supported the work of 5 Ph.D. students, 2 M.S. students and 5 postdoctoral researchers.

  5. Simple model of a coherent molecular photocell

    Science.gov (United States)

    Ernzerhof, Matthias; Bélanger, Marc-André; Mayou, Didier; Nemati Aram, Tahereh

    2016-04-01

    Electron transport in molecular electronic devices is often dominated by a coherent mechanism in which the wave function extends from the left contact over the molecule to the right contact. If the device is exposed to light, photon absorption in the molecule might occur, turning the device into a molecular photocell. The photon absorption promotes an electron to higher energy levels and thus modifies the electron transmission probability through the device. A model for such a molecular photocell is presented that minimizes the complexity of the problem while providing a non-trivial description of the device mechanism. In particular, the role of the molecule in the photocell is investigated. It is described within the Hückel method and the source-sink potential approach [F. Goyer, M. Ernzerhof, and M. Zhuang, J. Chem. Phys. 126, 144104 (2007)] is used to eliminate the contacts in favor of complex-valued potentials. Furthermore, the photons are explicitly incorporated into the model through a second-quantized field. This facilitates the description of the photon absorption process with a stationary state calculation, where eigenvalues and eigenvectors are determined. The model developed is applied to various generic molecular photocells.

  6. Molecular modeling of nucleic Acid structure: electrostatics and solvation.

    Science.gov (United States)

    Bergonzo, Christina; Galindo-Murillo, Rodrigo; Cheatham, Thomas E

    2014-12-19

    This unit presents an overview of computer simulation techniques as applied to nucleic acid systems, ranging from simple in vacuo molecular modeling techniques to more complete all-atom molecular dynamics treatments that include an explicit representation of the environment. The third in a series of four units, this unit focuses on critical issues in solvation and the treatment of electrostatics. UNITS 7.5 & 7.8 introduced the modeling of nucleic acid structure at the molecular level. This included a discussion of how to generate an initial model, how to evaluate the utility or reliability of a given model, and ultimately how to manipulate this model to better understand its structure, dynamics, and interactions. Subject to an appropriate representation of the energy, such as a specifically parameterized empirical force field, the techniques of minimization and Monte Carlo simulation, as well as molecular dynamics (MD) methods, were introduced as a way of sampling conformational space for a better understanding of the relevance of a given model. This discussion highlighted the major limitations with modeling in general. When sampling conformational space effectively, difficult issues are encountered, such as multiple minima or conformational sampling problems, and accurately representing the underlying energy of interaction. In order to provide a realistic model of the underlying energetics for nucleic acids in their native environments, it is crucial to include some representation of solvation (by water) and also to properly treat the electrostatic interactions. These subjects are discussed in detail in this unit.

  7. Establishment and molecular modeling study of maltodextrin-based synergistic enantioseparation systems with two new hydroxy acid chiral ionic liquids as additives in capillary electrophoresis.

    Science.gov (United States)

    Yang, Xuan; Du, Yingxiang; Feng, Zijie; Liu, Zongran; Li, Jingtang

    2017-06-02

    Discovering more superior performance of ionic liquids for the separation science has triggered increasing interest. In this work, two new Hydroxy acid-based chiral ionic liquids (CILs) (tertramethylammonium-d-pantothenate (TMA-d-PAN), tertramethylammonium-d-quinate (TMA-d-QUI)) were designed and first used as additives to establish the maltodextrin-based synergistic systems for enantioseparation in capillary electrophoresis (CE). Compared to traditional single maltodextrin chiral separation system, significantly improved separations of all tested drugs in the CIL/Maltodextrin synergistic systems were obtained. Some parameters (CIL concentration, maltodextrin concentration, buffer pH, and applied voltage) in the TMA-d-PAN/Maltodextrin synergistic system have been examined and optimized for analytes. The molecular docking software AutoDock was applied to simulate the recognition process and surmise feasible resolution mechanism in the Maltodextrin/CILs synergistic systems, which has certain guiding value. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Realistic molecular model of kerogen's nanostructure

    Science.gov (United States)

    Bousige, Colin; Ghimbeu, Camélia Matei; Vix-Guterl, Cathie; Pomerantz, Andrew E.; Suleimenova, Assiya; Vaughan, Gavin; Garbarino, Gaston; Feygenson, Mikhail; Wildgruber, Christoph; Ulm, Franz-Josef; Pellenq, Roland J.-M.; Coasne, Benoit

    2016-05-01

    Despite kerogen's importance as the organic backbone for hydrocarbon production from source rocks such as gas shale, the interplay between kerogen's chemistry, morphology and mechanics remains unexplored. As the environmental impact of shale gas rises, identifying functional relations between its geochemical, transport, elastic and fracture properties from realistic molecular models of kerogens becomes all the more important. Here, by using a hybrid experimental-simulation method, we propose a panel of realistic molecular models of mature and immature kerogens that provide a detailed picture of kerogen's nanostructure without considering the presence of clays and other minerals in shales. We probe the models' strengths and limitations, and show that they predict essential features amenable to experimental validation, including pore distribution, vibrational density of states and stiffness. We also show that kerogen's maturation, which manifests itself as an increase in the sp2/sp3 hybridization ratio, entails a crossover from plastic-to-brittle rupture mechanisms.

  9. Realistic molecular model of kerogen's nanostructure.

    Science.gov (United States)

    Bousige, Colin; Ghimbeu, Camélia Matei; Vix-Guterl, Cathie; Pomerantz, Andrew E; Suleimenova, Assiya; Vaughan, Gavin; Garbarino, Gaston; Feygenson, Mikhail; Wildgruber, Christoph; Ulm, Franz-Josef; Pellenq, Roland J-M; Coasne, Benoit

    2016-05-01

    Despite kerogen's importance as the organic backbone for hydrocarbon production from source rocks such as gas shale, the interplay between kerogen's chemistry, morphology and mechanics remains unexplored. As the environmental impact of shale gas rises, identifying functional relations between its geochemical, transport, elastic and fracture properties from realistic molecular models of kerogens becomes all the more important. Here, by using a hybrid experimental-simulation method, we propose a panel of realistic molecular models of mature and immature kerogens that provide a detailed picture of kerogen's nanostructure without considering the presence of clays and other minerals in shales. We probe the models' strengths and limitations, and show that they predict essential features amenable to experimental validation, including pore distribution, vibrational density of states and stiffness. We also show that kerogen's maturation, which manifests itself as an increase in the sp(2)/sp(3) hybridization ratio, entails a crossover from plastic-to-brittle rupture mechanisms.

  10. Molecular model of the neural dopamine transporter

    Science.gov (United States)

    Ravna, Aina Westrheim; Sylte, Ingebrigt; Dahl, Svein G.

    2003-05-01

    The dopamine transporter (DAT) regulates the action of dopamine by reuptake of the neurotransmitter into presynaptic neurons, and is the main molecular target of amphetamines and cocaine. DAT and the Na+/H+ antiporter (NhaA) are secondary transporter proteins that carry small molecules across a cell membrane against a concentration gradient, using ion gradients as energy source. A 3-dimensional projection map of the E. coli NhaA has confirmed a topology of 12 membrane spanning domains, and was previously used to construct a 3-dimensional NhaA model with 12 trans-membrane α-helices (TMHs). The NhaA model, and site directed mutagenesis data on DAT, were used to construct a detailed 3-dimensional DAT model using interactive molecular graphics and empiric force field calculations. The model proposes a dopamine transport mechanism involving TMHs 1, 3, 4, 5, 7 and 11. Asp79, Tyr252 and Tyr274 were the primary cocaine binding residues. Binding of cocaine or its analogue, (-)-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT), seemed to lock the transporter in an inactive state, and thus inhibit dopamine transport. The present model may be used to design further experimental studies of the molecular structure and mechanisms of DAT and other secondary transporter proteins.

  11. Markov State Models for Rare Events in Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Marco Sarich

    2013-12-01

    Full Text Available Rare, but important, transition events between long-lived states are a key feature of many molecular systems. In many cases, the computation of rare event statistics by direct molecular dynamics (MD simulations is infeasible, even on the most powerful computers, because of the immensely long simulation timescales needed. Recently, a technique for spatial discretization of the molecular state space designed to help overcome such problems, so-called Markov State Models (MSMs, has attracted a lot of attention. We review the theoretical background and algorithmic realization of MSMs and illustrate their use by some numerical examples. Furthermore, we introduce a novel approach to using MSMs for the efficient solution of optimal control problems that appear in applications where one desires to optimize molecular properties by means of external controls.

  12. Intelligent systems for the molecular biologist

    Energy Technology Data Exchange (ETDEWEB)

    Brutlag, D.L.

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. In this paper, one objective is to identify properties of DNA sequences that determine their function, by computer-aided statistical analysis and to accurately predict its function, given a new sequence. A related problem is to predict protein structure and function from the sequence.

  13. Optical antenna for photofunctional molecular systems.

    Science.gov (United States)

    Ikeda, Katsuyoshi; Uosaki, Kohei

    2012-02-06

    Optical antennas can enhance the efficiency of photon-molecule interactions. To design efficient antenna structures, it is essential to consider physicochemical aspects in addition to electromagnetic considerations. Specifically, chemical interactions between optical antennas and molecules have to be controlled to enhance the overall efficiency. For this purpose, sphere-plane nanostructures are suitable optical antennas for molecular-modified functional electrode systems when a well-defined electrode is utilized as a platform.

  14. Continuous system modeling

    Science.gov (United States)

    Cellier, Francois E.

    1991-01-01

    A comprehensive and systematic introduction is presented for the concepts associated with 'modeling', involving the transition from a physical system down to an abstract description of that system in the form of a set of differential and/or difference equations, and basing its treatment of modeling on the mathematics of dynamical systems. Attention is given to the principles of passive electrical circuit modeling, planar mechanical systems modeling, hierarchical modular modeling of continuous systems, and bond-graph modeling. Also discussed are modeling in equilibrium thermodynamics, population dynamics, and system dynamics, inductive reasoning, artificial neural networks, and automated model synthesis.

  15. A model for processivity of molecular motors

    Institute of Scientific and Technical Information of China (English)

    Xie Ping; Dou Shuo-Xing; Wang Peng-Ye

    2004-01-01

    We propose a two-dimensional model for a complete description of the dynamics of molecular motors, including both the processive movement along track filaments and the dissociation from the filaments. Theoretical results on the distributions of the run length and dwell time at a given adenosine triphosphate (ATP) concentration, the dependences of mean run length, mean dwell time and mean velocity on ATP concentration and load are in good agreement with the previous experimental results.

  16. Molecular dynamics modelling of solidification in metals

    Energy Technology Data Exchange (ETDEWEB)

    Boercker, D.B.; Belak, J.; Glosli, J. [Lawrence Livermore National Lab., CA (United States)

    1997-12-31

    Molecular dynamics modeling is used to study the solidification of metals at high pressure and temperature. Constant pressure MD is applied to a simulation cell initially filled with both solid and molten metal. The solid/liquid interface is tracked as a function of time, and the data are used to estimate growth rates of crystallites at high pressure and temperature in Ta and Mg.

  17. Molecular recognition effects in atomistic models of imprinted polymers.

    Science.gov (United States)

    Dourado, Eduardo M A; Herdes, Carmelo; van Tassel, Paul R; Sarkisov, Lev

    2011-01-01

    In this article we present a model for molecularly imprinted polymers, which considers both complexation processes in the pre-polymerization mixture and adsorption in the imprinted structures within a single consistent framework. As a case study we investigate MAA/EGDMA polymers imprinted with pyrazine and pyrimidine. A polymer imprinted with pyrazine shows substantial selectivity towards pyrazine over pyrimidine, thus exhibiting molecular recognition, whereas the pyrimidine imprinted structure shows no preferential adsorption of the template. Binding sites responsible for the molecular recognition of pyrazine involve one MAA molecule and one EGDMA molecule, forming associations with the two functional groups of the pyrazine molecule. Presence of these specific sites in the pyrazine imprinted system and lack of the analogous sites in the pyrimidine imprinted system is directly linked to the complexation processes in the pre-polymerization solution. These processes are quite different for pyrazine and pyrimidine as a result of both enthalpic and entropic effects.

  18. Molecular Recognition Effects in Atomistic Models of Imprinted Polymers

    Directory of Open Access Journals (Sweden)

    Carmelo Herdes

    2011-07-01

    Full Text Available In this article we present a model for molecularly imprinted polymers, which considers both complexation processes in the pre-polymerization mixture and adsorption in the imprinted structures within a single consistent framework. As a case study we investigate MAA/EGDMA polymers imprinted with pyrazine and pyrimidine. A polymer imprinted with pyrazine shows substantial selectivity towards pyrazine over pyrimidine, thus exhibiting molecular recognition, whereas the pyrimidine imprinted structure shows no preferential adsorption of the template. Binding sites responsible for the molecular recognition of pyrazine involve one MAA molecule and one EGDMA molecule, forming associations with the two functional groups of the pyrazine molecule. Presence of these specific sites in the pyrazine imprinted system and lack of the analogous sites in the pyrimidine imprinted system is directly linked to the complexation processes in the pre-polymerization solution. These processes are quite different for pyrazine and pyrimidine as a result of both enthalpic and entropic effects.

  19. Molecular Code Division Multiple Access: Gaussian Mixture Modeling

    Science.gov (United States)

    Zamiri-Jafarian, Yeganeh

    Communications between nano-devices is an emerging research field in nanotechnology. Molecular Communication (MC), which is a bio-inspired paradigm, is a promising technique for communication in nano-network. In MC, molecules are administered to exchange information among nano-devices. Due to the nature of molecular signals, traditional communication methods can't be directly applied to the MC framework. The objective of this thesis is to present novel diffusion-based MC methods when multi nano-devices communicate with each other in the same environment. A new channel model and detection technique, along with a molecular-based access method, are proposed in here for communication between asynchronous users. In this work, the received molecular signal is modeled as a Gaussian mixture distribution when the MC system undergoes Brownian noise and inter-symbol interference (ISI). This novel approach demonstrates a suitable modeling for diffusion-based MC system. Using the proposed Gaussian mixture model, a simple receiver is designed by minimizing the error probability. To determine an optimum detection threshold, an iterative algorithm is derived which minimizes a linear approximation of the error probability function. Also, a memory-based receiver is proposed to improve the performance of the MC system by considering previously detected symbols in obtaining the threshold value. Numerical evaluations reveal that theoretical analysis of the bit error rate (BER) performance based on the Gaussian mixture model match simulation results very closely. Furthermore, in this thesis, molecular code division multiple access (MCDMA) is proposed to overcome the inter-user interference (IUI) caused by asynchronous users communicating in a shared propagation environment. Based on the selected molecular codes, a chip detection scheme with an adaptable threshold value is developed for the MCDMA system when the proposed Gaussian mixture model is considered. Results indicate that the

  20. Molecular model with quantum mechanical bonding information.

    Science.gov (United States)

    Bohórquez, Hugo J; Boyd, Russell J; Matta, Chérif F

    2011-11-17

    The molecular structure can be defined quantum mechanically thanks to the theory of atoms in molecules. Here, we report a new molecular model that reflects quantum mechanical properties of the chemical bonds. This graphical representation of molecules is based on the topology of the electron density at the critical points. The eigenvalues of the Hessian are used for depicting the critical points three-dimensionally. The bond path linking two atoms has a thickness that is proportional to the electron density at the bond critical point. The nuclei are represented according to the experimentally determined atomic radii. The resulting molecular structures are similar to the traditional ball and stick ones, with the difference that in this model each object included in the plot provides topological information about the atoms and bonding interactions. As a result, the character and intensity of any given interatomic interaction can be identified by visual inspection, including the noncovalent ones. Because similar bonding interactions have similar plots, this tool permits the visualization of chemical bond transferability, revealing the presence of functional groups in large molecules.

  1. Low-molecular-weight metabolite systems chemistry

    Directory of Open Access Journals (Sweden)

    Franz eHadacek

    2015-03-01

    Full Text Available Low-molecular-weight metabolites (LMWMs comprise primary or central and a plethora of intermediary or secondary metabolites, all of which are characterized by a molecular weight below 900 Dalton. The latter are especially prominent in sessile higher organisms, such as plants, corals, sponges and fungi, but are produced by all types of microbial organisms too. Common to all of these carbon molecules are oxygen, nitrogen and, to a lesser extent, sulfur, as heteroatoms. The latter can contribute as electron donators or acceptors to cellular redox chemistry and define the potential of the molecule to enter charge-transfer complexes. Furthermore, they allow LMWMs to serve as organic ligands in coordination complexes of various inorganic metals as central atoms. Especially the transition metals Fe, Cu and Mn can catalyze one electron reduction of molecular oxygen, which results in formation of free radical species and reactive follow-up reaction products. As antioxidants LMWMs can scavenge free radicals. Depending on the chemical environment, the same LMWMs can act as pro-oxidants by reducing molecular oxygen. The cellular regulation of redox homeostasis, a balance between oxidation and reduction, is still far from being understood. Charge-transfer and coordination complex formation with metals shapes LMWMs into gel-like matrices in the cytosol. The quasi-polymer structure is lost usually during the isolation procedure. In the gel state, LMWMs possess semiconductor properties. Also proteins and membranes are semiconductors. Together they can represent biotransistor components that can be part of a chemoelectrical signaling system that coordinates systems chemistry by initiating cell differentiation or tissue homeostasis, the activated and the resting cell state, when it is required. This concept is not new and dates back to Albert Szent-Györgyi.

  2. A Series of Molecular Dynamics and Homology Modeling Computer Labs for an Undergraduate Molecular Modeling Course

    Science.gov (United States)

    Elmore, Donald E.; Guayasamin, Ryann C.; Kieffer, Madeleine E.

    2010-01-01

    As computational modeling plays an increasingly central role in biochemical research, it is important to provide students with exposure to common modeling methods in their undergraduate curriculum. This article describes a series of computer labs designed to introduce undergraduate students to energy minimization, molecular dynamics simulations,…

  3. A Series of Molecular Dynamics and Homology Modeling Computer Labs for an Undergraduate Molecular Modeling Course

    Science.gov (United States)

    Elmore, Donald E.; Guayasamin, Ryann C.; Kieffer, Madeleine E.

    2010-01-01

    As computational modeling plays an increasingly central role in biochemical research, it is important to provide students with exposure to common modeling methods in their undergraduate curriculum. This article describes a series of computer labs designed to introduce undergraduate students to energy minimization, molecular dynamics simulations,…

  4. Molecular Modeling of the Chain Structures of Polybenzoxazines

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The structures and properties of benzoxazines were investigated by virtue of molecular modeling at a molecular level. By means of Cerius software(version 4.0) supplied by Molecular Simulations Inc., the molecular mechanics and the molecular dynamics were performed under a PCFF force field. Five kinds of the polymeric chains of benzoxazines were created by using polymer builder and energy minimization. The relaxation process was conducted with both energy minimization and molecular dynamics.

  5. Molecular and Crystal Magnetic Engineering of Polymetallic Coupling System: From Magnetic Molecules to Molecular Magnets

    Institute of Scientific and Technical Information of China (English)

    程鹏; 廖代正

    2001-01-01

    One of the main challenges in the field of molecular materials is the design of molecular ferromagnets. General design strategy includes two steps, that is molecular magnetic engineering and crystal magnetic engineering. The first step is the synthesis of ferromagnetically coupled polymetallic systems.Tne second step is the assembly of polymetallic systems with muti-dimensional structure and exhibiting a ferromagnetic transition.This paper summarized the strategies of molecular design and crystal engineering allowed to obtain such systems and our efforts in the fields of molecular magnetism and molecular-based magnets.

  6. Advances in molecular genetic systems in malaria.

    Science.gov (United States)

    de Koning-Ward, Tania F; Gilson, Paul R; Crabb, Brendan S

    2015-06-01

    Robust tools for analysing gene function in Plasmodium parasites, which are the causative agents of malaria, are being developed at an accelerating rate. Two decades after genetic technologies for use in Plasmodium spp. were first described, a range of genetic tools are now available. These include conditional systems that can regulate gene expression at the genome, transcriptional or protein level, as well as more sophisticated tools for gene editing that use piggyBac transposases, integrases, zinc-finger nucleases or the CRISPR-Cas9 system. In this Review, we discuss the molecular genetic systems that are currently available for use in Plasmodium falciparum and Plasmodium berghei, and evaluate the advantages and limitations of these tools. We examine the insights that have been gained into the function of genes that are important during the blood stages of the parasites, which may help to guide the development and improvement of drug therapies and vaccines.

  7. Molecular ecology of anaerobic reactor systems

    DEFF Research Database (Denmark)

    Hofman-Bang, H. Jacob Peider; Zheng, D.; Westermann, Peter

    2003-01-01

    Anaerobic reactor systems are essential for the treatment of solid and liquid wastes and constitute a core facility in many waste treatment plants. Although much is known about the basic metabolism in different types of anaerobic reactors, little is known about the microbes responsible for these ...... specific nucleic acid probes are discussed and exemplified by studies of anaerobic granular sludge, biofilm and digester systems......Anaerobic reactor systems are essential for the treatment of solid and liquid wastes and constitute a core facility in many waste treatment plants. Although much is known about the basic metabolism in different types of anaerobic reactors, little is known about the microbes responsible...... and malfunctions of anaerobic digesters occasionally experienced, leading to sub-optimal methane production and wastewater treatment. Using a variety of molecular techniques, we are able to determine which microorganisms are active, where they are active, and when they are active, but we still need to determine...

  8. New hybrid method for reactive systems from integrating molecular orbital or molecular mechanics methods with analytical potential energy surfaces.

    Science.gov (United States)

    Espinosa-Garciá, Joaquín; Rangel, Cipriano; Navarrete, Marta; Corchado, José C

    2004-09-15

    A computational approach to calculating potential energy surfaces for reactive systems is presented and tested. This hybrid approach is based on integrated methods where calculations for a small model system are performed by using analytical potential energy surfaces, and for the real system by using molecular orbital or molecular mechanics methods. The method is tested on a hydrogen abstraction reaction by using the variational transition-state theory with multidimensional tunneling corrections. The agreement between the calculated and experimental information depends on the quality of the method chosen for the real system. When the real system is treated by accurate quantum mechanics methods, the rate constants are in excellent agreement with the experimental measurements over a wide temperature range. When the real system is treated by molecular mechanics methods, the results are still good, which is very encouraging since molecular mechanics itself is not at all capable of describing this reactive system. Since no experimental information or additional fits are required to apply this method, it can be used to improve the accuracy of molecular orbital methods or to extend the molecular mechanics method to treat any reactive system with the single constraint of the availability of an analytical potential energy surface that describes the model system.

  9. Microelectromechanical systems integrating molecular spin crossover actuators

    Science.gov (United States)

    Manrique-Juarez, Maria D.; Rat, Sylvain; Mathieu, Fabrice; Saya, Daisuke; Séguy, Isabelle; Leïchlé, Thierry; Nicu, Liviu; Salmon, Lionel; Molnár, Gábor; Bousseksou, Azzedine

    2016-08-01

    Silicon MEMS cantilevers coated with a 200 nm thin layer of the molecular spin crossover complex [Fe(H2B(pz)2)2(phen)] (H2B(pz)2 = dihydrobis(pyrazolyl)borate and phen = 1,10-phenantroline) were actuated using an external magnetic field and their resonance frequency was tracked by means of integrated piezoresistive detection. The light-induced spin-state switching of the molecules from the ground low spin to the metastable high spin state at 10 K led to a well-reproducible shift of the cantilever's resonance frequency (Δfr = -0.52 Hz). Control experiments at different temperatures using coated as well as uncoated devices along with simple calculations support the assignment of this effect to the spin transition. This latter translates into changes in mechanical behavior of the cantilever due to the strong spin-state/lattice coupling. A guideline for the optimization of device parameters is proposed so as to efficiently harness molecular scale movements for large-scale mechanical work, thus paving the road for nanoelectromechanical systems (NEMS) actuators based on molecular materials.

  10. Modeling of nanotoxicity molecular interactions of nanomaterials with bionanomachines

    CERN Document Server

    Zhou, Ruhong

    2015-01-01

    This book provides a comprehensive overview of the fundamentals of nanotoxicity modeling and its implications for the development of novel nanomedicines. It lays out the fundamentals of nanotoxicity modeling for an array of nanomaterial systems, ranging from carbon-based nanoparticles to noble metals, metal oxides, and quantum dots. The author illustrates how molecular (classical mechanics) and atomic (quantum mechanics) modeling approaches can be applied to bolster our understanding of many important aspects of this critical nanotoxicity issue. Each chapter is organized by types of nanomaterials for practicality, making this an ideal book for senior undergraduate students, graduate students, and researchers in nanotechnology, chemistry, physics, molecular biology, and computer science. It is also of interest to academic and industry professionals who work on nanodrug delivery and related biomedical applications, and aids readers in their biocompatibility assessment efforts in the coming age of nanotechnology...

  11. Systems Pharmacology in Small Molecular Drug Discovery.

    Science.gov (United States)

    Zhou, Wei; Wang, Yonghua; Lu, Aiping; Zhang, Ge

    2016-02-18

    Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity), target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

  12. Systems Pharmacology in Small Molecular Drug Discovery

    Science.gov (United States)

    Zhou, Wei; Wang, Yonghua; Lu, Aiping; Zhang, Ge

    2016-01-01

    Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity), target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level. PMID:26901192

  13. Systems Pharmacology in Small Molecular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    2016-02-01

    Full Text Available Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity, target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

  14. Molecular hydrogen absorption systems in SDSS

    CERN Document Server

    Balashev, S A; Ivanchik, A V; Varshalovich, D A; Petitjean, P; Noterdaeme, P

    2014-01-01

    We present a systematic search for molecular hydrogen absorption systems at high redshift in quasar spectra from the Sloan Digital Sky Survey (SDSS) II Data Release 7 and SDSS-III Data Release 9. We have selected candidates using a modified profile fitting technique taking into account that the Ly$\\alpha$ forest can effectively mimic H$_2$ absorption systems at the resolution of SDSS data. To estimate the confidence level of the detections, we use two methods: a Monte-Carlo sampling and an analysis of control samples. The analysis of control samples allows us to define regions of the spectral quality parameter space where H$_2$ absorption systems can be confidently identified. We find that H$_2$ absorption systems with column densities $\\log {\\rm N_{H_2}} > 19$ can be detected in only less than 3% of SDSS quasar spectra. We estimate the upper limit on the detection rate of saturated H$_2$ absorption systems ($\\log {\\rm N_{H_2}} > 19$) in Damped Ly-$\\alpha$ (DLA) systems to be about 7%. We provide a sample of ...

  15. Molecular Imaging with Activatable Reporter Systems

    Directory of Open Access Journals (Sweden)

    Gang Niu, Xiaoyuan Chen

    2012-01-01

    Full Text Available Molecular imaging is a newly emerged multiple disciplinary field that aims to visualize, characterize and quantitatively measure biological processes at cellular and molecular levels in humans and other living systems. A reporter gene is a piece of DNA encoding reporter protein, which presents as a readily measurable phenotype that can be distinguished easily from the background of endogenous protein. After being transferred into cells of organ systems (transgenes, the reporter gene can be utilized to visualize transcriptional and posttranscriptional regulation of gene expression, protein-protein interactions, or trafficking of proteins or cells in living subjects. Herein, we review previous classification of reporter genes and regroup the reporter gene based imaging as basic, inducible and activatable, based on the regulation of reporter gene transcription and post-translational modification of reporter proteins. We then focus on activatable reporters, in which the signal can be activated at the posttranslational level for visualizing protein-protein interactions, protein phosphorylation or tertiary structure changes. The applications of several types of activatable reporters will also be summarized. We conclude that activatable reporter imaging can benefit both basic biomedical research and drug development.

  16. Modeling ion sensing in molecular electronics

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Caroline J.; Smeu, Manuel, E-mail: manuel.smeu@northwestern.edu; Ratner, Mark A., E-mail: ratner@northwestern.edu [Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208 (United States)

    2014-02-07

    We examine the ability of molecules to sense ions by measuring the change in molecular conductance in the presence of such charged species. The detection of protons (H{sup +}), alkali metal cations (M{sup +}), calcium ions (Ca{sup 2+}), and hydronium ions (H{sub 3}O{sup +}) is considered. Density functional theory (DFT) is used within the Keldysh non-equilibrium Green's function framework (NEGF) to model electron transport properties of quinolinedithiol (QDT, C{sub 9}H{sub 7}NS{sub 2}), bridging Al electrodes. The geometry of the transport region is relaxed with DFT. The transport properties of the device are modeled with NEGF-DFT to determine if this device can distinguish among the M{sup +} + QDT species containing monovalent cations, where M{sup +} = H{sup +}, Li{sup +}, Na{sup +}, or K{sup +}. Because of the asymmetry of QDT in between the two electrodes, both positive and negative biases are considered. The electron transmission function and conductance properties are simulated for electrode biases in the range from −0.5 V to 0.5 V at increments of 0.1 V. Scattering state analysis is used to determine the molecular orbitals that are the main contributors to the peaks in the transmission function near the Fermi level of the electrodes, and current-voltage relationships are obtained. The results show that QDT can be used as a proton detector by measuring transport through it and can conceivably act as a pH sensor in solutions. In addition, QDT may be able to distinguish among different monovalent species. This work suggests an approach to design modern molecular electronic conductance sensors with high sensitivity and specificity using well-established quantum chemistry.

  17. MODELING THE MOLECULAR COMPOSITION IN AN ACTIVE GALACTIC NUCLEUS DISK

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Nanase [Max Planck Institute for Radio Astronomy, D-53121 Bonn (Germany); Thompson, Todd A. [Department of Astronomy, Ohio State University, Columbus, OH 43210 (United States); Herbst, Eric [Departments of Chemistry, Astronomy, and Physics, University of Virginia, Charlottesville, VA 22904 (United States)

    2013-03-10

    We use a high-temperature chemical network to derive the molecular abundances in axisymmetric accretion disk models around active galactic nuclei (AGNs) within 100 pc using simple radial and vertical density and temperature distributions motivated by more detailed physical models. We explore the effects of X-ray irradiation and cosmic-ray ionization on the spatial distribution of the molecular abundances of CO, CN, CS, HCN, HCO{sup +}, HC{sub 3}N, C{sub 2}H, and c-C{sub 3}H{sub 2} using a variety of plausible disk structures. These simple models have molecular regions with an X-ray-dominated region layer, a midplane without the strong influence of X-rays, and a high-temperature region in the inner portion with moderate X-ray flux where families of polyynes (C{sub n}H{sub 2}) and cyanopolyynes can be enhanced. For the high midplane density disks we explore, we find that cosmic rays produced by supernovae do not significantly affect the regions unless the star formation efficiency significantly exceeds that of the Milky Way. We highlight molecular abundance observations and ratios that may distinguish among theoretical models of the density distribution in AGN disks. Finally, we assess the importance of the shock crossing time and the accretion time relative to the formation time for various chemical species. Vertical column densities are tabulated for a number of molecular species at both the characteristic shock crossing time and steady state. Although we do not attempt to fit any particular system or set of observations, we discuss our models and results in the context of the nearby AGN NGC 1068.

  18. Molecular interaction of PCB153 to human serum albumin: Insights from spectroscopic and molecular modeling studies

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chao; Fang, Senbiao; Cao, Huiming; Lu, Yan; Ma, Yaqiong [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Wei, Dongfeng [Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700 (China); Xie, Xiaoyun [College of Earth and Environmental Science, Lanzhou University, Lanzhou 730000 (China); Liu, Xiaohua [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Li, Xin [College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471003 (China); Fei, Dongqing [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Zhao, Chunyan, E-mail: zhaochy07@lzu.edu.cn [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China)

    2013-03-15

    Highlights: ► We identify the binding mode of PCB153 to human serum albumin (HSA). ► Spectroscopic and molecular modeling results reveal that PCB153 binds at the site II. ► The interaction is mainly governed by hydrophobic and hydrogen bond forces. ► The work helps to probe transporting, distribution and toxicity effect of PCBs. -- Abstract: Polychlorinated biphenyls (PCBs) possessed much potential hazard to environment because of its chemical stability and biological toxicity. Here, we identified the binding mode of a representative compound, PCB153, to human serum albumin (HSA) using fluorescence and molecular dynamics simulation methods. The fluorescence study showed that the intrinsic fluorescence of HSA was quenched by addition of PCB153 through a static quenching mechanism. The thermodynamic analysis proved the binding behavior was mainly governed by hydrophobic force. Furthermore, as evidenced by site marker displacement experiments using two probe compounds, it revealed that PCB153 acted exactly on subdomain IIIA (site II) of HSA. On the other hand, the molecular dynamics studies as well as free energy calculations made another important contribution to understand the conformational changes of HSA and the stability of HSA-PCB153 system. Molecular docking revealed PCB153 can bind in a large hydrophobic activity of subdomain IIIA by the hydrophobic interaction and hydrogen bond interactions between chlorine atoms and residue ASN391. The present work provided reasonable models helping us further understand the transporting, distribution and toxicity effect of PCBs when it spread into human blood serum.

  19. High-order-harmonic generation in atomic and molecular systems

    Science.gov (United States)

    Suárez, Noslen; Chacón, Alexis; Pérez-Hernández, Jose A.; Biegert, Jens; Lewenstein, Maciej; Ciappina, Marcelo F.

    2017-03-01

    High-order-harmonic generation (HHG) results from the interaction of ultrashort laser pulses with matter. It configures an invaluable tool to produce attosecond pulses, moreover, to extract electron structural and dynamical information of the target, i.e., atoms, molecules, and solids. In this contribution, we introduce an analytical description of atomic and molecular HHG, that extends the well-established theoretical strong-field approximation (SFA). Our approach involves two innovative aspects: (i) First, the bound-continuum and rescattering matrix elements can be analytically computed for both atomic and multicenter molecular systems, using a nonlocal short range model, but separable, potential. When compared with the standard models, these analytical derivations make possible to directly examine how the HHG spectra depend on the driven media and laser-pulse features. Furthermore, we can turn on and off contributions having distinct physical origins or corresponding to different mechanisms. This allows us to quantify their importance in the various regions of the HHG spectra. (ii) Second, as reported recently [N. Suárez et al., Phys. Rev. A 94, 043423 (2016), 10.1103/PhysRevA.94.043423], the multicenter matrix elements in our theory are free from nonphysical gauge- and coordinate-system-dependent terms; this is accomplished by adapting the coordinate system to the center from which the corresponding time-dependent wave function originates. Our SFA results are contrasted, when possible, with the direct numerical integration of the time-dependent Schrödinger equation in reduced and full dimensionality. Very good agreement is found for single and multielectronic atomic systems, modeled under the single active electron approximation, and for simple diatomic molecular systems. Interference features, ubiquitously present in every strong-field phenomenon involving a multicenter target, are also captured by our model.

  20. Towards synthetic molecular motors: a model elastic-network study

    Science.gov (United States)

    Sarkar, Amartya; Flechsig, Holger; Mikhailov, Alexander S.

    2016-04-01

    Protein molecular motors play a fundamental role in biological cells and development of their synthetic counterparts is a major challenge. Here, we show how a model motor system with the operation mechanism resembling that of muscle myosin can be designed at the concept level, without addressing the implementation aspects. The model is constructed as an elastic network, similar to the coarse-grained descriptions used for real proteins. We show by numerical simulations that the designed synthetic motor can operate as a deterministic or Brownian ratchet and that there is a continuous transition between such two regimes. The motor operation under external load, approaching the stall condition, is also analysed.

  1. Computational molecular basis for improved silica surface complexation models

    Energy Technology Data Exchange (ETDEWEB)

    Sahai, Nita; Rosso, Kevin M.

    2006-06-06

    The acidity and reactivity of surface sites on amorphous and crystalline polymorphs of silica and other oxides control their thermodynamic stability and kinetic reactivity towards reactants in surface-controlled processes of environmental, industrial, biomedical and technological relevance. Recent advances in computational methodologies such as CPMD and increasing computer power combined with spectroscopic measurements are now making it possible to link, with an impressive degree of accuracy, the molecular-level description of these processes to phenomenological, surface complexation models The future challenge now lies in linking mesoscale properties at the nanometer scale to phenomenological models that will afford a more intuitive understanding of the systems under consideration.

  2. Thermodynamic Models from Fluctuation Solution Theory Analysis of Molecular Simulations

    DEFF Research Database (Denmark)

    Christensen, Steen; Peters, Günther H.j.; Hansen, Flemming Yssing

    2007-01-01

    Fluctuation solution theory (FST) is employed to analyze results of molecular dynamics (MD) simulations of liquid mixtures. The objective is to generate parameters for macroscopic GE-models, here the modified Margules model. We present a strategy for choosing the number of parameters included......, Mol. Simul. 33 (4–5) (2007) 449–457.]. The new one has advantages for systems with data points at dilute conditions. Prediction of bubble point pressures using parameters from the two objective functions are compared with experimental data for the binary mixtures methyl acetate–n-pentane and methyl...

  3. Molecular Thermodynamic Modeling of Fluctuation Solution Theory Properties

    DEFF Research Database (Denmark)

    O’Connell, John P.; Abildskov, Jens

    2013-01-01

    Fluctuation Solution Theory provides relationships between integrals of the molecular pair total and direct correlation functions and the pressure derivative of solution density, partial molar volumes, and composition derivatives of activity coefficients. For dense fluids, the integrals follow...... for densities and gas solubilities, including ionic liquids and complex mixtures such as coal liquids. The approach is especially useful in systems with strong nonidealities. This chapter describes successful application of such modeling to a wide variety of systems treated over several decades and suggests how...

  4. Low Molecular Weight Glucosamine/L-lactide Copolymers as Potential Carriers for the Development of a Sustained Rifampicin Release System: Mycobacterium Smegmatis as a Tuberculosis Model

    Science.gov (United States)

    Ragusa, Jorge Alejandro

    Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged release (>14 days) of RIF from these particles is demonstrated. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism, and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) (reference material) particles did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated an increment in cell death as particle dose increased, but was not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. GluN-LLA particles led to higher uptakes than the PLA particles. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and the particles showed a favorable long term drug release effect in killing intracellular bacteria compared to free RIF. The studies presented and discussed in this dissertation

  5. Molecular Models of Genetic and Organismic Structures

    CERN Document Server

    Baianu, I C

    2004-01-01

    In recent studies we showed that the earlier relational theories of organismic sets (Rashevsky,1967), Metabolic-Replication (M,R)-systems (Rosen,1958)and molecular sets (Bartholomay,1968) share a joint foundation that can be studied within a unified categorical framework of functional organismic structures (Baianu,1980. This is possible because all relational theories have a biomolecular basis, that is, complex structures such as genomes, cells,organs and biological organisms are mathematically represented in terms of biomolecular properties and entities,(that are often implicit in their representation axioms. The definition of organismic sets, for example, requires that certain essential quantities be determined from experiment: these are specified by special sets of values of general observables that are derived from physicochemical measurements(Baianu,1970; Baianu,1980; Baianu et al, 2004a.)Such observables are context-dependent and lead directly to natural transformations in categories and Topoi, that are...

  6. Modelling the Molecular Gas in NGC 6240

    CERN Document Server

    Tunnard, R; Garcia-Burillo, S; Carpio, J Graciá; Fuente, A; Tacconi, L; Neri, R; Usero, A

    2015-01-01

    We present the first observations of H$^{13}$CN$(1-0)$, H$^{13}$CO$^+(1-0)$ and SiO$(2-1)$ in NGC 6240, obtained with the IRAM PdBI. Combining a Markov Chain Monte Carlo (MCMC) code with Large Velocity Gradient (LVG) modelling we derive posterior probability density functions (pdfs) for the dense gas parameters, including mass$-$luminosity conversion factors, finding a large amount of dense molecular gas $(\\sim10^{10}M_\\odot)$ in cold, dense clouds ($T_k\\sim10$ K, $n_{{\\rm H}_2}\\sim10^6$ cm$^{-3}$) with a small volume filling factor $(<0.002)$. Including literature CO data we present simultaneously fitted multi-species, two phase models which spontaneously separate into a hot, diffuse phase ($\\log_{10}\\left(T_k / [{\\rm K}]\\right) = 3.2^{3.3}_{3.1}$, $\\log_{10}\\left(n_{{\\rm H}_2} / [{\\rm cm}^{-3}]\\right)=3.6^{3.8}_{3.5}$) and a cold, dense phase ($\\log_{10}\\left(T_k / [{\\rm K}]\\right) = 0.9^{0.9}_{0.8}$, $\\log_{10}\\left(n_{{\\rm H}_2} / [{\\rm cm}^{-3}]\\right)=6.6^{6.8}_{6.3}$). A restricted three phase model...

  7. Mechanistic modeling confronts the complexity of molecular cell biology.

    Science.gov (United States)

    Phair, Robert D

    2014-11-05

    Mechanistic modeling has the potential to transform how cell biologists contend with the inescapable complexity of modern biology. I am a physiologist-electrical engineer-systems biologist who has been working at the level of cell biology for the past 24 years. This perspective aims 1) to convey why we build models, 2) to enumerate the major approaches to modeling and their philosophical differences, 3) to address some recurrent concerns raised by experimentalists, and then 4) to imagine a future in which teams of experimentalists and modelers build-and subject to exhaustive experimental tests-models covering the entire spectrum from molecular cell biology to human pathophysiology. There is, in my view, no technical obstacle to this future, but it will require some plasticity in the biological research mind-set.

  8. Influence of Random Potentials on the Current of the Molecular Motor Model

    Institute of Scientific and Technical Information of China (English)

    贾亚; 李家荣

    2001-01-01

    The current of the molecular motor model disturbed by random potentials, which involve the dichotomous and Ornstein-Uhlenbeck potentials, is studied using a finite-space correlation function. It is found that: (i) the amplitude and the correlation length of random potentials play opposing roles in the transport of the molecular motor model; (ii) a random potential with small amplitude and large correlation length is very useful in the molecular motor system.

  9. Modelling Railway Interlocking Systems

    DEFF Research Database (Denmark)

    Lindegaard, Morten Peter; Viuf, P.; Haxthausen, Anne Elisabeth

    2000-01-01

    In this report we present a model of interlocking systems, and describe how the model may be validated by simulation. Station topologies are modelled by graphs in which the nodes denote track segments, and the edges denote connectivity for train traÆc. Points and signals are modelled by annotatio...

  10. A 3D visualization system for molecular structures

    Science.gov (United States)

    Green, Terry J.

    1989-01-01

    The properties of molecules derive in part from their structures. Because of the importance of understanding molecular structures various methodologies, ranging from first principles to empirical technique, were developed for computing the structure of molecules. For large molecules such as polymer model compounds, the structural information is difficult to comprehend by examining tabulated data. Therefore, a molecular graphics display system, called MOLDS, was developed to help interpret the data. MOLDS is a menu-driven program developed to run on the LADC SNS computer systems. This program can read a data file generated by the modeling programs or data can be entered using the keyboard. MOLDS has the following capabilities: draws the 3-D representation of a molecule using stick, ball and ball, or space filled model from Cartesian coordinates, draws different perspective views of the molecule; rotates the molecule on the X, Y, Z axis or about some arbitrary line in space, zooms in on a small area of the molecule in order to obtain a better view of a specific region; and makes hard copy representation of molecules on a graphic printer. In addition, MOLDS can be easily updated and readily adapted to run on most computer systems.

  11. Integrated Multiscale Modeling of Molecular Computing Devices

    Energy Technology Data Exchange (ETDEWEB)

    Weinan E

    2012-03-29

    The main bottleneck in modeling transport in molecular devices is to develop the correct formulation of the problem and efficient algorithms for analyzing the electronic structure and dynamics using, for example, the time-dependent density functional theory. We have divided this task into several steps. The first step is to developing the right mathematical formulation and numerical algorithms for analyzing the electronic structure using density functional theory. The second step is to study time-dependent density functional theory, particularly the far-field boundary conditions. The third step is to study electronic transport in molecular devices. We are now at the end of the first step. Under DOE support, we have made subtantial progress in developing linear scaling and sub-linear scaling algorithms for electronic structure analysis. Although there has been a huge amount of effort in the past on developing linear scaling algorithms, most of the algorithms developed suffer from the lack of robustness and controllable accuracy. We have made the following progress: (1) We have analyzed thoroughly the localization properties of the wave-functions. We have developed a clear understanding of the physical as well as mathematical origin of the decay properties. One important conclusion is that even for metals, one can choose wavefunctions that decay faster than any algebraic power. (2) We have developed algorithms that make use of these localization properties. Our algorithms are based on non-orthogonal formulations of the density functional theory. Our key contribution is to add a localization step into the algorithm. The addition of this localization step makes the algorithm quite robust and much more accurate. Moreover, we can control the accuracy of these algorithms by changing the numerical parameters. (3) We have considerably improved the Fermi operator expansion (FOE) approach. Through pole expansion, we have developed the optimal scaling FOE algorithm.

  12. Integrated Multiscale Modeling of Molecular Computing Devices

    Energy Technology Data Exchange (ETDEWEB)

    Weinan E

    2012-03-29

    The main bottleneck in modeling transport in molecular devices is to develop the correct formulation of the problem and efficient algorithms for analyzing the electronic structure and dynamics using, for example, the time-dependent density functional theory. We have divided this task into several steps. The first step is to developing the right mathematical formulation and numerical algorithms for analyzing the electronic structure using density functional theory. The second step is to study time-dependent density functional theory, particularly the far-field boundary conditions. The third step is to study electronic transport in molecular devices. We are now at the end of the first step. Under DOE support, we have made subtantial progress in developing linear scaling and sub-linear scaling algorithms for electronic structure analysis. Although there has been a huge amount of effort in the past on developing linear scaling algorithms, most of the algorithms developed suffer from the lack of robustness and controllable accuracy. We have made the following progress: (1) We have analyzed thoroughly the localization properties of the wave-functions. We have developed a clear understanding of the physical as well as mathematical origin of the decay properties. One important conclusion is that even for metals, one can choose wavefunctions that decay faster than any algebraic power. (2) We have developed algorithms that make use of these localization properties. Our algorithms are based on non-orthogonal formulations of the density functional theory. Our key contribution is to add a localization step into the algorithm. The addition of this localization step makes the algorithm quite robust and much more accurate. Moreover, we can control the accuracy of these algorithms by changing the numerical parameters. (3) We have considerably improved the Fermi operator expansion (FOE) approach. Through pole expansion, we have developed the optimal scaling FOE algorithm.

  13. Final Report for Integrated Multiscale Modeling of Molecular Computing Devices

    Energy Technology Data Exchange (ETDEWEB)

    Glotzer, Sharon C.

    2013-08-28

    In collaboration with researchers at Vanderbilt University, North Carolina State University, Princeton and Oakridge National Laboratory we developed multiscale modeling and simulation methods capable of modeling the synthesis, assembly, and operation of molecular electronics devices. Our role in this project included the development of coarse-grained molecular and mesoscale models and simulation methods capable of simulating the assembly of millions of organic conducting molecules and other molecular components into nanowires, crossbars, and other organized patterns.

  14. Light scattering from macromolecular systems: Molecular crystals and polymers

    Science.gov (United States)

    Bernstein, E. R.

    1981-11-01

    The research objectives were to: (1) characterize phase transitions theoretically and experimentally in molecular crystal systems; (2) use the above understanding gained by light scattering studies and theoretical interpretation to apply to the more complex system of lyotropic liquid crystals; and (3) then apply knowledge gained on the model systems of increasing complexity to polymer liquid crystals and solid polymers as observed by laser light scattering techniques. Systems experimentally and theoretically discussed are: trioxane, triazine, benzil, and chloranil. Studies of lyotropic liquid crystals (sodium decyl sulfate, sodium sulfate, decanol, water) have progressed. The major findings are: a number of phase transitions occur between 20 and 60 C; these transitions evidence strong critical behavior and long correlation times for fluctuations; and liquid crystals can be studied by light scattering. Spectra of solid powders, ribbons, and liquid crystals of PBT and solid PBO were obtained.

  15. Molecular modeling and multiscaling issues for electronic material applications

    CERN Document Server

    Iwamoto, Nancy; Yuen, Matthew; Fan, Haibo

    Volume 1 : Molecular Modeling and Multiscaling Issues for Electronic Material Applications provides a snapshot on the progression of molecular modeling in the electronics industry and how molecular modeling is currently being used to understand material performance to solve relevant issues in this field. This book is intended to introduce the reader to the evolving role of molecular modeling, especially seen through the eyes of the IEEE community involved in material modeling for electronic applications.  Part I presents  the role that quantum mechanics can play in performance prediction, such as properties dependent upon electronic structure, but also shows examples how molecular models may be used in performance diagnostics, especially when chemistry is part of the performance issue.  Part II gives examples of large-scale atomistic methods in material failure and shows several examples of transitioning between grain boundary simulations (on the atomistic level)and large-scale models including an example ...

  16. Multiscale molecular modeling of tertiary supported lipid bilayers

    Science.gov (United States)

    Ranz, Holden T.; Faller, Roland

    2015-08-01

    Ternary lipid bilayer systems assembled from mixtures of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and cholesterol have been studied using coarse-grained molecular dynamics at biologically relevant temperatures (280 K to 310 K), which are between the chain melting temperatures of the pure lipid component. Free lipid bilayers were simulated using the MARTINI model (Stage I) and a variant with water-water interactions reduced to 76% (Stage II). The latter was subsequently used for preparing supported lipid bilayer simulations (Stage III). Clustering of like lipids was observed, but the simulation timescale did not yield larger phaseseparated domains.

  17. A consistent transported PDF model for treating differential molecular diffusion

    Science.gov (United States)

    Wang, Haifeng; Zhang, Pei

    2016-11-01

    Differential molecular diffusion is a fundamentally significant phenomenon in all multi-component turbulent reacting or non-reacting flows caused by the different rates of molecular diffusion of energy and species concentrations. In the transported probability density function (PDF) method, the differential molecular diffusion can be treated by using a mean drift model developed by McDermott and Pope. This model correctly accounts for the differential molecular diffusion in the scalar mean transport and yields a correct DNS limit of the scalar variance production. The model, however, misses the molecular diffusion term in the scalar variance transport equation, which yields an inconsistent prediction of the scalar variance in the transported PDF method. In this work, a new model is introduced to remedy this problem that can yield a consistent scalar variance prediction. The model formulation along with its numerical implementation is discussed, and the model validation is conducted in a turbulent mixing layer problem.

  18. Molecular communications and nanonetworks from nature to practical systems

    CERN Document Server

    Atakan, Barış

    2014-01-01

    In this book, the concepts of molecular communications and nanonetworks are introduced. Throughout the book, the existing molecular communication paradigms are categorized into two main groups. The first group includes the Passive Molecular Communication (PMC) paradigms in which molecules freely diffuse to transfer information from a transmitter to a receiver. The second group includes the Active Molecular Communication (AMC) paradigms in which molecules are carried or guided by some mediators such as molecular motors, gap junction channels and bacteria. In the book, after briefly discussing why molecular communication is needed for the sophisticated nano and biotechnology applications, the existing molecular communication systems are first presented. Then, the principles of diffusion phenomena and molecular reception with absorbers and the ligand-receptor binding mechanism are introduced. Based on these principles, the communication theories and techniques are given for the PMC. Then, the physical dynamics o...

  19. Selected System Models

    Science.gov (United States)

    Schmidt-Eisenlohr, F.; Puñal, O.; Klagges, K.; Kirsche, M.

    Apart from the general issue of modeling the channel, the PHY and the MAC of wireless networks, there are specific modeling assumptions that are considered for different systems. In this chapter we consider three specific wireless standards and highlight modeling options for them. These are IEEE 802.11 (as example for wireless local area networks), IEEE 802.16 (as example for wireless metropolitan networks) and IEEE 802.15 (as example for body area networks). Each section on these three systems discusses also at the end a set of model implementations that are available today.

  20. Fracture of Carbon Nanotube - Amorphous Carbon Composites: Molecular Modeling

    Science.gov (United States)

    Jensen, Benjamin D.; Wise, Kristopher E.; Odegard, Gregory M.

    2015-01-01

    Carbon nanotubes (CNTs) are promising candidates for use as reinforcements in next generation structural composite materials because of their extremely high specific stiffness and strength. They cannot, however, be viewed as simple replacements for carbon fibers because there are key differences between these materials in areas such as handling, processing, and matrix design. It is impossible to know for certain that CNT composites will represent a significant advance over carbon fiber composites before these various factors have been optimized, which is an extremely costly and time intensive process. This work attempts to place an upper bound on CNT composite mechanical properties by performing molecular dynamics simulations on idealized model systems with a reactive forcefield that permits modeling of both elastic deformations and fracture. Amorphous carbon (AC) was chosen for the matrix material in this work because of its structural simplicity and physical compatibility with the CNT fillers. It is also much stiffer and stronger than typical engineering polymer matrices. Three different arrangements of CNTs in the simulation cell have been investigated: a single-wall nanotube (SWNT) array, a multi-wall nanotube (MWNT) array, and a SWNT bundle system. The SWNT and MWNT array systems are clearly idealizations, but the SWNT bundle system is a step closer to real systems in which individual tubes aggregate into large assemblies. The effect of chemical crosslinking on composite properties is modeled by adding bonds between the CNTs and AC. The balance between weakening the CNTs and improving fiber-matrix load transfer is explored by systematically varying the extent of crosslinking. It is, of course, impossible to capture the full range of deformation and fracture processes that occur in real materials with even the largest atomistic molecular dynamics simulations. With this limitation in mind, the simulation results reported here provide a plausible upper limit on

  1. Commute Maps: Separating Slowly Mixing Molecular Configurations for Kinetic Modeling.

    Science.gov (United States)

    Noé, Frank; Banisch, Ralf; Clementi, Cecilia

    2016-11-08

    Identification of the main reaction coordinates and building of kinetic models of macromolecular systems require a way to measure distances between molecular configurations that can distinguish slowly interconverting states. Here we define the commute distance that can be shown to be closely related to the expected commute time needed to go from one configuration to the other, and back. A practical merit of this quantity is that it can be easily approximated from molecular dynamics data sets when an approximation of the Markov operator eigenfunctions is available, which can be achieved by the variational approach to approximate eigenfunctions of Markov operators, also called variational approach of conformation dynamics (VAC) or the time-lagged independent component analysis (TICA). The VAC or TICA components can be scaled such that a so-called commute map is obtained in which Euclidean distance corresponds to the commute distance, and thus kinetic models such as Markov state models can be computed based on Euclidean operations, such as standard clustering. In addition, the distance metric gives rise to a quantity we call total kinetic content, which is an excellent score to rank input feature sets and kinetic model quality.

  2. Phase computations and phase models for discrete molecular oscillators

    Science.gov (United States)

    2012-01-01

    Background Biochemical oscillators perform crucial functions in cells, e.g., they set up circadian clocks. The dynamical behavior of oscillators is best described and analyzed in terms of the scalar quantity, phase. A rigorous and useful definition for phase is based on the so-called isochrons of oscillators. Phase computation techniques for continuous oscillators that are based on isochrons have been used for characterizing the behavior of various types of oscillators under the influence of perturbations such as noise. Results In this article, we extend the applicability of these phase computation methods to biochemical oscillators as discrete molecular systems, upon the information obtained from a continuous-state approximation of such oscillators. In particular, we describe techniques for computing the instantaneous phase of discrete, molecular oscillators for stochastic simulation algorithm generated sample paths. We comment on the accuracies and derive certain measures for assessing the feasibilities of the proposed phase computation methods. Phase computation experiments on the sample paths of well-known biological oscillators validate our analyses. Conclusions The impact of noise that arises from the discrete and random nature of the mechanisms that make up molecular oscillators can be characterized based on the phase computation techniques proposed in this article. The concept of isochrons is the natural choice upon which the phase notion of oscillators can be founded. The isochron-theoretic phase computation methods that we propose can be applied to discrete molecular oscillators of any dimension, provided that the oscillatory behavior observed in discrete-state does not vanish in a continuous-state approximation. Analysis of the full versatility of phase noise phenomena in molecular oscillators will be possible if a proper phase model theory is developed, without resorting to such approximations. PMID:22687330

  3. Exactly solvable models for multiatomic molecular Bose-Einstein condensates

    Science.gov (United States)

    Santos, G.

    2011-08-01

    I introduce two families of exactly solvable models for multiatomic hetero-nuclear and homo-nuclear molecular Bose-Einstein condensates through the algebraic Bethe ansatz method. The conserved quantities of the respective models are also shown.

  4. Exactly solvable models for multiatomic molecular Bose-Einstein condensates

    Energy Technology Data Exchange (ETDEWEB)

    Santos, G, E-mail: gfilho@if.ufrgs.br, E-mail: gfilho@cbpf.br [Instituto de Fisica da UFRGS, Av. Bento Goncalves, 9500, Agronomia, Porto Alegre, RS (Brazil)

    2011-08-26

    I introduce two families of exactly solvable models for multiatomic hetero-nuclear and homo-nuclear molecular Bose-Einstein condensates through the algebraic Bethe ansatz method. The conserved quantities of the respective models are also shown. (paper)

  5. Molecular modeling of PMR-15 polyimide

    Science.gov (United States)

    Kokkada Ravindranath, Pruthul

    PMR-15 polyimide is a polymer that is used as a matrix in composites. These composites with PMR-15 matrices are called advanced polymer matrix composite that is abundantly used in the aerospace and electronics industries because of its high temperature resistivity. Apart from having high temperature sustainability, PMR-15 composites also display good thermal-oxidative stability, mechanical properties, processability and low costs, which makes it a suitable material for manufacturing aircraft structures. PMR-15 uses the reverse Diels-Alder (RDA) method for crosslinking which provides it with the groundwork for its distinctive thermal stability and a range of 280--300°C use temperature. Regardless of such desirable properties, this material has a number of limitations that compromises its application on a large scale basis. PMR-15 composites has been known to be very vulnerable to micro-cracking at inter and intra-laminar cracking. But the major factor that hinders its demand is PMR-15's carcinogenic constituent, methylene dianilineme (MDA), also a liver toxin. The necessity of providing a safe working environment during its production adds up to the cost of this material. In this study, Molecular Dynamics and Energy Minimization techniques are utilized to simulate a structure of PMR-15 at a given density of 1.324 g/cc and an attempt to recreate the polyimide to reduce the number of experimental testing and hence subdue the health hazards as well as the cost involved in its production. Even though this study does not involve in validating any mechanical properties of the model, it could be used in future for the validation of its properties and further testing for different properties like aging, microcracking, creep etc.

  6. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  7. Dynamical Systems and Control Theory Inspired by Molecular Biology

    Science.gov (United States)

    2014-10-02

    in both bacterial and eukaryotic signaling pathways. A common theme in the systems biology literature is that certain systems whose output variables...AFRL-OSR-VA-TR-2014-0282 DYNAMICAL SYSTEMS AND CONTROL THEORY INSPIRED BY MOLECULAR BIOLOGY Eduardo Sontag RUTGERS THE STATE UNIVERSITY OF NEW JERSEY...Standard Form 298 (Re . 8-98) v Prescribed by ANSI Std. Z39.18 DYNAMICAL SYSTEMS AND CONTROL THEORY INSPIRED BY MOLECULAR BIOLOGY AFOSR FA9550-11-1-0247

  8. Multiscale Cloud System Modeling

    Science.gov (United States)

    Tao, Wei-Kuo; Moncrieff, Mitchell W.

    2009-01-01

    The central theme of this paper is to describe how cloud system resolving models (CRMs) of grid spacing approximately 1 km have been applied to various important problems in atmospheric science across a wide range of spatial and temporal scales and how these applications relate to other modeling approaches. A long-standing problem concerns the representation of organized precipitating convective cloud systems in weather and climate models. Since CRMs resolve the mesoscale to large scales of motion (i.e., 10 km to global) they explicitly address the cloud system problem. By explicitly representing organized convection, CRMs bypass restrictive assumptions associated with convective parameterization such as the scale gap between cumulus and large-scale motion. Dynamical models provide insight into the physical mechanisms involved with scale interaction and convective organization. Multiscale CRMs simulate convective cloud systems in computational domains up to global and have been applied in place of contemporary convective parameterizations in global models. Multiscale CRMs pose a new challenge for model validation, which is met in an integrated approach involving CRMs, operational prediction systems, observational measurements, and dynamical models in a new international project: the Year of Tropical Convection, which has an emphasis on organized tropical convection and its global effects.

  9. Dynamic Systems Modeling

    Directory of Open Access Journals (Sweden)

    Sorin Dan ŞANDOR

    2003-01-01

    Full Text Available System Dynamics was introduced by Jay W. Forrester in the 1960s. Since then the methodology was adopted in many areas of natural or social sciences. This article tries to present briefly how this methodology works, both as Systems Thinking and as Modelling with Vensim computer software.

  10. Ins and outs of systems biology vis-à-vis molecular biology: continuation or clear cut?

    Science.gov (United States)

    De Backer, Philippe; De Waele, Danny; Van Speybroeck, Linda

    2010-03-01

    The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology 'revolutionizes' molecular biology and 'transcends' its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology's use of modelling and bioinformatics, and by its scale enlargement.

  11. Dense Molecular Gas: A Sensitive Probe of Stellar Feedback Models

    CERN Document Server

    Hopkins, Philip F; Murray, Norman; Quataert, Eliot

    2012-01-01

    We show that the mass fraction of GMC gas (n>100 cm^-3) in dense (n>>10^4 cm^-3) star-forming clumps, observable in dense molecular tracers (L_HCN/L_CO(1-0)), is a sensitive probe of the strength and mechanism(s) of stellar feedback. Using high-resolution galaxy-scale simulations with pc-scale resolution and explicit models for feedback from radiation pressure, photoionization heating, stellar winds, and supernovae (SNe), we make predictions for the dense molecular gas tracers as a function of GMC and galaxy properties and the efficiency of stellar feedback. In models with weak/no feedback, much of the mass in GMCs collapses into dense sub-units, predicting L_HCN/L_CO(1-0) ratios order-of-magnitude larger than observed. By contrast, models with feedback properties taken directly from stellar evolution calculations predict dense gas tracers in good agreement with observations. Changing the strength or timing of SNe tends to move systems along, rather than off, the L_HCN-L_CO relation (because SNe heat lower-de...

  12. Multiensemble Markov models of molecular thermodynamics and kinetics.

    Science.gov (United States)

    Wu, Hao; Paul, Fabian; Wehmeyer, Christoph; Noé, Frank

    2016-06-07

    We introduce the general transition-based reweighting analysis method (TRAM), a statistically optimal approach to integrate both unbiased and biased molecular dynamics simulations, such as umbrella sampling or replica exchange. TRAM estimates a multiensemble Markov model (MEMM) with full thermodynamic and kinetic information at all ensembles. The approach combines the benefits of Markov state models-clustering of high-dimensional spaces and modeling of complex many-state systems-with those of the multistate Bennett acceptance ratio of exploiting biased or high-temperature ensembles to accelerate rare-event sampling. TRAM does not depend on any rate model in addition to the widely used Markov state model approximation, but uses only fundamental relations such as detailed balance and binless reweighting of configurations between ensembles. Previous methods, including the multistate Bennett acceptance ratio, discrete TRAM, and Markov state models are special cases and can be derived from the TRAM equations. TRAM is demonstrated by efficiently computing MEMMs in cases where other estimators break down, including the full thermodynamics and rare-event kinetics from high-dimensional simulation data of an all-atom protein-ligand binding model.

  13. Modeling Sustainable Food Systems

    Science.gov (United States)

    Allen, Thomas; Prosperi, Paolo

    2016-05-01

    The processes underlying environmental, economic, and social unsustainability derive in part from the food system. Building sustainable food systems has become a predominating endeavor aiming to redirect our food systems and policies towards better-adjusted goals and improved societal welfare. Food systems are complex social-ecological systems involving multiple interactions between human and natural components. Policy needs to encourage public perception of humanity and nature as interdependent and interacting. The systemic nature of these interdependencies and interactions calls for systems approaches and integrated assessment tools. Identifying and modeling the intrinsic properties of the food system that will ensure its essential outcomes are maintained or enhanced over time and across generations, will help organizations and governmental institutions to track progress towards sustainability, and set policies that encourage positive transformations. This paper proposes a conceptual model that articulates crucial vulnerability and resilience factors to global environmental and socio-economic changes, postulating specific food and nutrition security issues as priority outcomes of food systems. By acknowledging the systemic nature of sustainability, this approach allows consideration of causal factor dynamics. In a stepwise approach, a logical application is schematized for three Mediterranean countries, namely Spain, France, and Italy.

  14. On Atomistic Models for Molecular Oxygen

    DEFF Research Database (Denmark)

    Javanainen, Matti; Vattulainen, Ilpo; Monticelli, Luca

    2017-01-01

    Molecular oxygen (O2) is key to all life on earth, as it is constantly cycled via photosynthesis and cellular respiration. Substantial scientific effort has been devoted to understanding every part of this cycle. Classical molecular dynamics (MD) simulations have been used to study some of the key...... processes involved in cellular respiration: O2 permeation through alveolar monolayers and cellular membranes, its binding to hemoglobin during transport in the bloodstream, as well as its transport along optimal pathways toward its reduction sites in proteins. Moreover, MD simulations can help interpret...

  15. The VSEPR model of molecular geometry

    CERN Document Server

    Gillespie, Ronald J

    2012-01-01

    Valence Shell Electron Pair Repulsion (VSEPR) theory is a simple technique for predicting the geometry of atomic centers in small molecules and molecular ions. This authoritative reference was written by Istvan Hartiggai and the developer of VSEPR theory, Ronald J. Gillespie. In addition to its value as a text for courses in molecular geometry and chemistry, it constitutes a classic reference for professionals.Starting with coverage of the broader aspects of VSEPR, this volume narrows its focus to a succinct survey of the methods of structural determination. Additional topics include the appli

  16. Stochastic modeling of cargo transport by teams of molecular motors

    CERN Document Server

    Klein, Sarah; Santen, Ludger

    2014-01-01

    Many different types of cellular cargos are transported bidirectionally along microtubules by teams of molecular motors. The motion of this cargo-motors system has been experimentally characterized in vivo as processive with rather persistent directionality. Different theoretical approaches have been suggested in order to explore the origin of this kind of motion. An effective theoretical approach, introduced by M\\"uller et al., describes the cargo dynamics as a tug-of-war between different kinds of motors. An alternative approach has been suggested recently by Kunwar et al., who considered the coupling between motor and cargo in more detail. Based on this framework we introduce a model considering single motor positions which we propagate in continuous time. Furthermore, we analyze the possible influence of the discrete time update schemes used in previous publications on the system's dynamic.

  17. Fluctuation theorem for the flashing ratchet model of molecular motors

    Science.gov (United States)

    Lacoste, D.; Mallick, K.

    2009-08-01

    Molecular motors convert chemical energy derived from the hydrolysis of adenosine triphosphate (ATP) into mechanical energy. A well-studied model of a molecular motor is the flashing ratchet model. We show that this model exhibits a fluctuation relation known as the Gallavotti-Cohen symmetry. Our study highlights the fact that the symmetry is present only if the chemical and mechanical degrees of freedom are both included in the description.

  18. Molecular dynamics modeling of structural battery components

    NARCIS (Netherlands)

    Verners, O.; Van Duin, A.C.T.; Wagemaker, M.; Simone, A.

    2015-01-01

    A crosslinked polymer based solid electrolyte prototype material –poly(propylene glycol) diacrylate– is studied using the reactive molecular dynamics force field ReaxFF. The focus of the study is the evaluation of the effects of equilibration and added plasticizer (ethylene carbonate) or anion compo

  19. Modelling the global tropospheric molecular hydrogen cycle

    NARCIS (Netherlands)

    Pieterse, G.

    2013-01-01

    Would urban air quality and climate improve if we replaced the fossil fuels by molecular hydrogen (H2) as an energy carrier? A quantitative answer to this question requires a thorough understanding of the current role of H2 in the Earth’s atmosphere. On its own, H2 does not impact climate, as for ex

  20. Modelling the global tropospheric molecular hydrogen cycle

    NARCIS (Netherlands)

    Pieterse, G.

    2013-01-01

    Would urban air quality and climate improve if we replaced the fossil fuels by molecular hydrogen (H2) as an energy carrier? A quantitative answer to this question requires a thorough understanding of the current role of H2 in the Earth’s atmosphere. On its own, H2 does not impact climate, as for

  1. In vitro and in vivo models for analysis of resistance to anticancer molecular therapies.

    Science.gov (United States)

    Rosa, Roberta; Monteleone, Francesca; Zambrano, Nicola; Bianco, Roberto

    2014-01-01

    The efficacy of classical and molecular therapies in cancer is hampered by the occurrence of primary (intrinsic) and secondary (acquired) refractoriness of tumours to selected therapeutic regimens. Nevertheless, the increased knowledge of the genetic, molecular and metabolic mechanisms underlying cancer results in the generation of a correspondingly increasing number of druggable targets and molecular drugs. Thus, a current challenge in molecular oncology and medicinal chemistry is to cope with the increased need for modelling, both in cellular and animal systems, the genetic assets associated to cancer resistance to drugs. In this review, we summarize the current strategies for generation and analysis of in vitro and in vivo models, which may reveal useful to extract information on the molecular basis of intrinsic and acquired resistance to anticancer molecular agents.

  2. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    Science.gov (United States)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    ) experience with methods of protein purification; (iii) incorporation of appropriate controls into experiments; (iv) use of basic statistics in data analysis; (v) writing papers and grant proposals in accepted scientific style; (vi) peer review; (vii) oral presentation of results and proposals; and (viii) introduction to molecular modeling. Figure 1 illustrates the modular nature of the lab curriculum. Elements from each of the exercises can be separated and treated as stand-alone exercises, or combined into short or long projects. We have been able to offer the opportunity to use sophisticated molecular modeling in the final module through funding from an NSF-ILI grant. However, many of the benefits of the research proposal can be achieved with other computer programs, or even by literature survey alone. Figure 1.Design of project-based biochemistry laboratory. Modules (projects, or portions of projects) are indicated as boxes. Each of these can be treated independently, or used as part of a larger project. Solid lines indicate some suggested paths from one module to the next. The skills and knowledge required for protein purification and design are developed in three units: (i) an introduction to critical assays needed to monitor degree of purification, including an evaluation of assay parameters; (ii) partial purification by ion-exchange techniques; and (iii) preparation of a grant proposal on protein design by mutagenesis. Brief descriptions of each of these units follow, with experimental details of each project at the end of this paper. Assays for Lysozyme Activity and Protein Concentration (4 weeks) The assays mastered during the first unit are a necessary tool for determining the purity of the enzyme during the second unit on purification by ion exchange. These assays allow an introduction to the concept of specific activity (units of enzyme activity per milligram of total protein) as a measure of purity. In this first sequence, students learn a turbidimetric assay

  3. Diffusion in Liquids: Equilibrium Molecular Simulations and Predictive Engineering Models

    OpenAIRE

    Liu, X.

    2013-01-01

    The aim of this thesis is to study multicomponent diffusion in liquids using Molecular Dynamics (MD) simulations. Diffusion plays an important role in mass transport processes. In binary systems, mass transfer processes have been studied extensively using both experiments and molecular simulations. From a practical point of view, systems consisting more than two components are more interesting. However, experimental and simulation data on transport diffusion for such systems are scarce. There...

  4. Modeling Complex Systems

    CERN Document Server

    Boccara, Nino

    2010-01-01

    Modeling Complex Systems, 2nd Edition, explores the process of modeling complex systems, providing examples from such diverse fields as ecology, epidemiology, sociology, seismology, and economics. It illustrates how models of complex systems are built and provides indispensable mathematical tools for studying their dynamics. This vital introductory text is useful for advanced undergraduate students in various scientific disciplines, and serves as an important reference book for graduate students and young researchers. This enhanced second edition includes: . -recent research results and bibliographic references -extra footnotes which provide biographical information on cited scientists who have made significant contributions to the field -new and improved worked-out examples to aid a student’s comprehension of the content -exercises to challenge the reader and complement the material Nino Boccara is also the author of Essentials of Mathematica: With Applications to Mathematics and Physics (Springer, 2007).

  5. Extended master equation models for molecular communication networks

    CERN Document Server

    Chou, Chun Tung

    2012-01-01

    We consider molecular communication networks consisting of transmitters and receivers distributed in a fluidic medium. In such networks, a transmitter sends one or more signalling molecules, which are diffused over the medium, to the receiver to realise the communication. In order to be able to engineer synthetic molecular communication networks, mathematical models for these networks are required. This paper proposes a new stochastic model for molecular communication networks called reaction-diffusion master equation with exogenous input (RDMEX). The key idea behind RDMEX is to model the transmitters as time sequences specify the emission patterns of signalling molecules, while diffusion in the medium and chemical reactions at the receivers are modelled as Markov processes using master equation. An advantage of RDMEX is that it can readily be used to model molecular communication networks with multiple transmitters and receivers. For the case where the reaction kinetics at the receivers is linear, we show ho...

  6. Molecular Dynamics Studies of Energy Transfer Processes in Crystal Systems.

    Science.gov (United States)

    1984-11-30

    Computer molecular dynamics studies have been carried out on the problem of attaining a fundamental understanding of shock-induced initiation of...intramolecular energy exchange in shock-loaded systems are presented. Originator-supplied keywords include: Molecular dynamics , Energy transfer, Shock front, Shock wave, Explosives, Shock structure.

  7. Giant Nuclear Systems of Molecular Type

    Science.gov (United States)

    Zagrebaev, Valery; Greiner, Walter

    Low-energy dynamics of heavy nuclear systems is studied within the extended version of the two-center shell model and Langevin type equations of motion. The shell effects lead to the appearance of local minima and deep valleys on the multi-dimensional potential energy surface. It is shown that the local minima on the fission path of a heavy nucleus—so called isomeric states—are nothing else but the two-cluster configurations with magic or semi-magic cores surrounded with a certain number of shared nucleons. Clustering phenomena caused by the shell effects play an important role also in low-energy dynamics of heavy nuclear systems. Fission and quasi-fission are the well-known processes of such kind discussed in the paper. We found that in low-energy damped multi-nucleon transfer reactions the shell effects may significantly enhance the yield of new heavy neutron-rich nuclei located in the unexplored "north-east" area of the nuclear map which is important for astrophysical nucleosynthesis. A possibility for the production of long-living neutron-rich superheavy nuclei in collisions of actinide ions (such as 238U + 248Cm) is another important finding. In these reactions a large mass and charge transfer due to the inverse (anti-symmetrized) quasi-fission process is significantly enhanced by the clustering process with formation of closed shell nuclei around Z = 82 and N = 126. In many such collisions the lifetime of a composite system consisting of two touching actinide nuclei turns out to be rather long (> 10-20S). This time delay is sufficient for the observation of the line structure in spontaneous e + e - production from the supercritical electric field of a giant quasi-atom—a fundamental QED process not observed yet experimentally. In addition, this giant nuclear molecule might undergo to a three-body clusterization (ternary quasi-fission) with formation of two heavy lead-like fragments in the exit channel. The "true ternary fission" is also possible for

  8. Open quantum system parameters from molecular dynamics

    CERN Document Server

    Wang, Xiaoqing; Wüster, Sebastian; Eisfeld, Alexander

    2015-01-01

    We extract the site energies and spectral densities of the Fenna-Matthews-Olson (FMO) pigment protein complex of green sulphur bacteria from simulations of molecular dynamics combined with energy gap calculations. Comparing four different combinations of methods, we investigate the origin of quantitative differences regarding site energies and spectral densities obtained previously in the literature. We find that different forcefields for molecular dynamics and varying local energy minima found by the structure relaxation yield significantly different results. Nevertheless, a picture averaged over these variations is in good agreement with experiments and some other theory results. Throughout, we discuss how vibrations external- or internal to the pigment molecules enter the extracted quantities differently and can be distinguished. Our results offer some guidance to set up more computationally intensive calculations for a precise determination of spectral densities in the future. These are required to determ...

  9. Distributed generation systems model

    Energy Technology Data Exchange (ETDEWEB)

    Barklund, C.R.

    1994-12-31

    A slide presentation is given on a distributed generation systems model developed at the Idaho National Engineering Laboratory, and its application to a situation within the Idaho Power Company`s service territory. The objectives of the work were to develop a screening model for distributed generation alternatives, to develop a better understanding of distributed generation as a utility resource, and to further INEL`s understanding of utility concerns in implementing technological change.

  10. Modeling the earth system

    Energy Technology Data Exchange (ETDEWEB)

    Ojima, D. [ed.

    1992-12-31

    The 1990 Global Change Institute (GCI) on Earth System Modeling is the third of a series organized by the Office for Interdisciplinary Earth Studies to look in depth at particular issues critical to developing a better understanding of the earth system. The 1990 GCI on Earth System Modeling was organized around three themes: defining critical gaps in the knowledge of the earth system, developing simplified working models, and validating comprehensive system models. This book is divided into three sections that reflect these themes. Each section begins with a set of background papers offering a brief tutorial on the subject, followed by working group reports developed during the institute. These reports summarize the joint ideas and recommendations of the participants and bring to bear the interdisciplinary perspective that imbued the institute. Since the conclusion of the 1990 Global Change Institute, research programs, nationally and internationally, have moved forward to implement a number of the recommendations made at the institute, and many of the participants have maintained collegial interactions to develop research projects addressing the needs identified during the two weeks in Snowmass.

  11. Pentameric models as alternative molecular targets for the design of new antiaggregant agents.

    Science.gov (United States)

    Barrera Guisasola, Exequiel E; Gutierrez, Lucas J; Andujar, Sebastián A; Angelina, Emilio; Rodríguez, Ana M; Enriz, Ricardo D

    2016-01-01

    The structure-based drug design has been an extremely useful technique used for searching and developing of new therapeutic agents in various biological systems. In the case of AD, this approach has been difficult to implement. Among other several causes, the main problem might be the lack of a specific stable and reliable molecular target. In this paper the results obtained using a pentameric amyloid beta (Aβ) model as a molecular target are discussed. Our MD simulations have shown that this system is relatively structured and stable, displaying a lightly conformational flexibility during 2.0 μs of simulation time. This study allowed us to distinguish characteristic structural features in specific regions of the pentamer which should be taken into account when choosing this model as a molecular target. This represents a clear advantage compared to the monomer or dimer models which are highly flexible structures with large numbers of possible conformers. Using this pentameric model we performed two types of studies usually carried out on a molecular target: a virtual screening and the design on structural basis of new mimetic peptides with antiaggregant properties. Our results indicate that this pentameric model might be a good molecular target for these particular studies of molecular modeling. Details about the predictive power of our virtual screening as well as about the molecular interactions that stabilize the mimetic peptide-pentamer Aβ complexes are discussed in this paper.

  12. Molecular Modeling and Computational Chemistry at Humboldt State University.

    Science.gov (United States)

    Paselk, Richard A.; Zoellner, Robert W.

    2002-01-01

    Describes a molecular modeling and computational chemistry (MM&CC) facility for undergraduate instruction and research at Humboldt State University. This facility complex allows the introduction of MM&CC throughout the chemistry curriculum with tailored experiments in general, organic, and inorganic courses as well as a new molecular modeling…

  13. Aggregation of model asphaltenes: a molecular dynamics study

    Science.gov (United States)

    Costa, J. L. L. F. S.; Simionesie, D.; Zhang, Z. J.; Mulheran, P. A.

    2016-10-01

    Natural asphaltenes are defined as polyaromatic compounds whose chemical composition and structure are dependent on their geological origin and production history, hence are regarded as complex molecules with aromatic cores and aliphatic tails that occur in the heaviest fraction of crude oil. The aggregation of asphaltenes presents a range of technical challenges to the production and processing of oil. In this work we study the behaviour of the model asphaltene-like molecule hexa-tert-butylhexa-peri-hexabenzocoronene (HTBHBC) using molecular dynamics simulation. It was found that the regular arrangement of the tert-butyl side chains prevents the formation of strongly-bound dimers by severely restricting the configurational space of the aggregation pathway. In contrast, a modified molecule with only 3 side chains is readily able to form dimers. This work therefore confirms the influence of the molecular structure of polyaromatic compounds on their aggregation mechanism, and reveals the unexpected design rules required for model systems that can mimic the behavior of asphaltenes.

  14. Diffusion in Liquids: Equilibrium Molecular Simulations and Predictive Engineering Models

    NARCIS (Netherlands)

    Liu, X.

    2013-01-01

    The aim of this thesis is to study multicomponent diffusion in liquids using Molecular Dynamics (MD) simulations. Diffusion plays an important role in mass transport processes. In binary systems, mass transfer processes have been studied extensively using both experiments and molecular simulations.

  15. A General Random Walk Model of Molecular Motor

    Institute of Scientific and Technical Information of China (English)

    WANG Xian-Ju; AI Bao-Quan; LIU Guo-Tao; LIU Liang-Gang

    2003-01-01

    A general random walk model framework is presented which can be used to statistically describe the internaldynamics and external mechanical movement of molecular motors along filament track. The motion of molecular motorin a periodic potential and a constant force is considered. We show that the molecular motor's movement becomesslower with the potential barrier increasing, but if the forceis increased, the molecular motor's movement becomesfaster. The relation between the effective rate constant and the potential barrier's height, and that between the effectiverate constant and the value of the force are discussed. Our results are consistent with the experiments and relevanttheoretical consideration, and can be used to explain some physiological phenomena.

  16. Modeling of the continuum and molecular line emission from the Sagittarius B2 molecular cloud

    Energy Technology Data Exchange (ETDEWEB)

    Lis, D.C.; Goldsmith, P.F. (Massachusetts Univ., Amherst (USA))

    1990-06-01

    The continuum and molecular line emission from the Sagittarius B2 molecular cloud are modeled in order to determine the conditions in the core and the envelope of the cloud. The continuum models suggest that the total luminosity of the middle source Sgr B2(M) is an order of magnitude higher than that of the northern source Sgr B2(N). The microturbulent models of the molecular line emission predict the correct spatial intensity distribution of the J = 1 - 0 transitions of C(O-18) and (C-13)O. They have difficulties, however, reproducing the observed intensities of the higher transitions of these molecules. This may indicate that the envelope has a clumpy structure. Sgr B2 differs significantly from typical disk giant molecular clouds in that it has higher mass and luminosity of the continuum sources, much greater H2 column density and mean volume density, and different fractional abundances of many interstellar molecules. 43 refs.

  17. Modelling [CI] emission from turbulent molecular clouds

    CERN Document Server

    Glover, Simon C O; Micic, Milica; Molina, Faviola

    2014-01-01

    We use detailed numerical simulations of the coupled chemical, thermal and dynamical evolution of the gas in a turbulent molecular cloud to study the usefulness of the [CI] 609 micron and 370 micron fine structure emission lines as tracers of cloud structure. Emission from these lines is observed throughout molecular clouds, and yet the question of what we can learn from them about the physics of the clouds remains largely unexplored. We show that the fact that [CI] emission is widespread within molecular clouds is a simple consequence of the fact that the clouds are dominated by turbulent motions. Turbulence creates large density inhomogeneities, allowing radiation to penetrate deeply into the clouds. As a result, [CI] emitting gas is found throughout the cloud, rather than being concentrated at the edges. We examine how well we can use [CI] emission to trace the structure of the cloud, and show that the integrated intensity of the 609 micron line traces column density accurately over a wide range of visual ...

  18. Systems theoretic analysis of the central dogma of molecular biology: some recent results.

    Science.gov (United States)

    Gao, Rui; Yu, Juanyi; Zhang, Mingjun; Tarn, Tzyh-Jong; Li, Jr-Shin

    2010-03-01

    This paper extends our early study on a mathematical formulation of the central dogma of molecular biology, and focuses discussions on recent insights obtained by employing advanced systems theoretic analysis. The goal of this paper is to mathematically represent and interpret the genetic information flow at the molecular level, and explore the fundamental principle of molecular biology at the system level. Specifically, group theory was employed to interpret concepts and properties of gene mutation, and predict backbone torsion angle along the peptide chain. Finite state machine theory was extensively applied to interpret key concepts and analyze the processes related to DNA hybridization. Using the proposed model, we have transferred the character-based model in molecular biology to a sophisticated mathematical model for calculation and interpretation.

  19. DISSYMMETRY MODEL OF MOLECULAR POLARIZABILITY AND OPTICAL ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    周志华; 汤杰

    1991-01-01

    Dissymmetry model of molecular polarizability divided into some layers within a sphere,some rules and sequence according to the magnitude of polarizability replaced by bond refraction for many groups have been suggested.The relationship between the dissymmetry of molecular polarizability arrounding the dissymmetric carbon atom and the direction of optical activity has been discussed .The accuracy is above 95 persent to use our model and rules to determine over 6000 compounds of optical activity.

  20. Molecular dynamic simulations of the sputtering of multilayer organic systems

    CERN Document Server

    Postawa, Z; Piaskowy, J; Krantzman, K; Winograd, N; Garrison, B J

    2003-01-01

    Sputtering of organic overlayers has been modeled using molecular dynamics computer simulations. The investigated systems are composed of benzene molecules condensed into one, two and three layers on an Ag left brace 1 1 1 right brace surface. The formed organic overlayers were bombarded with 4 keV Ar projectiles at normal incidence. The development of the collision cascade in the organic overlayer was investigated. The sputtering yield, mass, internal and kinetic energy distributions of ejected particles have been analyzed as a function of the thickness of the organic layer. The results show that all emission characteristics are sensitive to the variation of layer thickness. Although most of the ejected intact benzene molecules originate from the topmost layer, the emission of particles located initially in second and third layers is significant. The analysis indicates that the metallic substrate plays a dominant role in the ejection of intact organic molecules.

  1. Molecular dynamic simulations of the sputtering of multilayer organic systems

    Energy Technology Data Exchange (ETDEWEB)

    Postawa, Z. E-mail: zp@castor.if.uj.edu.pl; Ludwig, K.; Piaskowy, J.; Krantzman, K.; Winograd, N.; Garrison, B.J

    2003-04-01

    Sputtering of organic overlayers has been modeled using molecular dynamics computer simulations. The investigated systems are composed of benzene molecules condensed into one, two and three layers on an Ag{l_brace}1 1 1{r_brace} surface. The formed organic overlayers were bombarded with 4 keV Ar projectiles at normal incidence. The development of the collision cascade in the organic overlayer was investigated. The sputtering yield, mass, internal and kinetic energy distributions of ejected particles have been analyzed as a function of the thickness of the organic layer. The results show that all emission characteristics are sensitive to the variation of layer thickness. Although most of the ejected intact benzene molecules originate from the topmost layer, the emission of particles located initially in second and third layers is significant. The analysis indicates that the metallic substrate plays a dominant role in the ejection of intact organic molecules.

  2. The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR.

    Science.gov (United States)

    Roxo-Rosa, Mónica; Jacinto, Raquel; Sampaio, Pedro; Lopes, Susana Santos

    2015-10-02

    In autosomal dominant polycystic kidney disease (ADPKD), cyst inflation and continuous enlargement are associated with marked transepithelial ion and fluid secretion into the cyst lumen via cystic fibrosis transmembrane conductance regulator (CFTR). Indeed, the inhibition or degradation of CFTR prevents the fluid accumulation within cysts. The in vivo mechanisms by which the lack of Polycystin-2 leads to CFTR stimulation are an outstanding challenge in ADPKD research and may bring important biomarkers for the disease. However, hampering their study, the available ADPKD in vitro cellular models lack the three-dimensional architecture of renal cysts and the ADPKD mouse models offer limited access for live-imaging experiments in embryonic kidneys. Here, we tested the zebrafish Kupffer's vesicle (KV) as an alternative model-organ. KV is a fluid-filled vesicular organ, lined by epithelial cells that express both CFTR and Polycystin-2 endogenously, being each of them easily knocked-down. Our data on the intracellular distribution of Polycystin-2 support its involvement in the KV fluid-flow induced Ca(2+)-signalling. Mirroring kidney cysts, the KV lumen inflation is dependent on CFTR activity and, as we clearly show, the knockdown of Polycystin-2 results in larger KV lumens through overstimulation of CFTR. In conclusion, we propose the zebrafish KV as a model organ to study the renal cyst inflation. Favouring its use, KV volume can be easily determined by in vivo imaging offering a live readout for screening compounds and genes that may prevent cyst enlargement through CFTR inhibition.

  3. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2009-01-01

    This third volume completes the Work Mechanical Systems, Classical Models. The first two volumes dealt with particle dynamics and with discrete and continuous mechanical systems. The present volume studies analytical mechanics. Topics like Lagrangian and Hamiltonian mechanics, the Hamilton-Jacobi method, and a study of systems with separate variables are thoroughly discussed. Also included are variational principles and canonical transformations, integral invariants and exterior differential calculus, and particular attention is given to non-holonomic mechanical systems. The author explains in detail all important aspects of the science of mechanics, regarded as a natural science, and shows how they are useful in understanding important natural phenomena and solving problems of interest in applied and engineering sciences. Professor Teodorescu has spent more than fifty years as a Professor of Mechanics at the University of Bucharest and this book relies on the extensive literature on the subject as well as th...

  4. NEP systems model

    Science.gov (United States)

    George, Jeffrey A.

    A new nuclear electric propulsion (NEP) systems analysis code is discussed. The new code is modular and consists of a driver code and various subsystem models. The code models five different subsystems: (1) reactor/shield; (2) power conversion; (3) heat rejection; (4) power management and distribution (PMAD); and (5) thrusters. The code optimizes for the following design criteria: minimum mass; minimum radiator area; and low mass/low area. The code also optimizes the following parameters: separation distance; temperature ratio; pressure ratio; and transmission frequency. The discussion is presented in vugraph form.

  5. Continuous Molecular Fields Approach Applied to Structure-Activity Modeling

    CERN Document Server

    Baskin, Igor I

    2013-01-01

    The Method of Continuous Molecular Fields is a universal approach to predict various properties of chemical compounds, in which molecules are represented by means of continuous fields (such as electrostatic, steric, electron density functions, etc). The essence of the proposed approach consists in performing statistical analysis of functional molecular data by means of joint application of kernel machine learning methods and special kernels which compare molecules by computing overlap integrals of their molecular fields. This approach is an alternative to traditional methods of building 3D structure-activity and structure-property models based on the use of fixed sets of molecular descriptors. The methodology of the approach is described in this chapter, followed by its application to building regression 3D-QSAR models and conducting virtual screening based on one-class classification models. The main directions of the further development of this approach are outlined at the end of the chapter.

  6. Applications of Molecular Modeling in Endocrinology- Review Article

    Directory of Open Access Journals (Sweden)

    Azadeh EBRAHIM-HABIBI

    2015-10-01

    Full Text Available Modeling and simulation techniques are now widely used alongside with their experimental counterparts in order to complement them, or sometimes to bring first insights into the possible outcome of experiments. “Modeling” is a general word that could encompass a wide range of methods that could be applied to a variety of subjects and problems. Here, the use of selected molecular modeling methods has been described in the field of endocrinology, throughout of some concrete examples. Keywords: Molecular modeling, Homology model, Docking, Endocrinology

  7. A comparison between algebraic models of molecular spectroscopy

    CERN Document Server

    Bijker, R; Lemus, R; Arias, J M; Pérez-Bernal, F

    1998-01-01

    We discuss a symmetry-adapted algebraic (or vibron) model for molecular spectroscopy. The model is formulated in terms of tensor operators under the molecular point group. In this way, we have identified interactions that are absent in previous versions of the vibron model, in which the Hamiltonian is expressed in terms of Casimir operators and their products. The inclusion of these new interactions leads to reliable spectroscopic predictions. As an example we study the vibrational excitations of the methane molecule, and compare our results with those obtained in other algebraic models.

  8. Molecular dynamics

    NARCIS (Netherlands)

    Bergstra, J.A.; Bethke, I.

    2002-01-01

    Molecular dynamics is a model for the structure and meaning of object based programming systems. In molecular dynamics the memory state of a system is modeled as a fluid consisting of a collection of molecules. Each molecule is a collection of atoms with bindings between them. A computation is model

  9. Direct Calculation of Ice Homogeneous Nucleation Rate for a Molecular Model of Water

    CERN Document Server

    Haji-Akbari, Amir

    2015-01-01

    Ice formation is ubiquitous in nature, with important consequences in a variety of systems and environments, including biological cells [1], soil [2], aircraft [3], transportation infrastructure [4] and atmospheric clouds [5,6]. However, its intrinsic kinetics and microscopic mechanism are difficult to discern with current experiments. Molecular simulations of ice nucleation are also challenging, and direct rate calculations have only been performed for coarse-grained models of water [7-9]. For the more realistic molecular models, only indirect estimates have been obtained, e.g.~by assuming the validity of classical nucleation theory [10]. Here, we use a path sampling approach to perform the first direct rate calculation of homogeneous nucleation of ice in a molecular model of water. We use TIP4P/Ice [11], the most accurate among the existing molecular models for studying ice polymorphs. By using a novel topological order parameter for distinguishing different polymorphs, we are able to identify a freezing me...

  10. A new parametrizable model of molecular electronic structure

    CERN Document Server

    Laikov, Dimitri N

    2011-01-01

    A new electronic structure model is developed in which the ground state energy of a molecular system is given by a Hartree-Fock-like expression with parametrized one- and two-electron integrals over an extended (minimal + polarization) set of orthogonalized atom-centered basis functions, the variational equations being solved formally within the minimal basis but the effect of polarization functions being included in the spirit of second-order perturbation theory. It is designed to yield good dipole polarizabilities and improved intermolecular potentials with dispersion terms. The molecular integrals include up to three-center one-electron and two-center two-electron terms, all in simple analytical forms. A method to extract the effective one-electron Hamiltonian of nonlocal-exchange Kohn-Sham theory from the coupled-cluster one-electron density matrix is designed and used to get its matrix representation in a molecule-intrinsic minimal basis as an input to the paramtrization procedure -- making a direct link...

  11. National Energy Modeling System

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, C.W. (Energy Information Administration, Washington, DC (United States))

    1993-01-01

    The Energy Information Administration is developing a new National Energy Modeling System to provide annual forecasts of energy supply, demand, and prices on a regional basis in the United States and, to a limited extent, in the rest of the world. The design for the system was based on a requirements analysis, a comparison of requirements with existing modeling capabilities, and a series of widely circulated issue papers defining the choices and tradeoffs for 13 key design decisions. An initial prototpye of the new NEMS was implemented in late 1992, with a more complete, operational version in 1993. NEMS is expected to provide EIA and other users with a greatly enhanced ability to illustrate quickly and effectively the effects of a wide range of energy policy proposals.

  12. Comparative molecular modelling of biologically active sterols

    Science.gov (United States)

    Baran, Mariusz; Mazerski, Jan

    2015-04-01

    Membrane sterols are targets for a clinically important antifungal agent - amphotericin B. The relatively specific antifungal action of the drug is based on a stronger interaction of amphotericin B with fungal ergosterol than with mammalian cholesterol. Conformational space occupied by six sterols has been defined using the molecular dynamics method to establish if the conformational features correspond to the preferential interaction of amphotericin B with ergosterol as compared with cholesterol. The compounds studied were chosen on the basis of structural features characteristic for cholesterol and ergosterol and on available experimental data on the ability to form complexes with the antibiotic. Statistical analysis of the data obtained has been performed. The results show similarity of the conformational spaces occupied by all the sterols tested. This suggests that the conformational differences of sterol molecules are not the major feature responsible for the differential sterol - drug affinity.

  13. Modeling Novo Nordisk Production Systems

    DEFF Research Database (Denmark)

    Miller, Thomas Dedenroth

    1997-01-01

    This report describes attributes of models and systems, and how models can be used for description of production systems. There are special attention on the 'Theory of Domains'.......This report describes attributes of models and systems, and how models can be used for description of production systems. There are special attention on the 'Theory of Domains'....

  14. Molecular Model of the Contractile Ring

    CERN Document Server

    Biron, D; Tlusty, Tsvi; Moses, Elisha; 10.1103/PhysRevLett.95.098102

    2010-01-01

    We present a model for the actin contractile ring of adherent animal cells. The model suggests that the actin concentration within the ring and consequently the power that the ring exerts both increase during contraction. We demonstrate the crucial role of actin polymerization and depolymerization throughout cytokinesis, and the dominance of viscous dissipation in the dynamics. The physical origin of two phases in cytokinesis dynamics ("biphasic cytokinesis") follows from a limitation on the actin density. The model is consistent with a wide range of measurements of the midzone of dividing animal cells.

  15. Molecular Modeling on the PC (by Matthew F. Schlecht)

    Science.gov (United States)

    Rioux, Reviewed Frank

    2000-06-01

    "Computeraided molecular modeling doesn't exist for its own sake, but to contribute to scientific endeavor, and enable the scientist to work smarter." This is the last sentence of Schlecht's preface and it says something very important about contemporary scientific research in the academic and industrial venues. Owing to the accelerating improvement in computer technology (hardware and software) and its widespread availability, molecular modeling has become a reliable and important tool in chemical research. Consequently, experimentalists have incorporated molecular modeling techniques in their research, and partnerships with computational chemists have become common. This is a wellorganized and thorough monograph that devotes its attention to one type of molecular modeling, molecular mechanics, and one molecular modeling software package, PCMODEL. Schlecht targets two reader-user groups, the novice and the journeyman modeler, and articulates three goals. He wants to provide the novice with an introduction to molecular mechanics, and after that with some practical examples of the use of empirical force field calculations. His third goal is to provide the journeyman modeler with a reference work that will aid "further study and practice". These are potentially conflicting goals, but Schlecht is, in my opinion, successful because of the way his book is organized. A comprehensive treatment such as this one is not meant to be read from cover to cover, because it is both an exposition of basic principles and a user's manual. Therefore, the novice and the experienced modeler will undoubtedly use this book in different ways. For example, a novice modeler might be advised to read the Preface and Chapter 1, which together provide a broad introduction to the historical development and goals of molecular mechanics. From there the novice could go to Chapter 5 and read section 5.1 on the components of the molecular mechanics force field, which is presented in 22 pages with

  16. A Heuristic Molecular Model of Hydrophobic Interactions

    OpenAIRE

    Hummer, G; Garde, S; Garcia, A.E.; Pohorille, A; Pratt, L.R.

    1995-01-01

    Hydrophobic interactions provide driving forces for protein folding, membrane formation, and oil-water separation. Motivated by information theory, the poorly understood nonpolar solute interactions in water are investigated. A simple heuristic model of hydrophobic effects in terms of density fluctuations is developed. This model accounts quantitatively for the central hydrophobic phenomena of cavity formation and association of inert gas solutes; it therefore clarifies the underlying physics...

  17. Enhanced sampling techniques in molecular dynamics simulations of biological systems.

    Science.gov (United States)

    Bernardi, Rafael C; Melo, Marcelo C R; Schulten, Klaus

    2015-05-01

    Molecular dynamics has emerged as an important research methodology covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local minima separated by high-energy barriers, which govern the biomolecular motion. In the past few decades methods have been developed that address the sampling problem, such as replica-exchange molecular dynamics, metadynamics and simulated annealing. Here we present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Enhanced sampling methods have been employed for a broad range of biological systems and the choice of a suitable method is connected to biological and physical characteristics of the system, in particular system size. While metadynamics and replica-exchange molecular dynamics are the most adopted sampling methods to study biomolecular dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromolecular complexes. Molecular dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biological function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. The Role of the Environment in Molecular Systems

    CERN Document Server

    Kilin, D S

    2000-01-01

    The work is devoted to the investigation of the influence of a heat bath on the physical processes in a quantum system. We use the density matrix theory as one of the most powerfool tool for investigation of quantum relaxation. In the beginning of the work (chapter 2) we mention and recall the most important steps of derivation of the equation of motion for the reduced density matrix (master equation) for an arbitrary quantum system in diabatic representation interacting with the environment modeled by a set of independent harmonic oscillators. Chapter 3 deals with the question of the border between classical and quantum effects and reports on a study of the environmental influence on the time evolution of a coherent state or the superposition of two coherent states of a harmonic oscillator as a simple system displaying the peculiarities of the transition from quantum to classical regime. Chapters 4 and 5 concern the electron transfer (ET) problem, namely the mathematical description of the ET in molecular zi...

  19. Electromagnetically induced grating in a crystal of molecular magnets system

    Science.gov (United States)

    Liu, Jibing; Liu, Na; Shan, Chuanjia; Liu, Tangkun; Li, Hong; Zheng, Anshou; Xie, Xiao-Tao

    2016-07-01

    We investigate the response of the molecular system to the magnetic field modulation. Molecular magnets are subjected to a strong standing ac magnetic field and a weak probe magnetic field. The transmission and absorption of the weak probe magnetic field can be changed due to quantum coherence and the spatially modulating of the standing field. And a electromagnetically induced grating is formed in the crystal of molecular magnets via electromagnetically induced transparency (EIT). The diffraction efficiency of the grating can be adjusted efficiently by tuning the intensity of the standing wave field and the single photon detuning.

  20. Testing the molecular clock using mechanistic models of fossil preservation and molecular evolution

    Science.gov (United States)

    2017-01-01

    Molecular sequence data provide information about relative times only, and fossil-based age constraints are the ultimate source of information about absolute times in molecular clock dating analyses. Thus, fossil calibrations are critical to molecular clock dating, but competing methods are difficult to evaluate empirically because the true evolutionary time scale is never known. Here, we combine mechanistic models of fossil preservation and sequence evolution in simulations to evaluate different approaches to constructing fossil calibrations and their impact on Bayesian molecular clock dating, and the relative impact of fossil versus molecular sampling. We show that divergence time estimation is impacted by the model of fossil preservation, sampling intensity and tree shape. The addition of sequence data may improve molecular clock estimates, but accuracy and precision is dominated by the quality of the fossil calibrations. Posterior means and medians are poor representatives of true divergence times; posterior intervals provide a much more accurate estimate of divergence times, though they may be wide and often do not have high coverage probability. Our results highlight the importance of increased fossil sampling and improved statistical approaches to generating calibrations, which should incorporate the non-uniform nature of ecological and temporal fossil species distributions. PMID:28637852

  1. Computational Modeling of Biological Systems From Molecules to Pathways

    CERN Document Server

    2012-01-01

    Computational modeling is emerging as a powerful new approach for studying and manipulating biological systems. Many diverse methods have been developed to model, visualize, and rationally alter these systems at various length scales, from atomic resolution to the level of cellular pathways. Processes taking place at larger time and length scales, such as molecular evolution, have also greatly benefited from new breeds of computational approaches. Computational Modeling of Biological Systems: From Molecules to Pathways provides an overview of established computational methods for the modeling of biologically and medically relevant systems. It is suitable for researchers and professionals working in the fields of biophysics, computational biology, systems biology, and molecular medicine.

  2. Fermi resonance-algebraic model for molecular vibrational spectra

    Institute of Scientific and Technical Information of China (English)

    侯喜文; 董世海; 谢汨; 马中骐

    1999-01-01

    A Fermi resonance-algebraic model is proposed for molecular vibrations, where a U(2) algebra is used for describing the vibrations of each bond, and Fermi resonances between stretching and bending modes are taken into account. The model for a bent molecule XY2 and a molecule XY3 is successfully applied to fitting the recently observed vibrational spectrum of the water molecule and arsine (AsH3), respectively, and the results are compared with those of other models. Calculations show that algebraic approaches can be used as an effective method to describe molecular vibrations with small standard deviations.

  3. Adaptive modelling of structured molecular representations for toxicity prediction

    Science.gov (United States)

    Bertinetto, Carlo; Duce, Celia; Micheli, Alessio; Solaro, Roberto; Tiné, Maria Rosaria

    2012-12-01

    We investigated the possibility of modelling structure-toxicity relationships by direct treatment of the molecular structure (without using descriptors) through an adaptive model able to retain the appropriate structural information. With respect to traditional descriptor-based approaches, this provides a more general and flexible way to tackle prediction problems that is particularly suitable when little or no background knowledge is available. Our method employs a tree-structured molecular representation, which is processed by a recursive neural network (RNN). To explore the realization of RNN modelling in toxicological problems, we employed a data set containing growth impairment concentrations (IGC50) for Tetrahymena pyriformis.

  4. Photoelectrochemical solar conversion systems molecular and electronic aspects

    CERN Document Server

    Munoz, Andres G

    2012-01-01

    Providing new insights into the molecular and electronic processes involved in the conversion of sunlight into chemical products, Photoelectrochemical Solar Conversion Systems: Molecular and Electronic Aspects begins with an historical overview and a survey of recent developments in the electrochemistry of semiconductors and spectroscopic techniques. It then provides a comprehensive introduction to the science of conversion cells, reviews current issues and potential directions, and covers a wide range of materials from organic to inorganic cells.Employing a tutorial organization with balanced

  5. Modeling of ultrafast THz interactions in molecular crystals

    DEFF Research Database (Denmark)

    Pedersen, Pernille Klarskov; Clark, Stewart J.; Jepsen, Peter Uhd

    2014-01-01

    In this paper we present a numerical study of terahertz pulses interacting with crystals of cesium iodide. We model the molecular dynamics of the cesium iodide crystals with the Density Functional Theory software CASTEP, where ultrafast terahertz pulses are implemented to the CASTEP software...... to interact with molecular crystals. We investigate the molecular dynamics of cesium iodide crystals when interacting with realistic terahertz pulses of field strengths from 0 to 50 MV/cm. We find nonlinearities in the response of the CsI crystals at field strengths higher than 10 MV/cm....

  6. Energy conservation in molecular dynamics simulations of classical systems

    DEFF Research Database (Denmark)

    Toxværd, Søren; Heilmann, Ole; Dyre, J. C.

    2012-01-01

    Classical Newtonian dynamics is analytic and the energy of an isolated system is conserved. The energy of such a system, obtained by the discrete “Verlet” algorithm commonly used in molecular dynamics simulations, fluctuates but is conserved in the mean. This is explained by the existence...

  7. A Heuristic Molecular Model of Hydrophobic Interactions

    CERN Document Server

    Hummer, G; García, A E; Pohorille, A; Pratt, L R

    1995-01-01

    Hydrophobic interactions provide driving forces for protein folding, membrane formation, and oil-water separation. Motivated by information theory, the poorly understood nonpolar solute interactions in water are investigated. A simple heuristic model of hydrophobic effects in terms of density fluctuations is developed. This model accounts quantitatively for the central hydrophobic phenomena of cavity formation and association of inert gas solutes; it therefore clarifies the underlying physics of hydrophobic effects and permits important applications to conformational equilibria of nonpolar solutes and hydrophobic residues in biopolymers.

  8. Active site modeling in copper azurin molecular dynamics simulations

    NARCIS (Netherlands)

    Rizzuti, B; Swart, M; Sportelli, L; Guzzi, R

    2004-01-01

    Active site modeling in molecular dynamics simulations is investigated for the reduced state of copper azurin. Five simulation runs (5 ns each) were performed at room temperature to study the consequences of a mixed electrostatic/constrained modeling for the coordination between the metal and the po

  9. A dipole interaction model for the molecular second hyperpolarizability

    NARCIS (Netherlands)

    Jensen, L; Sylvester-Hvid, KO; Mikkelsen, KV; Astrand, PO

    2003-01-01

    A dipole interaction model (IM) for calculating the molecular second hyperpolarizability, gamma, of aliphatic and aromatic molecules has been investigated. The model has been parametrized from quantum chemical calculations of gamma at the self-consistent field (SCF) level of theory for 72 molecules.

  10. Reasoning with Atomic-Scale Molecular Dynamic Models

    Science.gov (United States)

    Pallant, Amy; Tinker, Robert F.

    2004-01-01

    The studies reported in this paper are an initial effort to explore the applicability of computational models in introductory science learning. Two instructional interventions are described that use a molecular dynamics model embedded in a set of online learning activities with middle and high school students in 10 classrooms. The studies indicate…

  11. System of systems modeling and analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, James E.; Anderson, Dennis James; Longsine, Dennis E. (Intera, Inc., Austin, TX); Shirah, Donald N.

    2005-01-01

    This report documents the results of an LDRD program entitled 'System of Systems Modeling and Analysis' that was conducted during FY 2003 and FY 2004. Systems that themselves consist of multiple systems (referred to here as System of Systems or SoS) introduce a level of complexity to systems performance analysis and optimization that is not readily addressable by existing capabilities. The objective of the 'System of Systems Modeling and Analysis' project was to develop an integrated modeling and simulation environment that addresses the complex SoS modeling and analysis needs. The approach to meeting this objective involved two key efforts. First, a static analysis approach, called state modeling, has been developed that is useful for analyzing the average performance of systems over defined use conditions. The state modeling capability supports analysis and optimization of multiple systems and multiple performance measures or measures of effectiveness. The second effort involves time simulation which represents every system in the simulation using an encapsulated state model (State Model Object or SMO). The time simulation can analyze any number of systems including cross-platform dependencies and a detailed treatment of the logistics required to support the systems in a defined mission.

  12. Molecular modeling: An open invitation for applied mathematics

    Science.gov (United States)

    Mezey, Paul G.

    2013-10-01

    Molecular modeling methods provide a very wide range of challenges for innovative mathematical and computational techniques, where often high dimensionality, large sets of data, and complicated interrelations imply a multitude of iterative approximations. The physical and chemical basis of these methodologies involves quantum mechanics with several non-intuitive aspects, where classical interpretation and classical analogies are often misleading or outright wrong. Hence, instead of the everyday, common sense approaches which work so well in engineering, in molecular modeling one often needs to rely on rather abstract mathematical constraints and conditions, again emphasizing the high level of reliance on applied mathematics. Yet, the interdisciplinary aspects of the field of molecular modeling also generates some inertia and perhaps too conservative reliance on tried and tested methodologies, that is at least partially caused by the less than up-to-date involvement in the newest developments in applied mathematics. It is expected that as more applied mathematicians take up the challenge of employing the latest advances of their field in molecular modeling, important breakthroughs may follow. In this presentation some of the current challenges of molecular modeling are discussed.

  13. Applications of Molecular and Materials Modeling

    Science.gov (United States)

    2002-01-01

    nittalabo-e.html Osaka University, Institute for Protein Research Protein modeling Prof. Haruki Nakamura http://www.protein.osaka- u.ac.jp/kessho/members...band structure of YH3. Phys. Rev. B 61, 16491- 16496. Nagashima, U., S. Obara, K. Murakami , T. Yoshii, S. Shirakawa, T. Amisake, K. Kitamura, O. Kitao

  14. Corn Storage Protein - A Molecular Genetic Model

    Energy Technology Data Exchange (ETDEWEB)

    Messing, Joachim [Rutgers, The State University of New Jersey

    2013-05-31

    Corn is the highest yielding crop on earth and probably the most valuable agricultural product of the United States. Because it converts sun energy through photosynthesis into starch and proteins, we addressed energy savings by focusing on protein quality. People and animals require essential amino acids derived from the digestion of proteins. If proteins are relatively low in certain essential amino acids, the crop becomes nutritionally defective and has to be supplemented. Such deficiency affects meat and fish production and countries where corn is a staple. Because corn seed proteins have relatively low levels of lysine and methionine, a diet has to be supplemented with soybeans for the missing lysine and with chemically synthesized methionine. We therefore have studied genes expressed during maize seed development and their chromosomal organization. A critical technical requirement for the understanding of the molecular structure of genes and their positional information was DNA sequencing. Because of the length of sequences, DNA sequencing methods themselves were insufficient for this type of analysis. We therefore developed the so-called “DNA shotgun sequencing” strategy, where overlapping DNA fragments were sequenced in parallel and used to reconstruct large DNA molecules via overlaps. Our publications became the most frequently cited ones during the decade of 1981-1990 and former Associate Director of Science for the Office of Basic Energy Sciences Patricia M. Dehmer presented our work as one of the great successes of this program. A major component of the sequencing strategy was the development of bacterial strains and vectors, which were also used to develop the first biotechnology crops. These crops possessed new traits thanks to the expression of foreign genes in plants. To enable such expression, chimeric genes had to be constructed using our materials and methods by the industry. Because we made our materials and methods freely available to

  15. 分子动力学模拟几种生物柴油模拟系统的冷滤点%Molecular Dynamics Simulation on Cold Filter Plugging Point (CFPP)of Several Modeled Biodiesel Systems

    Institute of Scientific and Technical Information of China (English)

    王共元; 周勋; 万霞; 殷开梁

    2012-01-01

    为研究生物柴油的低温流动性,构建了6种用于模拟常见植物油生物柴油的含21条链和4种十八酸甲酯的模型.利用正则系综和COMPASS力场,对模型进行了不同温度下的分子动力学研究.计算了不同温度下模拟系统的热容和碳原子自扩散系数,得到两者随温度显著变化的区间交集.模拟发现,该交集和系统的冷滤点几乎一致,证明了本模拟模型和方法的可行性,对冷滤点前后系统的微观结构变化进行了观察,发现当温度降至冷滤点以下时,分子链趋于伸展,且局部排列更为有序,这与冷滤点的定义及热力学的熵原理是一致的.%Six models of common vegetable oil biodiesel were constructed , Each contains 21 chains and four kinds of methyl octadecanate to study their low temperature fluidity. Molecular dynamics system at different temperatures were calculated, and the interval intersection of both significant changes with the simulation temperature was then achieved. It was found that the intersection of each system was consistent with its Cold Filter Plugging Point (CFPP), which proved that the model and method mentioned here is feasible for the entitled study. The investigation on the microstructures of different temperatures before and after CFPP revealed that when the temperature drops to the CFPP below, molecular chains tend to be coordinated and extended, and local arrangement is more orderly, which is consistent with the definition of the CFPP and the fundamentaLof entropy-decrease.

  16. Relationship between Multi-Phase Formation and Molecular Structure for Liquid Crystal System

    Institute of Scientific and Technical Information of China (English)

    LI Zhenxin; MA Heng; LI Shipu

    2005-01-01

    A mechanical model of liquid crystals ( LCs ) was used to explain the phase formation and thermal properties. The LC phases in the model are micro-machine systems consisting of an ensemble of molecular rotors, and some dynamic parameters in a semi-experiment molecular orbit method. A novel explanation on the multi-phase formation of LC system is obtained. It is found that the value of the critical rotational velocity is a key parameter for the characterization of each homologous series. The dipole moment of the molecules was also discussed.

  17. Evolution of dust and molecular hydrogen in the Magellanic System

    CERN Document Server

    Yozin, Cameron

    2014-01-01

    We investigate the evolution of the interstellar medium (ISM) in self-consistent, chemodynamical simulations of the Magellanic Clouds (MCs) during their recent (z<0.3) past. An explicit modelling of dust and molecular hydrogen lifecycles enables the comparison of our models against the observed properties of the ISM, including elemental depletion from the gas-phase. Combining this model with a tidal-dominated paradigm for the formation for the Magellanic Stream and Bridge, we reproduce the age-metallicity relations, long gas depletion timescales, and presently observed dust and molecular hydrogen masses of the MCs to within their respective uncertainties. We find that these models' enrichment depends sensitively on the processing of dust within the ISM and the dynamical influence of external tides/stellar bars. The ratio of characteristic dust destruction timescales in our SMC and LMC models, a governing parameter of our models' evolution, is consistent with estimates based on observed supernova (SN) rates...

  18. Extended master equation models for molecular communication networks.

    Science.gov (United States)

    Chou, Chun Tung

    2013-06-01

    We consider molecular communication networks consisting of transmitters and receivers distributed in a fluidic medium. In such networks, a transmitter sends one or more signaling molecules, which are diffused over the medium, to the receiver to realize the communication. In order to be able to engineer synthetic molecular communication networks, mathematical models for these networks are required. This paper proposes a new stochastic model for molecular communication networks called reaction-diffusion master equation with exogenous input (RDMEX). The key idea behind RDMEX is to model the transmitters as time series of signaling molecule counts, while diffusion in the medium and chemical reactions at the receivers are modeled as Markov processes using master equation. An advantage of RDMEX is that it can readily be used to model molecular communication networks with multiple transmitters and receivers. For the case where the reaction kinetics at the receivers is linear, we show how RDMEX can be used to determine the mean and covariance of the receiver output signals, and derive closed-form expressions for the mean receiver output signal of the RDMEX model. These closed-form expressions reveal that the output signal of a receiver can be affected by the presence of other receivers. Numerical examples are provided to demonstrate the properties of the model.

  19. The canonical equilibrium of constrained molecular models

    CERN Document Server

    Echenique, Pablo; García-Risueño, Pablo

    2011-01-01

    In order to increase the efficiency of the computer simulation of biological molecules, it is very common to impose holonomic constraints on the fastest degrees of freedom; normally bond lengths, but also possibly bond angles. However, as any other element that affects the physical model, the imposition of constraints must be assessed from the point of view of accuracy: both the dynamics and the equilibrium statistical mechanics are model-dependent, and they will be changed if constraints are used. In this review, we investigate the accuracy of constrained models at the level of the equilibrium statistical mechanics distributions produced by the different dynamics. We carefully derive the canonical equilibrium distributions of both the constrained and unconstrained dynamics, comparing the two of them by means of a "stiff" approximation to the latter. We do so both in the case of flexible and hard constraints, i.e., when the value of the constrained coordinates depends on the conformation and when it is a cons...

  20. Molecular Transmission Band Models for LOWTRAN

    Science.gov (United States)

    1986-12-31

    5.7866 80 75 -7.2 856 8315 -5.3351 6995 -4.7632 7600 -5.7224 80BO -7.1969 A320 -5.7802 1ovo -5.4270 7605 -5. 7048 8085 -7 .()745 8325 -6.5387 7005...Shaw, Appl. Opt. 4, 1113 (1965). 15. IBM Manual System/360, "Scientific Subroutine Package H20-0205-3" (IBM, New York, 1968). 16. S. L. Valley, Ed

  1. ABO System: molecular mimicry of Ascaris lumbricoides

    Directory of Open Access Journals (Sweden)

    Ponce de León Patricia

    2003-01-01

    Full Text Available A. lumbricoides has been associated to the ABO System by various authors. The objective was to detect ABO System epitopes in A. lumbricoides of groups O, A, B and AB patients. 28 adult parasites were obtained from children to be used as assay material. The patients ABO blood groups were determined. Extracts of A. lumbricoides [AE] were prepared by surgical remotion of the cuticle and refrigerated mechanical rupture. Agglutination Inhibition (AI and Hemoagglutination Kinetics (HK tests were used with the [AE]. Of the 28 [AE], eight belonged to O group patients, 15 to A group, three to B group and the remaining two to AB children. The AI Test showed A epitopes in two [AE] of group A patients and B epitopes in two [AE] of group B patients. The HK Test showed B antigenic determiners in two [AE] of group B patients and in two [AE] of group AB patients as well as A antigenic determiners in one [AE] of A group patient. Of the 28 [AE] studied in both tests B epitopes were detected in all [AE] from B and AB patients and A epitopes in three of the 15 [AE] of group A patients. The experiments carried out suggest that A. lumbricoides might absorb A and B antigens from the host, and/or modify the cuticular carbohydrates expression as a kind of antigenic mimicry.

  2. Continuous-terahertz-wave molecular imaging system for biomedical applications

    Science.gov (United States)

    Zhang, Rui; Zhang, Liangliang; Wu, Tong; Wang, Ruixue; Zuo, Shasha; Wu, Dong; Zhang, Cunlin; Zhang, Jue; Fang, Jing

    2016-07-01

    Molecular imaging techniques are becoming increasingly important in biomedical research and potentially in clinical practice. We present a continuous-terahertz (THz)-wave molecular imaging system for biomedical applications, in which an infrared (IR) laser is integrated into a 0.2-THz reflection-mode continuous-THz-wave imaging system to induce surface plasmon polaritons on the nanoparticles and further improve the intensity of the reflected signal from the water around the nanoparticles. A strong and rapid increment of the reflected THz signal in the nanoparticle solution upon the IR laser irradiation is demonstrated, using either gold or silver nanoparticles. This low-cost, simple, and stable continuous-THz-wave molecular imaging system is suitable for miniaturization and practical imaging applications; in particular, it shows great promise for cancer diagnosis and nanoparticle drug-delivery monitoring.

  3. Development of a Molecular System for Studying Microbial Arsenate Respiration

    Science.gov (United States)

    Saltikov, C. W.; Newman, D. K.

    2002-12-01

    The toxic element arsenic is a major contaminant of many groundwaters and surface waters throughout the world. Arsenic enrichment is primarily of geological origin resulting from weathering processes and geothermal activity. Not surprisingly, microorganisms inhabiting anoxic arsenic-contaminated environments have evolved to exploit arsenate during respiration. Numerous bacteria have been isolated that use arsenate as a terminal electron acceptor for respiratory growth. The diversity of this metabolism appears to be widespread throughout the microbial tree of life, suggesting respiratory arsenate reduction is ancient in origin. Yet little is known about the molecular mechanisms for how these organisms respire arsenate. We have developed a model system in Shewanella trabarsenatis, strain ANA-3, a facultative anaerobe that respires arsenate and tolerates high concentrations of arsenite (10 mM). Through loss-of-function studies, we have identified genes involved in both arsenic resistance and arsenate respiration. The genes that confer resistance to arsenic are homologous to the well-characterized ars operon of E. coli. However, the respiratory arsenate reductase is predicted to encode a novel protein that shares homologous regions (~ 40 % similarity) to molybdopterin anaerobic reductases specific for DMSO, thiosulfate, nitrate, and polysulfide. I will discuss our emerging model for how strain ANA-3 respires arsenate and the relationship between arsenite resistance and arsenate respiration. I will also highlight the relevance of this type of analysis for biogeochemical studies.

  4. Systematic improvement of molecular representations for machine learning models

    CERN Document Server

    Huang, Bing

    2016-01-01

    The predictive accuracy of Machine Learning (ML) models of molecular properties depends on the choice of the molecular representation. We introduce a hierarchy of representations based on uniqueness and target similarity criteria. To systematically control target similarity, we rely on interatomic many body expansions including Bonding, Angular, and higher order terms (BA). Addition of higher order contributions systematically increases similarity to the potential energy function as well as predictive accuracy of the resulting ML models. Numerical evidence is presented for the performance of BAML models trained on molecular properties pre-calculated at electron-correlated and density functional theory level of theory for thousands of small organic molecules. Properties studied include enthalpies and free energies of atomization, heatcapacity, zero-point vibrational energies, dipole-moment, polarizability, HOMO/LUMO energies and gap, ionization potential, electron affinity, and electronic excitations. After tr...

  5. The emerging role of cloud computing in molecular modelling.

    Science.gov (United States)

    Ebejer, Jean-Paul; Fulle, Simone; Morris, Garrett M; Finn, Paul W

    2013-07-01

    There is a growing recognition of the importance of cloud computing for large-scale and data-intensive applications. The distinguishing features of cloud computing and their relationship to other distributed computing paradigms are described, as are the strengths and weaknesses of the approach. We review the use made to date of cloud computing for molecular modelling projects and the availability of front ends for molecular modelling applications. Although the use of cloud computing technologies for molecular modelling is still in its infancy, we demonstrate its potential by presenting several case studies. Rapid growth can be expected as more applications become available and costs continue to fall; cloud computing can make a major contribution not just in terms of the availability of on-demand computing power, but could also spur innovation in the development of novel approaches that utilize that capacity in more effective ways. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Exciton Seebeck effect in molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Yun-An, E-mail: yunan@nano.gznc.edu.cn [Guizhou Provincial Key Laboratory of Computational Nanomaterial Science, Guizhou Normal College, Guiyang, Guizhou 550018 (China); Cai, Shaohong [Guizhou Key Laboratory of Economic System Simulation, Guizhou University of Finance and Economics, Guiyang 550004 (China)

    2014-08-07

    We investigate the exciton dynamics under temperature difference with the hierarchical equations of motion. Through a nonperturbative simulation of the transient absorption of a heterogeneous trimer model, we show that the temperature difference causes exciton population redistribution and affects the exciton transfer time. It is found that one can reproduce not only the exciton population redistribution but also the change of the exciton transfer time induced by the temperature difference with a proper tuning of the site energies of the aggregate. In this sense, there exists a site energy shift equivalence for any temperature difference in a broad range. This phenomenon is similar to the Seebeck effect as well as spin Seebeck effect and can be named as exciton Seebeck effect.

  7. Exciton Seebeck effect in molecular systems.

    Science.gov (United States)

    Yan, Yun-An; Cai, Shaohong

    2014-08-07

    We investigate the exciton dynamics under temperature difference with the hierarchical equations of motion. Through a nonperturbative simulation of the transient absorption of a heterogeneous trimer model, we show that the temperature difference causes exciton population redistribution and affects the exciton transfer time. It is found that one can reproduce not only the exciton population redistribution but also the change of the exciton transfer time induced by the temperature difference with a proper tuning of the site energies of the aggregate. In this sense, there exists a site energy shift equivalence for any temperature difference in a broad range. This phenomenon is similar to the Seebeck effect as well as spin Seebeck effect and can be named as exciton Seebeck effect.

  8. Reaction Ensemble Monte Carlo Simulation of Complex Molecular Systems.

    Science.gov (United States)

    Rosch, Thomas W; Maginn, Edward J

    2011-02-08

    Acceptance rules for reaction ensemble Monte Carlo (RxMC) simulations containing classically modeled atomistic degrees of freedom are derived for complex molecular systems where insertions and deletions are achieved gradually by utilizing the continuous fractional component (CFC) method. A self-consistent manner in which to utilize statistical mechanical data contained in ideal gas free energy parameters during RxMC moves is presented. The method is tested by applying it to two previously studied systems containing intramolecular degrees of freedom: the propene metathesis reaction and methyl-tert-butyl-ether (MTBE) synthesis. Quantitative agreement is found between the current results and those of Keil et al. (J. Chem. Phys. 2005, 122, 164705) for the propene metathesis reaction. Differences are observed between the equilibrium concentrations of the present study and those of Lísal et al. (AIChE J. 2000, 46, 866-875) for the MTBE reaction. It is shown that most of this difference can be attributed to an incorrect formulation of the Monte Carlo acceptance rule. Efficiency gains using CFC MC as opposed to single stage molecule insertions are presented.

  9. Molecular Thermodynamic Modeling of Mixed Solvent Solubility

    DEFF Research Database (Denmark)

    Ellegaard, Martin Dela; Abildskov, Jens; O’Connell, John P.

    2010-01-01

    A method based on statistical mechanical fluctuation solution theory for composition derivatives of activity coefficients is employed for estimating dilute solubilities of 11 solid pharmaceutical solutes in nearly 70 mixed aqueous and nonaqueous solvent systems. The solvent mixtures range from...... nearly ideal to strongly nonideal. The database covers a temperature range from 293 to 323 K. Comparisons with available data and other existing solubility methods show that the method successfully describes a variety of observed mixed solvent solubility behaviors using solute−solvent parameters from...

  10. Spectroscopic Studies of Molecular Systems relevant in Astrobiology

    Science.gov (United States)

    Fornaro, Teresa

    2016-01-01

    In the Astrobiology context, the study of the physico-chemical interactions involving "building blocks of life" in plausible prebiotic and space-like conditions is fundamental to shed light on the processes that led to emergence of life on Earth as well as to molecular chemical evolution in space. In this PhD Thesis, such issues have been addressed both experimentally and computationally by employing vibrational spectroscopy, which has shown to be an effective tool to investigate the variety of intermolecular interactions that play a key role in self-assembling mechanisms of nucleic acid components and their binding to mineral surfaces. In particular, in order to dissect the contributions of the different interactions to the overall spectroscopic signals and shed light on the intricate experimental data, feasible computational protocols have been developed for the characterization of the spectroscopic properties of such complex systems. This study has been carried out through a multi-step strategy, starting the investigation from the spectroscopic properties of the isolated nucleobases, then studying the perturbation induced by the interaction with another molecule (molecular dimers), towards condensed phases like the molecular solid, up to the case of nucleic acid components adsorbed on minerals. A proper modeling of these weakly bound molecular systems has required, firstly, a validation of dispersion-corrected Density Functional Theory methods for simulating anharmonic vibrational properties. The isolated nucleobases and some of their dimers have been used as benchmark set for identifying a general, reliable and effective computational procedure based on fully anharmonic quantum mechanical computations of the vibrational wavenumbers and infrared intensities within the generalized second order vibrational perturbation theory (GVPT2) approach, combined with the cost-effective dispersion-corrected density functional B3LYP-D3, in conjunction with basis sets of

  11. Two-dimensional model of elastically coupled molecular motors

    Institute of Scientific and Technical Information of China (English)

    Zhang Hong-Wei; Wen Shu-Tang; Chen Gai-Rong; Li Yu-Xiao; Cao Zhong-Xing; Li Wei

    2012-01-01

    A flashing ratchet model of a two-headed molecular motor in a two-dimensional potential is proposed to simulate the hand-over-hand motion of kinesins.Extensive Langevin simulations of the model are performed.We discuss the dependences of motion and efficiency on the model parameters,including the external force and the temperature.A good qualitative agreement with the expected behavior is observed.

  12. Molecular response functions for the polarizable continuum model physical basis and quantum mechanical formalism

    CERN Document Server

    Cammi, Roberto

    2013-01-01

    This Brief presents the main aspects of the response functions theory (RFT) for molecular solutes described within the framework of the Polarizable Continuum Model (PCM). PCM is a solvation model for a Quantum Mechanical molecular system in which the solvent is represented as a continuum distribution of matter. Particular attention is devoted to the description of the basic features of the PCM model, and to the problems characterizing the study of the response function theory for molecules in solution with respect to the analogous theory on isolated molecules.

  13. Systems biology for molecular life sciences and its impact in biomedicine.

    Science.gov (United States)

    Medina, Miguel Ángel

    2013-03-01

    Modern systems biology is already contributing to a radical transformation of molecular life sciences and biomedicine, and it is expected to have a real impact in the clinical setting in the next years. In this review, the emergence of systems biology is contextualized with a historic overview, and its present state is depicted. The present and expected future contribution of systems biology to the development of molecular medicine is underscored. Concerning the present situation, this review includes a reflection on the "inflation" of biological data and the urgent need for tools and procedures to make hidden information emerge. Descriptions of the impact of networks and models and the available resources and tools for applying them in systems biology approaches to molecular medicine are provided as well. The actual current impact of systems biology in molecular medicine is illustrated, reviewing two cases, namely, those of systems pharmacology and cancer systems biology. Finally, some of the expected contributions of systems biology to the immediate future of molecular medicine are commented.

  14. A simplified electrophoretic system for determining molecular weights of proteins.

    Science.gov (United States)

    Manwell, C

    1977-09-01

    Electrophoresis of 31 different proteins in commercially prepared polyacrylamide gradient gels, Gradipore, yields a linear relationship between a hypothetical limiting pore size (the reciprocal of a limiting gel concentration, GL) and the cube root of the mol.wt., over the range 13 500-9000 000. A regression analysis of these data reveals that 98.6% of all variability in 1/GL is explained by the molecular weight, and this degree of accuracy compares favourably with existing methods for the determination of molecular weight by retardation of mobility in polyacrylamide. This new procedure has the additional advantages that molecular-weight standards can be obtained from readily available body fluids or tissue extracts by localizing enzymes and other proteins by standard histochemical methods, and that the same electrophoretic system can be used in determining molecular weights as is used in routine surveys of populations for individual and species variation in protein heterogeneity.

  15. Molecular Modeling of Prion Transmission to Humans

    Directory of Open Access Journals (Sweden)

    Etienne Levavasseur

    2014-10-01

    Full Text Available Using different prion strains, such as the variant Creutzfeldt-Jakob disease agent and the atypical bovine spongiform encephalopathy agents, and using transgenic mice expressing human or bovine prion protein, we assessed the reliability of protein misfolding cyclic amplification (PMCA to model interspecies and genetic barriers to prion transmission. We compared our PMCA results with in vivo transmission data characterized by attack rates, i.e., the percentage of inoculated mice that developed the disease. Using 19 seed/substrate combinations, we observed that a significant PMCA amplification was only obtained when the mouse line used as substrate is susceptible to the corresponding strain. Our results suggest that PMCA provides a useful tool to study genetic barriers to transmission and to study the zoonotic potential of emerging prion strains.

  16. Transient Changes in Molecular Geometries and How to Model Them

    DEFF Research Database (Denmark)

    Dohn, Asmus Ougaard

    changes in molecular structure, vibrations and solvation. In this thesis, we employ our recently developed Quantum-/Molecular -Mechanical Direct Dynamics method to do simulations of transition metal complexes in solution, to uncover their energy dissipation channels, and how they are affected...... quantum mechanic descriptions, to ascertain the accuracy of the quantum model in the Direct Dynamics simulations. We then test - and improve - the framework for calculating the experimental X-ray Diffuse Scattering Difference signal from (any kind of) Molecular Dynamics (MD) simulations. Comparisons......Light-induced chemical processes are accompanied by molecular motion on the femtosecond time scale. Uncovering this dynamical motion is central to understanding the chemical reaction on a fundamental level. This thesis focuses on the aspects of excess excitation energy dissipation via dynamic...

  17. A General Random Walk Model of Molecular Motor

    Institute of Scientific and Technical Information of China (English)

    WANGXian-Ju; AIBao-Quan; LIUGuo-Tao; LIULiang-Gang

    2003-01-01

    A general random walk model framework is presented which can be used to statistically describe the internal dynamics and external mechanical movement of molecular motors along filament track. The motion of molecular motor in a periodic potential and a constant force is considered. We show that the molecular motor's movement becomes slower with the potential barrier increasing, but if the force is increased, the molecular motor''s movement becomes faster. The relation between the effective rate constant and the potential battler's height, and that between the effective rate constant and the value of the force are discussed. Our results are consistent with the experiments and relevant theoretical consideration, and can be used to explain some physiological phenomena.

  18. Theoretical Studies of the Relaxation Matrix for Molecular Systems

    Science.gov (United States)

    Ma, Qiancheng; Boulet, C.

    2016-06-01

    The phenomenon of collisional transfer of intensity due to line mixing has an increasing importance for atmospheric monitoring. From a theoretical point of view, all relevant information about the collisional processes is contained in the relaxation matrix where the diagonal elements give half-widths and shifts, and the off-diagonal elements correspond to line interferences. For simple systems such as those consisting of diatom-atom or diatom-diatom, accurate fully quantum calculations based on interaction potentials are feasible. However, fully quantum calculations become unrealistic for more complex systems. On the other hand, the semi-classical Robert-Bonamy formalism, which has been widely used to calculate half-widths and shifts for decades, fails in calculating the off-diagonal matrix elements resulting from applying the isolated line approximation. As a result, in order to simulate atmospheric spectra where the effects from line mixing are important, semi-empirical fitting or scaling laws such as the energy corrected sudden (ECS) and the infinite order sudden (IOS) models are commonly used. Recently, we have found that in developing this semi-classical line shape theory, to rely on the isolated line approximation is not necessary. By eliminating this unjustified assumption, and accurately evaluating matrix elements of the exponential operators, we have developed a more capable formalism that enables one not only to reduce uncertainties for calculated half-widths and shifts, but also to calculate the whole relaxation matrix. This implies that we can address the line mixing with the semi-classical theory based on interaction potentials between molecular absorber and molecular perturber. We have applied this formalism for Raman and infrared spectra of linear and asymmetric-top molecules. Recently, the method has been extended into symmetric-tops with inverse symmetry such as the NH3 molecule. Our calculated half-widths of NH3 lines in the νb{1} and the pure

  19. Molecular Modeling Approach to Cardiovascular Disease Targetting

    Directory of Open Access Journals (Sweden)

    Chandra Sekhar Akula,

    2010-05-01

    Full Text Available Cardiovascular disease, including stroke, is the leading cause of illness and death in the India. A number of studies have shown that inflammation of blood vessels is one of the major factors that increase the incidence of heart diseases, including arteriosclerosis (clogging of the arteries, stroke and myocardial infraction or heart attack. Studies have associated obesity and other components of metabolic syndrome, cardiovascular risk factors, with lowgradeinflammation. Furthermore, some findings suggest that drugs commonly prescribed to the lower cholesterol also reduce this inflammation, suggesting an additional beneficial effect of the stains. The recent development of angiotensin 11 (Ang11 receptor antagonists has enabled to improve significantly the tolerability profile of thisgroup of drugs while maintaining a high clinical efficacy. ACE2 is expressed predominantly in the endothelium and in renal tubular epithelium, and it thus may be an import new cardiovascular target. In the present study we modeled the structure of ACE and designed an inhibitor through using ARGUS lab and the validation of the Drug molecule is done basing on QSAR properties and Cache for this protein through CADD.

  20. Molecular modeling of protein materials: case study of elastin

    Science.gov (United States)

    Tarakanova, Anna; Buehler, Markus J.

    2013-09-01

    Molecular modeling of protein materials is a quickly growing area of research that has produced numerous contributions in fields ranging from structural engineering to medicine and biology. We review here the history and methods commonly employed in molecular modeling of protein materials, emphasizing the advantages for using modeling as a complement to experimental work. We then consider a case study of the protein elastin, a critically important ‘mechanical protein’ to exemplify the approach in an area where molecular modeling has made a significant impact. We outline the progression of computational modeling studies that have considerably enhanced our understanding of this important protein which endows elasticity and recoil to the tissues it is found in, including the skin, lungs, arteries and the heart. A vast collection of literature has been directed at studying the structure and function of this protein for over half a century, the first molecular dynamics study of elastin being reported in the 1980s. We review the pivotal computational works that have considerably enhanced our fundamental understanding of elastin's atomistic structure and its extraordinary qualities—focusing on two in particular: elastin's superb elasticity and the inverse temperature transition—the remarkable ability of elastin to take on a more structured conformation at higher temperatures, suggesting its effectiveness as a biomolecular switch. Our hope is to showcase these methods as both complementary and enriching to experimental approaches that have thus far dominated the study of most protein-based materials.

  1. MacSyFinder: a program to mine genomes for molecular systems with an application to CRISPR-Cas systems.

    Directory of Open Access Journals (Sweden)

    Sophie S Abby

    Full Text Available Biologists often wish to use their knowledge on a few experimental models of a given molecular system to identify homologs in genomic data. We developed a generic tool for this purpose.Macromolecular System Finder (MacSyFinder provides a flexible framework to model the properties of molecular systems (cellular machinery or pathway including their components, evolutionary associations with other systems and genetic architecture. Modelled features also include functional analogs, and the multiple uses of a same component by different systems. Models are used to search for molecular systems in complete genomes or in unstructured data like metagenomes. The components of the systems are searched by sequence similarity using Hidden Markov model (HMM protein profiles. The assignment of hits to a given system is decided based on compliance with the content and organization of the system model. A graphical interface, MacSyView, facilitates the analysis of the results by showing overviews of component content and genomic context. To exemplify the use of MacSyFinder we built models to detect and class CRISPR-Cas systems following a previously established classification. We show that MacSyFinder allows to easily define an accurate "Cas-finder" using publicly available protein profiles.MacSyFinder is a standalone application implemented in Python. It requires Python 2.7, Hmmer and makeblastdb (version 2.2.28 or higher. It is freely available with its source code under a GPLv3 license at https://github.com/gem-pasteur/macsyfinder. It is compatible with all platforms supporting Python and Hmmer/makeblastdb. The "Cas-finder" (models and HMM profiles is distributed as a compressed tarball archive as Supporting Information.

  2. Cellular modelling using P systems and process algebra

    Institute of Scientific and Technical Information of China (English)

    Francisco J.Romero-Campero; Marian Gheorghe; Gabriel Ciobanu; John M. Auld; Mario J. Pérez-Jiménez

    2007-01-01

    In this paper various molecular chemical interactions are modelled under different computational paradigms. P systems and π-calculus are used to describe intra-cellular reactions like protein-protein interactions and gene regulation control.

  3. Modeling stochastic kinetics of molecular machines at multiple levels: from molecules to modules.

    Science.gov (United States)

    Chowdhury, Debashish

    2013-06-04

    A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here.

  4. A Stochastic Markov Model for Coordinated Molecular Motors

    CERN Document Server

    Materassi, Donatello; Salapaka, Murti V

    2010-01-01

    Many cell functions are accomplished thanks to intracellular transport mechanisms of macromolecules along filaments. Molecular motors such as dynein or kinesin are proteins playing a primary role in these processes. The behavior of such proteins is quite well understood when there is only one of them moving a cargo particle. Indeed, numerous in vitro experiments have been performed to derive accurate models for a single molecular motor. However, in vivo macromolecules are often carried by multiple motors. The main focus of this paper is to provide an analysis of the behavior of more molecular motors interacting together in order to improve the understanding of their actual physiological behavior. Previous studies provide analyses based on results obtained from Monte Carlo simulations. Different from these studies, we derive an equipollent probabilistic model to describe the dynamics of multiple proteins coupled together and provide an exact theoretical analysis. We are capable of obtaining the probability den...

  5. Simulation of Dam Break Flow Using Quasi-Molecular Modelling

    Directory of Open Access Journals (Sweden)

    Sitthichai KULSRI

    2007-01-01

    Full Text Available We developed a new method based on quasi-molecular modelling to simulate dam break flow. Each quasi-molecule was a group of particles that interacted in a fashion entirely analogous to classical Newtonian molecular interactions. The tank had a base length of 58.4 cm. A water column with a base length of 14.6 cm and a height of 29.2 cm was initially supported on the right side by a vertical plate drawn up rapidly at time t = 0.0 s. The water fell under the influence of gravity acting vertically downwards. The numerical results were validated by quantitative comparison with a previous study. The predicted height and leading edge of the water column corresponded very well with experimental measurements from a previous study. Therefore, our new method based on quasi-molecular modelling showed its ability to adequately simulate a free surface problem.

  6. Interaction of quercetin with ovalbumin: Spectroscopic and molecular modeling studies

    Energy Technology Data Exchange (ETDEWEB)

    Lu Yan, E-mail: yanlu2001@sohu.co [College of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China); Wang Yunlai; Gao Shenghua; Wang Gongke; Yan Changling; Chen Dejun [College of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007 (China)

    2009-09-15

    The binding of quercetin (QCT) to ovalbumin (OVA) in aqueous solution was investigated by molecular spectroscopy and modeling at pH 7.4. The fluorescence, synchronous fluorescence and UV-absorption spectroscopies were employed to study the mode and the mechanism for this interaction. QCT binding is characterized by one high affinity binding site with the association constants of the order of 10{sup 5}. The distance between donor (OVA) and acceptor (QCT) was estimated according to Forster's theory of non-radiation energy transfer. Molecular docking showed that the QCT can bind to the active site of OVA. The binding dynamics was expounded by thermodynamic parameters, molecular modeling and accessible surface area calculation, which entails that hydrophobic interactions, hydrogen bonding and electrostatic forces stabilizes the interaction.

  7. Tunneling of electrons via rotor-stator molecular interfaces: combined ab initio and model study

    CERN Document Server

    Petreska, Irina; Pejov, Ljupco; Kocarev, Ljupco

    2015-01-01

    Tunneling of electrons through rotor-stator anthracene aldehyde molecular interfaces is studied with a combined ab initio and model approach. Molecular electronic structure calculated from first principles is utilized to model different shapes of tunneling barriers. Together with a rectangular barrier, we also consider a sinusoidal shape that captures the effects of the molecular internal structure more realistically. Quasiclassical approach with the Simmons' formula for current density is implemented. Special attention is paid on conformational dependence of the tunneling current. Our results confirm that the presence of the side aldehyde group enhances the interesting electronic properties of the pure anthracene molecule, making it a bistable system with geometry dependent transport properties. We also investigate the transition voltage and we show that confirmation dependent field emission could be observed in these molecular interfaces at realistically low voltages. The present study accompanies our previ...

  8. Ab initio centroid path integral molecular dynamics: Application to vibrational dynamics of diatomic molecular systems

    Science.gov (United States)

    Ohta, Yasuhito; Ohta, Koji; Kinugawa, Kenichi

    2004-01-01

    An ab initio centroid molecular dynamics (CMD) method is developed by combining the CMD method with the ab initio molecular orbital method. The ab initio CMD method is applied to vibrational dynamics of diatomic molecules, H2 and HF. For the H2 molecule, the temperature dependence of the peak frequency of the vibrational spectral density is investigated. The results are compared with those obtained by the ab initio classical molecular dynamics method and exact quantum mechanical treatment. It is shown that the vibrational frequency obtained from the ab initio CMD approaches the exact first excitation frequency as the temperature lowers. For the HF molecule, the position autocorrelation function is also analyzed in detail. The present CMD method is shown to well reproduce the exact quantum result for the information on the vibrational properties of the system.

  9. Multiscale Modeling of Complex Molecular Structure and Dynamics with MBN Explorer

    DEFF Research Database (Denmark)

    Solov'yov, Ilia A.; Korol, Andrei V.; Solov'yov, Andrey V.

    of molecular and random walk dynamics. The package allows the use of a broad variety of interatomic potentials and can, e.g., be configured to select any subset of a molecular system as rigid fragments, whenever a significant reduction in the number of dynamical degrees of freedom is required for computational......This book introduces readers to MesoBioNano (MBN) Explorer - a multi-purpose software package designed to model molecular systems at various levels of size and complexity. In addition, it presents a specially designed multi-task toolkit and interface - the MBN Studio - which enables the set......-up of input files, controls the simulations, and supports the subsequent visualization and analysis of the results obtained. The book subsequently provides a systematic description of the capabilities of this universal and powerful software package within the framework of computational molecular science...

  10. Multiscale Modeling of Complex Molecular Structure and Dynamics with MBN Explorer

    DEFF Research Database (Denmark)

    Solov'yov, Ilia A.; Korol, Andrei V.; Solov'yov, Andrey V.

    This book introduces readers to MesoBioNano (MBN) Explorer - a multi-purpose software package designed to model molecular systems at various levels of size and complexity. In addition, it presents a specially designed multi-task toolkit and interface - the MBN Studio - which enables the set......-up of input files, controls the simulations, and supports the subsequent visualization and analysis of the results obtained. The book subsequently provides a systematic description of the capabilities of this universal and powerful software package within the framework of computational molecular science...... of molecular and random walk dynamics. The package allows the use of a broad variety of interatomic potentials and can, e.g., be configured to select any subset of a molecular system as rigid fragments, whenever a significant reduction in the number of dynamical degrees of freedom is required for computational...

  11. Molecular mechanism of interaction between norfloxacin and trypsin studied by molecular spectroscopy and modeling

    Science.gov (United States)

    Lu, Yan; Wang, Gongke; Lu, Xiumin; Lv, Juan; Xu, Meihua; Zhang, Weiwei

    2010-01-01

    The molecular mechanism of the binding of norfloxacin (NRF) to trypsin was investigated by fluorescence, synchronous fluorescence and UV-vis absorbance spectroscopy and molecular modeling at physiological conditions. The quenching mechanism and the binding mode were investigated in terms of the association constants and basic thermodynamic parameters. The results of spectroscopic measurements suggested that NRF have a strong ability to quench the intrinsic fluorescence of trypsin through static quenching procedure. Moreover, fluorescence experiments were also performed at different values of pH to elucidate the effect of pH on the binding. The NRF-trypsin complex was stabilized by hydrophobic forces and hydrogen bonding, via tryptophan residue as indicated from the thermodynamic parameters, which was consistent with the results of molecular docking and accessible surface area calculations.

  12. ECO-BIOLOGICAL SYSTEM MODELING

    Directory of Open Access Journals (Sweden)

    T. I. Burak

    2015-01-01

    Full Text Available The methodology for computer modeling of complex eco-biological models is presented in this paper. It is based on system approach of J. Forrester. Developed methodology is universal for complex ecological and biological systems. Modeling algorithm considers specialties of eco-biological systems and shows adequate and accurate results in practice. 

  13. Design of optimal collimation for dedicated molecular breast imaging systems

    Energy Technology Data Exchange (ETDEWEB)

    Weinmann, Amanda L.; Hruska, Carrie B.; O' Connor, Michael K. [Department of Radiology, Division of Nuclear Medicine, Mayo Clinic, Rochester, Minnesota 55905 (United States)

    2009-03-15

    Molecular breast imaging (MBI) is a functional imaging technique that uses specialized small field-of-view gamma cameras to detect the preferential uptake of a radiotracer in breast lesions. MBI has potential to be a useful adjunct method to screening mammography for the detection of occult breast cancer. However, a current limitation of MBI is the high radiation dose (a factor of 7-10 times that of screening mammography) associated with current technology. The purpose of this study was to optimize the gamma camera collimation with the aim of improving sensitivity while retaining adequate resolution for the detection of sub-10-mm lesions. Square-hole collimators with holes matched to the pixilated cadmium zinc telluride detector elements of the MBI system were designed. Data from MBI patient studies and parameters of existing dual-head MBI systems were used to guide the range of desired collimator resolutions, source-to-collimator distances, pixel sizes, and collimator materials that were examined. General equations describing collimator performance for a conventional gamma camera were used in the design process along with several important adjustments to account for the specialized imaging geometry of the MBI system. Both theoretical calculations and a Monte Carlo model were used to measure the geometric efficiency (or sensitivity) and resolution of each designed collimator. Results showed that through optimal collimation, collimator sensitivity could be improved by factors of 1.5-3.2, while maintaining a collimator resolution of either {<=}5 or {<=}7.5 mm at a distance of 3 cm from the collimator face. These gains in collimator sensitivity permit an inversely proportional drop in the required dose to perform MBI.

  14. United polarizable multipole water model for molecular mechanics simulation

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Rui; Wang, Qiantao; Ren, Pengyu, E-mail: pren@mail.utexas.edu [Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712 (United States); Wang, Lee-Ping; Pande, Vijay S. [Department of Chemistry, Stanford University, Stanford, California 94305 (United States)

    2015-07-07

    We report the development of a united AMOEBA (uAMOEBA) polarizable water model, which is computationally 3–5 times more efficient than the three-site AMOEBA03 model in molecular dynamics simulations while providing comparable accuracy for gas-phase and liquid properties. In this coarse-grained polarizable water model, both electrostatic (permanent and induced) and van der Waals representations have been reduced to a single site located at the oxygen atom. The permanent charge distribution is described via the molecular dipole and quadrupole moments and the many-body polarization via an isotropic molecular polarizability, all located at the oxygen center. Similarly, a single van der Waals interaction site is used for each water molecule. Hydrogen atoms are retained only for the purpose of defining local frames for the molecular multipole moments and intramolecular vibrational modes. The parameters have been derived based on a combination of ab initio quantum mechanical and experimental data set containing gas-phase cluster structures and energies, and liquid thermodynamic properties. For validation, additional properties including dimer interaction energy, liquid structures, self-diffusion coefficient, and shear viscosity have been evaluated. The results demonstrate good transferability from the gas to the liquid phase over a wide range of temperatures, and from nonpolar to polar environments, due to the presence of molecular polarizability. The water coordination, hydrogen-bonding structure, and dynamic properties given by uAMOEBA are similar to those derived from the all-atom AMOEBA03 model and experiments. Thus, the current model is an accurate and efficient alternative for modeling water.

  15. Multi-Scale Molecular Deconstruction of the Serotonin Neuron System.

    Science.gov (United States)

    Okaty, Benjamin W; Freret, Morgan E; Rood, Benjamin D; Brust, Rachael D; Hennessy, Morgan L; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N; Dymecki, Susan M

    2015-11-18

    Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal principles underlying system organization, 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers sertonergic subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance.

  16. Promoting Representational Competence with Molecular Models in Organic Chemistry

    Science.gov (United States)

    Stull, Andrew T.; Gainer, Morgan; Padalkar, Shamin; Hegarty, Mary

    2016-01-01

    Mastering the many different diagrammatic representations of molecules used in organic chemistry is challenging for students. This article summarizes recent research showing that manipulating 3-D molecular models can facilitate the understanding and use of these representations. Results indicate that students are more successful in translating…

  17. The Use of Molecular Modeling Programs in Medicinal Chemistry Instruction.

    Science.gov (United States)

    Harrold, Marc W.

    1992-01-01

    This paper describes and evaluates the use of a molecular modeling computer program (Alchemy II) in a pharmaceutical education program. Provided are the hardware requirements and basic program features as well as several examples of how this program and its features have been applied in the classroom. (GLR)

  18. Promoting Representational Competence with Molecular Models in Organic Chemistry

    Science.gov (United States)

    Stull, Andrew T.; Gainer, Morgan; Padalkar, Shamin; Hegarty, Mary

    2016-01-01

    Mastering the many different diagrammatic representations of molecules used in organic chemistry is challenging for students. This article summarizes recent research showing that manipulating 3-D molecular models can facilitate the understanding and use of these representations. Results indicate that students are more successful in translating…

  19. Molecular biology of the renin-angiotensin system

    Energy Technology Data Exchange (ETDEWEB)

    Dzau, V.J.; Burt, D.W.; Pratt, R.E. (Harvard Medical School, Boston, MA (USA))

    1988-10-01

    This paper reviews the molecular biology of the renin-angiotensin system. The renin gene structure is analyzed in detail, including an examination of the putative regulatory regions. The combined action of these regulatory sequences would result in the complex, tissue-specific expression and regulation observed in vivo. The expression of the tissue renin-angiotensin systems, which may have important physiological functions, is also described. In addition, the pathway of renin biosynthesis and secretion is reviewed. This includes speculation on the fate of circulating prorenin and the physiological role of multiple renin forms and secretory pathways. The molecular approaches described in this paper have greatly advanced our knowledge of the biology of the renin-angiotensin system. Future studies using these and other approaches should provide further insight into this complex system.

  20. Molecular clocks and the early evolution of metazoan nervous systems.

    Science.gov (United States)

    Wray, Gregory A

    2015-12-19

    The timing of early animal evolution remains poorly resolved, yet remains critical for understanding nervous system evolution. Methods for estimating divergence times from sequence data have improved considerably, providing a more refined understanding of key divergences. The best molecular estimates point to the origin of metazoans and bilaterians tens to hundreds of millions of years earlier than their first appearances in the fossil record. Both the molecular and fossil records are compatible, however, with the possibility of tiny, unskeletonized, low energy budget animals during the Proterozoic that had planktonic, benthic, or meiofaunal lifestyles. Such animals would likely have had relatively simple nervous systems equipped primarily to detect food, avoid inhospitable environments and locate mates. The appearance of the first macropredators during the Cambrian would have changed the selective landscape dramatically, likely driving the evolution of complex sense organs, sophisticated sensory processing systems, and diverse effector systems involved in capturing prey and avoiding predation. © 2015 The Author(s).

  1. Validation of risk stratification models in acute myeloid leukemia using sequencing-based molecular profiling.

    Science.gov (United States)

    Wang, M; Lindberg, J; Klevebring, D; Nilsson, C; Mer, A S; Rantalainen, M; Lehmann, S; Grönberg, H

    2017-10-01

    Risk stratification of acute myeloid leukemia (AML) patients needs improvement. Several AML risk classification models based on somatic mutations or gene-expression profiling have been proposed. However, systematic and independent validation of these models is required for future clinical implementation. We performed whole-transcriptome RNA-sequencing and panel-based deep DNA sequencing of 23 genes in 274 intensively treated AML patients (Clinseq-AML). We also utilized the The Cancer Genome Atlas (TCGA)-AML study (N=142) as a second validation cohort. We evaluated six previously proposed molecular-based models for AML risk stratification and two revised risk classification systems combining molecular- and clinical data. Risk groups stratified by five out of six models showed different overall survival in cytogenetic normal-AML patients in the Clinseq-AML cohort (P-value0.5). Risk classification systems integrating mutational or gene-expression data were found to add prognostic value to the current European Leukemia Net (ELN) risk classification. The prognostic value varied between models and across cohorts, highlighting the importance of independent validation to establish evidence of efficacy and general applicability. All but one model replicated in the Clinseq-AML cohort, indicating the potential for molecular-based AML risk models. Risk classification based on a combination of molecular and clinical data holds promise for improved AML patient stratification in the future.

  2. Inducibility of a molecular bioreporter system by heavy metals

    Energy Technology Data Exchange (ETDEWEB)

    Klimowski, L.; Rayms-Keller, A.; Olson, K.E.; Yang, R.S.H.; Tessari, J.; Carlson, J.; Beaty, B. [Colorado State Univ., Fort Collins, CO (United States)

    1996-02-01

    The authors have developed a molecular bioreporter model for detecting an invertebrate response to heavy metals in streams. The bioreporter system, pMt2-luc, utilizes a Drosophila melanogaster metallothionein promoter to regulate luciferase expression in stably transformed mosquito cells.The LucC5 clone, which was isolated from pMt2-luc transformed, hygromycin-resistant C6/36 (Aedes albopictus) cells, demonstrated a 12-fold increase in luciferase-specific activity 48 h after exposure to 13 ppm copper (Cu). In addition to Cu, exposure of LucC5 cells to 19 ppm lead (Pb) or 3 ppm mercury (Hg) for 48 h induced luciferase expression threefold and fourfold, respectively. Exposures of up to 30 ppm arsenic (As), 8 ppm cadmium (Cd), 7 ppm chromium (Cr), or 5 ppm nickel (Ni) had no effect on luciferase induction. LucC5 cells exposed to metal mixtures of 13 ppm Cu and 19 ppm Pb yielded an additive response with a 14-fold increase in luciferase expression. When organic chemicals such as phenol (3 ppm) were mixed with 13 ppm Cu, 19 ppm Pb, or 3 ppm Hg a significant reduction in luciferase activity was noted. Additionally, atomic absorption spectroscopy suggested that two of the metals, Cu and Pb, show marked differences in accumulation within the LucC5 cell line.

  3. Quantum dynamics of bio-molecular systems in noisy environments

    OpenAIRE

    Huelga S.F.; Plenio M.B.

    2012-01-01

    We discuss three different aspects of the quantum dynamics of bio-molecular systems and more generally complex networks in the presence of strongly coupled environments. Firstly, we make a case for the systematic study of fundamental structural elements underlying the quantum dynamics of these systems, identify such elements and explore the resulting interplay of quantum dynamics and environmental decoherence. Secondly, we critically examine some existing approaches to the numerical descripti...

  4. Model HULIS compounds in nanoaerosol clusters - investigations of surface tension and aggregate formation using molecular dynamics simulations

    National Research Council Canada - National Science Library

    T. Hede; X. Li; C. Leck; Y. Tu; H. Ågren

    2011-01-01

    .... In this study we use molecular dynamics simulations to show that model humic-like substances (HULIS) in systems containing 10 000 water molecules mimic experimental data well referring to reduction of surface tension...

  5. Molecular model and ReaxFF molecular dynamics simulation of coal vitrinite pyrolysis.

    Science.gov (United States)

    Li, Wu; Zhu, Yan-ming; Wang, Geoff; Wang, Yang; Liu, Yu

    2015-08-01

    Vitrinite in coal, the mainly generating methane maceral, plays an important role in hydrocarbon generation of coal. This study aims at obtaining products formation mechanism of vitrinite pyrolysis, and hence determining the chemical bond, molecular liquefaction activity, and reactions mechanism of methane and C2-4 during pyrolysis. The ReaxFF molecular dynamics (MD) simulation was carried out at temperature of 1500 K in order to investigate the mechanism of vitrinite pyrolysis. Initially, a minimum energy conformational structure model was constrained by a combination of elemental and carbon-13 nuclear magnetic resonance ((13)C NMR) literature data. The model analysis shows the chemical and physical parameters of vitrinite pyrolysis are broadly consistent with the experimental data. Based on the molecular model, ReaxFF MD simulations further provide information of unimolecule such as bond length, and chemical shift, and hence the total population and energy of main products. Molecules bond and pyrolysis fragments, based on active bond analyzed, revealed pyrolysis products of single vitrinite molecule with aliphatic C-C bond, especially ring and chain aliphatic as liquefaction activity. The molecular cell whose density is 0.9 g/cm(3) with lowest energy accords with the experimental density 1.33 g/cm(3). The content of main products after pyrolysis, classifying as CH4, H2O, and H2, was changed along with the increasing temperature. The gas molecule, fragments and generation pathways of CO2, H2, CH4, and C2H6 were also elucidated. These results show agreement with experimental observations, implying that MD simulation can provide reasonable explanation for the reaction processes involved in coal vitrinite pyrolysis. Thus the mechanism of coal hydrocarbon generation was revealed at the molecular level.

  6. Molecular absorption cryogenic cooler for liquid hydrogen propulsion systems

    Science.gov (United States)

    Klein, G. A.; Jones, J. A.

    1982-01-01

    A light weight, long life molecular absorption cryogenic cooler (MACC) system is described which can use low temperature waste heat to provide cooling for liquid hydrogen propellant tanks for interplanetary spacecraft. Detailed tradeoff studies were made to evaluate the refrigeration system component interactions in order to minimize the mass of the spacecraft cooler system. Based on this analysis a refrigerator system mass of 31 kg is required to provide the .48 watts of cooling required by a 2.3 meter diameter liquid hydrogen tank.

  7. Modelling dishes and exploring culinary 'precisions': the two issues of molecular gastronomy.

    Science.gov (United States)

    This, Hervé

    2005-04-01

    The scientific strategy of molecular gastronomy includes modelling 'culinary definitions' and experimental explorations of 'culinary precisions'. A formalism that describes complex dispersed systems leads to a physical classification of classical sauces, as well as to the invention of an infinite number of new dishes.

  8. DYNAMIC SURFACE BOUNDARY-CONDITIONS - A SIMPLE BOUNDARY MODEL FOR MOLECULAR-DYNAMICS SIMULATIONS

    NARCIS (Netherlands)

    JUFFER, AH; BERENDSEN, HJC

    1993-01-01

    A simple model for the treatment of boundaries in molecular dynamics simulations is presented. The method involves the positioning of boundary atoms on a surface that surrounds a system of interest. The boundary atoms interact with the inner region and represent the effect of atoms outside the surfa

  9. Multiscale Modeling of Complex Molecular Structure and Dynamics with MBN Explorer

    DEFF Research Database (Denmark)

    Solov'yov, Ilia A.; Korol, Andrei V.; Solov'yov, Andrey V.

    This book introduces readers to MesoBioNano (MBN) Explorer - a multi-purpose software package designed to model molecular systems at various levels of size and complexity. In addition, it presents a specially designed multi-task toolkit and interface - the MBN Studio - which enables the set...

  10. Molecular system generation with strong resonance optical pumping

    Energy Technology Data Exchange (ETDEWEB)

    Kuntsevich, B.F.; Churakov, V.V.

    1977-03-01

    A study was made of molecular system generation modulated by three oscillating levels with a rotating structure with strong resonance optical pumping. Molecular behavior of the active medium is described by equations for the density matrix. The relationship between the amplification coefficient and pressure at various pumping intensities was examined. In approaching the assigned pumping field, an examination was made of how the generation field is affected by the volumetric density of the pumping energy, partial pressure of the buffer gas and frequency difference in the pumping channel.

  11. Role of multipole moments in electric-field-induced order of dense molecular systems.

    Science.gov (United States)

    Acebal, Pablo; Carretero, Luis; Blaya, Salvador

    2010-07-12

    A new model is developed to describe the orientational order of dense molecular systems under an applied external electric field as a function of the n-particle distribution functions of a system under no external perturbation. From an approximation of this expression, the effects of several variables on this orientational order, such as the microscopic properties of the oriented molecules (the molecular geometry and multipole moments) and the solvent or matrix properties, are studied. The theoretical predictions show that, for a correct description of the orientational order, quadrupole and octupole moments must be included, as they play an important role in the orientational order achieved, depending on the molecular geometry. Furthermore, to verify the validity of the model, theoretical predictions are compared with experimental results, and show a good concordance.

  12. Biomimetic polymers of plant cutin: an approach from molecular modeling.

    Science.gov (United States)

    San-Miguel, Miguel A; Oviedo, Jaime; Heredia-Guerrero, Jose Alejandro; Heredia, Antonio; Benitez, Jose Jesus

    2014-07-01

    Biomimetics of materials is based on adopting and reproducing a model in nature with a well-defined functionality optimized through evolution. An example is barrier polymers that protect living tissues from the environment. The protecting layer of fruits, leaves, and non-lignified stems is the plant cuticle. The cuticle is a complex system in which the cutin is the main component. Cutin is a biopolyester made of polyhydroxylated carboxylic acids of 16 and 18 carbon atoms. The biosynthesis of cutin in plants is not well understood yet, but a direct chemical route involving the self-assembly of either molecules or molecular aggregates has been proposed. In this work, we present a combined study using experimental and simulation techniques on self-assembled layers of monomers selectively functionalized with hydroxyl groups. Our results demonstrate that the number and position of the hydroxyl groups are critical for the interaction between single molecules and the further rearrangement. Also, the presence of lateral hydroxyl groups reinforces lateral interactions and favors the bi-dimensional growth (2D), while terminal hydroxyl groups facilitate the formation of a second layer caused by head-tail interactions. The balance of 2D/3D growth is fundamental for the plant to create a protecting layer both large enough in 2D and thick enough in 3D.

  13. Antibacterial kaolinite/urea/chlorhexidine nanocomposites: Experiment and molecular modelling

    Energy Technology Data Exchange (ETDEWEB)

    Holešová, Sylva, E-mail: sylva.holesova@vsb.cz [Nanotechnology Centre, VŠB – Technical University of Ostrava, 17.listopadu 15/2172, CZ-708 33 Ostrava, Poruba (Czech Republic); IT4Innovations Centre of Excellence, VŠB – Technical University of Ostrava, 17.listopadu 15/2172, CZ-708 33 Ostrava, Poruba (Czech Republic); Valášková, Marta; Hlaváč, Dominik [Nanotechnology Centre, VŠB – Technical University of Ostrava, 17.listopadu 15/2172, CZ-708 33 Ostrava, Poruba (Czech Republic); IT4Innovations Centre of Excellence, VŠB – Technical University of Ostrava, 17.listopadu 15/2172, CZ-708 33 Ostrava, Poruba (Czech Republic); Madejová, Jana [Institute of Inorganic Chemistry, SAS, Dúbravská cesta 9, SK-845 36 Bratislava (Slovakia); Samlíková, Magda; Tokarský, Jonáš [Nanotechnology Centre, VŠB – Technical University of Ostrava, 17.listopadu 15/2172, CZ-708 33 Ostrava, Poruba (Czech Republic); IT4Innovations Centre of Excellence, VŠB – Technical University of Ostrava, 17.listopadu 15/2172, CZ-708 33 Ostrava, Poruba (Czech Republic); Pazdziora, Erich [Institute of Public Health Ostrava, Centre of Clinical Laboratories, Partyzánské náměstí 7, CZ-702 00 Ostrava (Czech Republic)

    2014-06-01

    Clay minerals are commonly used materials in pharmaceutical production both as inorganic carriers or active agents. The purpose of this study is the preparation and characterization of clay/antibacterial drug hybrids which can be further included in drug delivery systems for treatment oral infections. Novel nanocomposites with antibacterial properties were successfully prepared by ion exchange reaction from two types of kaolinite/urea intercalates and chlorhexidine diacetate. Intercalation compounds of kaolinite were prepared by reaction with solid urea in the absence of solvents (dry method) as well as with urea aqueous solution (wet method). The antibacterial activity of two prepared samples against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa was evaluated by finding the minimum inhibitory concentration (MIC). Antibacterial studies of both samples showed the lowest MIC values (0.01%, w/v) after 1 day against E. faecalis, E. coli and S. aureus. A slightly worse antibacterial activity was observed against P. aeruginosa (MIC 0.12%, w/v) after 1 day. Since samples showed very good antibacterial activity, especially after 1 day of action, this means that these samples can be used as long-acting antibacterial materials. Prepared samples were characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The experimental data are supported by results of molecular modelling.

  14. Antibacterial kaolinite/urea/chlorhexidine nanocomposites: Experiment and molecular modelling

    Science.gov (United States)

    Holešová, Sylva; Valášková, Marta; Hlaváč, Dominik; Madejová, Jana; Samlíková, Magda; Tokarský, Jonáš; Pazdziora, Erich

    2014-06-01

    Clay minerals are commonly used materials in pharmaceutical production both as inorganic carriers or active agents. The purpose of this study is the preparation and characterization of clay/antibacterial drug hybrids which can be further included in drug delivery systems for treatment oral infections. Novel nanocomposites with antibacterial properties were successfully prepared by ion exchange reaction from two types of kaolinite/urea intercalates and chlorhexidine diacetate. Intercalation compounds of kaolinite were prepared by reaction with solid urea in the absence of solvents (dry method) as well as with urea aqueous solution (wet method). The antibacterial activity of two prepared samples against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa was evaluated by finding the minimum inhibitory concentration (MIC). Antibacterial studies of both samples showed the lowest MIC values (0.01%, w/v) after 1 day against E. faecalis, E. coli and S. aureus. A slightly worse antibacterial activity was observed against P. aeruginosa (MIC 0.12%, w/v) after 1 day. Since samples showed very good antibacterial activity, especially after 1 day of action, this means that these samples can be used as long-acting antibacterial materials. Prepared samples were characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The experimental data are supported by results of molecular modelling.

  15. Models for the study of whole systems.

    Science.gov (United States)

    Bell, Iris R; Koithan, Mary

    2006-12-01

    This article summarizes a network and complex systems science model for research on whole systems of complementary and alternative medicine (CAM) such as homeopathy and traditional Chinese medicine. The holistic concepts of networks and nonlinear dynamical complex systems are well matched to the global and interactive perspectives of whole systems of CAM, whereas the reductionistic science model is well matched to the isolated local organ, cell, and molecular mechanistic perspectives of pharmaceutically based biomedicine. Whole systems of CAM are not drugs with specific actions. The diagnostic and therapeutic approaches of whole systems of CAM produce effects that involve global and patterned shifts across multiple subsystems of the person as a whole. For homeopathy, several characteristics of complex systems, including the probabilistic nature of attractor patterns, variable sensitivity of complex systems to initial conditions, and emergent behaviors in the evolution of a system in its full environmental context over time, could help account for the mixed basic science and controlled clinical trial research findings, in contrast with the consistently positive outcomes of observational studies in the literature. Application of theories and methods from complex systems and network science can open a new era of advances in understanding factors that lead to good versus poor individual global outcome patterns and to rational triage of patients to one type of care over another. The growing reliance on complex systems thinking and systems biology for cancer research affords a unique opportunity to bridge between the CAM and conventional medical worlds with some common language and conceptual models.

  16. Mathematical System Theory and System Modeling

    OpenAIRE

    1980-01-01

    Choosing models related effectively to the questions to be addressed is a central issue in the craft of systems analysis. Since the mathematical description the analyst chooses constrains the types of issues he candeal with, it is important for these models to be selected so as to yield limitations that are acceptable in view of the questions the systems analysis seeks to answer. In this paper, the author gives an overview of the central issues affecting the question of model choice. To ...

  17. Mathematical model of an optically pumped molecular laser

    CSIR Research Space (South Africa)

    Botha, LR

    2009-07-01

    Full Text Available pumped molecular laser Dr L R Botha, Dr C Bollig, D Esser, C Jacobs, D Preussler SAIP 2009 Durban Page 2 © CSIR 2008 www.csir.co.za Structure of talk • Introduction • Overview of HBr laser • Numerical Model • Comparison... µm laser ring oscillator & pre-amplifier 1.9 µm Optically Pumped Molecular laser @ 4 µm 95:5 HBr Absorption cell Fast detector 2.064 µm ± 1 nm Feedback control box Feedback loop 1 P ie zo m o u nt Fast detector Feedback loop 2 Gas...

  18. Multi-level molecular modelling for plasma medicine

    Science.gov (United States)

    Bogaerts, Annemie; Khosravian, Narjes; Van der Paal, Jonas; Verlackt, Christof C. W.; Yusupov, Maksudbek; Kamaraj, Balu; Neyts, Erik C.

    2016-02-01

    Modelling at the molecular or atomic scale can be very useful for obtaining a better insight in plasma medicine. This paper gives an overview of different atomic/molecular scale modelling approaches that can be used to study the direct interaction of plasma species with biomolecules or the consequences of these interactions for the biomolecules on a somewhat longer time-scale. These approaches include density functional theory (DFT), density functional based tight binding (DFTB), classical reactive and non-reactive molecular dynamics (MD) and united-atom or coarse-grained MD, as well as hybrid quantum mechanics/molecular mechanics (QM/MM) methods. Specific examples will be given for three important types of biomolecules, present in human cells, i.e. proteins, DNA and phospholipids found in the cell membrane. The results show that each of these modelling approaches has its specific strengths and limitations, and is particularly useful for certain applications. A multi-level approach is therefore most suitable for obtaining a global picture of the plasma-biomolecule interactions.

  19. Preliminary results on molecular modeling of asphaltenes using structure elucidation programs in conjunction with molecular simulation programs

    Energy Technology Data Exchange (ETDEWEB)

    Kowalewski, I.; Vandenbroucke, M.; Huc, A.Y.; Taylor, M.J.; Faulon, J.L. [Institut Francais du Petrole, Rueil-Malmaison (France). Division Geologie-Geochimie

    1996-01-01

    Molecular modeling using structure elucidation programs in conjunction with molecular simulation programs has been performed on asphaltene molecules, the heaviest fraction of crude oil, in order to obtain a chemical model allowing the tentative study of their physicochemical properties. Boscan asphaltenes (Venezuela) derived from a marine source rock have been analysed. The different steps of this molecular modeling are described. First, a 3-D chemical representation of Boscan asphaltene is defined from an analytical data set. Second, the results of molecular dynamic simulations indicate that only a few stable conformations are possible due to the high reticulation of the model of the asphaltene unit obtained. 42 refs., 6 figs., 9 tabs.

  20. Meaningful timescales from Monte Carlo simulations of molecular systems

    CERN Document Server

    Costa, Liborio I

    2016-01-01

    A new Markov Chain Monte Carlo method for simulating the dynamics of molecular systems with atomistic detail is introduced. In contrast to traditional Kinetic Monte Carlo approaches, where the state of the system is associated with minima in the energy landscape, in the proposed method, the state of the system is associated with the set of paths traveled by the atoms and the transition probabilities for an atom to be displaced are proportional to the corresponding velocities. In this way, the number of possible state-to-state transitions is reduced to a discrete set, and a direct link between the Monte Carlo time step and true physical time is naturally established. The resulting rejection-free algorithm is validated against event-driven molecular dynamics: the equilibrium and non-equilibrium dynamics of hard disks converge to the exact results with decreasing displacement size.

  1. MOLECULAR VALIDATED MODEL FOR ADSORPTION OF PROTONATED DYE ON LDH

    Directory of Open Access Journals (Sweden)

    B. M. Braga

    Full Text Available Abstract Hydrotalcite-like compounds are anionic clays of scientific and technological interest for their use as ion exchange materials, catalysts and modified electrodes. Surface phenomenon are important for all these applications. Although conventional analytical methods have enabled progress in understanding the behavior of anionic clays in solution, an evaluation at the atomic scale of the dynamics of their ionic interactions has never been performed. Molecular simulation has become an extremely useful tool to provide this perspective. Our purpose is to validate a simplified model for the adsorption of 5-benzoyl-4-hydroxy-2-methoxy-benzenesulfonic acid (MBSA, a prototype molecule of anionic dyes, onto a hydrotalcite surface. Monte Carlo simulations were performed in the canonical ensemble with MBSA ions and a pore model of hydrotalcite using UFF and ClayFF force fields. The proposed molecular model has allowed us to reproduce experimental data of atomic force microscopy. Influences of protonation during the adsorption process are also presented.

  2. Quantum Mechanics/Molecular Mechanics Modeling of Drug Metabolism

    DEFF Research Database (Denmark)

    Lonsdale, Richard; Fort, Rachel M; Rydberg, Patrik;

    2016-01-01

    The mechanism of cytochrome P450(CYP)-catalyzed hydroxylation of primary amines is currently unclear and is relevant to drug metabolism; previous small model calculations have suggested two possible mechanisms: direct N-oxidation and H-abstraction/rebound. We have modeled the N-hydroxylation of (R......)-mexiletine in CYP1A2 with hybrid quantum mechanics/molecular mechanics (QM/MM) methods, providing a more detailed and realistic model. Multiple reaction barriers have been calculated at the QM(B3LYP-D)/MM(CHARMM27) level for the direct N-oxidation and H-abstraction/rebound mechanisms. Our calculated barriers...... indicate that the direct N-oxidation mechanism is preferred and proceeds via the doublet spin state of Compound I. Molecular dynamics simulations indicate that the presence of an ordered water molecule in the active site assists in the binding of mexiletine in the active site...

  3. Interferences in Photodetachment of a Negative Molecular Ion Model

    Institute of Scientific and Technical Information of China (English)

    A. Afaq; DU Meng-Li

    2008-01-01

    By employing a two-center model, the total and differential cross sections in the photodetachment of "a negative molecular ion" are studied theoretically and obtained for the case of light polarization parallel to the molecular axis. We find that in contrast to the smooth behavior of the total cross section for perpendicular polarized light, the cross section for parallel polarized light shows an interesting oscillatory structure. The oscillations in the total cross section may provide a method to determine the distance between the two centers. We explain the oscillation in the total cross section as an interference effect using closed-orbit theory. We also calculated the detached-electron flux distributions on a screen placed at a large distance from the negative molecular ion. The distributions display multiple-ring-like interference patterns. Such interference patterns are similar to those in the photodetachment microscopy experiments.

  4. SWIFT MODELLER: a Java based GUI for molecular modeling.

    Science.gov (United States)

    Mathur, Abhinav; Shankaracharya; Vidyarthi, Ambarish S

    2011-10-01

    MODELLER is command line argument based software which requires tedious formatting of inputs and writing of Python scripts which most people are not comfortable with. Also the visualization of output becomes cumbersome due to verbose files. This makes the whole software protocol very complex and requires extensive study of MODELLER manuals and tutorials. Here we describe SWIFT MODELLER, a GUI that automates formatting, scripting and data extraction processes and present it in an interactive way making MODELLER much easier to use than before. The screens in SWIFT MODELLER are designed keeping homology modeling in mind and their flow is a depiction of its steps. It eliminates the formatting of inputs, scripting processes and analysis of verbose output files through automation and makes pasting of the target sequence as the only prerequisite. Jmol (3D structure visualization tool) has been integrated into the GUI which opens and demonstrates the protein data bank files created by the MODELLER software. All files required and created by the software are saved in a folder named after the work instance's date and time of execution. SWIFT MODELLER lowers the skill level required for the software through automation of many of the steps in the original software protocol, thus saving an enormous amount of time per instance and making MODELLER very easy to work with.

  5. Anticipatory dynamics of biological systems: from molecular quantum states to evolution

    Science.gov (United States)

    Igamberdiev, Abir U.

    2015-08-01

    Living systems possess anticipatory behaviour that is based on the flexibility of internal models generated by the system's embedded description. The idea was suggested by Aristotle and is explicitly introduced to theoretical biology by Rosen. The possibility of holding the embedded internal model is grounded in the principle of stable non-equilibrium (Bauer). From the quantum mechanical view, this principle aims to minimize energy dissipation in expense of long relaxation times. The ideas of stable non-equilibrium were developed by Liberman who viewed living systems as subdivided into the quantum regulator and the molecular computer supporting coherence of the regulator's internal quantum state. The computational power of the cell molecular computer is based on the possibility of molecular rearrangements according to molecular addresses. In evolution, the anticipatory strategies are realized both as a precession of phylogenesis by ontogenesis (Berg) and as the anticipatory search of genetic fixation of adaptive changes that incorporates them into the internal model of genetic system. We discuss how the fundamental ideas of anticipation can be introduced into the basic foundations of theoretical biology.

  6. Model Reduction of Hybrid Systems

    DEFF Research Database (Denmark)

    Shaker, Hamid Reza

    systems are derived in this thesis. The results are used for output feedback control of switched nonlinear systems. Model reduction of piecewise affine systems is also studied in this thesis. The proposed method is based on the reduction of linear subsystems inside the polytopes. The methods which......High-Technological solutions of today are characterized by complex dynamical models. A lot of these models have inherent hybrid/switching structure. Hybrid/switched systems are powerful models for distributed embedded systems design where discrete controls are applied to continuous processes...... of hybrid systems, designing controllers and implementations is very high so that the use of these models is limited in applications where the size of the state space is large. To cope with complexity, model reduction is a powerful technique. This thesis presents methods for model reduction and stability...

  7. Molecular simulations of self-assembly processes in metal-organic frameworks: Model dependence

    Science.gov (United States)

    Biswal, Debasmita; Kusalik, Peter G.

    2017-07-01

    Molecular simulation is a powerful tool for investigating microscopic behavior in various chemical systems, where the use of suitable models is critical to successfully reproduce the structural and dynamic properties of the real systems of interest. In this context, molecular dynamics simulation studies of self-assembly processes in metal-organic frameworks (MOFs), a well-known class of porous materials with interesting chemical and physical properties, are relatively challenging, where a reasonably accurate representation of metal-ligand interactions is anticipated to play an important role. In the current study, we both investigate the performance of some existing models and introduce and test new models to help explore the self-assembly in an archetypal Zn-carboxylate MOF system. To this end, the behavior of six different Zn-ion models, three solvent models, and two ligand models was examined and validated against key experimental structural parameters. To explore longer time scale ordering events during MOF self-assembly via explicit solvent simulations, it is necessary to identify a suitable combination of simplified model components representing metal ions, organic ligands, and solvent molecules. It was observed that an extended cationic dummy atom (ECDA) Zn-ion model combined with an all-atom carboxylate ligand model and a simple dipolar solvent model can reproduce characteristic experimental structures for the archetypal MOF system. The successful use of these models in extensive sets of molecular simulations, which provide key insights into the self-assembly mechanism of this archetypal MOF system occurring during the early stages of this process, has been very recently reported.

  8. Modelling on fuzzy control systems

    Institute of Scientific and Technical Information of China (English)

    LI; Hongxing(李洪兴); WANG; Jiayin(王加银); MIAO; Zhihong(苗志宏)

    2002-01-01

    A kind of modelling method for fuzzy control systems is first proposed here, which is calledmodelling method based on fuzzy inference (MMFI). It should be regarded as the third modelling method thatis different from two well-known modelling methods, that is, the first modelling method, mechanism modellingmethod (MMM), and the second modelling method, system identification modelling method (SlMM). Thismethod can, based on the interpolation mechanism on fuzzy logic system, transfer a group of fuzzy inferencerules describing a practice system into a kind of nonlinear differential equation with variable coefficients, calledHX equations, so that the mathematical model of the system can be obtained. This means that we solve thedifficult problem of how to get a model represented as differential equations on a complicated or fuzzy controlsystem.

  9. Easy creation of polymeric systems for molecular dynamics with Assemble!

    Science.gov (United States)

    Degiacomi, Matteo T.; Erastova, Valentina; Wilson, Mark R.

    2016-05-01

    We present Assemble!, a program greatly simplifying the preparation of molecular dynamics simulations of polymeric systems. The program is controlled either via command line or an intuitive Graphical User Interface, and runs on all major operating systems. Assemble! allows the creation of a desired system of polymer chains from constituent monomers, packs the chains into a box according to the required concentration and returns all the files needed for simulation with Gromacs. We illustrate the capabilities of Assemble! by demonstrating the easy preparation of a 300 monomers-long polyisoprene in hexane, and a heterogeneous mixture of polybutadiene.

  10. Between algorithm and model: different Molecular Surface definitions for the Poisson-Boltzmann based electrostatic characterization of biomolecules in solution

    OpenAIRE

    2012-01-01

    The definition of a molecular surface which is physically sound and computationally efficient is a very interesting and long standing problem in the implicit solvent continuum modeling of biomolecular systems as well as in the molecular graphics field. In this work, two molecular surfaces are evaluated with respect to their suitability for electrostatic computation as alternatives to the widely used Connolly-Richards surface: the blobby surface, an implicit Gaussian atom centered surface, and...

  11. Coupling lattice Boltzmann and molecular dynamics models for dense fluids

    Science.gov (United States)

    Dupuis, A.; Kotsalis, E. M.; Koumoutsakos, P.

    2007-04-01

    We propose a hybrid model, coupling lattice Boltzmann (LB) and molecular dynamics (MD) models, for the simulation of dense fluids. Time and length scales are decoupled by using an iterative Schwarz domain decomposition algorithm. The MD and LB formulations communicate via the exchange of velocities and velocity gradients at the interface. We validate the present LB-MD model in simulations of two- and three-dimensional flows of liquid argon past and through a carbon nanotube. Comparisons with existing hybrid algorithms and with reference MD solutions demonstrate the validity of the present approach.

  12. Tailoring approach for obtaining molecular orbitals of large systems

    Indian Academy of Sciences (India)

    Anuja P Rahalkar; Shridhar R Gadre

    2012-01-01

    Molecular orbitals (MO’s) within Hartree-Fock (HF) theory are of vital importance as they provide preliminary information of bonding and features such as electron localization and chemical reactivity. The contemporary literature treats the Kohn-Sham orbitals within density functional theory (DFT) equivalently to the MO's obtained within HF framework. The high scaling order of ab initio methods is the main hurdle in obtaining the MO's for large molecular systems. With this view, an attempt is made in the present work to employ molecular tailoring approach (MTA) for obtaining the complete set of MO's including occupied and virtual orbitals, for large molecules at HF and B3LYP levels of theory. The energies of highest occupied and lowest unoccupied molecular orbitals, and hence the band gaps, are accurately estimated by MTA for most of the test cases benchmarked in this study, which include -conjugated molecules. Typically, the root mean square errors of valence MO's are in range of 0.001 to 0.010 a.u. for all the test cases examined. MTA shows a time advantage factor of 2 to 3 over the corresponding actual calculation, for many of the systems reported.

  13. ANN expert system screening for illicit amphetamines using molecular descriptors

    Science.gov (United States)

    Gosav, S.; Praisler, M.; Dorohoi, D. O.

    2007-05-01

    The goal of this study was to develop and an artificial neural network (ANN) based on computed descriptors, which would be able to classify the molecular structures of potential illicit amphetamines and to derive their biological activity according to the similarity of their molecular structure with amphetamines of known toxicity. The system is necessary for testing new molecular structures for epidemiological, clinical, and forensic purposes. It was built using a database formed by 146 compounds representing drugs of abuse (mainly central stimulants, hallucinogens, sympathomimetic amines, narcotics and other potent analgesics), precursors, or derivatized counterparts. Their molecular structures were characterized by computing three types of descriptors: 38 constitutional descriptors (CDs), 69 topological descriptors (TDs) and 160 3D-MoRSE descriptors (3DDs). An ANN system was built for each category of variables. All three networks (CD-NN, TD-NN and 3DD-NN) were trained to distinguish between stimulant amphetamines, hallucinogenic amphetamines, and nonamphetamines. A selection of variables was performed when necessary. The efficiency with which each network identifies the class identity of an unknown sample was evaluated by calculating several figures of merit. The results of the comparative analysis are presented.

  14. Energy System Modeling with REopt

    Energy Technology Data Exchange (ETDEWEB)

    Simpkins, Travis; Anderson, Kate; Cutler, Dylan; Olis, Dan; Elgqvist, Emma; DiOrio, Nick; Walker, Andy

    2016-07-15

    This poster details how REopt - NREL's software modeling platform for energy systems integration and optimization - can help to model energy systems. Some benefits of modeling with REopt include optimizing behind the meter storage for cost and resiliency, optimizing lab testing, optimizing dispatch of utility scale storage, and quantifying renewable energy impact on outage survivability.

  15. Modeling of diffuse molecular gas applied to HD 102065 observations

    CERN Document Server

    Nehme, Cyrine; Boulanger, Francois; Forets, Guillaume Pineau des; Gry, Cecile

    2008-01-01

    Aims. We model a diffuse molecular cloud present along the line of sight to the star HD 102065. We compare our modeling with observations to test our understanding of physical conditions and chemistry in diffuse molecular clouds. Methods. We analyze an extensive set of spectroscopic observations which characterize the diffuse molecular cloud observed toward HD 102065. Absorption observations provide the extinction curve, H2, C I, CO, CH, and CH+ column densities and excitation. These data are complemented by observations of CII, CO and dust emission. Physical conditions are determined using the Meudon PDR model of UV illuminated gas. Results. We find that all observational results, except column densities of CH, CH+ and H2 in its excited (J > 2) levels, are consistent with a cloud model implying a Galactic radiation field (G~0.4 in Draine's unit), a density of 80 cm-3 and a temperature (60-80 K) set by the equilibrium between heating and cooling processes. To account for excited (J >2) H2 levels column densit...

  16. Discovery of Potential Inhibitors of Aldosterone Synthase from Chinese Herbs Using Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation Studies

    Science.gov (United States)

    Lu, Fang; Qiao, Liansheng; Chen, Xi; Li, Gongyu

    2016-01-01

    Aldosterone synthase (CYP11B2) is a key enzyme for the biosynthesis of aldosterone, which plays a significant role for the regulation of blood pressure. Excess aldosterone can cause the dysregulation of the renin-angiotensin-aldosterone system (RAAS) and lead to hypertension. Therefore, research and development of CYP11B2 inhibitor are regarded as a novel approach for the treatment of hypertension. In this study, the pharmacophore models of CYP11B2 inhibitors were generated and the optimal model was used to identify potential CYP11B2 inhibitors from the Traditional Chinese Medicine Database (TCMD, Version 2009). The hits were further refined by molecular docking and the interactions between compounds and CYP11B2 were analyzed. Compounds with high Fitvalue, high docking score, and expected interactions with key residues were selected as potential CYP11B2 inhibitors. Two most promising compounds, ethyl caffeate and labiatenic acid, with high Fitvalue and docking score were reserved for molecular dynamics (MD) study. All of them have stability of ligand binding which suggested that they might perform the inhibitory effect on CYP11B2. This study provided candidates for novel drug-like CYP11B2 inhibitors by molecular simulation methods for the hypertension treatment. PMID:27781210

  17. Discovery of Potential Inhibitors of Aldosterone Synthase from Chinese Herbs Using Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation Studies

    Directory of Open Access Journals (Sweden)

    Ganggang Luo

    2016-01-01

    Full Text Available Aldosterone synthase (CYP11B2 is a key enzyme for the biosynthesis of aldosterone, which plays a significant role for the regulation of blood pressure. Excess aldosterone can cause the dysregulation of the renin-angiotensin-aldosterone system (RAAS and lead to hypertension. Therefore, research and development of CYP11B2 inhibitor are regarded as a novel approach for the treatment of hypertension. In this study, the pharmacophore models of CYP11B2 inhibitors were generated and the optimal model was used to identify potential CYP11B2 inhibitors from the Traditional Chinese Medicine Database (TCMD, Version 2009. The hits were further refined by molecular docking and the interactions between compounds and CYP11B2 were analyzed. Compounds with high Fitvalue, high docking score, and expected interactions with key residues were selected as potential CYP11B2 inhibitors. Two most promising compounds, ethyl caffeate and labiatenic acid, with high Fitvalue and docking score were reserved for molecular dynamics (MD study. All of them have stability of ligand binding which suggested that they might perform the inhibitory effect on CYP11B2. This study provided candidates for novel drug-like CYP11B2 inhibitors by molecular simulation methods for the hypertension treatment.

  18. Structural Modeling and Molecular Dynamics Simulation of the Actin Filament

    Energy Technology Data Exchange (ETDEWEB)

    Splettstoesser, Thomas [University of Heidelberg; Holmes, Kenneth [Max Planck Institute, Heidelberg, Germany; Noe, Frank [DFG Research Center Matheon, FU Berlin, Germany; Smith, Jeremy C [ORNL

    2011-01-01

    Actin is a major structural protein of the eukaryotic cytoskeleton and enables cell motility. Here, we present a model of the actin filament (F-actin) that not only incorporates the global structure of the recently published model by Oda et al. but also conserves internal stereochemistry. A comparison is made using molecular dynamics simulation of the model with other recent F-actin models. A number of structural determents such as the protomer propeller angle, the number of hydrogen bonds, and the structural variation among the protomers are analyzed. The MD comparison is found to reflect the evolution in quality of actin models over the last 6 years. In addition, simulations of the model are carried out in states with both ADP or ATP bound and local hydrogen-bonding differences characterized.

  19. On the coalescence-dispersion modeling of turbulent molecular mixing

    Science.gov (United States)

    Givi, Peyman; Kosaly, George

    1987-01-01

    The general coalescence-dispersion (C/D) closure provides phenomenological modeling of turbulent molecular mixing. The models of Curl and Dopazo and O'Brien appear as two limiting C/D models that bracket the range of results one can obtain by various models. This finding is used to investigate the sensitivtiy of the results to the choice of the model. Inert scalar mixing is found to be less model-sensitive than mixing accompanied by chemical reaction. Infinitely fast chemistry approximation is used to relate the C/D approach to Toor's earlier results. Pure mixing and infinite rate chemistry calculations are compared to study further a recent result of Hsieh and O'Brien who found that higher concentration moments are not sensitive to chemistry.

  20. Employing Power Graph Analysis to Facilitate Modeling Molecular Interaction Networks

    Directory of Open Access Journals (Sweden)

    Momchil Nenov

    2015-04-01

    Full Text Available Mathematical modeling is used to explore and understand complex systems ranging from weather patterns to social networks to gene-expression regulatory mechanisms. There is an upper limit to the amount of details that can be reflected in a model imposed by finite computational resources. Thus, there are methods to reduce the complexity of the modeled system to its most significant parameters. We discuss the suitability of clustering techniques, in particular Power Graph Analysis as an intermediate step of modeling.

  1. Insights into the molecular interactions between aminopeptidase and amyloid beta peptide using molecular modeling techniques.

    Science.gov (United States)

    Dhanavade, Maruti J; Sonawane, Kailas D

    2014-08-01

    Amyloid beta (Aβ) peptides play a central role in the pathogenesis of Alzheimer's disease. The accumulation of Aβ peptides in AD brain was caused due to overproduction or insufficient clearance and defects in the proteolytic degradation of Aβ peptides. Hence, Aβ peptide degradation could be a promising therapeutic approach in AD treatment. Recent experimental report suggests that aminopeptidase from Streptomyces griseus KK565 (SGAK) can degrade Aβ peptides but the interactive residues are yet to be known in detail at the atomic level. Hence, we developed the three-dimensional model of aminopeptidase (SGAK) using SWISS-MODEL, Geno3D and MODELLER. Model built by MODELLER was used for further studies. Molecular docking was performed between aminopeptidase (SGAK) with wild-type and mutated Aβ peptides. The docked complex of aminopeptidase (SGAK) and wild-type Aβ peptide (1IYT.pdb) shows more stability than the other complexes. Molecular docking and MD simulation results revealed that the residues His93, Asp105, Glu139, Glu140, Asp168 and His255 are involved in the hydrogen bonding with Aβ peptide and zinc ions. The interactions between carboxyl oxygen atoms of Glu139 of aminopeptidase (SGAK) with water molecule suggest that the Glu139 may be involved in the nucleophilic attack on Ala2-Glu3 peptide bond of Aβ peptide. Hence, amino acid Glu139 of aminopeptidase (SGAK) might play an important role to degrade Aβ peptides, a causative agent of Alzheimer's disease.

  2. Derivation of Distributed Models of Atomic Polarizability for Molecular Simulations.

    Science.gov (United States)

    Soteras, Ignacio; Curutchet, Carles; Bidon-Chanal, Axel; Dehez, François; Ángyán, János G; Orozco, Modesto; Chipot, Christophe; Luque, F Javier

    2007-11-01

    The main thrust of this investigation is the development of models of distributed atomic polarizabilities for the treatment of induction effects in molecular mechanics simulations. The models are obtained within the framework of the induced dipole theory by fitting the induction energies computed via a fast but accurate MP2/Sadlej-adjusted perturbational approach in a grid of points surrounding the molecule. Particular care is paid in the examination of the atomic quantities obtained from models of implicitly and explicitly interacting polarizabilities. Appropriateness and accuracy of the distributed models are assessed by comparing the molecular polarizabilities recovered from the models and those obtained experimentally and from MP2/Sadlej calculations. The behavior of the models is further explored by computing the polarization energy for aromatic compounds in the context of cation-π interactions and for selected neutral compounds in a TIP3P aqueous environment. The present results suggest that the computational strategy described here constitutes a very effective tool for the development of distributed models of atomic polarizabilities and can be used in the generation of new polarizable force fields.

  3. Complement system part I - molecular mechanisms of activation and regulation

    Directory of Open Access Journals (Sweden)

    Nicolas eMerle

    2015-06-01

    Full Text Available Complement is a complex innate immune surveillance system, playing a key role in defense against pathogens and in host homeostasis. The complement system is initiated by conformational changes in recognition molecular complexes upon sensing danger signals. The subsequent cascade of enzymatic reactions is tightly regulated to assure that complement is activated only at specific locations requiring defense against pathogens, thus avoiding host tissue damage. Here we discuss the recent advances describing the molecular and structural basis of activation and regulation of the complement pathways and their implication on physiology and pathology. This article will review the mechanisms of activation of alternative, classical and lectin pathways, the formation of C3 and C5 convertases, the action of anaphylatoxins and the membrane attack complex. We will also discuss the importance of structure-function relationships using the example of atypical hemolytic uremic syndrome. Lastly we will discuss the development and benefits of therapies using complement inhibitors.

  4. Extending Molecular Theory to Steady-State Diffusing Systems

    Energy Technology Data Exchange (ETDEWEB)

    FRINK,LAURA J. D.; SALINGER,ANDREW G.; THOMPSON,AIDAN P.

    1999-10-22

    Predicting the properties of nonequilibrium systems from molecular simulations is a growing area of interest. One important class of problems involves steady state diffusion. To study these cases, a grand canonical molecular dynamics approach has been developed by Heffelfinger and van Swol [J. Chem. Phys., 101, 5274 (1994)]. With this method, the flux of particles, the chemical potential gradients, and density gradients can all be measured in the simulation. In this paper, we present a complementary approach that couples a nonlocal density functional theory (DFT) with a transport equation describing steady-state flux of the particles. We compare transport-DFT predictions to GCMD results for a variety of ideal (color diffusion), and nonideal (uphill diffusion and convective transport) systems. In all cases excellent agreement between transport-DFT and GCMD calculations is obtained with diffusion coefficients that are invariant with respect to density and external fields.

  5. Assessing High School Chemistry Students' Modeling Sub-Skills in a Computerized Molecular Modeling Learning Environment

    Science.gov (United States)

    Dori, Yehudit Judy; Kaberman, Zvia

    2012-01-01

    Much knowledge in chemistry exists at a molecular level, inaccessible to direct perception. Chemistry instruction should therefore include multiple visual representations, such as molecular models and symbols. This study describes the implementation and assessment of a learning unit designed for 12th grade chemistry honors students. The organic…

  6. The system of molecular-genetic triggers as self--organizing computing system

    Directory of Open Access Journals (Sweden)

    A. Profir

    2001-05-01

    Full Text Available In this paper is shown, that the system of molecular-genetic triggers can solve the SAT problem. The molecular-genetic trigger represents the self-organizing structure and has attractors. The signal from one attractor is transmitted to other attractor, from the first level to the second level of the system. Molecular-genetic triggers work separately. The system of molecular-genetic triggers represents an example of parallel computing system. Suppose, that the system can receive two types of signals. In the first case, the system switches with the help of signals of a molecular nature (concentration of activators x1, x>sub>2, x3, x4. In the second case, the signals of wave nature of a resonant frequency can be utilized. It is possible to show, that the molecular--genetic system, can recognize images encoded by 2-dimensional vectors. Thus, the cells can be considered as parallel self-organizing system producing, receiving and transmitting the information.

  7. Buckling induced delamination of graphene composites through hybrid molecular modeling

    Science.gov (United States)

    Cranford, Steven W.

    2013-01-01

    The efficiency of graphene-based composites relies on mechanical stability and cooperativity, whereby separation of layers (i.e., delamination) can severely hinder performance. Here we study buckling induced delamination of mono- and bilayer graphene-based composites, utilizing a hybrid full atomistic and coarse-grained molecular dynamics approach. The coarse-grain model allows exploration of an idealized model material to facilitate parametric variation beyond any particular molecular structure. Through theoretical and simulation analyses, we show a critical delamination condition, where ΔD∝kL4, where ΔD is the change in bending stiffness (eV), k the stiffness of adhesion (eV/Å4), and L the length of the adhered section (Å).

  8. The Role of Molecular Modeling in TiO₂ Photocatalysis.

    Science.gov (United States)

    Cinar, Zekiye

    2017-03-30

    Molecular Modeling methods play a very important role in TiO₂ photocatalysis. Recent advances in TiO₂ photocatalysis have produced a number of interesting surface phenomena, reaction products, and various novel visible light active photocatalysts with improved properties. Quantum mechanical calculations appear promising as a means of describing the mechanisms and the product distributions of the photocatalytic degradation reactions of organic pollutants in both gas and aqueous phases. Since quantum mechanical methods utilize the principles of particle physics, their use may be extended to the design of new photocatalysts. This review introduces molecular modeling methods briefly and emphasizes the use of these methods in TiO₂ photocatalysis. The methods used for obtaining information about the degradabilities of the pollutant molecules, predicting reaction mechanisms, and evaluating the roles of the dopants and surface modifiers are explained.

  9. Stokes Efficiency of Molecular Motor-Cargo Systems

    Science.gov (United States)

    2008-01-01

    2655, 1994. 11 F. Reif , Fundamentals of Statistical and Thermal Physics, McGraw-Hill, New York, NY, USA, 1985. 12 H. Kleinert, Path Integrals in...Quantum Mechanics , Statistics , Polymer Physics, and Financial Markets, World Scientific, River Edge, NJ, USA, 3rd edition, 2004. 13 A. Einstein...Efficiency of Molecular Motor-Cargo Systems Hongyun Wang1 and Hong Zhou2 1Department of Applied Mathematics and Statistics , University of California

  10. Investigations with spectroscopy, zeta potential and molecular modeling of the non-cooperative behaviour between cyclophosphamide hydrochloride and aspirin upon interaction with human serum albumin: binary and ternary systems from multi-drug therapy.

    Science.gov (United States)

    Omidvar, Zahra; Parivar, Kazem; Sanee, Hamideh; Amiri-Tehranizadeh, Zeinab; Baratian, Ali; Saberi, Mohammad Reza; Asoodeh, Ahmad; Chamani, Jamshidkhan

    2011-08-01

    The interaction between cyclophosphamide hydrochloride (CYC) and aspirin (ASA) with human serum albumin (HSA) was studied by various kind of spectroscopic, ζ potential and molecular modeling under physiological conditions. The fluorescence data showed that the binding of drugs to proteins caused strong static fluorescence quenching. The analysis of the fluorescence quenching of HSA in the binary and ternary systems displayed that ASA was affected by the complex formed between CYC and HSA. Moreover, CYC was influenced by the HSA-ASA complex. The inherent binding information, including the quenching mechanism, binding constants, number of binding sites, effective quenching constant, fraction of the initial fluorescence and thermodynamic parameters were measured by the fluorescence quenching technique at various temperatures. In addition, according to the synchronous fluorescence spectra of HSA, the results showed that the fluorescence quenching of HSA originated from the Trp and Tyr residues, and indicated a conformational change of HSA with the addition of the drugs. Far-UV CD spectra of HSA were recorded before and after the addition of ASA and CYC as binary and ternary systems. An increase in intensity of the positive CD peak of HSA was observed in the presence of the drugs. The results were interpreted by excited interactions between the aromatic residues of the HSA binding sites and the drugs bound to them. The distance r between donor and acceptor was obtained by the Forster energy according to fluorescence resonance energy transfer (FRET) and found to be 2.35 nm and 1.78 nm for CYC and ASA, respectively. This confirmed the existence of static quenching for proteins in the presence of CYC and ASA. Furthermore, docking studies pointed at a reduction of the affinity of each of the drug compounds to the protein in the presence of the other in meaningful amounts. Pre-binding of any of the said compounds forced the second to bind in a non-optimized location and

  11. Modeling soft interface dominated systems

    NARCIS (Netherlands)

    Lamorgese, A.; Mauri, R.; Sagis, L.M.C.

    2017-01-01

    The two main continuum frameworks used for modeling the dynamics of soft multiphase systems are the Gibbs dividing surface model, and the diffuse interface model. In the former the interface is modeled as a two dimensional surface, and excess properties such as a surface density, or surface energy

  12. Phase Computations and Phase Models for Discrete Molecular Oscillators.

    OpenAIRE

    Demir, Alper; Şuvak, Önder

    2012-01-01

    RESEARCH Open Access Phase computations and phase models for discrete molecular oscillators Onder Suvak* and Alper Demir Abstract Background: Biochemical oscillators perform crucial functions in cells, e.g., they set up circadian clocks. The dynamical behavior of oscillators is best described and analyzed in terms of the scalar quantity, phase. A rigorous and useful definition for phase is based on the so-called isochrons of oscillators. Phase computation techniques for ...

  13. Kinetic modelling of molecular hydrogen transport in microporous carbon materials.

    Science.gov (United States)

    Hankel, Marlies; Zhang, Hong; Nguyen, Thanh X; Bhatia, Suresh K; Gray, Stephen K; Smith, Sean C

    2011-05-07

    The proposal of kinetic molecular sieving of hydrogen isotopes is explored by employing statistical rate theory methods to describe the kinetics of molecular hydrogen transport in model microporous carbon structures. A Lennard-Jones atom-atom interaction potential is utilized for the description of the interactions between H(2)/D(2) and the carbon framework, while the requisite partition functions describing the thermal flux of molecules through the transition state are calculated quantum mechanically in view of the low temperatures involved in the proposed kinetic molecular sieving application. Predicted kinetic isotope effects for initial passage from the gas phase into the first pore mouth are consistent with expectations from previous modeling studies, namely, that at sufficiently low temperatures and for sufficiently narrow pore mouths D(2) transport is dramatically favored over H(2). However, in contrast to expectations from previous modeling, the absence of any potential barrier along the minimum energy pathway from the gas phase into the first pore mouth yields a negative temperature dependence in the predicted absolute rate coefficients-implying a negative activation energy. In pursuit of the effective activation barrier, we find that the minimum potential in the cavity is significantly higher than in the pore mouth for nanotube-shaped models, throwing into question the common assumption that passage through the pore mouths should be the rate-determining step. Our results suggest a new mechanism that, depending on the size and shape of the cavity, the thermal activation barrier may lie in the cavity rather than at the pore mouth. As a consequence, design strategies for achieving quantum-mediated kinetic molecular sieving of H(2)/D(2) in a microporous membrane will need, at the very least, to take careful account of cavity shape and size in addition to pore-mouth size in order to ensure that the selective step, namely passage through the pore mouth, is also

  14. Comparison of two turbulent models in simulating evaporating liquid film in a wiped molecular distillator

    Institute of Scientific and Technical Information of China (English)

    XIANG Aishuang; XU Songlin

    2005-01-01

    Velocity field of evaporating liquid film in a wiped molecular distillator was simulated with a computational fluid dynamics (CFD) software, and two turbulent models treating near-wall flow were compared. Differences between wiped and other molecular distillations were introduced to explain why turbulent model should be used in this simulation. Three assumptions were made in order to simplify simulating processes. In rotating coordinate system, fixed other settings, the above two turbulent models were used, and the volume of fluid (VOF) multiphase model was also applied to tracking the liquid-gas surface. Both of the simulating results are basically identical with real situation and were compared in several aspects. It was concluded that both of the turbulent models are suitable in this simulation.

  15. Description Model of Warehouse Architecture for Clinical Test at the Molecular Immunology Centre

    Directory of Open Access Journals (Sweden)

    Anthony Rafael Sotolongo León

    2012-05-01

    Full Text Available Accurate and detailed description of the architecture of computer systems is very important to achieve success in their development. As informatic solutions, data warehouses and software support decision-making in institutions that need to implement a detailed description of the architecture. Ralph Kimball proposes the aspects to be considered of the description and explains how it is done. There are specific models used to describe the architecture such as Kruchten 4 +1 views of meta-model or the Common Warehouse Metamodel (CWM however these models do not meet the need of the description that requires a data warehouse that integrates information from clinical trials of the Molecular Immunology Centre (CIM. In this paper we propose a model for describing the data warehouse architecture that fits the needs of the Molecular Immunology Center following the Kimball framework and using as UML 2.0 modeling language.

  16. Chemical insight from density functional modeling of molecular adsorption: Tracking the bonding and diffusion of anthracene derivatives on Cu(111) with molecular orbitals

    Energy Technology Data Exchange (ETDEWEB)

    Wyrick, Jonathan; Bartels, Ludwig, E-mail: ludwig.bartels@ucr.edu [Pierce Hall, University of California-Riverside, Riverside, California 92521 (United States); Einstein, T. L. [Department of Physics and Condensed Matter Theory Center, University of Maryland, College Park, Maryland 20742-4111 (United States)

    2015-03-14

    We present a method of analyzing the results of density functional modeling of molecular adsorption in terms of an analogue of molecular orbitals. This approach permits intuitive chemical insight into the adsorption process. Applied to a set of anthracene derivates (anthracene, 9,10-anthraquinone, 9,10-dithioanthracene, and 9,10-diselenonanthracene), we follow the electronic states of the molecules that are involved in the bonding process and correlate them to both the molecular adsorption geometry and the species’ diffusive behavior. We additionally provide computational code to easily repeat this analysis on any system.

  17. Chemical insight from density functional modeling of molecular adsorption: Tracking the bonding and diffusion of anthracene derivatives on Cu(111) with molecular orbitals

    Science.gov (United States)

    Wyrick, Jonathan; Einstein, T. L.; Bartels, Ludwig

    2015-03-01

    We present a method of analyzing the results of density functional modeling of molecular adsorption in terms of an analogue of molecular orbitals. This approach permits intuitive chemical insight into the adsorption process. Applied to a set of anthracene derivates (anthracene, 9,10-anthraquinone, 9,10-dithioanthracene, and 9,10-diselenonanthracene), we follow the electronic states of the molecules that are involved in the bonding process and correlate them to both the molecular adsorption geometry and the species' diffusive behavior. We additionally provide computational code to easily repeat this analysis on any system.

  18. Molecular Modeling of Enzyme Dynamics Towards Understanding Solvent Effects

    DEFF Research Database (Denmark)

    Wedberg, Nils Hejle Rasmus Ingemar

    This thesis describes the development of a molecular simulation methodology to study properties of enzymes in non-aqueous media at fixed thermodynamic water activities. The methodology is applied in a molecular dynamics study of the industrially important enzyme Candida antarctica lipase B (CALB...... integration, while for small systems, it seems to be even better. The method is applied to compute the excess Gibbs energy of the mixtures of water and organic solvents used in the simulations of CALB. This allows to determine the water activity of the simulated systems and thus to compare protein properties......), BMC Struct. Biol., 8) and the approach to fix the water activity which often is used in experimental studies. The water activity is shown to have a profound effect on the structure and dynamics of CALB. Conformational flexibility, for instance, increases with increasing hydration in acetone, t...

  19. Efficient construction of nonorthogonal localized molecular orbitals in large systems.

    Science.gov (United States)

    Cui, Ganglong; Fang, Weihai; Yang, Weitao

    2010-08-26

    Localized molecular orbitals (LMOs) are much more compact representations of electronic degrees of freedom than canonical molecular orbitals (CMOs). The most compact representation is provided by nonorthogonal localized molecular orbitals (NOLMOs), which are linearly independent but are not orthogonal. Both LMOs and NOLMOs are thus useful for linear-scaling calculations of electronic structures for large systems. Recently, NOLMOs have been successfully applied to linear-scaling calculations with density functional theory (DFT) and to reformulating time-dependent density functional theory (TDDFT) for calculations of excited states and spectroscopy. However, a challenge remains as NOLMO construction from CMOs is still inefficient for large systems. In this work, we develop an efficient method to accelerate the NOLMO construction by using predefined centroids of the NOLMO and thereby removing the nonlinear equality constraints in the original method ( J. Chem. Phys. 2004 , 120 , 9458 and J. Chem. Phys. 2000 , 112 , 4 ). Thus, NOLMO construction becomes an unconstrained optimization. Its efficiency is demonstrated for the selected saturated and conjugated molecules. Our method for fast NOLMO construction should lead to efficient DFT and NOLMO-TDDFT applications to large systems.

  20. Modeling of deterministic chaotic systems

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Y. [Department of Physics and Astronomy and Department of Mathematics, The University of Kansas, Lawrence, Kansas 66045 (United States); Grebogi, C. [Institute for Plasma Research, University of Maryland, College Park, Maryland 20742 (United States); Grebogi, C.; Kurths, J. [Department of Physics and Astrophysics, Universitaet Potsdam, Postfach 601553, D-14415 Potsdam (Germany)

    1999-03-01

    The success of deterministic modeling of a physical system relies on whether the solution of the model would approximate the dynamics of the actual system. When the system is chaotic, situations can arise where periodic orbits embedded in the chaotic set have distinct number of unstable directions and, as a consequence, no model of the system produces reasonably long trajectories that are realized by nature. We argue and present physical examples indicating that, in such a case, though the model is deterministic and low dimensional, statistical quantities can still be reliably computed. {copyright} {ital 1999} {ital The American Physical Society}

  1. Modelling of wastewater systems

    DEFF Research Database (Denmark)

    Bechmann, Henrik

    In this thesis, models of pollution fluxes in the inlet to 2 Danish wastewater treatment plants (WWTPs) as well as of suspended solids (SS) concentrations in the aeration tanks of an alternating WWTP and in the effluent from the aeration tanks are developed. The latter model is furthermore used...

  2. Modelling Epistemic Systems

    CERN Document Server

    Martins, Andre C R

    2012-01-01

    In this Chapter, I will explore the use of modeling in order to understand how Science works. I will discuss the modeling of scientific communities, providing a general, non-comprehensive overview of existing models, with a focus on the use of the tools of Agent-Based Modeling and Opinion Dynamics. A special attention will be paid to models inspired by a Bayesian formalism of Opinion Dynamics. The objective of this exploration is to better understand the effect that different conditions might have on the reliability of the opinions of a scientific community. We will see that, by using artificial worlds as exploring grounds, we can prevent some epistemological problems with the definition of truth and obtain insights on the conditions that might cause the quest for more reliable knowledge to fail.

  3. Virtual-Wall Model for Molecular Dynamics Simulation

    Directory of Open Access Journals (Sweden)

    Lijuan Qian

    2016-12-01

    Full Text Available A large number of molecules are usually required to model atomic walls in molecular dynamics simulations. A virtual-wall model is proposed in this study to describe fluid-wall molecular interactions, for reducing the computational time. The infinite repetition of unit cell structures within the atomic wall causes the periodicity of the force acting on a fluid molecule from the wall molecules. This force is first calculated and then stored in the memory. A fluid molecule appearing in the wall force field is subjected to the force from the wall molecules. The force can then be determined by the position of the molecule relative to the wall. This model avoids excessive calculations of fluid-wall interactions and reduces the computational time drastically. The time reduction is significant for small fluid density and channel height. The virtual-wall model is applied to Poiseuille and Couette flows, and to a flow in a channel with a rough surface. Results of the virtual and atomic wall simulations agree well with each other, thereby indicating the usefulness of the virtual-wall model. The appropriate bin size and cut-off radius in the virtual-wall model are also discussed.

  4. A stochastic phase-field model determined from molecular dynamics

    KAUST Repository

    von Schwerin, Erik

    2010-03-17

    The dynamics of dendritic growth of a crystal in an undercooled melt is determined by macroscopic diffusion-convection of heat and by capillary forces acting on the nanometer scale of the solid-liquid interface width. Its modelling is useful for instance in processing techniques based on casting. The phase-field method is widely used to study evolution of such microstructural phase transformations on a continuum level; it couples the energy equation to a phenomenological Allen-Cahn/Ginzburg-Landau equation modelling the dynamics of an order parameter determining the solid and liquid phases, including also stochastic fluctuations to obtain the qualitatively correct result of dendritic side branching. This work presents a method to determine stochastic phase-field models from atomistic formulations by coarse-graining molecular dynamics. It has three steps: (1) a precise quantitative atomistic definition of the phase-field variable, based on the local potential energy; (2) derivation of its coarse-grained dynamics model, from microscopic Smoluchowski molecular dynamics (that is Brownian or over damped Langevin dynamics); and (3) numerical computation of the coarse-grained model functions. The coarse-grained model approximates Gibbs ensemble averages of the atomistic phase-field, by choosing coarse-grained drift and diffusion functions that minimize the approximation error of observables in this ensemble average. © EDP Sciences, SMAI, 2010.

  5. From Numeric Models to Granular System Modeling

    Directory of Open Access Journals (Sweden)

    Witold Pedrycz

    2015-03-01

    To make this study self-contained, we briefly recall the key concepts of granular computing and demonstrate how this conceptual framework and its algorithmic fundamentals give rise to granular models. We discuss several representative formal setups used in describing and processing information granules including fuzzy sets, rough sets, and interval calculus. Key architectures of models dwell upon relationships among information granules. We demonstrate how information granularity and its optimization can be regarded as an important design asset to be exploited in system modeling and giving rise to granular models. With this regard, an important category of rule-based models along with their granular enrichments is studied in detail.

  6. Modeling The Molecular Composition in an AGN Disk

    CERN Document Server

    Harada, Nanase; Herbst, Eric

    2013-01-01

    We use a high-temperature chemical network to derive the molecular abundances in axisymmetric accretion disk models around active galactic nuclei (AGNs) within 100 pc using simple radial and vertical density and temperature distributions motivated by more detailed physical models. We explore the effects of X-ray irradiation and cosmic ray ionization on the spatial distribution of the molecular abundances of CO, CN, CS, HCN, HCO+, HC3N, C2H, and c-C3H2 using a variety of plausible disk structures. These simple models have molecular regions with a layer of X-ray dominated regions, a midplane without the strong influence of X-rays, and a high-temperature region in the inner portion with moderate X-ray flux where families of polyynes (C$_{\\rm n}$H$_{2}$) and cyanopolyynes can be enhanced. For the high midplane density disks we explore, we find that cosmic rays produced by supernovae do not significantly affect the regions unless the star formation efficiency significantly exceeds that of the Milky Way. We highlig...

  7. Integrated Multiscale Modeling of Molecular Computing Devices. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, Tim [Univ. of Tennessee, Knoxville, TN (United States)

    2012-11-01

    The general theme of this research has been to expand the capabilities of a simulation technique, Kinetic Monte Carlo (KMC) and apply it to study self-assembled nano-structures on epitaxial thin films. KMC simulates thin film growth and evolution by replacing the detailed dynamics of the system's evolution, which might otherwise be studied using molecular dynamics, with an appropriate stochastic process.

  8. Integrated Multiscale Modeling of Molecular Computing Devices. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, Tim [Univ. of Tennessee, Knoxville, TN (United States)

    2012-11-01

    The general theme of this research has been to expand the capabilities of a simulation technique, Kinetic Monte Carlo (KMC) and apply it to study self-assembled nano-structures on epitaxial thin films. KMC simulates thin film growth and evolution by replacing the detailed dynamics of the system's evolution, which might otherwise be studied using molecular dynamics, with an appropriate stochastic process.

  9. Two Models of Magnetic Support for Photoevaporated Molecular Clouds

    Energy Technology Data Exchange (ETDEWEB)

    Ryutov, D; Kane, J; Mizuta, A; Pound, M; Remington, B

    2004-05-05

    The thermal pressure inside molecular clouds is insufficient for maintaining the pressure balance at an ablation front at the cloud surface illuminated by nearby UV stars. Most probably, the required stiffness is provided by the magnetic pressure. After surveying existing models of this type, we concentrate on two of them: the model of a quasi-homogeneous magnetic field and the recently proposed model of a ''magnetostatic turbulence''. We discuss observational consequences of the two models, in particular, the structure and the strength of the magnetic field inside the cloud and in the ionized outflow. We comment on the possible role of reconnection events and their observational signatures. We mention laboratory experiments where the most significant features of the models can be tested.

  10. Molecular model for solubility of gases in flexible polymers

    DEFF Research Database (Denmark)

    Neergaard, Jesper; Hassager, Ole; Szabo, Peter

    1999-01-01

    We propose a model for a priori prediction of the solubility of gases in flexible polymers. The model is based on the concept of ideal solubility of gases in liquids. According to this concept, the mole fraction of gases in liquids is given by Raoult's law with the total pressure and the vapor...... pressure of the gas, where the latter may have to be extrapolated. However, instead of considering each polymer molecule as a rigid structure, we estimate the effective number of degrees of freedom from an equivalent freely jointed bead-rod model for the flexible polymer. In this model, we associate...... the length of the rods with the molecular weight corresponding to a Kuhn step. The model provides a tool for crude estimation of the gas solubility on the basis of only the monomer unit of the polymer and properties of the gas. A comparison with the solubility data for several gases in poly...

  11. Steady state analysis of Boolean molecular network models via model reduction and computational algebra

    Science.gov (United States)

    2014-01-01

    Background A key problem in the analysis of mathematical models of molecular networks is the determination of their steady states. The present paper addresses this problem for Boolean network models, an increasingly popular modeling paradigm for networks lacking detailed kinetic information. For small models, the problem can be solved by exhaustive enumeration of all state transitions. But for larger models this is not feasible, since the size of the phase space grows exponentially with the dimension of the network. The dimension of published models is growing to over 100, so that efficient methods for steady state determination are essential. Several methods have been proposed for large networks, some of them heuristic. While these methods represent a substantial improvement in scalability over exhaustive enumeration, the problem for large networks is still unsolved in general. Results This paper presents an algorithm that consists of two main parts. The first is a graph theoretic reduction of the wiring diagram of the network, while preserving all information about steady states. The second part formulates the determination of all steady states of a Boolean network as a problem of finding all solutions to a system of polynomial equations over the finite number system with two elements. This problem can be solved with existing computer algebra software. This algorithm compares favorably with several existing algorithms for steady state determination. One advantage is that it is not heuristic or reliant on sampling, but rather determines algorithmically and exactly all steady states of a Boolean network. The code for the algorithm, as well as the test suite of benchmark networks, is available upon request from the corresponding author. Conclusions The algorithm presented in this paper reliably determines all steady states of sparse Boolean networks with up to 1000 nodes. The algorithm is effective at analyzing virtually all published models even those of moderate

  12. Steady state analysis of Boolean molecular network models via model reduction and computational algebra.

    Science.gov (United States)

    Veliz-Cuba, Alan; Aguilar, Boris; Hinkelmann, Franziska; Laubenbacher, Reinhard

    2014-06-26

    A key problem in the analysis of mathematical models of molecular networks is the determination of their steady states. The present paper addresses this problem for Boolean network models, an increasingly popular modeling paradigm for networks lacking detailed kinetic information. For small models, the problem can be solved by exhaustive enumeration of all state transitions. But for larger models this is not feasible, since the size of the phase space grows exponentially with the dimension of the network. The dimension of published models is growing to over 100, so that efficient methods for steady state determination are essential. Several methods have been proposed for large networks, some of them heuristic. While these methods represent a substantial improvement in scalability over exhaustive enumeration, the problem for large networks is still unsolved in general. This paper presents an algorithm that consists of two main parts. The first is a graph theoretic reduction of the wiring diagram of the network, while preserving all information about steady states. The second part formulates the determination of all steady states of a Boolean network as a problem of finding all solutions to a system of polynomial equations over the finite number system with two elements. This problem can be solved with existing computer algebra software. This algorithm compares favorably with several existing algorithms for steady state determination. One advantage is that it is not heuristic or reliant on sampling, but rather determines algorithmically and exactly all steady states of a Boolean network. The code for the algorithm, as well as the test suite of benchmark networks, is available upon request from the corresponding author. The algorithm presented in this paper reliably determines all steady states of sparse Boolean networks with up to 1000 nodes. The algorithm is effective at analyzing virtually all published models even those of moderate connectivity. The problem for

  13. Multiscale modeling of biological functions: from enzymes to molecular machines (Nobel Lecture).

    Science.gov (United States)

    Warshel, Arieh

    2014-09-15

    A detailed understanding of the action of biological molecules is a pre-requisite for rational advances in health sciences and related fields. Here, the challenge is to move from available structural information to a clear understanding of the underlying function of the system. In light of the complexity of macromolecular complexes, it is essential to use computer simulations to describe how the molecular forces are related to a given function. However, using a full and reliable quantum mechanical representation of large molecular systems has been practically impossible. The solution to this (and related) problems has emerged from the realization that large systems can be spatially divided into a region where the quantum mechanical description is essential (e.g. a region where bonds are being broken), with the remainder of the system being represented on a simpler level by empirical force fields. This idea has been particularly effective in the development of the combined quantum mechanics/molecular mechanics (QM/MM) models. Here, the coupling between the electrostatic effects of the quantum and classical subsystems has been a key to the advances in describing the functions of enzymes and other biological molecules. The same idea of representing complex systems in different resolutions in both time and length scales has been found to be very useful in modeling the action of complex systems. In such cases, starting with coarse grained (CG) representations that were originally found to be very useful in simulating protein folding, and augmenting them with a focus on electrostatic energies, has led to models that are particularly effective in probing the action of molecular machines. The same multiscale idea is likely to play a major role in modeling of even more complex systems, including cells and collections of cells.

  14. Pluralistic Modeling of Complex Systems

    CERN Document Server

    Helbing, Dirk

    2010-01-01

    The modeling of complex systems such as ecological or socio-economic systems can be very challenging. Although various modeling approaches exist, they are generally not compatible and mutually consistent, and empirical data often do not allow one to decide what model is the right one, the best one, or most appropriate one. Moreover, as the recent financial and economic crisis shows, relying on a single, idealized model can be very costly. This contribution tries to shed new light on problems that arise when complex systems are modeled. While the arguments can be transferred to many different systems, the related scientific challenges are illustrated for social, economic, and traffic systems. The contribution discusses issues that are sometimes overlooked and tries to overcome some frequent misunderstandings and controversies of the past. At the same time, it is highlighted how some long-standing scientific puzzles may be solved by considering non-linear models of heterogeneous agents with spatio-temporal inte...

  15. Structure and molecular modeling of tungsten borotellurate glasses

    Energy Technology Data Exchange (ETDEWEB)

    Rada, S., E-mail: Simona.Rada@phys.utcluj.ro [Department of Physics and Chemistry, Technical University of Cluj-Napoca, Cluj-Napoca 400020 (Romania); Rada, M. [Nat. Inst. for R and D of Isotopic and Molec. Technologies, Cluj-Napoca 400293 (Romania); Culea, E., E-mail: eugen.culea@phys.utcluj.ro [Department of Physics and Chemistry, Technical University of Cluj-Napoca, Cluj-Napoca 400020 (Romania)

    2013-03-05

    Highlights: ► The [WO{sub 6}] structural units are highly deformed. ► EPR spectra reveal the existence of W{sup +5} ions situated in distorted octahedral positions and the oxygen ions defects. ► The presence of W{sup +5} ions confers to the glass colors that change with composition. -- Abstract: Glasses of the xWO{sub 3} (100−x)[3TeO{sub 2}·2B{sub 2}O{sub 3}] system where x = 0–40 mol% WO{sub 3} were synthesized and characterized by investigations on FTIR, UV–VIS, EPR spectroscopy and molecular modeling calculations in order to obtain information about the structural changes of the glass network determined by the evolution of tungsten ions states, glass composition and WO{sub 3} concentration. Our spectroscopic data show that the incorporation of WO{sub 3} into borate–tellurate glasses causes both the formation of Te–O–W as well as B–O–W linkages and the increase of the number of non-bridging oxygens. The accommodation of the network with the excess of oxygen and the higher capacity of migration of the tungsten ions inside the host network can be associated with a change of tungsten coordination, from [WO{sub 4}] to [WO{sub 6}] structural units. This conversion is accompaniment of a large displacement of the tungsten atom from the centre of the octahedral geometry. EPR spectra reveal the existence of two signals associated with the presence of W{sup +5} ions situated in distorted octahedral positions and the oxygen ions defects. The presence of W{sup +5} ions confers to the glass colors that change with composition.

  16. Molecular Thermodynamic Model for Polyelectrolyte Solutions with Added Salts

    Institute of Scientific and Technical Information of China (English)

    ZHANGBo; CAIJun; 等

    2002-01-01

    A molecular thermodynamic model of polyelectrolyte developed previously was extended to polyelectrolyte solutions with added salts.Thermodynamic properties,such as activity coefficients of polyelectrolytes or added salts and osmotic coefficients of solvent, of a number of aqueous mixtures of polyelectrolytes and salts are analyzed with the proposed model.Successful correlation is obtained in the range of moderate or higher polyion concentration.For the same sample,thermodynamic properties of polyelectrolytes with and without simple electrolytes can be predicted mutually using parameters from regression data.

  17. Geant4 Applications for Modeling Molecular Transport in Complex Vacuum Geometries

    CERN Document Server

    Singal, J; Schindler, R

    2013-01-01

    This letter discusses a novel use of the Geant4 simulation toolkit to model molecular transport in a vacuum environment, in the molecular flow regime. The Geant4 toolkit was originally developed by the high energy physics community to simulate the interactions of elementary particles within complex detector systems. Here its capabilities are utilized to model molecular vacuum transport in geometries where other techniques are impractical. The techniques are verified with an application representing a simple vacuum geometry that has been studied previously both analytically and by basic Monte Carlo simulation. We discuss the use of an application with a very complicated geometry, that of the Large Synoptic Survey Telescope camera cryostat, to determine probabilities of transport of contaminant molecules to optical surfaces where control of contamination is crucial.

  18. A theoretical model for calculation of molecular stopping power. Ph.D. Thesis

    Science.gov (United States)

    Xu, Y. J.

    1984-01-01

    A modified local plasma model is established. The Gordon-Kim's molecular charged density model is employed to obtain a formula to evaluate the stopping power of many useful molecular systems. The stopping power of H2 and He gas was calculated for incident proton energy ranging from 100 keV to 2.5 MeV. The stopping power of O2, N2, and water vapor was also calculated for incident proton energy ranging from 40 keV. to 2.5 MeV. Good agreement with experimental data was obtained. A discussion of molecular effects leading to department from Bragg's rule is presented. The equipartition rule and the effect of nuclear momentum recoiling in stopping power are also discussed.

  19. The System of Molecular Clouds in the Gould Belt

    CERN Document Server

    Bobylev, V V

    2016-01-01

    Based on high-latitude molecular clouds with highly accurate distance estimates taken from the literature, we have redetermined the parameters of their spatial orientation. This system can be approximated by a 350x235x140 pc ellipsoid inclined by the angle i=17+/-2 degrees to the Galactic plane with the longitude of the ascending node l{\\Omega}=337+/-1 degrees. Based on the radial velocities of the clouds, we have found their group velocity relative to the Sun to be (u0,v0,w0) = (10.6,18.2,6.8)+/-(0.9,1.7,1.5) km/s. The trajectory of the center of the molecular cloud system in the past in a time interval of ~60 Myr has been constructed. Using data on masers associated with low-mass protostars, we have calculated the space velocities of the molecular complexes in Orion, Taurus, Perseus, and Ophiuchus. Their motion in the past is shown to be not random.

  20. Review and application of group theory to molecular systems biology

    Directory of Open Access Journals (Sweden)

    Rietman Edward A

    2011-06-01

    Full Text Available Abstract In this paper we provide a review of selected mathematical ideas that can help us better understand the boundary between living and non-living systems. We focus on group theory and abstract algebra applied to molecular systems biology. Throughout this paper we briefly describe possible open problems. In connection with the genetic code we propose that it may be possible to use perturbation theory to explore the adjacent possibilities in the 64-dimensional space-time manifold of the evolving genome. With regards to algebraic graph theory, there are several minor open problems we discuss. In relation to network dynamics and groupoid formalism we suggest that the network graph might not be the main focus for understanding the phenotype but rather the phase space of the network dynamics. We show a simple case of a C6 network and its phase space network. We envision that the molecular network of a cell is actually a complex network of hypercycles and feedback circuits that could be better represented in a higher-dimensional space. We conjecture that targeting nodes in the molecular network that have key roles in the phase space, as revealed by analysis of the automorphism decomposition, might be a better way to drug discovery and treatment of cancer.

  1. Review and application of group theory to molecular systems biology.

    Science.gov (United States)

    Rietman, Edward A; Karp, Robert L; Tuszynski, Jack A

    2011-06-22

    In this paper we provide a review of selected mathematical ideas that can help us better understand the boundary between living and non-living systems. We focus on group theory and abstract algebra applied to molecular systems biology. Throughout this paper we briefly describe possible open problems. In connection with the genetic code we propose that it may be possible to use perturbation theory to explore the adjacent possibilities in the 64-dimensional space-time manifold of the evolving genome. With regards to algebraic graph theory, there are several minor open problems we discuss. In relation to network dynamics and groupoid formalism we suggest that the network graph might not be the main focus for understanding the phenotype but rather the phase space of the network dynamics. We show a simple case of a C6 network and its phase space network. We envision that the molecular network of a cell is actually a complex network of hypercycles and feedback circuits that could be better represented in a higher-dimensional space. We conjecture that targeting nodes in the molecular network that have key roles in the phase space, as revealed by analysis of the automorphism decomposition, might be a better way to drug discovery and treatment of cancer.

  2. Parallel helix bundles and ion channels: molecular modeling via simulated annealing and restrained molecular dynamics.

    OpenAIRE

    Kerr, I. D.; Sankararamakrishnan, R; Smart, O.S.; Sansom, M S

    1994-01-01

    A parallel bundle of transmembrane (TM) alpha-helices surrounding a central pore is present in several classes of ion channel, including the nicotinic acetylcholine receptor (nAChR). We have modeled bundles of hydrophobic and of amphipathic helices using simulated annealing via restrained molecular dynamics. Bundles of Ala20 helices, with N = 4, 5, or 6 helices/bundle were generated. For all three N values the helices formed left-handed coiled coils, with pitches ranging from 160 A (N = 4) to...

  3. Quantum dynamics of bio-molecular systems in noisy environments

    CERN Document Server

    Plenio, M B

    2012-01-01

    We discuss three different aspects of the quantum dynamics of bio-molecular systems and more generally complex networks in the presence of strongly coupled environments. Firstly, we make a case for the systematic study of fundamental structural elements underlying the quantum dynamics of these systems, identify such elements and explore the resulting interplay of quantum dynamics and environmental decoherence. Secondly, we critically examine some existing approaches to the numerical description of system-environment interaction in the non-perturbative regime and present a promising new method that can overcome some limitations of existing methods. Thirdly, we present an approach towards deciding and quantifying the non-classicality of the action of the environment and the observed system-dynamics. We stress the relevance of these tools for strengthening the interplay between theoretical and experimental research in this field.

  4. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    Directory of Open Access Journals (Sweden)

    Sara Gargiulo

    2016-09-01

    Full Text Available Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR-1, VEGFR-2, intercellular adhesion molecule (ICAM-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies.

  5. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    Science.gov (United States)

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  6. A heterogeneous model for gas transport in carbon molecular sieves.

    Science.gov (United States)

    Ding, L P; Yuan, Y X; Farooq, S; Bhatia, S K

    2005-01-18

    A dual resistance model with distribution of either barrier or pore diffusional activation energy is proposed in this work for gas transport in carbon molecular sieve (CMS) micropores. This is a novel approach in which the equilibrium is homogeneous, but the kinetics is heterogeneous. The model seems to provide a possible explanation for the concentration dependence of the thermodynamically corrected barrier and pore diffusion coefficients observed in previous studies from this laboratory on gas diffusion in CMS. The energy distribution is assumed to follow the gamma distribution function. It is shown that the energy distribution model can fully capture the behavior described by the empirical model established in earlier studies to account for the concentration dependence of thermodynamically corrected barrier and pore diffusion coefficients. A methodology is proposed for extracting energy distribution parameters, and it is further shown that the extracted energy distribution parameters can effectively predict integral uptake and column breakthrough profiles over a wide range of operating pressures.

  7. Theoretical study on electromagnetically induced transparency in molecular aggregate models using quantum Liouville equation method

    Energy Technology Data Exchange (ETDEWEB)

    Minami, Takuya; Nakano, Masayoshi [Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531 (Japan)

    2015-01-22

    Electromagnetically induced transparency (EIT), which is known as an efficient control method of optical absorption property, is investigated using the polarizability spectra and population dynamics obtained by solving the quantum Liouville equation. In order to clarify the intermolecular interaction effect on EIT, we examine several molecular aggregate models composed of three-state monomers with the dipole-dipole coupling. On the basis of the present results, we discuss the applicability of EIT in molecular aggregate systems to a new type of optical switch.

  8. Subtle Monte Carlo Updates in Dense Molecular Systems

    DEFF Research Database (Denmark)

    Bottaro, Sandro; Boomsma, Wouter; Johansson, Kristoffer E.;

    2012-01-01

    Although Markov chain Monte Carlo (MC) simulation is a potentially powerful approach for exploring conformational space, it has been unable to compete with molecular dynamics (MD) in the analysis of high density structural states, such as the native state of globular proteins. Here, we introduce...... as correlations in a multivariate Gaussian distribution. We demonstrate that our method reproduces structural variation in proteins with greater efficiency than current state-of-the-art Monte Carlo methods and has real-time simulation performance on par with molecular dynamics simulations. The presented results...... a kinetic algorithm, CRISP, that greatly enhances the sampling efficiency in all-atom MC simulations of dense systems. The algorithm is based on an exact analytical solution to the classic chain-closure problem, making it possible to express the interdependencies among degrees of freedom in the molecule...

  9. Nucleocytoplasmic Transport: A Paradigm for Molecular Logistics in Artificial Systems.

    Science.gov (United States)

    Vujica, Suncica; Zelmer, Christina; Panatala, Radhakrishnan; Lim, Roderick Y H

    2016-01-01

    Artificial organelles, molecular factories and nanoreactors are membrane-bound systems envisaged to exhibit cell-like functionality. These constitute liposomes, polymersomes or hybrid lipo-polymersomes that display different membrane-spanning channels and/or enclose molecular modules. To achieve more complex functionality, an artificial organelle should ideally sustain a continuous influx of essential macromolecular modules (i.e. cargoes) and metabolites against an outflow of reaction products. This would benefit from the incorporation of selective nanopores as well as specific trafficking factors that facilitate cargo selectivity, translocation efficiency, and directionality. Towards this goal, we describe how proteinaceous cargoes are transported between the nucleus and cytoplasm by nuclear pore complexes and the biological trafficking machinery in living cells (i.e. nucleocytoplasmic transport). On this basis, we discuss how biomimetic control may be implemented to selectively import, compartmentalize and accumulate diverse macromolecular modules against concentration gradients in artificial organelles.

  10. Radiative Corrections and Quantum Gates in Molecular Systems

    Science.gov (United States)

    Reina, John H.; Beausoleil, Ray G.; Spiller, Tim P.; Munro, William J.

    2004-12-01

    We propose a method for quantum information processing using molecules coupled to an external laser field. This utilizes molecular interactions, control of the external field, and an effective energy shift of the doubly excited state of two coupled molecules. Such a level shift has been seen in the two-photon resonance experiments recently reported by Hettich etal. Here we show that this can be explained in terms of the QED Lamb shift. We quantify the performance of the proposed quantum logic gates in the presence of dissipative mechanisms. The unitary transformations required for performing one- and two-qubit operations can be implemented with present day molecular technology. The proposed techniques can also be applied to coupled quantum dot and biomolecular systems.

  11. Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations.

    Science.gov (United States)

    Fang, Jiansong; Pang, Xiaocong; Wu, Ping; Yan, Rong; Gao, Li; Li, Chao; Lian, Wenwen; Wang, Qi; Liu, Ai-lin; Du, Guan-hua

    2016-05-01

    A dataset of 67 berberine derivatives for the inhibition of butyrylcholinesterase (BuChE) was studied based on the combination of quantitative structure-activity relationships models, molecular docking, and molecular dynamics methods. First, a series of berberine derivatives were reported, and their inhibitory activities toward butyrylcholinesterase (BuChE) were evaluated. By 2D- quantitative structure-activity relationships studies, the best model built by partial least-square had a conventional correlation coefficient of the training set (R(2)) of 0.883, a cross-validation correlation coefficient (Qcv2) of 0.777, and a conventional correlation coefficient of the test set (Rpred2) of 0.775. The model was also confirmed by Y-randomization examination. In addition, the molecular docking and molecular dynamics simulation were performed to better elucidate the inhibitory mechanism of three typical berberine derivatives (berberine, C2, and C55) toward BuChE. The predicted binding free energy results were consistent with the experimental data and showed that the van der Waals energy term (ΔEvdw) difference played the most important role in differentiating the activity among the three inhibitors (berberine, C2, and C55). The developed quantitative structure-activity relationships models provide details on the fine relationship linking structure and activity and offer clues for structural modifications, and the molecular simulation helps to understand the inhibitory mechanism of the three typical inhibitors. In conclusion, the results of this study provide useful clues for new drug design and discovery of BuChE inhibitors from berberine derivatives.

  12. Accurate model selection of relaxed molecular clocks in bayesian phylogenetics.

    Science.gov (United States)

    Baele, Guy; Li, Wai Lok Sibon; Drummond, Alexei J; Suchard, Marc A; Lemey, Philippe

    2013-02-01

    Recent implementations of path sampling (PS) and stepping-stone sampling (SS) have been shown to outperform the harmonic mean estimator (HME) and a posterior simulation-based analog of Akaike's information criterion through Markov chain Monte Carlo (AICM), in bayesian model selection of demographic and molecular clock models. Almost simultaneously, a bayesian model averaging approach was developed that avoids conditioning on a single model but averages over a set of relaxed clock models. This approach returns estimates of the posterior probability of each clock model through which one can estimate the Bayes factor in favor of the maximum a posteriori (MAP) clock model; however, this Bayes factor estimate may suffer when the posterior probability of the MAP model approaches 1. Here, we compare these two recent developments with the HME, stabilized/smoothed HME (sHME), and AICM, using both synthetic and empirical data. Our comparison shows reassuringly that MAP identification and its Bayes factor provide similar performance to PS and SS and that these approaches considerably outperform HME, sHME, and AICM in selecting the correct underlying clock model. We also illustrate the importance of using proper priors on a large set of empirical data sets.

  13. Integrated Modeling Systems

    Science.gov (United States)

    1989-01-01

    American Economic Review , 71:1 (March 1981). 181 J.M. Jones and F. Zufryden. "Adding Explanatory Variables to a Consumer Purchase Behavior Model: An...McCall. "An Operational Measure of Liquidity," The American Economic Review , 761 (March 1986). WMSI Working Paper 329. 212 Nelson, R., R. Sarin, and R

  14. Robust Disaster Recovery System Model

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Highly security-critical system should possess features of continuous service. We present a new Robust Disaster Recovery System Model (RDRSM). Through strengthening the ability of safe communications, RDRSM guarantees the secure and reliable command on disaster recovery. Its self-supervision capability can monitor the integrality and security of disaster recovery system itself. By 2D and 3D real-time visible platform provided by GIS, GPS and RS, the model makes the using, management and maintenance of disaster recovery system easier. RDRSM possesses predominant features of security, robustness and controllability. And it can be applied to highly security-critical environments such as E-government and bank. Conducted by RDRSM, an important E-government disaster recovery system has been constructed successfully. The feasibility of this model is verified by practice. We especially emphasize the significance of some components of the model, such as risk assessment, disaster recovery planning, system supervision and robust communication support.

  15. A molecular model for positron complexes: long-range effects on 2{gamma} pair-annihilation rates

    Energy Technology Data Exchange (ETDEWEB)

    Mohallem, Jose R; Rolim, Flavia; Goncalves, Cristina P [Laboratorio de Atomos e Moleculas Especiais, Departamento de FIsica, ICEx, Universidade Federal de Minas Gerais, PO Box 702, 30123-970, Belo Horizonte, MG (Brazil)

    2004-03-14

    A molecular model for positron complexes is developed and used to study the effects of the nucleus-positron distance long-range regime on the 2{gamma} annihilation rates ({gamma}) of atomic complexes. The available data for {gamma} of some systems are then rationalized on its basis and some predictions are made. The model is shown to be capable of generating information on positron positioning and of making predictions of values of {gamma} in molecular complexes as well.

  16. Adiabatic bias molecular dynamics: A method to navigate the conformational space of complex molecular systems

    Science.gov (United States)

    Marchi, Massimo; Ballone, Pietro

    1999-02-01

    This study deals with a novel molecular simulation technique, named adiabatic bias molecular dynamics (MD), which provides a simple and reasonably inexpensive route to generate MD trajectories joining points in conformational space separated by activation barriers. Because of the judicious way the biasing potential is updated during the MD runs, the technique allows with some additional effort the computation of the free energy change experienced during the trajectory. The adiabatic bias method has been applied to a nontrivial problem: The unfolding of an atomistic model of lysozyme. Here, the radius of gyration (Rg) was used as a convenient reaction coordinate. For changes in Rg between 19.7 and 28 Å, we observe a net loss of the native tertiary structure of lysozyme. At the same time, secondary structure elements such as α-helices are retained although some of the original order is diminished. The calculated free energy profile for the unfolding transition shows a monotonous increase with Rg and depends crucially on the nonbonded cutoff used in the potential model.

  17. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2007-01-01

    All phenomena in nature are characterized by motion; this is an essential property of matter, having infinitely many aspects. Motion can be mechanical, physical, chemical or biological, leading to various sciences of nature, mechanics being one of them. Mechanics deals with the objective laws of mechanical motion of bodies, the simplest form of motion. In the study of a science of nature mathematics plays an important role. Mechanics is the first science of nature which was expressed in terms of mathematics by considering various mathematical models, associated to phenomena of the surrounding nature. Thus, its development was influenced by the use of a strong mathematical tool; on the other hand, we must observe that mechanics also influenced the introduction and the development of many mathematical notions. In this respect, the guideline of the present book is precisely the mathematical model of mechanics. A special accent is put on the solving methodology as well as on the mathematical tools used; vectors, ...

  18. An analytic approach to 2D electronic PE spectra of molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Szoecs, V., E-mail: szocs@fns.uniba.sk [Institute of Chemistry, Comenius University, Mlynska dolina CH2, 842 15 Bratislava (Slovakia)

    2011-05-26

    Graphical abstract: The three-pulse photon echo (3P-PE) spectra of finite molecular systems using direct calculation from electronic Hamiltonians allows peak classification from 3P-PE spectra dynamics. Display Omitted Highlights: {yields} RWA approach to electronic photon echo. {yields} A straightforward calculation of 2D electronic spectrograms in finite molecular systems. {yields} Importance of population time dynamics in relation to inter-site coherent coupling. - Abstract: The three-pulse photon echo (3P-PE) spectra of finite molecular systems and simplified line broadening models is presented. The Fourier picture of a heterodyne detected three-pulse rephasing PE signal in the {delta}-pulse limit of the external field is derived in analytic form. The method includes contributions of one and two-excitonic states and allows direct calculation of Fourier PE spectrogram from corresponding Hamiltonian. As an illustration, the proposed treatment is applied to simple systems, e.g. 2-site two-level system (TLS) and n-site TLS model of photosynthetic unit. The importance of relation between Fourier picture of 3P-PE dynamics (corresponding to nonzero population time, T) and coherent inter-state coupling is emphasized.

  19. Molecular physiology of vesicular glutamate transporters in the digestive system

    Institute of Scientific and Technical Information of China (English)

    Tao Li; Fayez K. Ghishan; Liqun Bai

    2005-01-01

    Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Packaging and storage of glutamate into glutamatergic neuronal vesicles require ATP-dependent vesicular glutamate uptake systems, which utilize the electrochemical proton gradient as a driving force. Three vesicular glutamate transporters (VGLUT1-3) have been recently identified from neuronal tissue where they play a key role to maintain the vesicular glutamate level. Recently, it has been demonstrated that glutamate signaling is also functional in peripheral neuronal and non-neuronal tissues, and occurs in sites of pituitary, adrenal, pineal glands, bone, GI tract, pancreas,skin, and testis. The glutamate receptors and VGLUTs in digestivesystem have been found in both neuronal and endocrinal cells. The glutamate signaling in the digestive system may have significant relevance to diabetes and GI tract motility disorders. This review will focus on the most recent update of molecular physiology of digestive VGLUTs.

  20. Microscale Symmetrical Electroporator Array as a Versatile Molecular Delivery System

    Science.gov (United States)

    Ouyang, Mengxing; Hill, Winfield; Lee, Jung Hyun; Hur, Soojung Claire

    2017-03-01

    Successful developments of new therapeutic strategies often rely on the ability to deliver exogenous molecules into cytosol. We have developed a versatile on-chip vortex-assisted electroporation system, engineered to conduct sequential intracellular delivery of multiple molecules into various cell types at low voltage in a dosage-controlled manner. Micro-patterned planar electrodes permit substantial reduction in operational voltages and seamless integration with an existing microfluidic technology. Equipped with real-time process visualization functionality, the system enables on-chip optimization of electroporation parameters for cells with varying properties. Moreover, the system’s dosage control and multi-molecular delivery capabilities facilitate intracellular delivery of various molecules as a single agent or in combination and its utility in biological research has been demonstrated by conducting RNA interference assays. We envision the system to be a powerful tool, aiding a wide range of applications, requiring single-cell level co-administrations of multiple molecules with controlled dosages.

  1. Charge Transport by Superexchange in Molecular Host-Guest Systems

    Science.gov (United States)

    Symalla, Franz; Friederich, Pascal; Massé, Andrea; Meded, Velimir; Coehoorn, Reinder; Bobbert, Peter; Wenzel, Wolfgang

    2016-12-01

    Charge transport in disordered organic semiconductors is generally described as a result of incoherent hopping between localized states. In this work, we focus on multicomponent emissive host-guest layers as used in organic light-emitting diodes (OLEDs), and show using multiscale ab initio based modeling that charge transport can be significantly enhanced by the coherent process of molecular superexchange. Superexchange increases the rate of emitter-to-emitter hopping, in particular if the emitter molecules act as relatively deep trap states, and allows for percolation path formation in charge transport at low guest concentrations.

  2. A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Nil Turan

    2011-09-01

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

  3. Studies of Catalytic Model Systems

    DEFF Research Database (Denmark)

    Holse, Christian

    The overall topic of this thesis is within the field of catalysis, were model systems of different complexity have been studied utilizing a multipurpose Ultra High Vacuum chamber (UHV). The thesis falls in two different parts. First a simple model system in the form of a ruthenium single crystal...... is investigated. Second the development of a complex Cu/ZnO nanoparticle model system is described and gas-induced dynamical changes in the model system is investigated. The ruthenium crystal serves as an extremely simple model for studying CO dissociation which is the rate limiting step of the methanation...... process. The Ru(0 1 54) surface is studied by means of Scanning Tunneling Microscopy (STM), Temperature Programmed Desoprtion (TPD), and Oxygen Titration (OT) experiments. Real space evidence of periodic features on every second monatomic step is observed via STM when the a clean ruthenium surface...

  4. Molecular bases of myelodysplastic syndromes: lessons from animal models.

    Science.gov (United States)

    Komeno, Yukiko; Kitaura, Jiro; Kitamura, Toshio

    2009-06-01

    Myelodysplastic syndrome (MDS) is a clonal disorder of hematopietic stem cells characterized by ineffective hematopoiesis, peripheral blood cytopenia, morphologic dysplasia, and susceptibility to acute myeloid leukemia. Several mechanisms have been suggested as causes of MDS: unbalanced chromosomal abnormalities reflecting a gain or loss of chromosomal material, point mutations of transcription factors, and inactivation of p53. However, appropriate animal models that mimic MDS have long been lacking. We recently reported a novel murine model of MDS that recapitulates trilineage dysplasia and transformation to AML. In this review, we summarize the animal models of MDS and discuss the molecular bases of MDS as well as those of leukemia and myeloproliferative disorders (MPD). J. Cell. Physiol. 219: 529-534, 2009. (c) 2009 Wiley-Liss, Inc.

  5. Probabilistic Model to Treat Flexibility in Molecular Contacts

    CERN Document Server

    Hakulinen, Riku

    2016-01-01

    Evaluating accessible conformational space is computationally expensive and thermal motions are partly neglected in computer models of molecular interactions. This produces error into the estimates of binding strength. We introduce a method for modelling interactions so that structural flexibility is inherently taken into account. It has a statistical model for 3D properties of 'nonlocal' contacts and a physics based description of 'local' interactions, based on mechanical torque. The form of the torque barrier is derived using a representation of the local electronic structure, which is presumed to improve transferability, compared to traditional force fields. The nonlocal contacts are more distant than 1-4 interactions and Target-atoms are represented by 3D probability densities. Probability mass quantifies strength of contact and is calculated as an overlap integral. Repulsion is described by negative probability density, allowing probability mass to be used as the descriptor of contact preference. As a re...

  6. Structural and Molecular Modeling Features of P2X Receptors

    Directory of Open Access Journals (Sweden)

    Luiz Anastacio Alves

    2014-03-01

    Full Text Available Currently, adenosine 5'-triphosphate (ATP is recognized as the extracellular messenger that acts through P2 receptors. P2 receptors are divided into two subtypes: P2Y metabotropic receptors and P2X ionotropic receptors, both of which are found in virtually all mammalian cell types studied. Due to the difficulty in studying membrane protein structures by X-ray crystallography or NMR techniques, there is little information about these structures available in the literature. Two structures of the P2X4 receptor in truncated form have been solved by crystallography. Molecular modeling has proven to be an excellent tool for studying ionotropic receptors. Recently, modeling studies carried out on P2X receptors have advanced our knowledge of the P2X receptor structure-function relationships. This review presents a brief history of ion channel structural studies and shows how modeling approaches can be used to address relevant questions about P2X receptors.

  7. Subtle Monte Carlo Updates in Dense Molecular Systems.

    Science.gov (United States)

    Bottaro, Sandro; Boomsma, Wouter; E Johansson, Kristoffer; Andreetta, Christian; Hamelryck, Thomas; Ferkinghoff-Borg, Jesper

    2012-02-14

    Although Markov chain Monte Carlo (MC) simulation is a potentially powerful approach for exploring conformational space, it has been unable to compete with molecular dynamics (MD) in the analysis of high density structural states, such as the native state of globular proteins. Here, we introduce a kinetic algorithm, CRISP, that greatly enhances the sampling efficiency in all-atom MC simulations of dense systems. The algorithm is based on an exact analytical solution to the classic chain-closure problem, making it possible to express the interdependencies among degrees of freedom in the molecule as correlations in a multivariate Gaussian distribution. We demonstrate that our method reproduces structural variation in proteins with greater efficiency than current state-of-the-art Monte Carlo methods and has real-time simulation performance on par with molecular dynamics simulations. The presented results suggest our method as a valuable tool in the study of molecules in atomic detail, offering a potential alternative to molecular dynamics for probing long time-scale conformational transitions.

  8. Analytical solutions for a soil vapor extraction model that incorporates gas phase dispersion and molecular diffusion

    Science.gov (United States)

    Huang, Junqi; Goltz, Mark N.

    2017-06-01

    To greatly simplify their solution, the equations describing radial advective/dispersive transport to an extraction well in a porous medium typically neglect molecular diffusion. While this simplification is appropriate to simulate transport in the saturated zone, it can result in significant errors when modeling gas phase transport in the vadose zone, as might be applied when simulating a soil vapor extraction (SVE) system to remediate vadose zone contamination. A new analytical solution for the equations describing radial gas phase transport of a sorbing contaminant to an extraction well is presented. The equations model advection, dispersion (including both mechanical dispersion and molecular diffusion), and rate-limited mass transfer of dissolved, separate phase, and sorbed contaminants into the gas phase. The model equations are analytically solved by using the Laplace transform with respect to time. The solutions are represented by confluent hypergeometric functions in the Laplace domain. The Laplace domain solutions are then evaluated using a numerical Laplace inversion algorithm. The solutions can be used to simulate the spatial distribution and the temporal evolution of contaminant concentrations during operation of a soil vapor extraction well. Results of model simulations show that the effect of gas phase molecular diffusion upon concentrations at the extraction well is relatively small, although the effect upon the distribution of concentrations in space is significant. This study provides a tool that can be useful in designing SVE remediation strategies, as well as verifying numerical models used to simulate SVE system performance.

  9. Molecular Communication Model for Targeted Drug Delivery in Multiple Disease Sites With Diversely Expressed Enzymes.

    Science.gov (United States)

    Chude-Okonkwo, Uche A K; Malekian, Reza; Maharaj, B T Sunil

    2016-04-01

    Targeted drug delivery (TDD) for disease therapy using liposomes as nanocarriers has received extensive attention in the literature. The liposome's ability to incorporate capabilities such as long circulation, stimuli responsiveness, and targeting characteristics, makes it a versatile nanocarrier. Timely drug release at the targeted site requires that trigger stimuli such as pH, light, and enzymes be uniquely overexpressed at the targeted site. However, in some cases, the targeted sites may not express trigger stimuli significantly, hence, achieving effective TDD at those sites is challenging. In this paper, we present a molecular communication-based TDD model for the delivery of therapeutic drugs to multiple sites that may or may not express trigger stimuli. The nanotransmitter and nanoreceiver models for the molecular communication system are presented. Here, the nanotransmitter and nanoreceiver are injected into the targeted body system's blood network. The compartmental pharmacokinetics model is employed to model the transportation of these therapeutic nanocarriers to the targeted sites where they are meant to anchor before the delivery process commences. We also provide analytical expressions for the delivered drug concentration. The effectiveness of the proposed model is investigated for drug delivery on tissue surfaces. Results show that the effectiveness of the proposed molecular communication-based TDD depends on parameters such as the total transmitter volume capacity, the receiver radius, the diffusion characteristic of the microenvironment of the targeted sites, and the concentration of the enzymes associated with the nanotransmitter and the nanoreceiver designs.

  10. Molecular dynamics studies of a generalised multipole model of molecular asymmetry in apolar and polar liquid crystals

    CERN Document Server

    Johnston, S J

    2001-01-01

    was identified as the system cooled whereas for gamma = 70 deg no ordered phase formed. The study was repeated with the addition of a transverse electric dipole of mu* = 1.5 which was seen to stabilise a range of smectic phases. The nematic phase was destabilised in the rod-like model with a transition directly to a smectic B phase then to a ferroelectric crystal. As the angle gamma increased the transition temperature to the first ordered phase decreased more markedly than for the apolar models. Smectic A, tilted smectic B and a spontaneously polarised smectic B phase were observed in the gamma = 10 deg bent-core model. The gamma = 20 deg model showed smectic A and tilted antiferroelectric smectic B phases. The gamma = 40 deg model showed an antiferroelectric phase that exhibited unusual packing behaviour. Both the gamma = 20 deg and gamma = 40 deg models showed a significant phase biaxiality in the smectic B phases. This study has successfully reproduced some of the complex features seen in real molecular p...

  11. Relocatable Coastal Modeling System

    Science.gov (United States)

    2016-06-07

    These relationships are stored on a variable-resolution grid (illustrated in figure 1b below) with sampling of 1 degree in deep water (and in data...version is referred to as MODAS2.1, which is now operational at NAVO. The NOMADS interface is being replaced by a system-independent, web -based version...inside the user’s web browser plus Perl CGI scripts which ran on a webserver. This permitted the user to run MODAS (and POM and other modules as they are

  12. Advances of Molecular Imaging for Monitoring the Anatomical and Functional Architecture of the Olfactory System.

    Science.gov (United States)

    Zhang, Xintong; Bi, Anyao; Gao, Quansheng; Zhang, Shuai; Huang, Kunzhu; Liu, Zhiguo; Gao, Tang; Zeng, Wenbin

    2016-01-20

    The olfactory system of organisms serves as a genetically and anatomically model for studying how sensory input can be translated into behavior output. Some neurologic diseases are considered to be related to olfactory disturbance, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis, and so forth. However, it is still unclear how the olfactory system affects disease generation processes and olfaction delivery processes. Molecular imaging, a modern multidisciplinary technology, can provide valid tools for the early detection and characterization of diseases, evaluation of treatment, and study of biological processes in living subjects, since molecular imaging applies specific molecular probes as a novel approach to produce special data to study biological processes in cellular and subcellular levels. Recently, molecular imaging plays a key role in studying the activation of olfactory system, thus it could help to prevent or delay some diseases. Herein, we present a comprehensive review on the research progress of the imaging probes for visualizing olfactory system, which is classified on different imaging modalities, including PET, MRI, and optical imaging. Additionally, the probes' design, sensing mechanism, and biological application are discussed. Finally, we provide an outlook for future studies in this field.

  13. High-pressure Brillouin scattering in a simple molecular system

    CERN Document Server

    Shimizu, H

    2002-01-01

    Recent developments in high-pressure in situ Brillouin spectroscopy of a simple molecular system are reviewed by demonstrating experimental and analytical methods for the study of acoustic velocities in any direction, adiabatic elastic constants, and elastic anisotropy. Detailed applications to solid argon (Ar) are presented, at pressures up to 70 GPa in a diamond anvil cell, using recently developed approaches that combine the method of in situ Brillouin spectroscopy, for a single crystal of Ar up to 4 GPa, and the envelope method applied to both longitudinal acoustic and transverse acoustic modes, for recrystallized Ar between 4 and 70 GPa.

  14. Analysis of conjugation of chloramphenicol and hemoglobin by fluorescence, circular dichroism and molecular modeling

    Science.gov (United States)

    Ding, Fei; Liu, Wei; Sun, Ye; Yang, Xin-Ling; Sun, Ying; Zhang, Li

    2012-01-01

    Chloramphenicol is a low cost, broad spectrum, highly active antibiotic, and widely used in the treatment of serious infections, including typhoid fever and other life-threatening infections of the central nervous system and respiratory tract. The purpose of the present study was to examine the conjugation of chloramphenicol with hemoglobin (Hb) and compared with albumin at molecular level, utilizing fluorescence, UV/vis absorption, circular dichroism (CD) as well as molecular modeling. Fluorescence data indicate that drug bind Hb generate quenching via static mechanism, this corroborates UV/vis absorption measurements that the ground state complex formation with an affinity of 10 4 M -1, and the driving forces in the Hb-drug complex are hydrophilic interactions and hydrogen bonds, as derived from computational model. The accurate binding site of drug has been identified from the analysis of fluorescence and molecular modeling, α1β2 interface of Hb was assigned to possess high-affinity for drug, which located at the β-37 Trp nearby. The structural investigation of the complexed Hb by synchronous fluorescence, UV/vis absorption, and CD observations revealed some degree of Hb structure unfolding upon complexation. Based on molecular modeling, we can draw the conclusion that the binding affinity of drug with albumin is superior, compared with Hb. These phenomena can provide salient information on the absorption, distribution, pharmacology, and toxicity of chloramphenicol and other drugs which have analogous configuration with chloramphenicol.

  15. Application of Molecular Modeling to Urokinase Inhibitors Development

    Directory of Open Access Journals (Sweden)

    V. B. Sulimov

    2014-01-01

    Full Text Available Urokinase-type plasminogen activator (uPA plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis. Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs. The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods. Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program, postprocessing (DISCORE program, direct generalized docking (FLM program, and the application of the quantum chemical calculations (MOPAC package, search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination. On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro. Eight of them display inhibitory activity and two of them display activity about 10 μM.

  16. Cross-link guided molecular modeling with ROSETTA.

    Directory of Open Access Journals (Sweden)

    Abdullah Kahraman

    Full Text Available Chemical cross-links identified by mass spectrometry generate distance restraints that reveal low-resolution structural information on proteins and protein complexes. The technology to reliably generate such data has become mature and robust enough to shift the focus to the question of how these distance restraints can be best integrated into molecular modeling calculations. Here, we introduce three workflows for incorporating distance restraints generated by chemical cross-linking and mass spectrometry into ROSETTA protocols for comparative and de novo modeling and protein-protein docking. We demonstrate that the cross-link validation and visualization software Xwalk facilitates successful cross-link data integration. Besides the protocols we introduce XLdb, a database of chemical cross-links from 14 different publications with 506 intra-protein and 62 inter-protein cross-links, where each cross-link can be mapped on an experimental structure from the Protein Data Bank. Finally, we demonstrate on a protein-protein docking reference data set the impact of virtual cross-links on protein docking calculations and show that an inter-protein cross-link can reduce on average the RMSD of a docking prediction by 5.0 Å. The methods and results presented here provide guidelines for the effective integration of chemical cross-link data in molecular modeling calculations and should advance the structural analysis of particularly large and transient protein complexes via hybrid structural biology methods.

  17. Modelling Alkali Line Absorption and Molecular Bands in Cool DAZs

    CERN Document Server

    Homeier, D; Allard, F; Hauschildt, P H; Schweitzer, A; Stancil, P C; Weck, P F; Homeier, Derek; Allard, Nicole F.; Allard, France; Hauschildt, Peter H.; Schweitzer, Andreas; Stancil, Phillip C.; Weck, Philippe F.

    2005-01-01

    Two peculiar stars showing an apparent extremely broadened and strong NaI D absorption have been discovered in surveys for cool white dwarfs by Oppenheimer et al. (2001) and Harris et al. (SDSS, 2003). We discuss the nature of these objects using PHOENIX atmosphere models for metal-poor brown dwarfs/very low mass stars, and new white dwarf LTE and NLTE models for hydrogen- and helium-dominated atmospheres with metals. These include complete molecular formation in chemical equilibrium and a model for the alkali resonance line broadening based on the damping profiles of Allard et al. (2003), as well as new molecular line opacities for metal hydrides. First results of our calculations indicate good agreement with a hydrogen-dominated WD atmosphere with a Na abundance roughly consistent with a state of high accretion. We analyse deviations of the abundances of Na, K, Mg and Ca from the cosmic pattern and comment on implications of these results for standard accretion scenarios.

  18. Coupled continuum and molecular model of flow through fibrous filter

    Science.gov (United States)

    Zhao, Shunliu; Povitsky, Alex

    2013-11-01

    A coupled approach combining the continuum boundary singularity method (BSM) and the molecular direct simulation Monte Carlo (DSMC) is developed and validated using Taylor-Couette flow and the flow about a single fiber confined between two parallel walls. In the proposed approach, the DSMC is applied to an annular region enclosing the fiber and the BSM is employed in the entire flow domain. The parameters used in the DSMC and the coupling procedure, such as the number of simulated particles, the cell size, and the size of the coupling zone are determined by inspecting the accuracy of pressure drop obtained for the range of Knudsen numbers between zero and unity. The developed approach is used to study flowfield of fibrous filtration flows. It is observed that in the partial-slip flow regime, Kn ⩽ 0.25, the results obtained by the proposed coupled BSM-DSMC method match the solution by BSM combined with the heuristic partial-slip boundary conditions. For transition molecular-to-continuum Knudsen numbers, 0.25 pressure drop and velocity between these two approaches is significant. This difference increases with the Knudsen number that confirms the usefulness of coupled continuum and molecular methods in numerical modeling of transition low Reynolds number flows in fibrous filters.

  19. Molecular modeling of epsilon RNA from hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Huai Ren Pan; Hai Jun Zhu; Zhong Rong Song; Xu Dong Zhang; Huai Cao

    2009-01-01

    An initial model of the HBV epsilon RNA was built by the Biopolymer module of Insight Ⅱ. While its three-dimensional structure was obtained through structure optimization based on molecular dynamics simulation, the two active sites were found. A comparison with the experimental result indicated that the active sites may be the binding sites of the epsilon RNA in the RT-epsilon interaction. The result will be helpful to further discussion about the mechanism of RT-epsilon interaction and the study of HBV genome replication.

  20. Novel regularized sparse model for fluorescence molecular tomography reconstruction

    Science.gov (United States)

    Liu, Yuhao; Liu, Jie; An, Yu; Jiang, Shixin

    2017-01-01

    Fluorescence molecular tomography (FMT) is an imaging modality that exploits the specificity of fluorescent biomarkers to enable 3D visualization of molecular targets and pathways in small animals. FMT has been used in surgical navigation for tumor resection and has many potential applications at the physiological, metabolic, and molecular levels in tissues. The hybrid system combined FMT and X-ray computed tomography (XCT) was pursued for accurate detection. However, the result is usually over-smoothed and over-shrunk. In this paper, we propose a region reconstruction method for FMT in which the elastic net (E-net) regularization is used to combine L1-norm and L2-norm. The E-net penalty corresponds to adding the L1-norm penalty and a L2-norm penalty. Elastic net combines the advantages of L1-norm regularization and L2-norm regularization. It could achieve the balance between the sparsity and smooth by simultaneously employing the L1-norm and the L2-norm. To solve the problem effectively, the proximal gradient algorithms was used to accelerate the computation. To evaluate the performance of the proposed E-net method, numerical phantom experiments are conducted. The simulation study shows that the proposed method achieves accurate and is able to reconstruct image effectively.

  1. Molecular modeling studies of polymer electrolytes for power sources

    Energy Technology Data Exchange (ETDEWEB)

    Balbuena, Perla B. [Department of Chemical Engineering, Texas A and M University, College Station, TX 77843 (United States)]. E-mail: balbuena@tamu.edu; Lamas, Eduardo J. [Department of Chemical Engineering, Texas A and M University, College Station, TX 77843 (United States); Wang, Yixuan [Department of Chemical Engineering, Texas A and M University, College Station, TX 77843 (United States)

    2005-06-30

    Density functional theory and classical molecular dynamics simulations permit us to elucidate details of ionic and molecular transport useful for the design of polymer electrolyte membranes. We consider two systems of current interest: (a) ionic transport in polyethylene-oxide compared to that in a polyphosphazene membrane targeted to be a good ionic carrier but a bad water carrier and (b) transport of oxygen and protons through hydrated nafion in the vicinity of a catalyst phase. It is shown that in polyphosphazene membranes, nitrogen atoms interact more strongly with lithium ions than ether oxygens do. As a result of the different complexation of Li{sup +} with the polymer sites, Li{sup +} has a much higher diffusion coefficient in polyphosphazene than in polyethylene oxide electrolyte membranes, with the consequent relevance to lithium-water battery technology. For the hydrated membrane/catalyst interface, our simulations show that the Nafion membrane used in low-temperature fuel cells interacts strongly with the catalytic metal nanoparticles directing the side chain towards the catalyst surface. Results at various degrees of hydration of the membrane illustrate the formation of water clusters surrounding the polymer hydrophilic sites, and reveal how the connectivity of these clusters may determine the transport mechanism of protons and molecular species.

  2. Autonomous Agents: The Origins and Co-Evolution of Reproducing Molecular Systems

    Science.gov (United States)

    Kauffman, Stuart

    1999-01-01

    The central aim of this award concerned an investigation into, and adequate formulation of, the concept of an "autonomous agent." If we consider a bacterium swimming upstream in a glucose gradient, we are willing to say of the bacterium that it is going to get food. That is, we are willing, and do, describe the bacterium as acting on its own behalf in an environment. All free living cells are, in this sense, autonomous agents. But the bacterium is "just" a set of molecules. We define an autonomous agent as a physical system able to act on its own behalf in an environment, then ask, "What must a physical system be to be an autonomous agent?" The tentative definition for a molecular autonomous agent is that it must be self-reproducing and carry out at least one thermodynamic work cycle. The work carried out in this grant involved, among other features, the development of a detailed model of a molecular autonomous agent, and study of the kinetics of this system. In particular, a molecular autonomous agent must, by the above tentative definition, not only reproduce, but must carry out at least one work cycle. I took, as a simple example of a self-reproducing molecular system, the single-stranded DNA hexamer 3'CCGCGG5' which can line up and ligate its two complementary trimers, 5'CCG3' and 5'CGG3'. But the two ligated trimers constitute the same molecular sequence in the 3' to 5' direction as the initial hexamer, hence this system is autocatalytic. On the other hand the above system is not yet an autonomous agent. At the minimum, autonomous agents, as I have defined them, are a new class of chemical reaction network. At a maximum, they may constitute a proper definition of life itself.

  3. Graphene symmetry-breaking with molecular adsorbates: modeling and experiment

    Science.gov (United States)

    Groce, M. A.; Hawkins, M. K.; Wang, Y. L.; Cullen, W. G.; Einstein, T. L.

    2012-02-01

    Graphene's structure and electronic properties provide a framework for understanding molecule-substrate interactions and developing techniques for band gap engineering. Controlled deposition of molecular adsorbates can create superlattices which break the degeneracy of graphene's two-atom unit cell, opening a band gap. We simulate scanning tunneling microscopy and spectroscopy measurements for a variety of organic molecule/graphene systems, including pyridine, trimesic acid, and isonicotinic acid, based on density functional theory calculations using VASP. We also compare our simulations to ultra-high vacuum STM and STS results.

  4. Molecular Simulation towards Efficient and Representative Subsurface Reservoirs Modeling

    KAUST Repository

    Kadoura, Ahmad

    2016-09-01

    This dissertation focuses on the application of Monte Carlo (MC) molecular simulation and Molecular Dynamics (MD) in modeling thermodynamics and flow of subsurface reservoir fluids. At first, MC molecular simulation is proposed as a promising method to replace correlations and equations of state in subsurface flow simulators. In order to accelerate MC simulations, a set of early rejection schemes (conservative, hybrid, and non-conservative) in addition to extrapolation methods through reweighting and reconstruction of pre-generated MC Markov chains were developed. Furthermore, an extensive study was conducted to investigate sorption and transport processes of methane, carbon dioxide, water, and their mixtures in the inorganic part of shale using both MC and MD simulations. These simulations covered a wide range of thermodynamic conditions, pore sizes, and fluid compositions shedding light on several interesting findings. For example, the possibility to have more carbon dioxide adsorbed with more preadsorbed water concentrations at relatively large basal spaces. The dissertation is divided into four chapters. The first chapter corresponds to the introductory part where a brief background about molecular simulation and motivations are given. The second chapter is devoted to discuss the theoretical aspects and methodology of the proposed MC speeding up techniques in addition to the corresponding results leading to the successful multi-scale simulation of the compressible single-phase flow scenario. In chapter 3, the results regarding our extensive study on shale gas at laboratory conditions are reported. At the fourth and last chapter, we end the dissertation with few concluding remarks highlighting the key findings and summarizing the future directions.

  5. Intramolecular charge ordering in the multi molecular orbital system (TTM-TTP)I3

    Science.gov (United States)

    Bonnet, Marie-Laure; Robert, Vincent; Tsuchiizu, Masahisa; Omori, Yukiko; Suzumura, Yoshikazu

    2010-06-01

    Starting from the structure of the (TTM-TTP)I3 molecular-based material, we examine the characteristics of frontier molecular orbitals using ab initio (CASSCF/CASPT2) configurations interaction calculations. It is shown that the singly occupied and second-highest-occupied molecular orbitals are close to each other, i.e., this compound should be regarded as a two-orbital system. By dividing virtually the [TTM-TTP] molecule into three fragments, an effective model is constructed to rationalize the origin of this picture. In order to investigate the low-temperature, symmetry breaking experimentally observed in the crystal, the electronic distribution in a pair of [TTM-TTP] molecules is analyzed from CASPT2 calculations. Our inspection supports and explains the speculated intramolecular charge ordering which is likely to give rise to low-energy magnetic properties.

  6. Hydronic distribution system computer model

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, J.W.; Strasser, J.J.

    1994-10-01

    A computer model of a hot-water boiler and its associated hydronic thermal distribution loop has been developed at Brookhaven National Laboratory (BNL). It is intended to be incorporated as a submodel in a comprehensive model of residential-scale thermal distribution systems developed at Lawrence Berkeley. This will give the combined model the capability of modeling forced-air and hydronic distribution systems in the same house using the same supporting software. This report describes the development of the BNL hydronics model, initial results and internal consistency checks, and its intended relationship to the LBL model. A method of interacting with the LBL model that does not require physical integration of the two codes is described. This will provide capability now, with reduced up-front cost, as long as the number of runs required is not large.

  7. Data management system performance modeling

    Science.gov (United States)

    Kiser, Larry M.

    1993-01-01

    This paper discusses analytical techniques that have been used to gain a better understanding of the Space Station Freedom's (SSF's) Data Management System (DMS). The DMS is a complex, distributed, real-time computer system that has been redesigned numerous times. The implications of these redesigns have not been fully analyzed. This paper discusses the advantages and disadvantages for static analytical techniques such as Rate Monotonic Analysis (RMA) and also provides a rationale for dynamic modeling. Factors such as system architecture, processor utilization, bus architecture, queuing, etc. are well suited for analysis with a dynamic model. The significance of performance measures for a real-time system are discussed.

  8. Classical and quantum dynamics of a model for atomic-molecular Bose--Einstein condensates

    OpenAIRE

    Santos Filho, Gilberto Nascimento; Tonel, Arlei Prestes; Foerster, Angela; Links, Jon(Centre for Mathematical Physics, School of Mathematics and Physics, The University of Queensland, 4072, Australia)

    2005-01-01

    We study a model for a two-mode atomic-molecular Bose--Einstein condensate. Starting with a classical analysis we determine the phase space fixed points of the system. It is found that bifurcations of the fixed points naturally separate the coupling parameter space into four regions. The different regions give rise to qualitatively different dynamics. We then show that this classification holds true for the quantum dynamics.

  9. Use of Computational Modeling to Evaluate Hypotheses About the Molecular and Cellular Mechanisms of Bystander Effects

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yuchao; Conolly, Rory B; Andersen, Melvin E.

    2006-11-21

    This report describes the development of a computational systems biology approach to evaluate the hypotheses of molecular and cellular mechanisms of adaptive response to low dose ionizing radiation. Our concept is that computational models of signaling pathways can be developed and linked to biologically based dose response models to evaluate the underlying molecular mechanisms which lead to adaptive response. For development of quantitatively accurate, predictive models, it will be necessary to describe tissues consisting of multiple cell types where the different types each contribute in their own way to the overall function of the tissue. Such a model will probably need to incorporate not only cell type-specific data but also spatial information on the architecture of the tissue and on intercellular signaling. The scope of the current model was more limited. Data obtained in a number of different biological systems were synthesized to describe a chimeric, “average” population cell. Biochemical signaling pathways involved in sensing of DNA damage and in the activation of cell cycle checkpoint controls and the apoptotic path were also included. As with any computational modeling effort, it was necessary to develop these simplified initial descriptions (models) that can be iteratively refined. This preliminary model is a starting point which, with time, can evolve to a level of refinement where large amounts of detailed biological information are synthesized and a capability for robust predictions of dose- and time-response behaviors is obtained.

  10. Coarse Grained Molecular Dynamics Simulations of Transmembrane Protein-Lipid Systems

    Directory of Open Access Journals (Sweden)

    Peter Spijker

    2010-06-01

    Full Text Available Many biological cellular processes occur at the micro- or millisecond time scale. With traditional all-atom molecular modeling techniques it is difficult to investigate the dynamics of long time scales or large systems, such as protein aggregation or activation. Coarse graining (CG can be used to reduce the number of degrees of freedom in such a system, and reduce the computational complexity. In this paper the first version of a coarse grained model for transmembrane proteins is presented. This model differs from other coarse grained protein models due to the introduction of a novel angle potential as well as a hydrogen bonding potential. These new potentials are used to stabilize the backbone. The model has been validated by investigating the adaptation of the hydrophobic mismatch induced by the insertion of WALP-peptides into a lipid membrane, showing that the first step in the adaptation is an increase in the membrane thickness, followed by a tilting of the peptide.

  11. Consistent interpretation of molecular simulation kinetics using Markov state models biased with external information

    CERN Document Server

    Rudzinski, Joseph F; Bereau, Tristan

    2016-01-01

    Molecular simulations can provide microscopic insight into the physical and chemical driving forces of complex molecular processes. Despite continued advancement of simulation methodology, model errors may lead to inconsistencies between simulated and reference (e.g., from experiments or higher-level simulations) observables. To bound the microscopic information generated by computer simulations within reference measurements, we propose a method that reweights the microscopic transitions of the system to improve consistency with a set of coarse kinetic observables. The method employs the well-developed Markov state modeling framework to efficiently link microscopic dynamics with long-time scale constraints, thereby consistently addressing a wide range of time scales. To emphasize the robustness of the method, we consider two distinct coarse-grained models with significant kinetic inconsistencies. When applied to the simulated conformational dynamics of small peptides, the reweighting procedure systematically ...

  12. Vibrational spectroscopy modeling of a drug in molecular solvents and enzymes

    Science.gov (United States)

    Devereux, Christian J.; Fulfer, Kristen D.; Zhang, Xiaoliu; Kuroda, Daniel G.

    2017-09-01

    Modeling of drugs in enzymes is of immensurable value to many areas of science. We present a theoretical study on the vibrational spectroscopy of Rilpivirine, a HIV reverse transcriptase inhibitor, in conventional solvents and in clinically relevant enzymes. The study is based on vibrational spectroscopy modeling of the drug using molecular dynamics simulations, DFT frequency maps, and theory. The modeling of the infrared lineshape shows good agreement with experimental data for the drug in molecular solvents where the local environment motions define the vibrational band lineshape. On the other hand, the theoretical description of the drug in the different enzymes does not match previous experimental findings indicating that the utilized methodology might not apply to heterogeneous environments. Our findings show that the lack of reproducibility might be associated with the development of the frequency map which does not contain all of the possible interactions observed in such systems.

  13. Advances on plant-pathogen interactions from molecular toward systems biology perspectives.

    Science.gov (United States)

    Peyraud, Rémi; Dubiella, Ullrich; Barbacci, Adelin; Genin, Stéphane; Raffaele, Sylvain; Roby, Dominique

    2016-11-21

    In the past 2 decades, progress in molecular analyses of the plant immune system has revealed key elements of a complex response network. Current paradigms depict the interaction of pathogen-secreted molecules with host target molecules leading to the activation of multiple plant response pathways. Further research will be required to fully understand how these responses are integrated in space and time, and exploit this knowledge in agriculture. In this review, we highlight systems biology as a promising approach to reveal properties of molecular plant-pathogen interactions and predict the outcome of such interactions. We first illustrate a few key concepts in plant immunity with a network and systems biology perspective. Next, we present some basic principles of systems biology and show how they allow integrating multiomics data and predict cell phenotypes. We identify challenges for systems biology of plant-pathogen interactions, including the reconstruction of multiscale mechanistic models and the connection of host and pathogen models. Finally, we outline studies on resistance durability through the robustness of immune system networks, the identification of trade-offs between immunity and growth and in silico plant-pathogen co-evolution as exciting perspectives in the field. We conclude that the development of sophisticated models of plant diseases incorporating plant, pathogen and climate properties represent a major challenge for agriculture in the future.

  14. Modelling and enhanced molecular dynamics to steer structure-based drug discovery.

    Science.gov (United States)

    Kalyaanamoorthy, Subha; Chen, Yi-Ping Phoebe

    2014-05-01

    The ever-increasing gap between the availabilities of the genome sequences and the crystal structures of proteins remains one of the significant challenges to the modern drug discovery efforts. The knowledge of structure-dynamics-functionalities of proteins is important in order to understand several key aspects of structure-based drug discovery, such as drug-protein interactions, drug binding and unbinding mechanisms and protein-protein interactions. This review presents a brief overview on the different state of the art computational approaches that are applied for protein structure modelling and molecular dynamics simulations of biological systems. We give an essence of how different enhanced sampling molecular dynamics approaches, together with regular molecular dynamics methods, assist in steering the structure based drug discovery processes.

  15. Charge transport in high mobility molecular semiconductors: classical models and new theories.

    Science.gov (United States)

    Troisi, Alessandro

    2011-05-01

    The theories developed since the fifties to describe charge transport in molecular crystals proved to be inadequate for the most promising classes of high mobility molecular semiconductors identified in the recent years, including for example pentacene and rubrene. After reviewing at an elementary level the classical theories, which still provide the language for the understanding of charge transport in these systems, this tutorial review outlines the recent experimental and computational evidence that prompted the development of new theories of charge transport in molecular crystals. A critical discussion will illustrate how very rarely it is possible to assume a charge hopping mechanism for high mobility organic crystals at any temperature. Recent models based on the effect of non-local electron-phonon coupling, dynamic disorder, coexistence of localized and delocalized states are reviewed. Additionally, a few more recent avenues of theoretical investigation, including the study of defect states, are discussed.

  16. ePMV Embeds Molecular Modeling into Professional Animation Software Environments

    Science.gov (United States)

    Johnson, Graham T.; Autin, Ludovic; Goodsell, David S.; Sanner, Michel F.; Olson, Arthur J.

    2011-01-01

    SUMMARY Increasingly complex research has made it more difficult to prepare data for publication, education, and outreach. Many scientists must also wade through black-box code to interface computational algorithms from diverse sources to supplement their bench work. To reduce these barriers, we have developed an open-source plug-in, embedded Python Molecular Viewer (ePMV), that runs molecular modeling software directly inside of professional 3D animation applications (hosts) to provide simultaneous access to the capabilities of these newly connected systems. Uniting host and scientific algorithms into a single interface allows users from varied backgrounds to assemble professional quality visuals and to perform computational experiments with relative ease. By enabling easy exchange of algorithms, ePMV can facilitate interdisciplinary research, smooth communication between broadly diverse specialties and provide a common platform to frame and visualize the increasingly detailed intersection(s) of cellular and molecular biology. PMID:21397181

  17. Molecular Evolution of Freshwater Snails with Contrasting Mating Systems.

    Science.gov (United States)

    Burgarella, Concetta; Gayral, Philippe; Ballenghien, Marion; Bernard, Aurélien; David, Patrice; Jarne, Philippe; Correa, Ana; Hurtrez-Boussès, Sylvie; Escobar, Juan; Galtier, Nicolas; Glémin, Sylvain

    2015-09-01

    Because mating systems affect population genetics and ecology, they are expected to impact the molecular evolution of species. Self-fertilizing species experience reduced effective population size, recombination rates, and heterozygosity, which in turn should decrease the efficacy of natural selection, both adaptive and purifying, and the strength of meiotic drive processes such as GC-biased gene conversion. The empirical evidence is only partly congruent with these predictions, depending on the analyzed species, some, but not all, of the expected effects have been observed. One possible reason is that self-fertilization is an evolutionary dead-end, so that most current selfers recently evolved self-fertilization, and their genome has not yet been strongly impacted by selfing. Here, we investigate the molecular evolution of two groups of freshwater snails in which mating systems have likely been stable for several millions of years. Analyzing coding sequence polymorphism, divergence, and expression levels, we report a strongly reduced genetic diversity, decreased efficacy of purifying selection, slower rate of adaptive evolution, and weakened codon usage bias/GC-biased gene conversion in the selfer Galba compared with the outcrosser Physa, in full agreement with theoretical expectations. Our results demonstrate that self-fertilization, when effective in the long run, is a major driver of population genomic and molecular evolutionary processes. Despite the genomic effects of selfing, Galba truncatula seems to escape the demographic consequences of the genetic load. We suggest that the particular ecology of the species may buffer the negative consequences of selfing, shedding new light on the dead-end hypothesis.

  18. DNA-enabled integrated molecular systems for computation and sensing.

    Science.gov (United States)

    LaBoda, Craig; Duschl, Heather; Dwyer, Chris L

    2014-06-17

    CONSPECTUS: Nucleic acids have become powerful building blocks for creating supramolecular nanostructures with a variety of new and interesting behaviors. The predictable and guided folding of DNA, inspired by nature, allows designs to manipulate molecular-scale processes unlike any other material system. Thus, DNA can be co-opted for engineered and purposeful ends. This Account details a small portion of what can be engineered using DNA within the context of computer architectures and systems. Over a decade of work at the intersection of DNA nanotechnology and computer system design has shown several key elements and properties of how to harness the massive parallelism created by DNA self-assembly. This work is presented, naturally, from the bottom-up beginning with early work on strand sequence design for deterministic, finite DNA nanostructure synthesis. The key features of DNA nanostructures are explored, including how the use of small DNA motifs assembled in a hierarchical manner enables full-addressability of the final nanostructure, an important property for building dense and complicated systems. A full computer system also requires devices that are compatible with DNA self-assembly and cooperate at a higher level as circuits patterned over many, many replicated units. Described here is some work in this area investigating nanowire and nanoparticle devices, as well as chromophore-based circuits called resonance energy transfer (RET) logic. The former is an example of a new way to bring traditional silicon transistor technology to the nanoscale, which is increasingly problematic with current fabrication methods. RET logic, on the other hand, introduces a framework for optical computing at the molecular level. This Account also highlights several architectural system studies that demonstrate that even with low-level devices that are inferior to their silicon counterparts and a substrate that harbors abundant defects, self-assembled systems can still

  19. Optimal methyl labeling for studies of supra-molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Religa, Tomasz L.; Kay, Lewis E., E-mail: kay@pound.med.utoronto.c [The University of Toronto, Departments of Molecular Genetics, Biochemistry and Chemistry (Canada)

    2010-07-15

    Selective methyl labeling combined with HMQC spectroscopy that exploits a TROSY effect in {sup 13}CH{sub 3} spin systems has significantly extended the utility of solution NMR spectroscopy in studies of high molecular weight particles. Herein we compare the utility of {sup 13}CH{sub 3}- versus {sup 13}CHD{sub 2}-labeling of Ile, Leu, Val probes in supra-molecular systems through quantification of relative signal-to-noise ratios in optimized spectra of highly deuterated, {sup 13}CH{sub 3}- and {sup 13}CHD{sub 2}-labeled samples of the half proteasome ({alpha}{sub 7}{alpha}{sub 7}, 360 kDa). It is shown that the sensitivity of spectra recorded on Ile, Leu, Val {sup 13}CH{sub 3}-labeled samples is between 1.5 and 2 fold higher than the corresponding data sets obtained on {alpha}{sub 7}{alpha}{sub 7} with {sup 13}CHD{sub 2} probes. Thus, labeling of supra-molecules with {sup 13}CH{sub 3} isotopomers remains the method of choice, but in applications where {sup 13}CHD{sub 2} moieties are required, sensitivity will in general not be limiting.

  20. International Conference on Intelligent Systems for Molecular Biology (ISMB)

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, Debra; Hibbs, Matthew; Kall, Lukas; Komandurglayavilli, Ravikumar; Mahony, Shaun; Marinescu, Voichita; Mayrose, Itay; Minin, Vladimir; Neeman, Yossef; Nimrod, Guy; Novotny, Marian; Opiyo, Stephen; Portugaly, Elon; Sadka, Tali; Sakabe, Noboru; Sarkar, Indra; Schaub, Marc; Shafer, Paul; Shmygelska, Olena; Singer, Gregory; Song, Yun; Soumyaroop, Bhattacharya; Stadler, Michael; Strope, Pooja; Su, Rong; Tabach, Yuval; Tae, Hongseok; Taylor, Todd; Terribilini, Michael; Thomas, Asha; Tran, Nam; Tseng, Tsai-Tien; Vashist, Akshay; Vijaya, Parthiban; Wang, Kai; Wang, Ting; Wei, Lai; Woo, Yong; Wu, Chunlei; Yamanishi, Yoshihiro; Yan, Changhui; Yang, Jack; Yang, Mary; Ye, Ping; Zhang, Miao

    2009-12-29

    The Intelligent Systems for Molecular Biology (ISMB) conference has provided a general forum for disseminating the latest developments in bioinformatics on an annual basis for the past 13 years. ISMB is a multidisciplinary conference that brings together scientists from computer science, molecular biology, mathematics and statistics. The goal of the ISMB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on "intelligent systems" and actual biological data makes ISMB a unique and highly important meeting, and 13 years of experience in holding the conference has resulted in a consistently well organized, well attended, and highly respected annual conference. The ISMB 2005 meeting was held June 25-29, 2005 at the Renaissance Center in Detroit, Michigan. The meeting attracted over 1,730 attendees. The science presented was exceptional, and in the course of the five-day meeting, 56 scientific papers, 710 posters, 47 Oral Abstracts, 76 Software demonstrations, and 14 tutorials were presented. The attendees represented a broad spectrum of backgrounds with 7% from commercial companies, over 28% qualifying for student registration, and 41 countries were represented at the conference, emphasizing its important international aspect. The ISMB conference is especially important because the cultures of computer science and biology are so disparate. ISMB, as a full-scale technical conference with refereed proceedings that have been indexed by both MEDLINE and Current Contents since 1996, bridges this cultural gap.

  1. Pipe Phantoms With Applications in Molecular Imaging and System Characterization.

    Science.gov (United States)

    Wang, Shiying; Herbst, Elizabeth B; Pye, Stephen D; Moran, Carmel M; Hossack, John A

    2017-01-01

    Pipe (vessel) phantoms mimicking human tissue and blood flow are widely used for cardiovascular related research in medical ultrasound. Pipe phantom studies require the development of materials and liquids that match the acoustic properties of soft tissue, blood vessel wall, and blood. Over recent years, pipe phantoms have been developed to mimic the molecular properties of the simulated blood vessels. In this paper, the design, construction, and functionalization of pipe phantoms are introduced and validated for applications in molecular imaging and ultrasound imaging system characterization. There are three major types of pipe phantoms introduced: 1) a gelatin-based pipe phantom; 2) a polydimethylsiloxane-based pipe phantom; and 3) the "Edinburgh pipe phantom." These phantoms may be used in the validation and assessment of the dynamics of microbubble-based contrast agents and, in the case of a small diameter tube phantom, for assessing imaging system spatial resolution/contrast performance. The materials and procedures required to address each of the phantoms are described.

  2. The generation of meaningful information in molecular systems.

    Science.gov (United States)

    Wills, Peter R

    2016-03-13

    The physico-chemical processes occurring inside cells are under the computational control of genetic (DNA) and epigenetic (internal structural) programming. The origin and evolution of genetic information (nucleic acid sequences) is reasonably well understood, but scant attention has been paid to the origin and evolution of the molecular biological interpreters that give phenotypic meaning to the sequence information that is quite faithfully replicated during cellular reproduction. The near universality and age of the mapping from nucleotide triplets to amino acids embedded in the functionality of the protein synthetic machinery speaks to the early development of a system of coding which is still extant in every living organism. We take the origin of genetic coding as a paradigm of the emergence of computation in natural systems, focusing on the requirement that the molecular components of an interpreter be synthesized autocatalytically. Within this context, it is seen that interpreters of increasing complexity are generated by series of transitions through stepped dynamic instabilities (non-equilibrium phase transitions). The early phylogeny of the amino acyl-tRNA synthetase enzymes is discussed in such terms, leading to the conclusion that the observed optimality of the genetic code is a natural outcome of the processes of self-organization that produced it.

  3. INTERNATIONAL CONFERENCE ON INTELLIGENT SYSTEMS FOR MOLECULAR BIOLOGY (ISMB)

    Energy Technology Data Exchange (ETDEWEB)

    Debra Goldberg; Matthew Hibbs; Lukas Kall; Ravikumar Komandurglayavilli; Shaun Mahony; Voichita Marinescu; Itay Mayrose; Vladimir Minin; Yossef Neeman; Guy Nimrod; Marian Novotny; Stephen Opiyo; Elon Portugaly; Tali Sadka; Noboru Sakabe; Indra Sarkar; Marc Schaub; Paul Shafer; Olena Shmygelska; Gregory Singer; Yun Song; Bhattacharya Soumyaroop; Michael Stadler; Pooja Strope; Rong Su; Yuval Tabach; Hongseok Tae; Todd Taylor; Michael Terribilini; Asha Thomas; Nam Tran; Tsai-Tien Tseng; Akshay Vashist; Parthiban Vijaya; Kai Wang; Ting Wang; Lai Wei; Yong Woo; Chunlei Wu; Yoshihiro Yamanishi; Changhui Yan; Jack Yang; Mary Yang; Ping Ye; Miao Zhang

    2009-12-29

    The Intelligent Systems for Molecular Biology (ISMB) conference has provided a general forum for disseminating the latest developments in bioinformatics on an annual basis for the past 13 years. ISMB is a multidisciplinary conference that brings together scientists from computer science, molecular biology, mathematics and statistics. The goal of the ISMB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on “intelligent systems” and actual biological data makes ISMB a unique and highly important meeting, and 13 years of experience in holding the conference has resulted in a consistently well organized, well attended, and highly respected annual conference. The ISMB 2005 meeting was held June 25-29, 2005 at the Renaissance Center in Detroit, Michigan. The meeting attracted over 1,730 attendees. The science presented was exceptional, and in the course of the five-day meeting, 56 scientific papers, 710 posters, 47 Oral Abstracts, 76 Software demonstrations, and 14 tutorials were presented. The attendees represented a broad spectrum of backgrounds with 7% from commercial companies, over 28% qualifying for student registration, and 41 countries were represented at the conference, emphasizing its important international aspect. The ISMB conference is especially important because the cultures of computer science and biology are so disparate. ISMB, as a full-scale technical conference with refereed proceedings that have been indexed by both MEDLINE and Current Contents since 1996, bridges this cultural gap.

  4. Characterization of ionic, dipolar and molecular mobility in polymer systems

    Science.gov (United States)

    Guo, Zhenrong

    Changes in the ionic and dipolar molecular mobility in a polymer system are the basis for the changes in the dielectric mechanical properties of polymer materials. Frequency Dependent Dielectric Measurements (FDEMS) and Ion Time-of-Flight (ITOF) are two important techniques to investigate ionic and dipolar molecular mobility in polymer systems. The results can be related to the macro- and molecular dielectric, electrical and dynamic properties of polymeric materials. The combination of these two methods provides a full view of electric, dielectric and dynamic behavior for the systems as they undergo chemical and/or physical changes during polymerization crystallization, vitrification, and/or phase separation. The research on microscopic mass mobility in polymer systems was done on three aspects: (1) ion mobility in an epoxy-amine reaction system; (2) dipolar mobility and relaxation during dimethacrylate resin cure and (3) dye molecule migration and diffusion in polymer films. In the ion mobility study, we separately monitor the changes in the ion mobility and the number of charge carriers during the epoxy-amine polymerization with FDEMS and ITOF measurements. The isolation of the number of carriers and their mobility allows significant improvement in monitoring changes in the state and structure of a material as it cures. For the dipolar mobility and relaxation study, FDEMS measurements were used to detect structural evolution and spatial heterogeneity formation during the polymerization process of dimethacrylate resins. The dielectric spectra, glass transition (Tg) profiles and dynamic mechanical measurements were used to investigate the existence of two cooperative regions of sufficient size to create two alpha-relaxation processes representing oligomer rich and polymer microgel regions during the polymerization. For the dye migration research, we tried to develop a visually color changing paper (VCP) due to dye molecule migration in polymer films. The mobility

  5. Nonlinear Absorption and Refraction in Multilevel Organic Molecular System

    Institute of Scientific and Technical Information of China (English)

    LI Chun-Fei; DENG Xiao-Xu; WANG Yu-Xiao

    2000-01-01

    The nonlinear absorption and refraction in a multilevel organic molecular system is described by using the density matrix theory. The total absorptive coefficient of the system in the low-density case is equal to a linear sum of contributions from each energy level. Similarly, the total refractive index is equal to a linear sum of contributions from each energy level plus the refractive index of the vacuum. The absorption coefficient or refractive index due to each level is proportional to the population of that level, where the constant of proportionality is called the absorption cross-section or the refraction volume, respectively. The relation between the absorption cross-section and the refraction volume for each level is also given.

  6. Modeling and analysis of the molecular basis of pain in sensory neurons.

    Directory of Open Access Journals (Sweden)

    Sang Ok Song

    Full Text Available Intracellular calcium dynamics are critical to cellular functions like pain transmission. Extracellular ATP plays an important role in modulating intracellular calcium levels by interacting with the P2 family of surface receptors. In this study, we developed a mechanistic mathematical model of ATP-induced P2 mediated calcium signaling in archetype sensory neurons. The model architecture, which described 90 species connected by 162 interactions, was formulated by aggregating disparate molecular modules from literature. Unlike previous models, only mass action kinetics were used to describe the rate of molecular interactions. Thus, the majority of the 252 unknown model parameters were either association, dissociation or catalytic rate constants. Model parameters were estimated from nine independent data sets taken from multiple laboratories. The training data consisted of both dynamic and steady-state measurements. However, because of the complexity of the calcium network, we were unable to estimate unique model parameters. Instead, we estimated a family or ensemble of probable parameter sets using a multi-objective thermal ensemble method. Each member of the ensemble met an error criterion and was located along or near the optimal trade-off surface between the individual training data sets. The model quantitatively reproduced experimental measurements from dorsal root ganglion neurons as a function of extracellular ATP forcing. Hypothesized architecture linking phosphoinositide regulation with P2X receptor activity explained the inhibition of P2X-mediated current flow by activated metabotropic P2Y receptors. Sensitivity analysis using individual and the whole system outputs suggested which molecular subsystems were most important following P2 activation. Taken together, modeling and analysis of ATP-induced P2 mediated calcium signaling generated qualitative insight into the critical interactions controlling ATP induced calcium dynamics

  7. Dust properties inside molecular clouds from coreshine modeling and observations

    CERN Document Server

    Lefèvre, Charlène; Juvela, Mika; Paladini, Roberta; Lallement, Rosine; Marshall, D J; Andersen, Morten; Bacmann, Aurore; Mcgee, Peregrine M; Montier, Ludovic; Noriega-Crespo, Alberto; Pelkonen, V -M; Ristorcelli, Isabelle; Steinacker, Jürgen

    2014-01-01

    Context. Using observations to deduce dust properties, grain size distribution, and physical conditions in molecular clouds is a highly degenerate problem. Aims. The coreshine phenomenon, a scattering process at 3.6 and 4.5 $\\mu$m that dominates absorption, has revealed its ability to explore the densest parts of clouds. We want to use this effect to constrain the dust parameters. The goal is to investigate to what extent grain growth (at constant dust mass) inside molecular clouds is able to explain the coreshine observations. We aim to find dust models that can explain a sample of Spitzer coreshine data. We also look at the consistency with near-infrared data we obtained for a few clouds. Methods. We selected four regions with a very high occurrence of coreshine cases: Taurus-Perseus, Cepheus, Chameleon and L183/L134. We built a grid of dust models and investigated the key parameters to reproduce the general trend of surface bright- nesses and intensity ratios of both coreshine and near-infrared observation...

  8. Prediction of antigenic determinants of trichosanthin by molecular modeling

    Institute of Scientific and Technical Information of China (English)

    HEYONGNING; ZONGXIANGXIA; 等

    1996-01-01

    The antigenic determinants of trichosanthin were predicted by molecular modeling.First,the threedimensional structure model of the antigen-binding fragment of anti-trichosanthin immunoglobulin E was built on the basis of its amino-acid sequence and the known three-dimensional structure of an antibody with similar sequence.Secondly,the preferable antigen-antibody interactions were obtained based on the known three-dimensional structure of trichosanthin and of the hypervariable regions of anti-trichosanthin immunoglobulin E.Two regions in the molecular surface of trichosanthin were found to form extensive interactions with the hypervariable regions of the antibody and have been predicted to be the possible antigenic determinants:one is composed of two polypeptide segments,Ile201-Glu210 and Ile225-Asp229,which are close to each other in the three-dimensional structure;and the other is the segment Lys173-Thr178.The former region seems to be the more reasonable antigenic determinant than the latter one.

  9. Energetics and efficiency of a molecular motor model

    DEFF Research Database (Denmark)

    C. Fogedby, Hans; Svane, Axel

    2013-01-01

    The energetics and efficiency of a linear molecular motor model proposed by Mogilner et al. (Phys. Lett. 237, 297 (1998)) is analyzed from an analytical point of view. The model which is based on protein friction with a track is described by coupled Langevin equations for the motion in combination...... with coupled master equations for the ATP hydrolysis. Here the energetics and efficiency of the motor is addressed using a many body scheme with focus on the efficiency at maximum power (EMP). It is found that the EMP is reduced from about 10 pct in a heuristic description of the motor to about 1 per mille...... when incorporating the full motor dynamics, owing to the strong dissipation associated with the motor action....

  10. Modeling and Reconstruction of Mixed Functional and Molecular Patterns

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Functional medical imaging promises powerful tools for the visualization and elucidation of important disease-causing biological processes in living tissue. Recent research aims to dissect the distribution or expression of multiple biomarkers associated with disease progression or response, where the signals often represent a composite of more than one distinct source independent of spatial resolution. Formulating the task as a blind source separation or composite signal factorization problem, we report here a statistically principled method for modeling and reconstruction of mixed functional or molecular patterns. The computational algorithm is based on a latent variable model whose parameters are estimated using clustered component analysis. We demonstrate the principle and performance of the approaches on the breast cancer data sets acquired by dynamic contrast-enhanced magnetic resonance imaging.

  11. National Energy Outlook Modelling System

    Energy Technology Data Exchange (ETDEWEB)

    Volkers, C.M. [ECN Policy Studies, Petten (Netherlands)

    2013-12-15

    For over 20 years, the Energy research Centre of the Netherlands (ECN) has been developing the National Energy Outlook Modelling System (NEOMS) for Energy projections and policy evaluations. NEOMS enables 12 energy models of ECN to exchange data and produce consistent and detailed results.

  12. ABSTRACT MODELS FOR SYSTEM VIRTUALIZATION

    Directory of Open Access Journals (Sweden)

    M. G. Koveshnikov

    2015-05-01

    Full Text Available The paper is dedicated to issues of system objects securing (system files and user system or application configuration files against unauthorized access including denial of service attacks. We have suggested the method and developed abstract system virtualization models, which are used toresearch attack scenarios for different virtualization modes. Estimation for system tools virtualization technology effectiveness is given. Suggested technology is based on redirection of access requests to system objects shared among access subjects. Whole and partial system virtualization modes have been modeled. The difference between them is the following: in the whole virtualization mode all copies of access system objects are created whereon subjects’ requests are redirected including corresponding application objects;in the partial virtualization mode corresponding copies are created only for part of a system, for example, only system objects for applications. Alternative solutions effectiveness is valued relating to different attack scenarios. We consider proprietary and approved technical solution which implements system virtualization method for Microsoft Windows OS family. Administrative simplicity and capabilities of correspondingly designed system objects security tools are illustrated on this example. Practical significance of the suggested security method has been confirmed.

  13. Aerodynamic and Mechanical System Modelling

    DEFF Research Database (Denmark)

    Jørgensen, Martin Felix

    This thesis deals with mechanical multibody-systems applied to the drivetrain of a 500 kW wind turbine. Particular focus has been on gearbox modelling of wind turbines. The main part of the present project involved programming multibody systems to investigate the connection between forces, moments...

  14. Experimental Modeling of Dynamic Systems

    DEFF Research Database (Denmark)

    Knudsen, Morten Haack

    2006-01-01

    An engineering course, Simulation and Experimental Modeling, has been developed that is based on a method for direct estimation of physical parameters in dynamic systems. Compared with classical system identification, the method appears to be easier to understand, apply, and combine with physical...

  15. A Unique Large-Scale Undergraduate Research Experience in Molecular Systems Biology for Non-Mathematics Majors

    Science.gov (United States)

    Kappler, Ulrike; Rowland, Susan L.; Pedwell, Rhianna K.

    2017-01-01

    Systems biology is frequently taught with an emphasis on mathematical modeling approaches. This focus effectively excludes most biology, biochemistry, and molecular biology students, who are not mathematics majors. The mathematical focus can also present a misleading picture of systems biology, which is a multi-disciplinary pursuit requiring…

  16. An extensible analysable system model

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, Rene Rydhof

    2008-01-01

    , this does not hold for real physical systems. Approaches such as threat modelling try to target the formalisation of the real-world domain, but still are far from the rigid techniques available in security research. Many currently available approaches to assurance of critical infrastructure security...... allows for easy development of analyses for the abstracted systems. We briefly present one application of our approach, namely the analysis of systems for potential insider threats....

  17. Bayesian modelling of compositional heterogeneity in molecular phylogenetics.

    Science.gov (United States)

    Heaps, Sarah E; Nye, Tom M W; Boys, Richard J; Williams, Tom A; Embley, T Martin

    2014-10-01

    In molecular phylogenetics, standard models of sequence evolution generally assume that sequence composition remains constant over evolutionary time. However, this assumption is violated in many datasets which show substantial heterogeneity in sequence composition across taxa. We propose a model which allows compositional heterogeneity across branches, and formulate the model in a Bayesian framework. Specifically, the root and each branch of the tree is associated with its own composition vector whilst a global matrix of exchangeability parameters applies everywhere on the tree. We encourage borrowing of strength between branches by developing two possible priors for the composition vectors: one in which information can be exchanged equally amongst all branches of the tree and another in which more information is exchanged between neighbouring branches than between distant branches. We also propose a Markov chain Monte Carlo (MCMC) algorithm for posterior inference which uses data augmentation of substitutional histories to yield a simple complete data likelihood function that factorises over branches and allows Gibbs updates for most parameters. Standard phylogenetic models are not informative about the root position. Therefore a significant advantage of the proposed model is that it allows inference about rooted trees. The position of the root is fundamental to the biological interpretation of trees, both for polarising trait evolution and for establishing the order of divergence among lineages. Furthermore, unlike some other related models from the literature, inference in the model we propose can be carried out through a simple MCMC scheme which does not require problematic dimension-changing moves. We investigate the performance of the model and priors in analyses of two alignments for which there is strong biological opinion about the tree topology and root position.

  18. Diffusion energy profiles in silica mesoporous molecular sieves modelled with the fragment molecular orbital method

    Science.gov (United States)

    Roskop, Luke; Fedorov, Dmitri G.; Gordon, Mark S.

    2013-07-01

    The fragment molecular orbital (FMO) method is used to model truncated portions of mesoporous silica nanoparticle (MSN) pores. The application of the FMO/RHF (restricted Hartree-Fock) method to MCM-41 type MSNs is discussed and an error analysis is given. The FMO/RHF method is shown to reliably approximate the RHF energy (error ∼0.2 kcal/mol), dipole moment (error ∼0.2 debye) and energy gradient (root mean square [RMS] error ∼0.2 × 10-3 a.u./bohr). Several FMO fragmentation schemes are employed to provide guidance for future applications to MSN models. An MSN pore model is functionalised with (phenyl)propyl substituents and the diffusion barrier for benzene passing through the pore is computed by the FMO/RHF-D method with the Grimme dispersion correction (RHF-D). For the reaction coordinates examined here, the maximum FMO/RHF-D interaction energies range from -0.3 to -5.8 kcal/mol.

  19. Molecular dynamics studies of a generalised multipole model of molecular asymmetry in apolar and polar liquid crystals

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, S.J

    2001-11-01

    Results are presented from molecular dynamics simulations in the NPT ensemble of novel bent-core liquid crystal systems with the aim of determining the effect of both the bent-core shape and the addition of a transverse electric dipole upon the phase behaviour. The design of these molecules has been prompted by the realisation that ferroelectric phases need not consist of chiral molecules, since in the case of bent-core systems, selective steric shape packing results in a reduced system symmetry and ferroelectric properties without the need for chirality. A simple apolar model of the interaction employed a two-site Gay-Berne potential with the sites separated by {+-}0.5 reduced units for all models investigated. The angle between the sites, 180 deg - {gamma}, and thus the steric dipole was varied in a range {gamma} = 0 deg to {gamma} = 70 deg suggested by real molecules, and was seen to influence the phase behaviour markedly. The rod-like model formed isotropic, nematic, smectic A and smectic B phases. As the angle {gamma} increased the transition temperature to the ordered phase decreased; the nematic phase was first destabilised and then stabilised with respect to the smectic phase. Increasing {gamma} had subtle effects on layer packing in the {gamma} = 10 deg and {gamma} = 20 deg models. The {gamma} = 20 deg model was seen to undergo a transition from the smectic A phase to a tilted smectic B phase. For {gamma} = 40 deg a 'TGB-like' phase similar to the Blue phase seen in real materials was identified as the system cooled whereas for {gamma} = 70 deg no ordered phase formed. The study was repeated with the addition of a transverse electric dipole of {mu}* = 1.5 which was seen to stabilise a range of smectic phases. The nematic phase was destabilised in the rod-like model with a transition directly to a smectic B phase then to a ferroelectric crystal. As the angle {gamma} increased the transition temperature to the first ordered phase decreased more

  20. Modeling Multi-Level Systems

    CERN Document Server

    Iordache, Octavian

    2011-01-01

    This book is devoted to modeling of multi-level complex systems, a challenging domain for engineers, researchers and entrepreneurs, confronted with the transition from learning and adaptability to evolvability and autonomy for technologies, devices and problem solving methods. Chapter 1 introduces the multi-scale and multi-level systems and highlights their presence in different domains of science and technology. Methodologies as, random systems, non-Archimedean analysis, category theory and specific techniques as model categorification and integrative closure, are presented in chapter 2. Chapters 3 and 4 describe polystochastic models, PSM, and their developments. Categorical formulation of integrative closure offers the general PSM framework which serves as a flexible guideline for a large variety of multi-level modeling problems. Focusing on chemical engineering, pharmaceutical and environmental case studies, the chapters 5 to 8 analyze mixing, turbulent dispersion and entropy production for multi-scale sy...

  1. Molecular modeling of water interactions with fossil wood from Victorian brown coal

    Energy Technology Data Exchange (ETDEWEB)

    Tham Vu; Irene Yarovsky; Alan L. Chaffee [Monash University, Vic. (Australia). School of Chemistry

    2005-07-01

    The chemical structure of a fossil wood sample (Podocarpus sp.) taken from the Latrobe Valley coal measures (Victoria) was probed by {sup 13}C solid-state NMR, ultimate analyses and functional group analyses. This information was then used to create a molecular model (C{sub 100}H{sub 80}O{sub 2}) of fossil wood based on polymerized, but degraded lignin subunits. Molecular dynamics methods were used to observe both static and dynamic aspects of the coal-water interactions at ambient temperature, and to compare these with the analogous interactions for model lignin systems based on both guaiacyl (common to most woods) and syringyl (specific to angiosperms) structural units, as well as with bulk water. Na- and Ca-exchanged forms of the fossil wood model were also considered. The mobility of water was significantly reduced in all systems relative to bulk water, with the fossil wood and guaiacyl systems providing very similar values (global diffusion constants {approximately} 2.2 x 10{sup -5}cm{sup 2}{center_dot}s{sup -1}) and the Ca-exchanged system exhibiting the lowest value of all. A further reduction in the mobility of water molecules was observed in regions where hydrogen bonding could occur. For the fossil wood system, water molecules in the vicinity of carboxylic groups were significantly less mobile than those in the vicinity of OH groups generally. 22 refs., 8 figs., 2 tabs.

  2. Effect of molecular weight on the electrophoretic deposition of carbon black nanoparticles in moderately viscous systems.

    Science.gov (United States)

    Modi, Satyam; Panwar, Artee; Mead, Joey L; Barry, Carol M F

    2013-08-06

    Electrophoretic deposition from viscous media has the potential to produce in-mold assembly of nanoparticles onto three-dimensional parts in high-rate, polymer melt-based processes like injection molding. The effects of the media's molecular weight on deposition behavior were investigated using a model system of carbon black and polystyrene in tetrahydrofuran. Increases in molecular weight reduced the electrophoretic deposition of the carbon black particles due to increases in suspension viscosity and preferential adsorption of the longer polystyrene chains on the carbon black particles. At low deposition times (≤5 s), only carbon black deposited onto the electrodes, but the deposition decreased with increasing molecular weight and the resultant increases in suspension viscosity. For longer deposition times, polystyrene codeposited with the carbon black, with the amount of polystyrene increasing with molecular weight and decreasing with greater charge on the polystyrene molecules. This deposition behavior suggests that use of lower molecular polymers and control of electrical properties will permit electrophoretic deposition of nanoparticles from polymer melts for high-rate, one-step fabrication of nano-optical devices, biochemical sensors, and nanoelectronics.

  3. Computer System for Analysis of Molecular Evolution Modes (SAMEM): analysis of molecular evolution modes at deep inner branches of the phylogenetic tree.

    Science.gov (United States)

    Gunbin, Konstantin V; Suslov, Valentin V; Genaev, Mikhail A; Afonnikov, Dmitry A

    SAMEM (System for Analysis of Molecular Evolution Modes), a web-based pipeline system for inferring modes of molecular evolution in genes and proteins (http://pixie.bionet.nsc.ru/samem/), is presented. Pipeline 1 performs analyses of protein-coding gene evolution; pipeline 2 performs analyses of protein evolution; pipeline 3 prepares datasets of genes and/or proteins, performs their primary analysis, and builds BLOSUM matrices; pipeline 4 checks if these genes really are protein-coding. Pipeline 1 has an all-new feature, which allows the user to obtain K(R)/K(C) estimates using several different methods. An important feature of pipeline 2 is an original method for analyzing the rates of amino acid substitutions at the branches of a phylogenetic tree. The method is based on Markov modeling and a non-parametric permutation test, which compares expected and observed frequencies of amino acid substitutions, and infers the modes of molecular evolution at deep inner branches.

  4. MODEL ORGANISMS USED IN MOLECULAR BIOLOGY OR MEDICAL RESEARCH

    Directory of Open Access Journals (Sweden)

    Pandey Govind

    2011-11-01

    Full Text Available A model organism is a non-human species that is studied to understand specific biological phenomena with the expectation that investigations made in the organism model will provide insight into the workings of other organisms. The model organisms are widely used to explore potential causes and treatments for human as well as animal diseases when experiments on animals or humans would be unfeasible or considered less ethical. Studying model organisms may be informative, but care must be taken when generalizing from one organism to another. Often, model organisms are chosen on the basis that they are amenable to experimental manipulation. When researchers look for an organism to use in their studies, they look for several traits. Among these are size, generation time, accessibility, manipulation, genetics, conservation of mechanisms and potential economic benefit. As comparative molecular biology has become more common, some researchers have sought model organisms from a wider assortment of lineages on the tree of life. There are many model organisms, such as viruses (e.g., Phage lambda virus, Tobacco mosaic virus, etc., bacteria (e.g., Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens, Vibrio fischeri, etc., algae (e.g., Chlamydomonas reinhardtii, Emiliania huxleyi, etc., molds (e.g., Aspergillus nidulans, Neurospora crassa, etc., yeasts (e.g., Saccharomyces cerevisiae, Ustilago maydis, etc., higher plants (e.g., Arabidopsis thaliana, Lemna gibba, Lotus japonicus, Nicotiana tabaccum, Oryza sativa, Physcomitrella patens, Zea mays, etc. and animals (e.g., Caenorhabditis elegans, guinea pig, hamster, mouse, rat, cat, chicken, dog, frog, Hydra, Drosophila melanogaster fruit fly, fish, etc..

  5. Universal iso-density polarizable continuum model for molecular solvents

    CERN Document Server

    Gunceler, Deniz

    2014-01-01

    Implicit electron-density solvation models based on joint density-functional theory offer a computationally efficient solution to the problem of calculating thermodynamic quantities of solvated systems from first-principles quantum mechanics. However, despite much recent interest in such models, to date the applicability of such models to non-aqueous solvents has been limited because the determination of the model parameters requires fitting to a large database of experimental solvation energies for each new solvent considered. This work presents an alternate approach which allows development of new solvation models for a large class of protic and aprotic solvents from only simple, single-molecule ab initio calculations and readily available bulk thermodynamic data. We find that this model is accurate to nearly 1.7 kcal/mol even for solvents outside our development set.

  6. Bayesian molecular design with a chemical language model.

    Science.gov (United States)

    Ikebata, Hisaki; Hongo, Kenta; Isomura, Tetsu; Maezono, Ryo; Yoshida, Ryo

    2017-03-09

    The aim of computational molecular design is the identification of promising hypothetical molecules with a predefined set of desired properties. We address the issue of accelerating the material discovery with state-of-the-art machine learning techniques. The method involves two different types of prediction; the forward and backward predictions. The objective of the forward prediction is to create a set of machine learning models on various properties of a given molecule. Inverting the trained forward models through Bayes' law, we derive a posterior distribution for the backward prediction, which is conditioned by a desired property requirement. Exploring high-probability regions of the posterior with a sequential Monte Carlo technique, molecules that exhibit the desired properties can computationally be created. One major difficulty in the computational creation of molecules is the exclusion of the occurrence of chemically unfavorable structures. To circumvent this issue, we derive a chemical language model that acquires commonly occurring patterns of chemical fragments through natural language processing of ASCII strings of existing compounds, which follow the SMILES chemical language notation. In the backward prediction, the trained language model is used to refine chemical strings such that the properties of the resulting structures fall within the desired property region while chemically unfavorable structures are successfully removed. The present method is demonstrated through the design of small organic molecules with the property requirements on HOMO-LUMO gap and internal energy. The R package iqspr is available at the CRAN repository.

  7. Development and Evaluation of Amino Acid Molecular Models

    Directory of Open Access Journals (Sweden)

    Aparecido R. Silva

    2007-05-01

    Full Text Available The comprehension of structure and function of proteins has a tight relationshipwith the development of structural biology. However, biochemistry students usuallyfind difficulty to visualize the structures when they use only schematic drawings ofdidactic books. The representation of three-dimensional structures of somebiomolecules with ludic models, built with representative units, have supplied tothe students and teachers a successfully experience to better visualize andcorrelate the structures to the real molecules. The present work shows thedeveloped models and the process to produce the representative units of the mainamino acids in industrial scale. The design and applicability of the representativeunits were discussed with many teachers and some suggestions wereimplemented to the models. The preliminary evaluation and perspective ofutilization by researchers show that the work is in the right direction. At the actualstage, the models are defined, prototypes were made and will be presented in thismeeting. The moulds for the units are at the final stage of construction and trial inspecialized tool facilities. The last term will consist of an effective evaluation of thedidactic tool for the teaching/learning process in Structural Molecular Biology. Theevaluation protocol is being elaborated containing simple and objective questions,similar to those used in research on science teaching.

  8. A computational toy model for shallow landslides: Molecular Dynamics approach

    CERN Document Server

    Martelloni, Gianluca; Massaro, Emanuele

    2012-01-01

    The aim of this paper is to propose a 2D computational algorithm for modeling of the trigger and the propagation of shallow landslides caused by rainfall. We used a Molecular Dynamics (MD) inspired model, similar to discrete element method (DEM), that is suitable to model granular material and to observe the trajectory of single particle, so to identify its dynamical properties. We consider that the triggering of shallow landslides is caused by the decrease of the static friction along the sliding surface due to water infiltration by rainfall. Thence the triggering is caused by two following conditions: (a) a threshold speed of the particles and (b) a condition on the static friction, between particles and slope surface, based on the Mohr-Coulomb failure criterion. The latter static condition is used in the geotechnical model to estimate the possibility of landslide triggering. Finally the interaction force between particles is defined trough a potential that, in the absence of experimental data, we have mode...

  9. A kinetic model for molecular diffusion through pores.

    Science.gov (United States)

    D'Agostino, Tommaso; Salis, Samuele; Ceccarelli, Matteo

    2016-07-01

    The number of pathogens developing multiple drug resistance is ever increasing. The impact on healthcare systems is huge and the need for novel antibiotics as well a new way to develop them is urgent, especially against Gram-negative bacteria. The first defense of these bacteria is the outer membrane, where unspecific protein channels (porins) modulate nutrients passive diffusion. Also polar antibiotics enter through this path and down-regulation and/or mutation of porins are very common in drug resistant strains. Our inability to come up with novel effective antibiotics mostly relies upon the insufficient comprehension of the key molecular features enabling better penetration through porins. Molecular dynamics simulations offer an extraordinary tool in the study of the dynamics of biological systems; however, one of the major drawbacks of this method is that its use is currently restricted to study time scales of the order of microsecond. Enhanced sampling methods like Metadynamics have been recently used to investigate the diffusion of antibiotics through bacterial porins. The main limitation is that dynamical properties cannot be estimated because of the different potential that the systems under study are experiencing. Recently, the scope of Metadynamics has been extended. By applying an a posteriori analysis one can obtain rates of transitions and rate-limiting steps of the process under study, directly comparable with kinetic data extracted from electrophysiology experiments. In this work, we apply this method to the study of the permeability of Escherichia coli's OmpF with respect to Meropenem, finding good agreement with the residence time obtained analyzing experimental current noise. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.

  10. Constrained Molecular Dynamics Modeling of Dielectric Response in Polar Polyethylene Analogs and Poly(vinylidene flouride)

    Science.gov (United States)

    Calame, Jeffrey

    2013-03-01

    A simplified molecular dynamics formalism for polymers, having united atoms with constrained bond lengths and bond angles along the backbone but allowing torsional motion, has been developed to model the dielectric response and ferroelectricity in polymers with permanent dipoles. Analytic relations existing on the backbone geometry and associated dihedral motion allow elimination of many dot and cross product evaluations. Also, constraint error correcting forces, symplectic integration with velocity prediction, random force excitation with damping and a momentum-conserving thermostat, and rapid neighbor list and long range force computation allow efficient computation and time steps as large as 20 fs to enable the study of relatively long time scale dielectric phenomena. Studies are performed on non-polar polyethylene for benchmarking, followed by a model system (polar polyethylene) which retains the molecular structure, dihedral potentials, and non-bonded interactions of polyethylene, except artificial partial charges are placed on the united atoms. The modeling is extended to poly(vinylidene fluoride) by changes to the molecular structure, potentials, and charges. Heterogeneous systems containing crystalline and amorphous arrangements of polymer chains are studied. Work supported by the U.S. Office of Naval Research.

  11. Chemoinformatics in the New Era: From Molecular Dynamics to Systems Dynamics.

    Science.gov (United States)

    Wang, Guanyu

    2016-03-03

    Chemoinformatics, due to its power in gathering information at the molecular level, has a wide array of important applications to biology, including fundamental biochemical studies and drug discovery and optimization. As modern "omics" based profiling and network based modeling and simulation techniques grow in sophistication, chemoinformatics now faces a great opportunity to include systems-level control mechanisms as one of its pillar components to extend and refine its various applications. This viewpoint article, through the example of computer aided targeting of the PI3K/Akt/mTOR pathway, outlines major steps of integrating systems dynamics simulations into molecular dynamics simulations to facilitate a higher level of chemoinformatics that would revolutionize drug lead optimization, personalized therapy, and possibly other applications.

  12. QUANTUM-MECHANICAL PROPERTIES OF PROTON TRANSPORT IN THE HYDROGEN-BONDED MOLECULAR SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    PANG XIAO-FENG; LI PING

    2000-01-01

    The dynamic equations of the proton transport along the hydrogen bonded molecular systems have been obtainedby using completely quantum-mechanical method to be based on new Hamiltonian and model we proposed. Somequantum-mechanical features of the proton-solitons have also been given in such a case. The alternate motion of twodefects resulting from proton transfer occurred in the systems can be explained by the results. The results obtainedshow that the proton-soliton has corpuscle feature and obey classical equations of motion, while the free soliton movesin uniform velocity along the hydrogen bonded chains.

  13. Molecular Diffusive Motion in a Monolayer of a Model Lubricant

    Science.gov (United States)

    Diama, A.; Criswell, L.; Mo, H.; Taub, H.; Herwig, K. W.; Hansen, F. Y.; Volkmann, U. G.; Dimeo, R.; Neumann, D.

    2003-03-01

    Squalane (C_30H_62), a branched alkane of intermediate length consisting of a tetracosane backbone (n-C_24H_50 or C24) and six symmetrically placed methyl sidegroups, is frequently taken as a model lubricant. We have conducted quasielastic neutron scattering (QNS) experiments to investigate the diffusive motion on different time scales in a squalane monolayer adsorbed on the (0001) surfaces of an exfoliated graphite substrate. Unlike tetracosane, high-energy resolution spectra (time scale ˜0.1 - 4 ns) at temperatures of 215 K and 230 K show the energy width of the QNS to have a maximum near Q = 1.2 ÅThis nonmonotonic Q dependence suggests a more complicated diffusive motion than the simple rotation about the long molecular axis believed to occur in a C24 monolayer at this temperature. Lower-energy-resolution spectra (time scale ˜4 - 40 ps) show evidence of two types of diffusive motion whose rates have opposite temperature dependences. The rate of the faster motion decreases as the monolayer is heated, and we speculate that it is due to hindered rotation of the methyl groups. The rate of the slower motion increases with temperature and may involve both uniaxial rotation and translational diffusion. Our experimental results will be compared with molecular dynamics simulations.

  14. Molecular model for force production and transmission during vertebrate gastrulation.

    Science.gov (United States)

    Pfister, Katherine; Shook, David R; Chang, Chenbei; Keller, Ray; Skoglund, Paul

    2016-02-15

    Vertebrate embryos undergo dramatic shape changes at gastrulation that require locally produced and anisotropically applied forces, yet how these forces are produced and transmitted across tissues remains unclear. We show that depletion of myosin regulatory light chain (RLC) levels in the embryo blocks force generation at gastrulation through two distinct mechanisms: destabilizing the myosin II (MII) hexameric complex and inhibiting MII contractility. Molecular dissection of these two mechanisms demonstrates that normal convergence force generation requires MII contractility and we identify a set of molecular phenotypes correlated with both this failure of convergence force generation in explants and of blastopore closure in whole embryos. These include reduced rates of actin movement, alterations in C-cadherin dynamics and a reduction in the number of polarized lamellipodia on intercalating cells. By examining the spatial relationship between C-cadherin and actomyosin we also find evidence for formation of transcellular linear arrays incorporating these proteins that could transmit mediolaterally oriented tensional forces. These data combine to suggest a multistep model to explain how cell intercalation can occur against a force gradient to generate axial extension forces. First, polarized lamellipodia extend mediolaterally and make new C-cadherin-based contacts with neighboring mesodermal cell bodies. Second, lamellipodial flow of actin coalesces into a tension-bearing, MII-contractility-dependent node-and-cable actin network in the cell body cortex. And third, this actomyosin network contracts to generate mediolateral convergence forces in the context of these transcellular arrays.

  15. Structure-based molecular modeling approaches to GPCR oligomerization.

    Science.gov (United States)

    Kaczor, Agnieszka A; Selent, Jana; Poso, Antti

    2013-01-01

    Classical structure-based drug design techniques using G-protein-coupled receptors (GPCRs) as targets focus nearly exclusively on binding at the orthosteric site of a single receptor. Dimerization and oligomerization of GPCRs, proposed almost 30 years ago, have, however, crucial relevance for drug design. Targeting these complexes selectively or designing small molecules that affect receptor-receptor interactions might provide new opportunities for novel drug discovery. In order to study the mechanisms and dynamics that rule GPCRs oligomerization, it is essential to understand the dynamic process of receptor-receptor association and to identify regions that are suitable for selective drug binding, which may be determined with experimental methods such as Förster resonance energy transfer (FRET) or Bioluminescence resonance energy transfer (BRET) and computational sequence- and structure-based approaches. The aim of this chapter is to provide a comprehensive description of the structure-based molecular modeling methods for studying GPCR dimerization, that is, protein-protein docking, molecular dynamics, normal mode analysis, and electrostatics studies.

  16. Distribution system modeling and analysis

    CERN Document Server

    Kersting, William H

    2002-01-01

    For decades, distribution engineers did not have the sophisticated tools developed for analyzing transmission systems-often they had only their instincts. Things have changed, and we now have computer programs that allow engineers to simulate, analyze, and optimize distribution systems. Powerful as these programs are, however, without a real understanding of the operating characteristics of a distribution system, engineers using the programs can easily make serious errors in their designs and operating procedures.Distribution System Modeling and Analysis helps prevent those errors. It gives re

  17. Stirling Engine Dynamic System Modeling

    Science.gov (United States)

    Nakis, Christopher G.

    2004-01-01

    The Thermo-Mechanical systems branch at the Glenn Research Center focuses a large amount time on Stirling engines. These engines will be used on missions where solar power is inefficient, especially in deep space. I work with Tim Regan and Ed Lewandowski who are currently developing and validating a mathematical model for the Stirling engines. This model incorporates all aspects of the system including, mechanical, electrical and thermodynamic components. Modeling is done through Simplorer, a program capable of running simulations of the model. Once created and then proven to be accurate, a model is used for developing new ideas for engine design. My largest specific project involves varying key parameters in the model and quantifying the results. This can all be done relatively trouble-free with the help of Simplorer. Once the model is complete, Simplorer will do all the necessary calculations. The more complicated part of this project is determining which parameters to vary. Finding key parameters depends on the potential for a value to be independently altered in the design. For example, a change in one dimension may lead to a proportional change to the rest of the model, and no real progress is made. Also, the ability for a changed value to have a substantial impact on the outputs of the system is important. Results will be condensed into graphs and tables with the purpose of better communication and understanding of the data. With the changing of these parameters, a more optimal design can be created without having to purchase or build any models. Also, hours and hours of results can be simulated in minutes. In the long run, using mathematical models can save time and money. Along with this project, I have many other smaller assignments throughout the summer. My main goal is to assist in the processes of model development, validation and testing.

  18. Review on Modeling Molecular Motor%分子马达模型综述

    Institute of Scientific and Technical Information of China (English)

    王先菊; 艾保全; 刘良钢

    2001-01-01

    The structure and function of three kinds of motor proteins are introduced. The fundamental importance on studying molecular motor in living systems is also discribed. With detailed review on several archetype theoretical models, the progress and application on modeling molecule motor are presented.%介绍三类马达酶的结构,功能和生命体内分子马达的研究状况,并详细介绍几类典型分子马达的理论模型,同时展望了分子马达的发展前景和应用.

  19. Time-dependent theoretical treatments of the dynamics of electrons and nuclei in molecular systems

    Science.gov (United States)

    Deumens, E.; Diz, A.; Longo, R.; Öhrn, Y.

    1994-07-01

    An overview is presented of methods for time-dependent treatments of molecules as systems of electrons and nuclei. The theoretical details of these methods are reviewed and contrasted in the light of a recently developed time-dependent method called electron-nuclear dynamics. Electron-nuclear dynamics (END) is a formulation of the complete dynamics of electrons and nuclei of a molecular system that eliminates the necessity of constructing potential-energy surfaces. Because of its general formulation, it encompasses many aspects found in other formulations and can serve as a didactic device for clarifying many of the principles and approximations relevant in time-dependent treatments of molecular systems. The END equations are derived from the time-dependent variational principle applied to a chosen family of efficiently parametrized approximate state vectors. A detailed analysis of the END equations is given for the case of a single-determinantal state for the electrons and a classical treatment of the nuclei. The approach leads to a simple formulation of the fully nonlinear time-dependent Hartree-Fock theory including nuclear dynamics. The nonlinear END equations with the ab initio Coulomb Hamiltonian have been implemented at this level of theory in a computer program, ENDyne, and have been shown feasible for the study of small molecular systems. Implementation of the Austin Model 1 semiempirical Hamiltonian is discussed as a route to large molecular systems. The linearized END equations at this level of theory are shown to lead to the random-phase approximation for the coupled system of electrons and nuclei. The qualitative features of the general nonlinear solution are analyzed using the results of the linearized equations as a first approximation. Some specific applications of END are presented, and the comparison with experiment and other theoretical approaches is discussed.

  20. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.