WorldWideScience

Sample records for dynamic molecular model

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  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. 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

  10. 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.

  11. 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

  12. 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,…

  13. 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,…

  14. 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

  15. 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…

  16. 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.

  17. 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+ ...

  18. Molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Ladd, A.J.C.

    1988-08-01

    The basic methodology of equilibrium molecular dynamics is described. Examples from the literature are used to illustrate how molecular dynamics has been used to resolve theoretical controversies, provide data to test theories, and occasionally to discover new phenomena. The emphasis is on the application of molecular dynamics to an understanding of the microscopic physics underlying the transport properties of simple fluids. 98 refs., 4 figs.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. First Principles Modelling of Shape Memory Alloys Molecular Dynamics Simulations

    CERN Document Server

    Kastner, Oliver

    2012-01-01

    Materials sciences relate the macroscopic properties of materials to their microscopic structure and postulate the need for holistic multiscale research. The investigation of shape memory alloys is a prime example in this regard. This particular class of materials exhibits strong coupling of temperature, strain and stress, determined by solid state phase transformations of their metallic lattices. The present book presents a collection of simulation studies of this behaviour. Employing conceptually simple but comprehensive models, the fundamental material properties of shape memory alloys are qualitatively explained from first principles. Using contemporary methods of molecular dynamics simulation experiments, it is shown how microscale dynamics may produce characteristic macroscopic material properties. The work is rooted in the materials sciences of shape memory alloys and  covers  thermodynamical, micro-mechanical  and crystallographical aspects. It addresses scientists in these research fields and thei...

  4. 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...

  5. Molecular dynamics simulations of water within models of ion channels.

    Science.gov (United States)

    Breed, J; Sankararamakrishnan, R; Kerr, I D; Sansom, M S

    1996-04-01

    The transbilayer pores formed by ion channel proteins contain extended columns of water molecules. The dynamic properties of such waters have been suggested to differ from those of water in its bulk state. Molecular dynamics simulations of ion channel models solvated within and at the mouths of their pores are used to investigate the dynamics and structure of intra-pore water. Three classes of channel model are investigated: a) parallel bundles of hydrophobic (Ala20) alpha-helices; b) eight-stranded hydrophobic (Ala10) antiparallel beta-barrels; and c) parallel bundles of amphipathic alpha-helices (namely, delta-toxin, alamethicin, and nicotinic acetylcholine receptor M2 helix). The self-diffusion coefficients of water molecules within the pores are reduced significantly relative to bulk water in all of the models. Water rotational reorientation rates are also reduced within the pores, particularly in those pores formed by alpha-helix bundles. In the narrowest pore (that of the Ala20 pentameric helix bundle) self-diffusion coefficients and reorientation rates of intra-pore waters are reduced by approximately an order of magnitude relative to bulk solvent. In Ala20 helix bundles the water dipoles orient antiparallel to the helix dipoles. Such dipole/dipole interaction between water and pore may explain how water-filled ion channels may be formed by hydrophobic helices. In the bundles of amphipathic helices the orientation of water dipoles is modulated by the presence of charged side chains. No preferential orientation of water dipoles relative to the pore axis is observed in the hydrophobic beta-barrel models.

  6. 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.

  7. A computational toy model for shallow landslides: Molecular dynamics approach

    Science.gov (United States)

    Martelloni, Gianluca; Bagnoli, Franco; Massaro, Emanuele

    2013-09-01

    The aim of this paper is to propose a 2D computational algorithm for modeling the triggering and propagation of shallow landslides caused by rainfall. We used a molecular dynamics (MD) approach, similar to the discrete element method (DEM), that is suitable to model granular material and to observe the trajectory of a single particle, so to possibly 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 the two following conditions: (a) a threshold speed of the particles and (b) a condition on the static friction, between the particles and the 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. The interaction force between particles is modeled, in the absence of experimental data, by means of a potential similar to the Lennard-Jones one. The viscosity is also introduced in the model and for a large range of values of the model's parameters, we observe a characteristic velocity pattern, with acceleration increments, typical of real landslides. The results of simulations are quite promising: the energy and time triggering distribution of local avalanches show a power law distribution, analogous to the observed Gutenberg-Richter and Omori power law distributions for earthquakes. Finally, it is possible to apply the method of the inverse surface displacement velocity [4] for predicting the failure time.

  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. A Langevin model for the Dynamic Contact Angle Parameterised Using Molecular Dynamics

    Science.gov (United States)

    Smith, Edward; Muller, Erich; Craster, Richard; Matar, Omar

    2016-11-01

    An understanding of droplet spreading is essential in a diverse range of applications, including coating processes, dip feed reactors, crop spraying and biomedical treatments such as surfactant replacement theory. The default modelling tools for engineering fluid dynamics assume that the continuum hypothesis is valid. The contact line motion is very difficult to capture in this paradigm and requires some form of closure model, often tuned a priori to experiments. Molecular dynamics (MD), by assuming only an inter-molecular potential, reproduces the full detail of the three-phase contact line with no additional modelling assumptions. This provides an ideal test-bed to understand contact line motion. In this talk, MD results for a sheared liquid bridge are presented. The evolution and fluctuations of the dynamic contact angle are paramterised over a range of wall sliding speeds and temperatures. A Langevin model is proposed to reproduce the fluctuations and evolution of the contact angle. Results from this model are compared to molecular simulation data showing excellent agreement. The potential applications of this model, as well as limitation and possible extensions, are discussed. EPSRC UK platform Grant MACIPh (EP/L020564/1).

  10. Acoustic response of cemented granular sedimentary rocks: molecular dynamics modeling.

    Science.gov (United States)

    García, Xavier; Medina, Ernesto

    2007-06-01

    The effect of cementation processes on the acoustical properties of sands is studied via molecular dynamics simulation methods. We propose numerical methods where the initial uncemented sand is built by simulating the settling process of sediments. Uncemented samples of different porosity are considered by emulating natural mechanical compaction of sediments due to overburden. Cementation is considered through a particle-based model that captures the underlying physics behind the process. In our simulations, we consider samples with different degrees of compaction and cementing materials with distinct elastic properties. The microstructure of cemented sands is taken into account while adding cement at specific locations within the pores, such as grain-to-grain contacts. Results show that the acoustical properties of cemented sands are strongly dependent on the amount of cement, its stiffness relative to the hosting medium, and its location within the pores. Simulation results are in good correspondence with available experimental data and compare favorably with some theoretical predictions for the sound velocity within a range of cement saturation, porosity, and confining pressure.

  11. 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...

  12. Molecular dynamics modeling of a nanomaterials-water surface interaction

    Science.gov (United States)

    Nejat Pishkenari, Hossein; Keramati, Ramtin; Abdi, Ahmad; Minary-Jolandan, Majid

    2016-04-01

    In this article, we study the formation of nanomeniscus around a nanoneedle using molecular dynamics simulation approach. The results reveal three distinct phases in the time-evolution of meniscus before equilibrium according to the contact angle, meniscus height, and potential energy. In addition, we investigated the correlation between the nanoneedle diameter and nanomeniscus characteristics. The results have applications in various fields such as scanning probe microscopy and rheological measurements.

  13. 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...

  14. Effect of solvent model when probing protein dynamics with molecular dynamics.

    Science.gov (United States)

    Genheden, Samuel

    2017-01-01

    We probe the dynamics of the Bpti and Galectin-3 proteins using molecular dynamics simulations employing three water models at different levels of resolution, viz. the atomistic TIP4P-Ewald, the coarse-grained Elba and an implicit generalised Born model. The dynamics are quantified indirectly by model-free order parameters, S(2) of the backbone NH and selected side-chain bond vectors, which also have been determined experimentally through NMR relaxation measurements. For the backbone, the order parameters produced with the three solvent models agree to a large extent with experiments, giving average unsigned deviations between 0.03 and 0.06. For the side-chains, for which the experimental data is incomplete, the deviations are considerably larger with mean deviations between 0.13 and 0.17. However, for both backbone and side-chains, it is difficult to pick a winner, as all models perform equally well overall. For a more complete set of side-chain vectors, we resort to analysing the variation among the estimates from different solvent models. Unfortunately, the variations are found to be sizeable with mean deviations between 0.11 and 0.15. Implications for computational assessment of protein dynamics are discussed.

  15. Molecular Dynamics Modeling of PPTA Crystals in Aramid Fibers

    Energy Technology Data Exchange (ETDEWEB)

    Mercer, Brian Scott [Univ. of California, Berkeley, CA (United States)

    2016-05-19

    In this work, molecular dynamics modeling is used to study the mechanical properties of PPTA crystallites, which are the fundamental microstructural building blocks of polymer aramid bers such as Kevlar. Particular focus is given to constant strain rate axial loading simulations of PPTA crystallites, which is motivated by the rate-dependent mechanical properties observed in some experiments with aramid bers. In order to accommodate the covalent bond rupture that occurs in loading a crystallite to failure, the reactive bond order force eld ReaxFF is employed to conduct the simulations. Two major topics are addressed: The rst is the general behavior of PPTA crystallites under strain rate loading. Constant strain rate loading simulations of crystalline PPTA reveal that the crystal failure strain increases with increasing strain rate, while the modulus is not a ected by the strain rate. Increasing temperature lowers both the modulus and the failure strain. The simulations also identify the C N bond connecting the aromatic rings as weakest primary bond along the backbone of the PPTA chain. The e ect of chain-end defects on PPTA micromechanics is explored, and it is found that the presence of a chain-end defect transfers load to the adjacent chains in the hydrogen-bonded sheet in which the defect resides, but does not in uence the behavior of any other chains in the crystal. Chain-end defects are found to lower the strength of the crystal when clustered together, inducing bond failure via stress concentrations arising from the load transfer to bonds in adjacent chains near the defect site. The second topic addressed is the nature of primary and secondary bond failure in crystalline PPTA. Failure of both types of bonds is found to be stochastic in nature and driven by thermal uctuations of the bonds within the crystal. A model is proposed which uses reliability theory to model bonds under constant strain rate loading as components with time-dependent failure rate

  16. 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.

  17. Molecular dynamical modelling of endohedral fullerenes formation in plasma

    Science.gov (United States)

    Fedorov, A. S.; Kovaleva, E. A.; Lubkova, T. A.; Popov, Z. I.; Kuzubov, A. A.; Visotin, M. A.; Irle, S.

    2016-02-01

    The initial stages of fullerene and endohedral metallofullerene (EMF) synthesis in carbon-helium plasma at 1500 K and 2500 K have been simulated with quantum chemical molecular dynamics (MD) based on density-functional tight-binding (DFTB). The cases of formation of large (>100 atoms) sp2-carbon clusters with scandium atoms inside were observed. These clusters are considered as precursors of fullerenes or EMFs, and thus it is shown that formation of EMFs can be explained within the framework of "shrinking hot giant" mechanism. Also, the dependence of formation rates on plasma parameters, including temperature, buffer gas and metal atoms concentrations, has been studied.

  18. Nonadiabatic Excited-State Molecular Dynamics Modeling of Photoinduced Dynamics in Conjugated Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Tammie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Center for Nonlinear Studies (CNLS) and Center for Integrated Nanotechnologies (CINT), Theoretical Division; Fernandez-Alberti, Sebastian [Univ. Nacional de Quilmes, Buenos Aires (Argentina); Chernyak, Vladimir [Wayne State Univ., Detroit, MI (United States). Dept. of Chemistry; Roitberg, Adrian E. [Univ. of Florida, Gainesville, FL (United States). Depts. of Physics and Chemistry. Quantum Theory Project; Tretiak, Sergei [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Center for Nonlinear Studies (CNLS) and Center for Integrated Nanotechnologies (CINT), Theoretical Division

    2011-01-10

    Nonadiabatic dynamics generally defines the entire evolution of electronic excitations in optically active molecular materials. It is commonly associated with a number of fundamental and complex processes such as intraband relaxation, energy transfer, and light harvesting influenced by the spatial evolution of excitations and transformation of photoexcitation energy into electrical energy via charge separation (e.g., charge injection at interfaces). To treat ultrafast excited-state dynamics and exciton/charge transport we have developed a nonadiabatic excited-state molecular dynamics (NA-ESMD) framework incorporating quantum transitions. Our calculations rely on the use of the Collective Electronic Oscillator (CEO) package accounting for many-body effects and actual potential energy surfaces of the excited states combined with Tully’s fewest switches algorithm for surface hopping for probing nonadiabatic processes. This method is applied to model the photoinduced dynamics of distyrylbenzene (a small oligomer of polyphenylene vinylene, PPV). Our analysis shows intricate details of photoinduced vibronic relaxation and identifies specific slow and fast nuclear motions that are strongly coupled to the electronic degrees of freedom, namely, torsion and bond length alternation, respectively. Nonadiabatic relaxation of the highly excited mA{sub g} state is predicted to occur on a femtosecond time scale at room temperature and on a picosecond time scale at low temperature.

  19. Can dynamic contact angle be measured using molecular modeling?

    Science.gov (United States)

    Malani, Ateeque; Raghavanpillai, Anilkumar; Wysong, Ernest B; Rutledge, Gregory C

    2012-11-02

    A method is presented for determining the dynamic contact angle at the three-phase contact between a solid, a liquid, and a vapor under an applied force, using molecular simulation. The method is demonstrated using a Lennard-Jones fluid in contact with a cylindrical shell of the fcc Lennard-Jones solid. Advancing and receding contact angles and the contact angle hysteresis are reported for the first time by this approach. The increase in force required to wet fully an array of solid cylinders (robustness) with decreasing separation distance between cylinders is evaluated. The dynamic contact angle is characterized by partial slipping of the three phase contact line when a force is applied.

  20. Poissonian reducibility and thermal scaling within the lattice gas model and molecular dynamics model

    OpenAIRE

    Ma, Y.G.

    2000-01-01

    The emission of clusters in the nuclear disassembly is investigated within the framework of isospin dependent lattice gas model and classical molecular dynamics model. As observed in the recent experimental data, it is found that the emission of individual cluster is poissonian and thermal scaling is observed in the linear Arrhenius plots made from the average multiplicity of each cluster. The mass, isotope and charge dependent "emission barriers" are extracted from the slopes of the Arrheniu...

  1. Molecular Dynamics Modeling of Tethered Organics in Confined Spaces

    Energy Technology Data Exchange (ETDEWEB)

    Waksburg, Avi [Monash University, Australia; Nguyen, M [Monash University, Australia; Chaffe, Alan [Monash University, Australia; Kidder, Michelle [ORNL; Buchanan III, A C [ORNL; Britt, Phillip F [ORNL

    2011-01-01

    A computational method for constructing and evaluating the dynamic behaviour of functionalised hexagonal mesoporous silica (HMS) MCM-41 models is reported. HMS with three pore diameters (1.7, 2.2 and 2.9 nm) were prepared, and, from these, two series of derivative structures were constructed - one with 1,3-diphenylpropyl (DPP) tethers and the other with smaller dimethylsilyl (DMS) tethers attached to the mesopores internal surfaces. Comparison with experimental data shows that simulation results correctly predict the maximum tether density that can be achieved for each tether and each pore diameter. For the smaller pore models, the extent of DPP functionalisation that can be achieved is limited by the available pore volume. However, for the larger pore model, the extent of functionalisation is limited by access to potentially reactive sites on the pore surface. The dynamic behaviour of the models was investigated over a range of temperatures (240-648 K). At lower temperatures (< 400 K), the mobility of DPP tethers in the 2.9 nm model is actually less than that observed in either the 2.2 nm model or the 1.7 nm model due to the extensive non-bonded interactions that are able to develop between tethers and the silica surface at this diameter. At higher temperatures, the free ends of these tethers break away from the surface, extend further into the pore space and the DPP mobility in the 2.9 nm model is higher than in the smaller pore systems.

  2. Molecular dynamics techniques for modeling G protein-coupled receptors.

    Science.gov (United States)

    McRobb, Fiona M; Negri, Ana; Beuming, Thijs; Sherman, Woody

    2016-10-01

    G protein-coupled receptors (GPCRs) constitute a major class of drug targets and modulating their signaling can produce a wide range of pharmacological outcomes. With the growing number of high-resolution GPCR crystal structures, we have the unprecedented opportunity to leverage structure-based drug design techniques. Here, we discuss a number of advanced molecular dynamics (MD) techniques that have been applied to GPCRs, including long time scale simulations, enhanced sampling techniques, water network analyses, and free energy approaches to determine relative binding free energies. On the basis of the many success stories, including those highlighted here, we expect that MD techniques will be increasingly applied to aid in structure-based drug design and lead optimization for GPCRs.

  3. Substructured multibody molecular dynamics.

    Energy Technology Data Exchange (ETDEWEB)

    Grest, Gary Stephen; Stevens, Mark Jackson; Plimpton, Steven James; Woolf, Thomas B. (Johns Hopkins University, Baltimore, MD); Lehoucq, Richard B.; Crozier, Paul Stewart; Ismail, Ahmed E.; Mukherjee, Rudranarayan M. (Rensselaer Polytechnic Institute, Troy, NY); Draganescu, Andrei I.

    2006-11-01

    We have enhanced our parallel molecular dynamics (MD) simulation software LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator, lammps.sandia.gov) to include many new features for accelerated simulation including articulated rigid body dynamics via coupling to the Rensselaer Polytechnic Institute code POEMS (Parallelizable Open-source Efficient Multibody Software). We use new features of the LAMMPS software package to investigate rhodopsin photoisomerization, and water model surface tension and capillary waves at the vapor-liquid interface. Finally, we motivate the recipes of MD for practitioners and researchers in numerical analysis and computational mechanics.

  4. Charge transport through biomolecular wires in a solvent: bridging molecular dynamics and model Hamiltonian approaches.

    Science.gov (United States)

    Gutiérrez, R; Caetano, R A; Woiczikowski, B P; Kubar, T; Elstner, M; Cuniberti, G

    2009-05-22

    We present a hybrid method based on a combination of classical molecular dynamics simulations, quantum-chemical calculations, and a model Hamiltonian approach to describe charge transport through biomolecular wires with variable lengths in presence of a solvent. The core of our approach consists in a mapping of the biomolecular electronic structure, as obtained from density-functional based tight-binding calculations of molecular structures along molecular dynamics trajectories, onto a low-dimensional model Hamiltonian including the coupling to a dissipative bosonic environment. The latter encodes fluctuation effects arising from the solvent and from the molecular conformational dynamics. We apply this approach to the case of pG-pC and pA-pT DNA oligomers as paradigmatic cases and show that the DNA conformational fluctuations are essential in determining and supporting charge transport.

  5. Phase behaviour and dynamics in primitive models of molecular ionic liquids

    Directory of Open Access Journals (Sweden)

    G.C. Ganzenmüller

    2011-09-01

    Full Text Available The phase behaviour and dynamics of molecular ionic liquids are studied using primitive models and extensive computer simulations. The models account for size disparity between cation and anion, charge location on the cation, and cation-shape anisotropy, which are all prominent features of important materials such as room-temperature ionic liquids. The vapour-liquid phase diagrams are determined using high-precision Monte Carlo simulations, setting the scene for in-depth studies of ion dynamics in the liquid state. Molecular dynamics simulations are used to explore the structure, single-particle translational and rotational autocorrelation functions, cation orientational autocorrelations, self diffusion, viscosity, and frequency-dependent conductivity. The results reveal some of the molecular-scale mechanisms for charge transport, involving molecular translation, rotation, and association.

  6. A comparison of molecular dynamics and diffuse interface model predictions of Lennard-Jones fluid evaporation

    Energy Technology Data Exchange (ETDEWEB)

    Barbante, Paolo [Dipartimento di Matematica, Politecnico di Milano - Piazza Leonardo da Vinci 32 - 20133 Milano (Italy); Frezzotti, Aldo; Gibelli, Livio [Dipartimento di Scienze e Tecnologie Aerospaziali, Politecnico di Milano - Via La Masa 34 - 20156 Milano (Italy)

    2014-12-09

    The unsteady evaporation of a thin planar liquid film is studied by molecular dynamics simulations of Lennard-Jones fluid. The obtained results are compared with the predictions of a diffuse interface model in which capillary Korteweg contributions are added to hydrodynamic equations, in order to obtain a unified description of the liquid bulk, liquid-vapor interface and vapor region. Particular care has been taken in constructing a diffuse interface model matching the thermodynamic and transport properties of the Lennard-Jones fluid. The comparison of diffuse interface model and molecular dynamics results shows that, although good agreement is obtained in equilibrium conditions, remarkable deviations of diffuse interface model predictions from the reference molecular dynamics results are observed in the simulation of liquid film evaporation. It is also observed that molecular dynamics results are in good agreement with preliminary results obtained from a composite model which describes the liquid film by a standard hydrodynamic model and the vapor by the Boltzmann equation. The two mathematical model models are connected by kinetic boundary conditions assuming unit evaporation coefficient.

  7. 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.

  8. Using molecular dynamics for the refinement of atomistic models of GPCRs by homology modeling.

    Science.gov (United States)

    Lupala, Cecylia S; Rasaeifar, Bahareh; Gomez-Gutierrez, Patricia; Perez, Juan J

    2017-08-14

    Despite GPCRs sharing a common seven helix bundle, analysis of the diverse crystallographic structures available reveal specific features that might be relevant for ligand design. Despite the number of crystallographic structures of GPCRs steadily increasing, there are still challenges that hamper the availability of new structures. In the absence of a crystallographic structure, homology modeling remains one of the important techniques for constructing 3D models of proteins. In the present study we investigated the use of molecular dynamics simulations for the refinement of GPCRs models constructed by homology modeling. Specifically, we investigated the relevance of template selection, ligand inclusion as well as the length of the simulation on the quality of the GPCRs models constructed. For this purpose we chose the crystallographic structure of the rat muscarinic M3 receptor as reference and constructed diverse atomistic models by homology modeling, using different templates. Specifically, templates used in the present work include the human muscarinic M2; the more distant human histamine H1 and the even more distant bovine rhodopsin as shown in the GPCRs phylogenetic tree. We also investigated the use or not of a ligand in the refinement process. Hence, we conducted the refinement process of the M3 model using the M2 muscarinic as template with tiotropium or NMS docked in the orthosteric site and compared with the results obtained with a model refined without any ligand bound.

  9. 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.

  10. Molecular dynamics modelling of EGCG clusters on ceramide bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, Jingjie; Cheng, Yuan; Li, Weifeng; Zhang, Yong-Wei [Institute of High Performance Computing, A*STAR, 138632 (Singapore)

    2015-12-31

    A novel method of atomistic modelling and characterization of both pure ceramide and mixed lipid bilayers is being developed, using only the General Amber ForceField. Lipid bilayers modelled as pure ceramides adopt hexagonal packing after equilibration, and the area per lipid and bilayer thickness are consistent with previously reported theoretical results. Mixed lipid bilayers are modelled as a combination of ceramides, cholesterol, and free fatty acids. This model is shown to be stable after equilibration. Green tea extract, also known as epigallocatechin-3-gallate, is introduced as a spherical cluster on the surface of the mixed lipid bilayer. It is demonstrated that the cluster is able to bind to the bilayers as a cluster without diffusing into the surrounding water.

  11. Molecular interpretation of nonclassical gas dynamics of dense vapors under the van der Waals model

    NARCIS (Netherlands)

    Colonna, P.; Guardone, A.

    2006-01-01

    The van der Waals polytropic gas model is used to investigate the role of attractive and repulsive intermolecular forces and the influence of molecular complexity on the possible nonclassical gas dynamic behavior of vapors near the liquid-vapor saturation curve. The decrease of the sound speed upon

  12. Molecular interpretation of nonclassical gas dynamics of dense vapors under the van der Waals model

    NARCIS (Netherlands)

    Colonna, P.; Guardone, A.

    2006-01-01

    The van der Waals polytropic gas model is used to investigate the role of attractive and repulsive intermolecular forces and the influence of molecular complexity on the possible nonclassical gas dynamic behavior of vapors near the liquid-vapor saturation curve. The decrease of the sound speed upon

  13. Modeling of the Electro-Mechanical Response of Carbon Nanotubes: Molecular Dynamics and Transport Calculations

    Science.gov (United States)

    Svizhenko, Alexel; Anantram, M. P.; Maiti, Amitesh

    2003-01-01

    This paper presents viewgraphs on the modeling of the electromechanical response of carbon nanotubes, utilizing molecular dynamics and transport calculations. The topics include: 1) Simulations of the experiment; 2) Effect of diameter, length and temperature; and 3) Study of sp3 coordination-"The Table experiment".

  14. Molecular dynamics and binary collision modeling of the primary damage state of collision cascades

    DEFF Research Database (Denmark)

    Heinisch, H.L.; Singh, B.N.

    1992-01-01

    Quantitative information on defect production in cascades in copper obtained from recent molecular dynamics simulations is compared to defect production information determined earlier with a model based on the binary collision approximation (BCA). The total numbers of residual defects, the fracti...

  15. 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.

  16. 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...

  17. 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...

  18. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    Full Text Available Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected

  19. Multicomponent ballistic transport in narrow single wall carbon nanotubes: Analytic model and molecular dynamics simulations

    Science.gov (United States)

    Mutat, T.; Adler, J.; Sheintuch, M.

    2011-01-01

    The transport of gas mixtures through molecular-sieve membranes such as narrow nanotubes has many potential applications, but there remain open questions and a paucity of quantitative predictions. Our model, based on extensive molecular dynamics simulations, proposes that ballistic motion, hindered by counter diffusion, is the dominant mechanism. Our simulations of transport of mixtures of molecules between control volumes at both ends of nanotubes give quantitative support to the model's predictions. The combination of simulation and model enable extrapolation to longer tubes and pore networks.

  20. A comparative study of model ingredients: Fragmentation in heavy-ion collisions using quantum molecular dynamics model

    Indian Academy of Sciences (India)

    Sanjeev Kumar; Suneel Kumar

    2010-05-01

    We aim to understand the role of NN cross-sections, equation of state as well as different model ingredients such as width of Gaussian, clusterization range and different clusterization algorithms in multifragmentation using quantum molecular dynamics model. We notice that all model ingredients have sizable effect on the fragment pattern.

  1. Multiscale modeling of dislocation-precipitate interactions in Fe: From molecular dynamics to discrete dislocations.

    Science.gov (United States)

    Lehtinen, Arttu; Granberg, Fredric; Laurson, Lasse; Nordlund, Kai; Alava, Mikko J

    2016-01-01

    The stress-driven motion of dislocations in crystalline solids, and thus the ensuing plastic deformation process, is greatly influenced by the presence or absence of various pointlike defects such as precipitates or solute atoms. These defects act as obstacles for dislocation motion and hence affect the mechanical properties of the material. Here we combine molecular dynamics studies with three-dimensional discrete dislocation dynamics simulations in order to model the interaction between different kinds of precipitates and a 1/2〈111〉{110} edge dislocation in BCC iron. We have implemented immobile spherical precipitates into the ParaDis discrete dislocation dynamics code, with the dislocations interacting with the precipitates via a Gaussian potential, generating a normal force acting on the dislocation segments. The parameters used in the discrete dislocation dynamics simulations for the precipitate potential, the dislocation mobility, shear modulus, and dislocation core energy are obtained from molecular dynamics simulations. We compare the critical stresses needed to unpin the dislocation from the precipitate in molecular dynamics and discrete dislocation dynamics simulations in order to fit the two methods together and discuss the variety of the relevant pinning and depinning mechanisms.

  2. Modeling ramp compression experiments using large-scale molecular dynamics simulation.

    Energy Technology Data Exchange (ETDEWEB)

    Mattsson, Thomas Kjell Rene; Desjarlais, Michael Paul; Grest, Gary Stephen; Templeton, Jeremy Alan; Thompson, Aidan Patrick; Jones, Reese E.; Zimmerman, Jonathan A.; Baskes, Michael I. (University of California, San Diego); Winey, J. Michael (Washington State University); Gupta, Yogendra Mohan (Washington State University); Lane, J. Matthew D.; Ditmire, Todd (University of Texas at Austin); Quevedo, Hernan J. (University of Texas at Austin)

    2011-10-01

    Molecular dynamics simulation (MD) is an invaluable tool for studying problems sensitive to atomscale physics such as structural transitions, discontinuous interfaces, non-equilibrium dynamics, and elastic-plastic deformation. In order to apply this method to modeling of ramp-compression experiments, several challenges must be overcome: accuracy of interatomic potentials, length- and time-scales, and extraction of continuum quantities. We have completed a 3 year LDRD project with the goal of developing molecular dynamics simulation capabilities for modeling the response of materials to ramp compression. The techniques we have developed fall in to three categories (i) molecular dynamics methods (ii) interatomic potentials (iii) calculation of continuum variables. Highlights include the development of an accurate interatomic potential describing shock-melting of Beryllium, a scaling technique for modeling slow ramp compression experiments using fast ramp MD simulations, and a technique for extracting plastic strain from MD simulations. All of these methods have been implemented in Sandia's LAMMPS MD code, ensuring their widespread availability to dynamic materials research at Sandia and elsewhere.

  3. Many-body quantum dynamics by adiabatic path-integral molecular dynamics: Disordered Frenkel Kontorova models

    Science.gov (United States)

    Krajewski, Florian R.; Müser, Martin H.

    2005-07-01

    The spectral density of quantum mechanical Frenkel Kontorova chains moving in disordered, external potentials is investigated by means of path-integral molecular dynamics. If the second moment of the embedding potential is well defined (roughness exponent H=0), there is one regime in which the chain is pinned (large masses m of chain particles) and one in which it is unpinned (small m). If the embedding potential can be classified as a random walk on large length scales ( H=1/2), then the chain is always pinned irrespective of the value of m. For H=1/2, two phonon-like branches appear in the spectra.

  4. Using Homology Modeling, Molecular Dynamics and Molecular Docking Techniques to Identify Inhibitor Binding Regions of Somatostatin Receptor 1

    Institute of Scientific and Technical Information of China (English)

    LAN Hai-nan; WANG Yue-xi; ZHENG Ming-zhu; HAN Wei-wei; ZHENG Xin

    2013-01-01

    The G protein coupled receptor(GPCR),one of the members in the superfamily,which consists of thousands of integral membrane proteins,exerts a wide variety of physiological functions and responses to a large portion of the drug targets.The 3D structure of somatostatin receptor 1(SSTR1) was modeled and refined by means of homology modeling and molecular dynamics simulation.This model was assessed by Verify-3D and Vadar,which confirmed the reliability of the refined model.The interaction between the inhibitor cysteamine,somatostatin(SST) and SSTRI was investigated by a molecular docking program,Affinity.The binding module not only showed the crucial residues involved in the interaction,but also provided important information about the interaction between SSTR1 on the one hand and ligands on the other,which might be the significant evidence for the structure-based design.

  5. Bacterial molecular networks: bridging the gap between functional genomics and dynamical modelling.

    Science.gov (United States)

    van Helden, Jacques; Toussaint, Ariane; Thieffry, Denis

    2012-01-01

    This introductory review synthesizes the contents of the volume Bacterial Molecular Networks of the series Methods in Molecular Biology. This volume gathers 9 reviews and 16 method chapters describing computational protocols for the analysis of metabolic pathways, protein interaction networks, and regulatory networks. Each protocol is documented by concrete case studies dedicated to model bacteria or interacting populations. Altogether, the chapters provide a representative overview of state-of-the-art methods for data integration and retrieval, network visualization, graph analysis, and dynamical modelling.

  6. Molecular modeling and molecular dynamics simulation of the polarization switching phenomena in the ferroelectric polymers PVDF at the nanoscale

    Energy Technology Data Exchange (ETDEWEB)

    Bystrov, V.S., E-mail: bystrov@ua.pt [Department of Materials and Ceramic Engineering and CICECO, University of Aveiro, 3810-193 Aveiro (Portugal); Institute of Mathematical Problems of Biology RAS, 142290, Pushchino (Russian Federation)

    2014-01-01

    The molecular modeling and molecular dynamics of polarization switching for the ferroelectric films model of polyvinylidene fluoride (PVDF) are investigated at the nanoscale. We consider a molecular model of PVDF film, consisting of two and four a chains [–CH2–CF2–]{sub n} limited by n=6 elementary units. The first-principle approach is applied to the switching and kinetics of these models. Two types of behavior were established for PVDF chains: simultaneous and sequential rotation in high and low electric fields. Kinetics of sequential polarization switching shows a homogeneous critical behavior in the low electric field with a critical point at Landau–Ginzburg–Devonshire (LGD) coercive field E=E{sub C}. This type of kinetics demonstrates a kink-like behavior for polarization solitary wave propagation. The simultaneous type of kinetics demonstrates the total domain-like polarization switching, corresponding to exponential behavior of switching time in high electric field as for bulk samples. Corresponding LGD intrinsic coercive field for a two-chain and four-chains model is E{sub C}∼2.0 GV/m with revealing size effect. Obtained results show common quantum nature of PVDF chains switching phenomena—the quantum interaction of the PVDF molecular orbitals under applied electric field at the nanoscale level. The results obtained are compared with experimental data.

  7. Thermodynamic scaling of dynamic properties of liquid crystals: verifying the scaling parameters using a molecular model.

    Science.gov (United States)

    Satoh, Katsuhiko

    2013-08-28

    The thermodynamic scaling of molecular dynamic properties of rotation and thermodynamic parameters in a nematic phase was investigated by a molecular dynamic simulation using the Gay-Berne potential. A master curve for the relaxation time of flip-flop motion was obtained using thermodynamic scaling, and the dynamic property could be solely expressed as a function of TV(γτ) , where T and V are the temperature and volume, respectively. The scaling parameter γτ was in excellent agreement with the thermodynamic parameter Γ, which is the logarithm of the slope of a line plotted for the temperature and volume at constant P2. This line was fairly linear, and as good as the line for p-azoxyanisole or using the highly ordered small cluster model. The equivalence relation between Γ and γ(τ) was compared with results obtained from the highly ordered small cluster model. The possibility of adapting the molecular model for the thermodynamic scaling of other dynamic rotational properties was also explored. The rotational diffusion constant and rotational viscosity coefficients, which were calculated using established theoretical and experimental expressions, were rescaled onto master curves with the same scaling parameters. The simulation illustrates the universal nature of the equivalence relation for liquid crystals.

  8. In silico modelling and molecular dynamics simulation studies of thiazolidine based PTP1B inhibitors.

    Science.gov (United States)

    Mahapatra, Manoj Kumar; Bera, Krishnendu; Singh, Durg Vijay; Kumar, Rajnish; Kumar, Manoj

    2017-04-21

    Protein tyrosine phosphatase 1B (PTP1B) has been identified as a negative regulator of insulin and leptin signalling pathway; hence, it can be considered as a new therapeutic target of intervention for the treatment of type 2 diabetes. Inhibition of this molecular target takes care of both diabetes and obesity, i.e. diabestiy. In order to get more information on identification and optimization of lead, pharmacophore modelling, atom-based 3D QSAR, docking and molecular dynamics studies were carried out on a set of ligands containing thiazolidine scaffold. A six-point pharmacophore model consisting of three hydrogen bond acceptor (A), one negative ionic (N) and two aromatic rings (R) with discrete geometries as pharmacophoric features were developed for a predictive 3D QSAR model. The probable binding conformation of the ligands within the active site was studied through molecular docking. The molecular interactions and the structural features responsible for PTP1B inhibition and selectivity were further supplemented by molecular dynamics simulation study for a time scale of 30 ns. The present investigation has identified some of the indispensible structural features of thiazolidine analogues which can further be explored to optimize PTP1B inhibitors.

  9. Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations.

    Science.gov (United States)

    Takada, Shoji; Kanada, Ryo; Tan, Cheng; Terakawa, Tsuyoshi; Li, Wenfei; Kenzaki, Hiroo

    2015-12-15

    Due to hierarchic nature of biomolecular systems, their computational modeling calls for multiscale approaches, in which coarse-grained (CG) simulations are used to address long-time dynamics of large systems. Here, we review recent developments and applications of CG modeling methods, focusing on our methods primarily for proteins, DNA, and their complexes. These methods have been implemented in the CG biomolecular simulator, CafeMol. Our CG model has resolution such that ∼10 non-hydrogen atoms are grouped into one CG particle on average. For proteins, each amino acid is represented by one CG particle. For DNA, one nucleotide is simplified by three CG particles, representing sugar, phosphate, and base. The protein modeling is based on the idea that proteins have a globally funnel-like energy landscape, which is encoded in the structure-based potential energy function. We first describe two representative minimal models of proteins, called the elastic network model and the classic Go̅ model. We then present a more elaborate protein model, which extends the minimal model to incorporate sequence and context dependent local flexibility and nonlocal contacts. For DNA, we describe a model developed by de Pablo's group that was tuned to well reproduce sequence-dependent structural and thermodynamic experimental data for single- and double-stranded DNAs. Protein-DNA interactions are modeled either by the structure-based term for specific cases or by electrostatic and excluded volume terms for nonspecific cases. We also discuss the time scale mapping in CG molecular dynamics simulations. While the apparent single time step of our CGMD is about 10 times larger than that in the fully atomistic molecular dynamics for small-scale dynamics, large-scale motions can be further accelerated by two-orders of magnitude with the use of CG model and a low friction constant in Langevin dynamics. Next, we present four examples of applications. First, the classic Go̅ model was used to

  10. Empirical tight-binding force model for molecular-dynamics simulation of Si

    Science.gov (United States)

    Wang, C. Z.; Chan, C. T.; Ho, K. M.

    1989-04-01

    A scheme of molecular-dynamics simulation using the empirical tight-binding force model is proposed. The scheme allows the interatomic interactions involved in the molecular dynamics to be determined by first-principles total-energy and electronic-structure calculations without resorting to fitting experimental data. For a first application of the scheme we show that a very simple nearest-neighbor two-center empirical tight-binding force model is able to stabilize the diamond structure of Si within a reasonable temperature range. We also show that the scheme makes possible the quantitative calculation of the temperature dependence of various anharmonic effects such as lattice thermal expansion, temperature-dependent phonon linewidths, and phonon frequency shifts.

  11. Parameter passing between molecular dynamics and continuum models for droplets on solid substrates: the static case.

    Science.gov (United States)

    Tretyakov, Nikita; Müller, Marcus; Todorova, Desislava; Thiele, Uwe

    2013-02-14

    We study equilibrium properties of polymer films and droplets on a solid substrate employing particle-based simulation techniques (molecular dynamics) and a continuum description. Parameter-passing techniques are explored that facilitate a detailed comparison of the two models. In particular, the liquid-vapor, solid-liquid, and solid-vapor interface tensions, and the Derjaguin or disjoining pressure are determined by molecular dynamics simulations. This information is then introduced into continuum descriptions accounting for (i) the full curvature and (ii) a long-wave approximation of the curvature (thin film model). A comparison of the dependence of the contact angle on droplet size indicates that the theories agree well if the contact angles are defined in a compatible manner.

  12. A structural and dynamic molecular model for the sodium channel of Electrophorus electricus.

    Science.gov (United States)

    Kosower, E M

    1985-03-25

    Chemical logic and single group rotation (SGR) theory are applied to the primary structure determined by Noda et al. [(1984) Nature 312, 121-127] to construct a molecular model of the sodium channel of Electrophorus electricus. Both structural and dynamic aspects of the channel are accounted for, including gating current, sensitivity to changes in membrane potential, channel opening, a binding site for sodium, selectivity for sodium over potassium, capacity for rapid sodium flow, sensitivity to batrachotoxin (or other toxins) and inactivation.

  13. Modeling of Car-Following Required Safe Distance Based on Molecular Dynamics

    OpenAIRE

    Dayi Qu; Xiufeng Chen; Wansan Yang; Xiaohua Bian

    2014-01-01

    In car-following procedure, some distances are reserved between the vehicles, through which drivers can avoid collisions with vehicles before and after them in the same lane and keep a reasonable clearance with lateral vehicles. This paper investigates characters of vehicle operating safety in car following state based on required safe distance. To tackle this problem, we probe into required safe distance and car-following model using molecular dynamics, covering longitudinal and lateral safe...

  14. A multiscale modeling technique for bridging molecular dynamics with finite element method

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yongchang, E-mail: yl83@buffalo.edu; Basaran, Cemal

    2013-11-15

    In computational mechanics, molecular dynamics (MD) and finite element (FE) analysis are well developed and most popular on nanoscale and macroscale analysis, respectively. MD can very well simulate the atomistic behavior, but cannot simulate macroscale length and time due to computational limits. FE can very well simulate continuum mechanics (CM) problems, but has the limitation of the lack of atomistic level degrees of freedom. Multiscale modeling is an expedient methodology with a potential to connect different levels of modeling such as quantum mechanics, molecular dynamics, and continuum mechanics. This study proposes a new multiscale modeling technique to couple MD with FE. The proposed method relies on weighted average momentum principle. A wave propagation example has been used to illustrate the challenges in coupling MD with FE and to verify the proposed technique. Furthermore, 2-Dimensional problem has also been used to demonstrate how this method would translate into real world applications. -- Highlights: •A weighted averaging momentum method is introduced for bridging molecular dynamics (MD) with finite element (FE) method. •The proposed method shows excellent coupling results in 1-D and 2-D examples. •The proposed method successfully reduces the spurious wave reflection at the border of MD and FE regions. •Big advantages of the proposed method are simplicity and inexpensive computational cost of multiscale analysis.

  15. Improved Quantum Molecular Dynamics Model and its Application to Fusion Reaction Near Barrier

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    An improved quantum molecular dynamics model is proposed. By using this model, the properties of ground state of nuclei from 6Li to 208Pb can be described very well with one set of parameters. The fusion reactions for 40Ca+90Zr, 40Ca+96Zr and 48Ca+90Zr at the energy near the barrier are studied by this model. The experimental data of the fusion cross sections for 40Ca+90,96Zr at the energy near the barrier can be reproduced remarkably well without introducing any new parameters. The mechanism

  16. Interactive molecular dynamics

    CERN Document Server

    Schroeder, Daniel V

    2015-01-01

    Physics students now have access to interactive molecular dynamics simulations that can model and animate the motions of hundreds of particles, such as noble gas atoms, that attract each other weakly at short distances but repel strongly when pressed together. Using these simulations, students can develop an understanding of forces and motions at the molecular scale, nonideal fluids, phases of matter, thermal equilibrium, nonequilibrium states, the Boltzmann distribution, the arrow of time, and much more. This article summarizes the basic features and capabilities of such a simulation, presents a variety of student exercises using it at the introductory and intermediate levels, and describes some enhancements that can further extend its uses. A working simulation code, in HTML5 and JavaScript for running within any modern Web browser, is provided as an online supplement.

  17. Interactive molecular dynamics

    Science.gov (United States)

    Schroeder, Daniel V.

    2015-03-01

    Physics students now have access to interactive molecular dynamics simulations that can model and animate the motions of hundreds of particles, such as noble gas atoms, that attract each other weakly at short distances but repel strongly when pressed together. Using these simulations, students can develop an understanding of forces and motions at the molecular scale, nonideal fluids, phases of matter, thermal equilibrium, nonequilibrium states, the Boltzmann distribution, the arrow of time, and much more. This article summarizes the basic features and capabilities of such a simulation, presents a variety of student exercises using it at the introductory and intermediate levels, and describes some enhancements that can further extend its uses. A working simulation code, in html5 and javascript for running within any modern Web browser, is provided as an online supplement.

  18. Nonlocal continuum model and molecular dynamics for free vibration of single-walled carbon nanotubes.

    Science.gov (United States)

    Hu, Yan-Gao; Liew, K M; Wang, Q

    2011-12-01

    Free transverse, longitudinal and torsional vibrations of single-walled carbon nanotubes (SWCNTs) are investigated through nonlocal beam model, nonlocal rod model and verified by molecular dynamics (MD) simulations. The nonlocal Timoshenko beam model offers a better prediction of the fundamental frequencies of shorter SWCNTs, such as a (5, 5) SWCNT shorter than 3.5 nm, than local beam models. The nonlocal rod model is employed to study the longitudinal and torsional vibrations of SWCNT and found to enable a good prediction of the MD results for shorter SWCNTs. Nonlocal and local continuum models provide a good agreement with MD results for relatively longer SWCNTs, such as (5, 5) SWCNTs longer than 3.5 nm. The scale parameter in nonlocal beam and rod models is estimated by calibrations from MD results.

  19. Molecular Dynamics Simulations of a Powder Model of the Intrinsically Disordered Protein Tau.

    Science.gov (United States)

    Fichou, Yann; Heyden, Matthias; Zaccai, Giuseppe; Weik, Martin; Tobias, Douglas J

    2015-10-01

    The tau protein, whose aggregates are involved in Alzheimer's disease, is an intrinsically disordered protein (IDP) that regulates microtubule activity in neurons. An IDP lacks a single, well-defined structure and, rather, constantly exchanges among multiple conformations. In order to study IDP dynamics, the combination of experimental techniques, such as neutron scattering, and computational techniques, such as molecular dynamics (MD) simulations, is a powerful approach. Amorphous hydrated powder samples have been very useful for studying protein internal dynamics experimentally, e.g., using neutron scattering. Thus, there is demand for realistic in silico models of hydrated protein powders. Here we present an MD simulation analysis of a powder hydrated at 0.4 g water/g protein of the IDP tau in the temperature range 20-300 K. By comparing with neutron scattering data, we identify the protein-water interface as the predominant feature determining IDP dynamics. The so-called protein dynamical transition is shown to be attenuated, but not suppressed, in the parts of the protein that are not exposed to the solvent. In addition, we find similarities in the mean-squared displacements of the core of a globular protein and "dry" clusters formed by the IDP in hydrated powders. Thus, the ps to ns dynamics of proteins in hydrated powders originate mainly from those residues in contact with solvent. We propose that by measuring the dynamics of protein assemblies, such as aggregates, one might assess qualitatively their state of hydration.

  20. Prediction of the Human EP1 Receptor Binding Site by Homology Modeling and Molecular Dynamics Simulation.

    Science.gov (United States)

    Zare, Behnoush; Madadkar-Sobhani, Armin; Dastmalchi, Siavoush; Mahmoudian, Masoud

    2011-01-01

    The prostanoid receptor EP1 is a G-protein-coupled receptor (GPCR) known to be involved in a variety of pathological disorders such as pain, fever and inflammation. These receptors are important drug targets, but design of subtype specific agonists and antagonists has been partially hampered by the absence of three-dimensional structures for these receptors. To understand the molecular interactions of the PGE2, an endogen ligand, with the EP1 receptor, a homology model of the human EP1 receptor (hEP1R) with all connecting loops was constructed from the 2.6 Å resolution crystal structure (PDB code: 1L9H) of bovine rhodopsin. The initial model generated by MODELLER was subjected to molecular dynamics simulation to assess quality of the model. Also, a step by step ligand-supported model refinement was performed, including initial docking of PGE2 and iloprost in the putative binding site, followed by several rounds of energy minimizations and molecular dynamics simulations. Docking studies were performed for PGE2 and some other related compounds in the active site of the final hEP1 receptor model. The docking enabled us to identify key molecular interactions supported by the mutagenesis data. Also, the correlation of r(2)=0.81 was observed between the Ki values and the docking scores of 15 prostanoid compounds. The results obtained in this study may provide new insights toward understanding the active site conformation of the hEP1 receptor and can be used for the structure-based design of novel specific ligands.

  1. Coarse-graining to the meso and continuum scales with molecular-dynamics-like models

    Science.gov (United States)

    Plimpton, Steve

    Many engineering-scale problems that industry or the national labs try to address with particle-based simulations occur at length and time scales well beyond the most optimistic hopes of traditional coarse-graining methods for molecular dynamics (MD), which typically start at the atomic scale and build upward. However classical MD can be viewed as an engine for simulating particles at literally any length or time scale, depending on the models used for individual particles and their interactions. To illustrate I'll highlight several coarse-grained (CG) materials models, some of which are likely familiar to molecular-scale modelers, but others probably not. These include models for water droplet freezing on surfaces, dissipative particle dynamics (DPD) models of explosives where particles have internal state, CG models of nano or colloidal particles in solution, models for aspherical particles, Peridynamics models for fracture, and models of granular materials at the scale of industrial processing. All of these can be implemented as MD-style models for either soft or hard materials; in fact they are all part of our LAMMPS MD package, added either by our group or contributed by collaborators. Unlike most all-atom MD simulations, CG simulations at these scales often involve highly non-uniform particle densities. So I'll also discuss a load-balancing method we've implemented for these kinds of models, which can improve parallel efficiencies. From the physics point-of-view, these models may be viewed as non-traditional or ad hoc. But because they are MD-style simulations, there's an opportunity for physicists to add statistical mechanics rigor to individual models. Or, in keeping with a theme of this session, to devise methods that more accurately bridge models from one scale to the next.

  2. Deformation-induced damage and recovery in model hydrogels - A molecular dynamics simulation

    Science.gov (United States)

    Zidek, Jan; Milchev, Andrey; Jancar, Josef; Vilgis, Thomas A.

    2016-09-01

    Using molecular dynamics simulation of a model hybrid cross-link hydrogel, we investigate the network damage evolution and the related structure transformations. We model the hydrogel structure as a network-connected assembly of crosslinked clusters whereby deformation-induced damage is considered along with network recovery. The two principal mechanisms involved in hydrogel recovery from deformation include segment hops of the building structure units (segments) between clusters and cluster shape modification. These mechanisms act either instantaneously, or with a certain time delay after the onset of deformation. By elucidating the conditions under which one of the mechanisms prevails, one may design hydrogel materials with a desired response to deformation.

  3. 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.

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

    Science.gov (United States)

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

    2014-03-01

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

  5. Molecular dynamics of silicon indentation

    Energy Technology Data Exchange (ETDEWEB)

    Kallman, J.S.; Hoover, W.G.; Hoover, C.G.; De Groot, A.J.; Lee, S.M.; Wooten, F. (Department of Applied Science Davis-Livermore, Lawrence Livermore National Laboratory, Livermore, California 94550 (United States))

    1993-04-01

    We use nonequilibrium molecular dynamics to simulate the elastic-plastic deformation of silicon under tetrahedral nanometer-sized indentors. The results are described in terms of a rate-dependent and temperature-dependent phenomenological yield strength. We follow the structural change during indentation with a computer technique that allows us to model the dynamic simulation of diffraction patterns.

  6. Nonequilibrium molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Hoover, W.G. (California Univ., Davis, CA (USA). Dept. of Applied Science Lawrence Livermore National Lab., CA (USA))

    1990-11-01

    The development of nonequilibrium molecular dynamics is described, with emphasis on massively-parallel simulations involving the motion of millions, soon to be billions, of atoms. Corresponding continuum simulations are also discussed. 14 refs., 8 figs.

  7. Molecular dynamics of polarizable point dipole models for molten NaI. Comparison with first principles simulations

    Directory of Open Access Journals (Sweden)

    Trullàs J.

    2011-05-01

    Full Text Available Molecular dynamics simulations of molten NaI at 995 K have been carried out using polarizable ion models based on rigid ion pair potentials to which the anion induced dipole polarization is added. The polarization is added in such a way that point dipoles are induced on the anions by both local electric field and deformation short-range damping interactions that oppose the electrically induced dipole moments. The structure and self-diffusion results are compared with those obtained by Galamba and Costa Cabral using first principles Hellmann-Feynman molecular dynamics simulations and using classical molecular dynamics of a shell model which allows only the iodide polarization

  8. 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

  9. 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.

  10. 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...

  11. Molecular dynamics simulation of diffusivity

    Institute of Scientific and Technical Information of China (English)

    Juanfang LIU; Danling ZENG; Qin LI; Hong GAO

    2008-01-01

    Equilibrium molecular dynamics simulation was performed on water to calculate its diffusivity by adopting different potential models. The results show that the potential models have great influence on the simulated results. In addition, the diffusivities obtained by the SPCE model conform well to the experimental values.

  12. A Langevin model for fluctuating contact angle behaviour parametrised using molecular dynamics.

    Science.gov (United States)

    Smith, E R; Müller, E A; Craster, R V; Matar, O K

    2016-12-06

    Molecular dynamics simulations are employed to develop a theoretical model to predict the fluid-solid contact angle as a function of wall-sliding speed incorporating thermal fluctuations. A liquid bridge between counter-sliding walls is studied, with liquid-vapour interface-tracking, to explore the impact of wall-sliding speed on contact angle. The behaviour of the macroscopic contact angle varies linearly over a range of capillary numbers beyond which the liquid bridge pinches off, a behaviour supported by experimental results. Nonetheless, the liquid bridge provides an ideal test case to study molecular scale thermal fluctuations, which are shown to be well described by Gaussian distributions. A Langevin model for contact angle is parametrised to incorporate the mean, fluctuation and auto-correlations over a range of sliding speeds and temperatures. The resulting equations can be used as a proxy for the fully-detailed molecular dynamics simulation allowing them to be integrated within a continuum-scale solver.

  13. Combining Coarse-Grained Protein Models with Replica-Exchange All-Atom Molecular Dynamics

    CERN Document Server

    Wabik, Jacek; Gront, Dominik; Kouza, Maksim; Kolinski, Andrzej

    2013-01-01

    We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a model system of protein folding. After reconstructing atomistic details, conformations derived from the CABS simulation were subjected to replica-exchange molecular dynamics simulations with OPLS-AA and AMBER99sb force fields in explicit solvent. Such a combination accelerates system convergence several times in comparison with all-atom simulations starting from the extended chain conformation, demonstrated by the analysis of melting curves, the number of native-like conformations as a function of time and secondary structure propagation. The results strongly suggest that the proposed multiscale method could be an efficient and accurate tool for high-resolution studies of protein folding dynamics in larger systems.

  14. Systematic study of 16O-induced fusions with the improved quantum molecular dynamics model

    CERN Document Server

    Wang, Ning; Li, Zhuxia

    2014-01-01

    The heavy-ion fusion reactions with 16O bombarding on 62Ni, 65Cu, 74Ge, 148Nd, 180Hf, 186W, 208Pb, 238U are systematically investigated with the improved quantum molecular dynamics (ImQMD) model. The fusion cross sections at energies near and above the Coulomb barriers can be reasonably well reproduced by using this semi-classical microscopic transport model with the parameter sets SkP* and IQ3a. The dynamical nucleus-nucleus potentials and the influence of Fermi constraint on the fusion process are also studied simultaneously. In addition to the mean field, the Fermi constraint also plays a key role for the reliable description of fusion process and for improving the stability of fragments in heavy-ion collisions.

  15. Combining Coarse-Grained Protein Models with Replica-Exchange All-Atom Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Andrzej Koliński

    2013-05-01

    Full Text Available We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a model system of protein folding. After reconstructing atomistic details, conformations derived from the CABS simulation were subjected to replica-exchange molecular dynamics simulations with OPLS-AA and AMBER99sb force fields in explicit solvent. Such a combination accelerates system convergence several times in comparison with all-atom simulations starting from the extended chain conformation, demonstrated by the analysis of melting curves, the number of native-like conformations as a function of time and secondary structure propagation. The results strongly suggest that the proposed multiscale method could be an efficient and accurate tool for high-resolution studies of protein folding dynamics in larger systems.

  16. Combining coarse-grained protein models with replica-exchange all-atom molecular dynamics.

    Science.gov (United States)

    Wabik, Jacek; Kmiecik, Sebastian; Gront, Dominik; Kouza, Maksim; Koliński, Andrzej

    2013-05-10

    We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a model system of protein folding. After reconstructing atomistic details, conformations derived from the CABS simulation were subjected to replica-exchange molecular dynamics simulations with OPLS-AA and AMBER99sb force fields in explicit solvent. Such a combination accelerates system convergence several times in comparison with all-atom simulations starting from the extended chain conformation, demonstrated by the analysis of melting curves, the number of native-like conformations as a function of time and secondary structure propagation. The results strongly suggest that the proposed multiscale method could be an efficient and accurate tool for high-resolution studies of protein folding dynamics in larger systems.

  17. Molecular dynamics simulations

    OpenAIRE

    Tarmyshov, Konstantin B.

    2007-01-01

    Molecular simulations can provide a detailed picture of a desired chemical, physical, or biological process. It has been developed over last 50 years and is being used now to solve a large variety of problems in many different fields. In particular, quantum calculations are very helpful to study small systems at a high resolution where electronic structure of compounds is accounted for. Molecular dynamics simulations, in turn, are employed to study development of a certain molecular ensemble ...

  18. Lipid Models for United-Atom Molecular Dynamics Simulations of Proteins.

    Science.gov (United States)

    Kukol, Andreas

    2009-03-10

    United-atom force fields for molecular dynamics (MD) simulations provide a higher computational efficiency, especially in lipid membrane simulations, with little sacrifice in accuracy, when compared to all-atom force fields. Excellent united-atom lipid models are available, but in combination with depreciated protein force fields. In this work, a united-atom model of the lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine has been built with standard parameters of the force field GROMOS96 53a6 that reproduces the experimental area per lipid of a lipid bilayer within 3% accuracy to a value of 0.623 ± 0.011 nm(2) without the assumption of a constant surface area or the inclusion of surface pressure. In addition, the lateral self-diffusion constant and deuterium order parameters of the acyl chains are in agreement with experimental data. Furthermore, models for 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) result in areas per lipid of 0.625 nm(2) (DMPC), 0.693 nm(2) (POPC), and 0.700 nm(2) (POPG) from 40 ns MD simulations. Experimental lateral self-diffusion coefficients are reproduced satisfactorily by the simulation. The lipid models can form the basis for molecular dynamics simulations of membrane proteins with current and future versions of united-atom protein force fields.

  19. Molecular modeling and molecular dynamics simulation studies on the interactions of hydroxylated polychlorinated biphenyls with estrogen receptor-β.

    Science.gov (United States)

    Li, Xiaolin; Ye, Li; Wang, Xiaoxiang; Shi, Wei; Qian, XiangPing; Zhu, YongLiang; Yu, HongXia

    2013-10-01

    Endocrine-disrupting chemicals have attracted great concern. As major metabolites of polychlorinated biphenyls (PCBs), hydroxylated polychlorinated biphenyls (HO-PCBs) may disrupt estrogen hormone status because of their structural similarity to estrogen endogenous compounds. However, interactions between HO-PCBs and estrogen receptors (ERs) are not fully understood. In the present work, a molecular modeling study combining molecular docking, molecular dynamics simulations, and binding free energy calculations was performed to characterize the interactions of three HO-PCBs (4'-HO-PCB50, 2'-HO-PCB65, and 4'-HO-PCB69) having much different estrogenic activities with ERβ. Docking results showed that binding between ligands and ERβ was stabilized by hydrogen bond and hydrophobic interactions. The binding free energies of three ligands with ERβ were calculated, and further binding free energy decomposition analysis indicated that the dominating driving force of the binding between the ligands and ERβ was the van der Waals interaction. Some key residues, such as Leu298, Phe356, Gly472, His475, and Leu476, played important roles in ligand-receptor interactions by forming hydrophobic and hydrogen bond interactions with ligands. The results may be beneficial to increase understanding of the interactions between HO-PCBs and ERβ.

  20. 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.

  1. A molecular dynamics model of rhodamine-labeled phospholipid incorporated into a lipid bilayer

    Science.gov (United States)

    Kyrychenko, Alexander

    2010-01-01

    Phospholipids, labeled covalently by a fluorescent dye, are commonly applied in membrane biophysics. In this work, a molecular dynamics model of sulforhodamine attached covalently to a headgroup of 1,2-dipalmitoyl- sn-glycero-3-phosphoethanolamine is developed. It is found that the incorporation of rhodamine-labeled phospholipids into a DPPC bilayer at the low concentration results in small perturbation of the bilayer. In the dye-labeled membrane, the sulforhodamine moiety binds favorably to a polar membrane interface, forming the tilt angle 44° ± 8° to the bilayer normal. The deep location and binding of a bulk sulforhodamine fluorophore lead, therefore, to some 'softening' of the membrane structure.

  2. Elastic Constants of Superconducting MgB2 from Molecular Dynamics Simulations with Shell Model

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The elastic constants of superconducting MgB2 are calculated using a molecular dynamics method (MD)with shell model. The lattice parameters, five independent elastic constants, equations of state (EOS), Debye temperature, and bulk modulus of MgB2 are obtained. Meanwhile, the dependence of the bulk modulus B, the lattice parameters a and c, and the unit cell volume V on the applied pressure are presented. It is demonstrated that the method introduced here can well reproduce the experimental results with a reasonable accuracy.

  3. Refinement of protein structure homology models via long, all-atom molecular dynamics simulations.

    Science.gov (United States)

    Raval, Alpan; Piana, Stefano; Eastwood, Michael P; Dror, Ron O; Shaw, David E

    2012-08-01

    Accurate computational prediction of protein structure represents a longstanding challenge in molecular biology and structure-based drug design. Although homology modeling techniques are widely used to produce low-resolution models, refining these models to high resolution has proven difficult. With long enough simulations and sufficiently accurate force fields, molecular dynamics (MD) simulations should in principle allow such refinement, but efforts to refine homology models using MD have for the most part yielded disappointing results. It has thus far been unclear whether MD-based refinement is limited primarily by accessible simulation timescales, force field accuracy, or both. Here, we examine MD as a technique for homology model refinement using all-atom simulations, each at least 100 μs long-more than 100 times longer than previous refinement simulations-and a physics-based force field that was recently shown to successfully fold a structurally diverse set of fast-folding proteins. In MD simulations of 24 proteins chosen from the refinement category of recent Critical Assessment of Structure Prediction (CASP) experiments, we find that in most cases, simulations initiated from homology models drift away from the native structure. Comparison with simulations initiated from the native structure suggests that force field accuracy is the primary factor limiting MD-based refinement. This problem can be mitigated to some extent by restricting sampling to the neighborhood of the initial model, leading to structural improvement that, while limited, is roughly comparable to the leading alternative methods.

  4. Polymer friction Molecular Dynamics

    DEFF Research Database (Denmark)

    Sivebæk, Ion Marius; Samoilov, Vladimir N.; Persson, Bo N. J.

    We present molecular dynamics friction calculations for confined hydrocarbon solids with molecular lengths from 20 to 1400 carbon atoms. Two cases are considered: a) polymer sliding against a hard substrate, and b) polymer sliding on polymer. In the first setup the shear stresses are relatively...... independent of molecular length. For polymer sliding on polymer the friction is significantly larger, and dependent on the molecular chain length. In both cases, the shear stresses are proportional to the squeezing pressure and finite at zero load, indicating an adhesional contribution to the friction force....

  5. Property Analysis of Exfoliated Graphite Nanoplatelets Modified Asphalt Model Using Molecular Dynamics (MD Method

    Directory of Open Access Journals (Sweden)

    Hui Yao

    2017-01-01

    Full Text Available This Molecular Dynamics (MD simulation paper presents a physical property comparison study between exfoliated graphite nanoplatelets (xGNP modified and control asphalt models, including density, glass transition temperature, viscosity and thermal conductivity. The three-component control asphalt model consists of asphaltenes, aromatics, and saturates based on previous references. The xGNP asphalt model was built by incorporating an xGNP and control asphalt model and controlling mass ratios to represent the laboratory prepared samples. The Amber Cornell Extension Force Field (ACEFF was used with assigned molecular electro-static potential (ESP charge from NWChem analysis. After optimization and ensemble relaxation, the properties of the control and xGNP modified asphalt models were computed and analyzed using the MD method. The MD simulated results have a similar trend as the test results. The property analysis showed that: (1 the density of the xGNP modified model is higher than that of the control model; (2 the glass transition temperature of the xGNP modified model is closer to the laboratory data of the Strategic Highway Research Program (SHRP asphalt binders than that of the control model; (3 the viscosities of the xGNP modified model at different temperatures are higher than those of the control model, and it coincides with the trend in the laboratory data; (4 the thermal conductivities of the xGNP modified asphalt model are higher than those of the control asphalt model at different temperatures, and it is consistent with the trend in the laboratory data.

  6. 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.

  7. A quantitative comparison between the flow factor approach model and the molecular dynamics simulation results for the flow of a confined molecularly thin fluid film

    Science.gov (United States)

    Zhang, Yongbin

    2015-06-01

    Quantitative comparisons were made between the flow factor approach model and the molecular dynamics simulation (MDS) results both of which describe the flow of a molecularly thin fluid film confined between two solid walls. Although these two approaches, respectively, calculate the flow of a confined molecularly thin fluid film by different ways, very good agreements were found between them when the Couette and Poiseuille flows, respectively, calculated from them were compared. It strongly indicates the validity of the flow factor approach model in modeling the flow of a confined molecularly thin fluid film.

  8. A restraint molecular dynamics and simulated annealing approach for protein homology modeling utilizing mean angles

    Directory of Open Access Journals (Sweden)

    Maurer Till

    2005-04-01

    Full Text Available Abstract Background We have developed the program PERMOL for semi-automated homology modeling of proteins. It is based on restrained molecular dynamics using a simulated annealing protocol in torsion angle space. As main restraints defining the optimal local geometry of the structure weighted mean dihedral angles and their standard deviations are used which are calculated with an algorithm described earlier by Döker et al. (1999, BBRC, 257, 348–350. The overall long-range contacts are established via a small number of distance restraints between atoms involved in hydrogen bonds and backbone atoms of conserved residues. Employing the restraints generated by PERMOL three-dimensional structures are obtained using standard molecular dynamics programs such as DYANA or CNS. Results To test this modeling approach it has been used for predicting the structure of the histidine-containing phosphocarrier protein HPr from E. coli and the structure of the human peroxisome proliferator activated receptor γ (Ppar γ. The divergence between the modeled HPr and the previously determined X-ray structure was comparable to the divergence between the X-ray structure and the published NMR structure. The modeled structure of Ppar γ was also very close to the previously solved X-ray structure with an RMSD of 0.262 nm for the backbone atoms. Conclusion In summary, we present a new method for homology modeling capable of producing high-quality structure models. An advantage of the method is that it can be used in combination with incomplete NMR data to obtain reasonable structure models in accordance with the experimental data.

  9. Molecular modeling of methyl-α-Neu5Ac analogues docked against cholera toxin--a molecular dynamics study.

    Science.gov (United States)

    Blessy, J Jino; Sharmila, D Jeya Sundara

    2015-02-01

    Molecular modeling of synthetic methyl-α-Neu5Ac analogues modified in C-9 position was investigated by molecular docking and molecular dynamics (MD) simulation methods. Methyl-α-Neu5Ac analogues were docked against cholera toxin (CT) B subunit protein and MD simulations were carried out for three Methyl-α-Neu5Ac analogue-CT complexes (30, 10 and 10 ns) to estimate the binding activity of cholera toxin-Methyl-α-Neu5Ac analogues using OPLS_2005 force field. In this study, direct and water mediated hydrogen bonds play a vital role that exist between the methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ)-cholera toxin active site residues. The Energy plot, RMSD and RMSF explain that the simulation was stable throughout the simulation run. Transition of phi, psi and omega angle for the complex was calculated. Molecular docking studies could be able to identify the binding mode of methyl-α-Neu5Ac analogues in the binding site of cholera toxin B subunit protein. MD simulation for Methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ), Methyl-α-9-N-acetyl-9-deoxy-9-amino-Neu5Ac and Methyl-α-9-N-biphenyl-4-acetyl-deoxy-amino-Neu5Ac complex with CT B subunit protein was carried out, which explains the stable nature of interaction. These methyl-α-Neu5Ac analogues that have computationally acceptable pharmacological properties may be used as novel candidates for drug design for cholera disease.

  10. Multiscale modeling of complex molecular structure and dynamics with MBN Explorer

    CERN Document Server

    Solov’yov, Ilia A; Solov’yov, Andrey V

    2017-01-01

    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, and guides readers through its applications in numerous areas of research in bio- and chemical physics and material science – ranging from the nano- to the meso-scale. MBN Explorer is particularly suited to computing the system’s energy, to optimizing molecular structure, and to exploring the various facets of molecular and random walk dynamics. The package allows the use of a broad variety of interatomic potenti...

  11. Application of JAERI quantum molecular dynamics model for collisions of heavy nuclei

    Directory of Open Access Journals (Sweden)

    Ogawa Tatsuhiko

    2016-01-01

    Full Text Available The quantum molecular dynamics (QMD model incorporated into the general-purpose radiation transport code PHITS was revised for accurate prediction of fragment yields in peripheral collisions. For more accurate simulation of peripheral collisions, stability of the nuclei at their ground state was improved and the algorithm to reject invalid events was modified. In-medium correction on nucleon-nucleon cross sections was also considered. To clarify the effect of this improvement on fragmentation of heavy nuclei, the new QMD model coupled with a statistical decay model was used to calculate fragment production cross sections of Ag and Au targets and compared with the data of earlier measurement. It is shown that the revised version can predict cross section more accurately.

  12. Interaction of the model alkyltrimethylammonium ions with alkali halide salts: an explicit water molecular dynamics study

    Directory of Open Access Journals (Sweden)

    M. Druchok

    2013-01-01

    Full Text Available We present an explicit water molecular dynamics simulation of dilute solutions of model alkyltrimethylammonium surfactant ions (number of methylene groups in the tail is 3, 5, 8, 10, and 12 in mixture with NaF, NaCl, NaBr, and NaI salts, respectively. The SPC/E model is used to describe water molecules. Results of the simulation at 298 K are presented in form of the radial distribution functions between nitrogen and carbon atoms of CH2 groups on the alkyltrimethylammonium ion, and the counterion species in the solution. The running coordination numbers between carbon atoms of surfactants and counterions are also calculated. We show that I- counterion exhibits the highest, and F- the lowest affinity to "bind" to the model surfactants. The results are discussed in view of the available experimental and simulation data for this and similar solutions.

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

    Directory of Open Access Journals (Sweden)

    Thomas Sandberg

    2012-08-01

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

  14. Inhibition of Mycobacterium-RmlA by Molecular Modeling, Dynamics Simulation, and Docking

    Science.gov (United States)

    Harathi, N.; Pulaganti, Madhusudana; Anuradha, C. M.; Kumar Chitta, Suresh

    2016-01-01

    The increasing resistance to anti-tb drugs has enforced strategies for finding new drug targets against Mycobacterium tuberculosis (Mtb). In recent years enzymes associated with the rhamnose pathway in Mtb have attracted attention as drug targets. The present work is on α-D-glucose-1-phosphate thymidylyltransferase (RmlA), the first enzyme involved in the biosynthesis of L-rhamnose, of Mtb cell wall. This study aims to derive a 3D structure of RmlA by using a comparative modeling approach. Structural refinement and energy minimization of the built model have been done with molecular dynamics. The reliability assessment of the built model was carried out with various protein checking tools such as Procheck, Whatif, ProsA, Errat, and Verify 3D. The obtained model investigates the relation between the structure and function. Molecular docking interactions of Mtb-RmlA with modified EMB (ethambutol) ligands and natural substrate have revealed specific key residues Arg13, Lys23, Asn109, and Thr223 which play an important role in ligand binding and selection. Compared to all EMB ligands, EMB-1 has shown better interaction with Mtb-RmlA model. The information thus discussed above will be useful for the rational design of safe and effective inhibitors specific to RmlA enzyme pertaining to the treatment of tuberculosis. PMID:26981117

  15. Inhibition of Mycobacterium-RmlA by Molecular Modeling, Dynamics Simulation, and Docking

    Directory of Open Access Journals (Sweden)

    N. Harathi

    2016-01-01

    Full Text Available The increasing resistance to anti-tb drugs has enforced strategies for finding new drug targets against Mycobacterium tuberculosis (Mtb. In recent years enzymes associated with the rhamnose pathway in Mtb have attracted attention as drug targets. The present work is on α-D-glucose-1-phosphate thymidylyltransferase (RmlA, the first enzyme involved in the biosynthesis of L-rhamnose, of Mtb cell wall. This study aims to derive a 3D structure of RmlA by using a comparative modeling approach. Structural refinement and energy minimization of the built model have been done with molecular dynamics. The reliability assessment of the built model was carried out with various protein checking tools such as Procheck, Whatif, ProsA, Errat, and Verify 3D. The obtained model investigates the relation between the structure and function. Molecular docking interactions of Mtb-RmlA with modified EMB (ethambutol ligands and natural substrate have revealed specific key residues Arg13, Lys23, Asn109, and Thr223 which play an important role in ligand binding and selection. Compared to all EMB ligands, EMB-1 has shown better interaction with Mtb-RmlA model. The information thus discussed above will be useful for the rational design of safe and effective inhibitors specific to RmlA enzyme pertaining to the treatment of tuberculosis.

  16. Quantum dynamics in the highly discrete, commensurate Frenkel Kontorova model: A path-integral molecular dynamics study

    Science.gov (United States)

    Krajewski, Florian R.; Müser, Martin H.

    2005-03-01

    The commensurate Frenkel Kontorova (FK) model is studied using path-integral molecular dynamics (PIMD). We focus on the highly discrete case, in which the embedding potential has a much greater maximum curvature than the harmonic potential connecting two particles in the FK chain. When efficient sampling methods are used, the dynamical interpretation of adiabatic PIMD appears to represent quite accurately the true time correlation functions of this highly correlated many-body system. We have found that the discrete, quantum FK model shows different behavior than its continuum version. The spectral density does not show the characteristic ω-2Θ(ω-ωc) cusp of the continuum solution in the pinned phase (m>mc). We also identify a dynamical quantum hysteresis in addition to the regular classical hysteresis when an external force is applied to the FK chain. In the unpinned phase (m⩽mc), we find a linear response damping coefficient which is finite and only weakly dependent on temperature T at small values of T.

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Machine learning for molecular scattering dynamics: Gaussian Process models for improved predictions of molecular collision observables

    Science.gov (United States)

    Krems, Roman; Cui, Jie; Li, Zhiying

    2016-05-01

    We show how statistical learning techniques based on kriging (Gaussian Process regression) can be used for improving the predictions of classical and/or quantum scattering theory. In particular, we show how Gaussian Process models can be used for: (i) efficient non-parametric fitting of multi-dimensional potential energy surfaces without the need to fit ab initio data with analytical functions; (ii) obtaining scattering observables as functions of individual PES parameters; (iii) using classical trajectories to interpolate quantum results; (iv) extrapolation of scattering observables from one molecule to another; (v) obtaining scattering observables with error bars reflecting the inherent inaccuracy of the underlying potential energy surfaces. We argue that the application of Gaussian Process models to quantum scattering calculations may potentially elevate the theoretical predictions to the same level of certainty as the experimental measurements and can be used to identify the role of individual atoms in determining the outcome of collisions of complex molecules. We will show examples and discuss the applications of Gaussian Process models to improving the predictions of scattering theory relevant for the cold molecules research field. Work supported by NSERC of Canada.

  19. 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.

  20. A molecular dynamics study of water nucleation using the TIP4P/2005 model

    Science.gov (United States)

    Pérez, Alejandro; Rubio, Angel

    2011-12-01

    Extensive molecular dynamics simulations were conducted using the TIP4P/2005 water model of Abascal and Vega [J. Chem. Phys. 123, 234505 (2005)] to investigate its condensation from supersaturated vapor to liquid at 330 K. The mean first passage time method [J. Wedekind, R. Strey, and D. Reguera, J. Chem. Phys. 126, 134103 (2007); L. S. Bartell and D. T. Wu, 125, 194503 (2006)] was used to analyze the influence of finite size effects, thermostats, and charged species on the nucleation dynamics. We find that the Nosé-Hoover thermostat and the one proposed by Bussi et al. [J. Chem. Phys. 126, 014101 (2007)] give essentially the same averages. We identify the maximum thermostat coupling time to guarantee proper thermostating for these simulations. The presence of charged species has a dramatic impact on the dynamics, inducing a marked change towards a pure growth regime, which highlights the importance of ions in the formation of liquid droplets in the atmosphere. It was found a small but noticeable sign preference at intermediate cluster sizes (between 5 and 30 water molecules) corresponding mostly to the formation of the second solvation shell around the ion. The TIP4P/2005 water model predicts that anions induce faster formation of water clusters than cations of the same magnitude of charge.

  1. Molecular dynamics of leucine and dopamine transporter proteins in a model cell membrane lipid bilayer.

    Science.gov (United States)

    Gedeon, Patrick C; Indarte, Martín; Surratt, Christopher K; Madura, Jeffry D

    2010-03-01

    The dopamine transporter (DAT) operates via facilitated diffusion, harnessing an inward Na(+) gradient to drive dopamine from the extracellular synaptic cleft to the neuron interior. The DAT is relevant to central nervous system disorders such as Parkinson disease and attention-deficit hyperactivity disorder and is the primary site of action for the abused psychostimulants cocaine and amphetamines. Crystallization of a DAT homolog, the bacterial leucine transporter LeuT, provided the first reliable 3-D DAT template. Here, the LeuT crystal structure and the DAT molecular model have been combined with their respective substrates, leucine and dopamine, in lipid bilayer molecular dynamics simulations toward tracking substrate movement along the protein's substrate/ion permeation pathway. Specifically, movement of residue pairs that comprise the "external gate" was followed as a function of substrate presence. The transmembrane (TM) 1 arginine-TM 10 aspartate strut formed less readily in DAT compared with LeuT, with or without substrate present. For LeuT but not DAT, the addition of substrate enhanced the chances of forming the TM 1-10 bridge. Also, movement of the fourth extracellular loop EL-4 in the presence of substrate was more pronounced for DAT, the EL-4 unwinding to a degree. The overall similarity between the LeuT and DAT molecular dynamics simulations indicated that LeuT was a legitimate model to guide DAT structure-function predictions. There were, nevertheless, differences significant enough to allow for DAT-unique insights, which may include how cocaine, methylphenidate (Ritalin, NIDA Drug Supply, Rockville, MD), and other DAT blockers are not recognized as substrates even though they can access the primary substrate binding pocket. Proteins 2010. (c) 2009 Wiley-Liss, Inc.

  2. Pygmy and Giant Dipole Resonances by Coulomb Excitation using a Quantum Molecular Dynamics model

    CERN Document Server

    Tao, C; Zhang, G Q; Cao, X G; Wang, D Q Fang H W

    2012-01-01

    Pygmy and Giant Dipole Resonance (PDR and GDR) in Ni isotopes have been investigated by Coulomb excitation in the framework of the Isospin-dependent Quantum Molecular Dynamics model (IQMD). The spectra of $\\gamma$ rays are calculated and the peak energy, the strength and Full Width at Half Maximum (FWHM) of GDR and PDR have been extracted. Their sensitivities to nuclear equation of state, especially to its symmetry energy term are also explored. By a comparison with the other mean-field calculations, we obtain the reasonable values for symmetry energy and its slope parameter at saturation, which gives an important constrain for IQMD model. In addition, we also studied the neutron excess dependence of GDR and PDR parameters for Ni isotopes and found that the energy-weighted sum rule (EWSR) $PDR_{m_1}/GDR_{m_1}%$ increases linearly with the neutron excess.

  3. Fusing heterogeneous data for the calibration of molecular dynamics force fields using hierarchical Bayesian models.

    Science.gov (United States)

    Wu, Stephen; Angelikopoulos, Panagiotis; Tauriello, Gerardo; Papadimitriou, Costas; Koumoutsakos, Petros

    2016-12-28

    We propose a hierarchical Bayesian framework to systematically integrate heterogeneous data for the calibration of force fields in Molecular Dynamics (MD) simulations. Our approach enables the fusion of diverse experimental data sets of the physico-chemical properties of a system at different thermodynamic conditions. We demonstrate the value of this framework for the robust calibration of MD force-fields for water using experimental data of its diffusivity, radial distribution function, and density. In order to address the high computational cost associated with the hierarchical Bayesian models, we develop a novel surrogate model based on the empirical interpolation method. Further computational savings are achieved by implementing a highly parallel transitional Markov chain Monte Carlo technique. The present method bypasses possible subjective weightings of the experimental data in identifying MD force-field parameters.

  4. Modeling of Car-Following Required Safe Distance Based on Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Dayi Qu

    2014-01-01

    Full Text Available In car-following procedure, some distances are reserved between the vehicles, through which drivers can avoid collisions with vehicles before and after them in the same lane and keep a reasonable clearance with lateral vehicles. This paper investigates characters of vehicle operating safety in car following state based on required safe distance. To tackle this problem, we probe into required safe distance and car-following model using molecular dynamics, covering longitudinal and lateral safe distance. The model was developed and implemented to describe the relationship between longitudinal safe distance and lateral safe distance under the condition where the leader keeps uniform deceleration. The results obtained herein are deemed valuable for car-following theory and microscopic traffic simulation.

  5. High-performance modeling of CO2 sequestration by coupling reservoir simulation and molecular dynamics

    KAUST Repository

    Bao, Kai

    2013-01-01

    The present work describes a parallel computational framework for CO2 sequestration simulation by coupling reservoir simulation and molecular dynamics (MD) on massively parallel HPC systems. In this framework, a parallel reservoir simulator, Reservoir Simulation Toolbox (RST), solves the flow and transport equations that describe the subsurface flow behavior, while the molecular dynamics simulations are performed to provide the required physical parameters. Numerous technologies from different fields are employed to make this novel coupled system work efficiently. One of the major applications of the framework is the modeling of large scale CO2 sequestration for long-term storage in the subsurface geological formations, such as depleted reservoirs and deep saline aquifers, which has been proposed as one of the most attractive and practical solutions to reduce the CO2 emission problem to address the global-warming threat. To effectively solve such problems, fine grids and accurate prediction of the properties of fluid mixtures are essential for accuracy. In this work, the CO2 sequestration is presented as our first example to couple the reservoir simulation and molecular dynamics, while the framework can be extended naturally to the full multiphase multicomponent compositional flow simulation to handle more complicated physical process in the future. Accuracy and scalability analysis are performed on an IBM BlueGene/P and on an IBM BlueGene/Q, the latest IBM supercomputer. Results show good accuracy of our MD simulations compared with published data, and good scalability are observed with the massively parallel HPC systems. The performance and capacity of the proposed framework are well demonstrated with several experiments with hundreds of millions to a billion cells. To our best knowledge, the work represents the first attempt to couple the reservoir simulation and molecular simulation for large scale modeling. Due to the complexity of the subsurface systems

  6. Stochastic dynamics of small ensembles of non-processive molecular motors: the parallel cluster model.

    Science.gov (United States)

    Erdmann, Thorsten; Albert, Philipp J; Schwarz, Ulrich S

    2013-11-07

    Non-processive molecular motors have to work together in ensembles in order to generate appreciable levels of force or movement. In skeletal muscle, for example, hundreds of myosin II molecules cooperate in thick filaments. In non-muscle cells, by contrast, small groups with few tens of non-muscle myosin II motors contribute to essential cellular processes such as transport, shape changes, or mechanosensing. Here we introduce a detailed and analytically tractable model for this important situation. Using a three-state crossbridge model for the myosin II motor cycle and exploiting the assumptions of fast power stroke kinetics and equal load sharing between motors in equivalent states, we reduce the stochastic reaction network to a one-step master equation for the binding and unbinding dynamics (parallel cluster model) and derive the rules for ensemble movement. We find that for constant external load, ensemble dynamics is strongly shaped by the catch bond character of myosin II, which leads to an increase of the fraction of bound motors under load and thus to firm attachment even for small ensembles. This adaptation to load results in a concave force-velocity relation described by a Hill relation. For external load provided by a linear spring, myosin II ensembles dynamically adjust themselves towards an isometric state with constant average position and load. The dynamics of the ensembles is now determined mainly by the distribution of motors over the different kinds of bound states. For increasing stiffness of the external spring, there is a sharp transition beyond which myosin II can no longer perform the power stroke. Slow unbinding from the pre-power-stroke state protects the ensembles against detachment.

  7. Stochastic dynamics of small ensembles of non-processive molecular motors: The parallel cluster model

    Science.gov (United States)

    Erdmann, Thorsten; Albert, Philipp J.; Schwarz, Ulrich S.

    2013-11-01

    Non-processive molecular motors have to work together in ensembles in order to generate appreciable levels of force or movement. In skeletal muscle, for example, hundreds of myosin II molecules cooperate in thick filaments. In non-muscle cells, by contrast, small groups with few tens of non-muscle myosin II motors contribute to essential cellular processes such as transport, shape changes, or mechanosensing. Here we introduce a detailed and analytically tractable model for this important situation. Using a three-state crossbridge model for the myosin II motor cycle and exploiting the assumptions of fast power stroke kinetics and equal load sharing between motors in equivalent states, we reduce the stochastic reaction network to a one-step master equation for the binding and unbinding dynamics (parallel cluster model) and derive the rules for ensemble movement. We find that for constant external load, ensemble dynamics is strongly shaped by the catch bond character of myosin II, which leads to an increase of the fraction of bound motors under load and thus to firm attachment even for small ensembles. This adaptation to load results in a concave force-velocity relation described by a Hill relation. For external load provided by a linear spring, myosin II ensembles dynamically adjust themselves towards an isometric state with constant average position and load. The dynamics of the ensembles is now determined mainly by the distribution of motors over the different kinds of bound states. For increasing stiffness of the external spring, there is a sharp transition beyond which myosin II can no longer perform the power stroke. Slow unbinding from the pre-power-stroke state protects the ensembles against detachment.

  8. Stochastic dynamics of small ensembles of non-processive molecular motors: the parallel cluster model

    CERN Document Server

    Erdmann, Thorsten; Schwarz, Ulrich S

    2013-01-01

    Non-processive molecular motors have to work together in ensembles in order to generate appreciable levels of force or movement. In skeletal muscle, for example, hundreds of myosin II molecules cooperate in thick filaments. In non-muscle cells, by contrast, small groups with few tens of non-muscle myosin II motors contribute to essential cellular processes such as transport, shape changes or mechanosensing. Here we introduce a detailed and analytically tractable model for this important situation. Using a three-state crossbridge model for the myosin II motor cycle and exploiting the assumptions of fast power stroke kinetics and equal load sharing between motors in equivalent states, we reduce the stochastic reaction network to a one-step master equation for the binding and unbinding dynamics (parallel cluster model) and derive the rules for ensemble movement. We find that for constant external load, ensemble dynamics is strongly shaped by the catch bond character of myosin II, which leads to an increase of th...

  9. State-Dependent Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Ciann-Dong Yang

    2014-10-01

    Full Text Available This paper proposes a new mixed quantum mechanics (QM—molecular mechanics (MM approach, where MM is replaced by quantum Hamilton mechanics (QHM, which inherits the modeling capability of MM, while preserving the state-dependent nature of QM. QHM, a single mechanics playing the roles of QM and MM simultaneously, will be employed here to derive the three-dimensional quantum dynamics of diatomic molecules. The resulting state-dependent molecular dynamics including vibration, rotation and spin are shown to completely agree with the QM description and well match the experimental vibration-rotation spectrum. QHM can be incorporated into the framework of a mixed quantum-classical Bohmian method to enable a trajectory interpretation of orbital-spin interaction and spin entanglement in molecular dynamics.

  10. 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.

  11. Total Reaction Cross Section in an Isospin-Dependent Quantum Molecular Dynamics Model

    Institute of Scientific and Technical Information of China (English)

    魏义彬; 蔡翔舟; 沈文庆; 马余刚; 张虎勇; 钟晨; 郭威; 陈金根; 马国亮; 王鲲

    2003-01-01

    The isospin-dependent quantum molecular dynamics (IDQMD) model is used to study the total reaction cross section σR. The energy-dependent Pauli volumes of neutrons and protons have been discussed and introduced into the IDQMD calculation to replace the widely used energy-independent Pauli volumes. The modified IDQMD calculation can reproduce the experimental cr R well for both stable and exotic nuclei induced reactions. Comparisons of the calculated σn induced by 11Li with different initial density distributions have been performed. It is shown that the calculation by using the experimentally deduced density distribution with a long tail can fit the experimental excitation function better than that by using the Skyrme-Hartree-Fock calculated density without long tails. It is also found that σR at high energy is sensitive to the long tail of density distribution.

  12. Isoscaling Behaviour in the Isospin-Dependent Quantum Molecular Dynamics Model

    Institute of Scientific and Technical Information of China (English)

    TIAN Wen-Dong; SHEN Wen-Qing; WANG Kun; WEI Yi-Bin; YAN Ting-Zhi; ZHONG Chen; ZUO Jia-Xu; MA Yu-Gang; CAI Xiang-Zhou; CHEN Jin-Gen; CHEN Jin-Hui; FANG De-Qing; GUO Wei; MA Chun-Wang; MA Guo-Liang

    2005-01-01

    @@ The isoscaling behaviour is investigated in a frame of isospin-dependent quantum molecular dynamics models. The isotopic yields ratio Y2/Y1 for reactions 48Ca+48Ca and 40 Ca+ 40 Ca at different entrance channels are simulated and presented, the relationship between the isoscaling parameter and the entrance channel is analysed, the results show that α and β reduce with the rise of incident energies and increase with the impact parameter b, which can be attributed to the temperature varying of the pre-fragments in different entrance channels. The relation of α and symmetry-term coefficient Csym reveals that the chemical potential difference △μ is sensitive to the symmetry-term coefficient Csym, and raises with the increasing Csym.

  13. Physical Model of Segregation of E.coli Chromosomes using Molecular Dynamics

    Science.gov (United States)

    Alnahhas, Faisal; Kharel, Savan

    2016-03-01

    Chromosome segregation is one of the most interesting physical processes during a bacterial cell cycle. We will use molecular dynamics simulations which will help us understand how strongly confined polymer segregates. In the presentation, we will discuss how segregation of initially overlapping circular chromosome occurs during a cell cycle. In particular, we will describe the role played by entropic mechanism in the demixing of overlapping circular polymer confined in a cylindrical boundary. We discuss how our polymer chains modeled as an E-coli chromosome experiences an effective repulsion, which ultimately leads to partition driven by the entropic forces. Also, we will also discuss how the segregation of circular chromosome in cylindrical confinement differs from a spherical confinement. Finally, we will discuss the role played by proteins and supercoiling in during the segregation process.

  14. Combined molecular dynamics and analytical model for repetitive cluster bombardment of solids

    Energy Technology Data Exchange (ETDEWEB)

    Garrison, Barbara J., E-mail: bjg@psu.edu [Department of Chemistry, 104 Chemistry Building, Penn State University, University Park, PA 16802 (United States); Paruch, Robert J.; Postawa, Zbigniew [Smoluchowski Institute of Physics, Jagiellonian University, ul. Reymonta 4, 30-059 Kraków (Poland)

    2013-05-15

    Molecular dynamics simulations of repetitive bombardment of solids by keV cluster beams have generated so much data that easy interpretations are not possible. Moreover, although the MD simulations remove 3–4 nm of material, that is not sufficient material to determine a depth profile. The recently developed steady-state statistical sputtering model (SS-SSM) uses information from the MD simulations and incorporates it into a set of differential equations to predict a depth profile. In this study the distributions that provide the input to the SS-SSM are compared for simulations of 15 keV bombardment of Ag(1 1 1) by C{sub 60}, Au{sub 3} and Ar{sub 872} cluster beams.

  15. Application of shell model in molecular dynamics simulation to MgO

    Institute of Scientific and Technical Information of China (English)

    Liu Zi-Jiang; Cheng Xin-Lu; Chen Xiang-Rong; Zhang Hong; Lu Lai-Yu

    2004-01-01

    The P-V-T equation of state of MgO has been simulated under high pressure and elevated temperature using the molecular dynamics (MD) method with the breathing shell model (BSM). It is found that the MD simulation with BSM is very successful in reproducing accurately the measured molar volumes of MgO over a wide range of temperature and pressure. In addition, the MD simulation reproduces accurately the measured volume compression data of MgO up to 100GPa at 300K. It is demonstrated that the MD simulated P-V-T equation of state of MgO could be applied as a useful internal pressure calibration standard at elevated temperatures and high pressures.

  16. Molecular dynamics study of lipid bilayers modeling the plasma membranes of mouse hepatocytes and hepatomas

    Science.gov (United States)

    Andoh, Yoshimichi; Aoki, Noriyuki; Okazaki, Susumu

    2016-02-01

    Molecular dynamics (MD) calculations of lipid bilayers modeling the plasma membranes of normal mouse hepatocytes and hepatomas in water have been performed under physiological isothermal-isobaric conditions (310.15 K and 1 atm). The changes in the membrane properties induced by hepatic canceration were investigated and were compared with previous MD calculations included in our previous study of the changes in membrane properties induced by murine thymic canceration. The calculated model membranes for normal hepatocytes and hepatomas comprised 23 and 24 kinds of lipids, respectively. These included phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, lysophospholipids, and cholesterol. We referred to previously published experimental values for the mole fraction of the lipids adopted in the present calculations. The calculated structural and dynamic properties of the membranes such as lateral structure, order parameters, lateral self-diffusion constants, and rotational correlation times all showed that hepatic canceration causes plasma membranes to become more ordered laterally and less fluid. Interestingly, this finding contrasts with the less ordered structure and increased fluidity of plasma membranes induced by thymic canceration observed in our previous MD study.

  17. A Stochastic Phase-Field Model Computed From Coarse-Grained Molecular Dynamics

    CERN Document Server

    von Schwerin, Erik

    2007-01-01

    Results are presented from numerical experiments aiming at the computation of stochastic phase-field models for phase transformations by coarse-graining molecular dynamics. The studied phase transformations occur between a solid crystal and a liquid. Nucleation and growth, sometimes dendritic, of crystal grains in a sub-cooled liquid is determined by diffusion and convection of heat, on the macroscopic level, and by interface effects, where the width of the solid-liquid interface is on an atomic length-scale. Phase-field methods are widely used in the study of the continuum level time evolution of the phase transformations; they introduce an order parameter to distinguish between the phases. The dynamics of the order parameter is modelled by an Allen--Cahn equation and coupled to an energy equation, where the latent heat at the phase transition enters as a source term. Stochastic fluctuations are sometimes added in the coupled system of partial differential equations to introduce nucleation and to get qualita...

  18. Reactive molecular dynamics simulation and chemical kinetic modeling of pyrolysis and combustion of n-dodecane

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Quan-De [College of Chemistry, Sichuan University, Chengdu (China); Wang, Jing-Bo; Li, Juan-Qin; Tan, Ning-Xin; Li, Xiang-Yuan [College of Chemical Engineering, Sichuan University, Chengdu (China)

    2011-02-15

    The initiation mechanisms and kinetics of pyrolysis and combustion of n-dodecane are investigated by using the reactive molecular dynamics (ReaxFF MD) simulation and chemical kinetic modeling. From ReaxFF MD simulations, we find the initiation mechanisms of pyrolysis of n-dodecane are mainly through two pathways, (1) the cleavage of C-C bond to form smaller hydrocarbon radicals, and (2) the dehydrogenation reaction to form an H radical and the corresponding n-C{sub 12}H{sub 25} radical. Another pathway is the H-abstraction reactions by small radicals including H, CH{sub 3}, and C{sub 2}H{sub 5}, which are the products after the initiation reaction of n-dodecane pyrolysis. ReaxFF MD simulations lead to reasonable Arrhenius parameters compared with experimental results based on first-order kinetic analysis of n-dodecane pyrolysis. The density/pressure effects on the pyrolysis of n-dodecane are also analyzed. By appropriate mapping of the length and time from macroscopic kinetic modeling to ReaxFF MD, a simple comparison of the conversion of n-dodecane from ReaxFF MD simulations and that from kinetic modeling is performed. In addition, the oxidation of n-dodecane is studied by ReaxFF MD simulations. We find that formaldehyde molecule is an important intermediate in the oxidation of n-dodecane, which has been confirmed by kinetic modeling, and ReaxFF leads to reasonable reaction pathways for the oxidation of n-dodecane. These results indicate that ReaxFF MD simulations can give an atomistic description of the initiation mechanism and product distributions of pyrolysis and combustion for hydrocarbon fuels, and can be further used to provide molecular based robust kinetic reaction mechanism for chemical kinetic modeling of hydrocarbon fuels. (author)

  19. 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.

  20. On interfacial properties of tetrahydrofuran: Atomistic and coarse-grained models from molecular dynamics simulation

    Science.gov (United States)

    Garrido, J. M.; Algaba, J.; Míguez, J. M.; Mendiboure, B.; Moreno-Ventas Bravo, A. I.; Piñeiro, M. M.; Blas, F. J.

    2016-04-01

    We have determined the interfacial properties of tetrahydrofuran (THF) from direct simulation of the vapor-liquid interface. The molecules are modeled using six different molecular models, three of them based on the united-atom approach and the other three based on a coarse-grained (CG) approach. In the first case, THF is modeled using the transferable parameters potential functions approach proposed by Chandrasekhar and Jorgensen [J. Chem. Phys. 77, 5073 (1982)] and a new parametrization of the TraPPE force fields for cyclic alkanes and ethers [S. J. Keasler et al., J. Phys. Chem. B 115, 11234 (2012)]. In both cases, dispersive and coulombic intermolecular interactions are explicitly taken into account. In the second case, THF is modeled as a single sphere, a diatomic molecule, and a ring formed from three Mie monomers according to the SAFT-γ Mie top-down approach [V. Papaioannou et al., J. Chem. Phys. 140, 054107 (2014)]. Simulations were performed in the molecular dynamics canonical ensemble and the vapor-liquid surface tension is evaluated from the normal and tangential components of the pressure tensor along the simulation box. In addition to the surface tension, we have also obtained density profiles, coexistence densities, critical temperature, density, and pressure, and interfacial thickness as functions of temperature, paying special attention to the comparison between the estimations obtained from different models and literature experimental data. The simulation results obtained from the three CG models as described by the SAFT-γ Mie approach are able to predict accurately the vapor-liquid phase envelope of THF, in excellent agreement with estimations obtained from TraPPE model and experimental data in the whole range of coexistence. However, Chandrasekhar and Jorgensen model presents significant deviations from experimental results. We also compare the predictions for surface tension as obtained from simulation results for all the models with

  1. 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

  2. Calculation of the distribution of eigenvalues and eigenvectors in Markovian state models for molecular dynamics.

    Science.gov (United States)

    Hinrichs, Nina Singhal; Pande, Vijay S

    2007-06-28

    Markovian state models (MSMs) are a convenient and efficient means to compactly describe the kinetics of a molecular system as well as a formalism for using many short simulations to predict long time scale behavior. Building a MSM consists of grouping the conformations into states and estimating the transition probabilities between these states. In a previous paper, we described an efficient method for calculating the uncertainty due to finite sampling in the mean first passage time between two states. In this paper, we extend the uncertainty analysis to derive similar closed-form solutions for the distributions of the eigenvalues and eigenvectors of the transition matrix, quantities that have numerous applications when using the model. We demonstrate the accuracy of the distributions on a six-state model of the terminally blocked alanine peptide. We also show how to significantly reduce the total number of simulations necessary to build a model with a given precision using these uncertainty estimates for the blocked alanine system and for a 2454-state MSM for the dynamics of the villin headpiece.

  3. Molecular dynamics model for nano-motions of FePd nanohelices

    Science.gov (United States)

    Taya, M.; Xu, C.; Matsuse, T.; Muraishi, S.

    2017-04-01

    Shrinkage and relaxation motions of flexible FePd nanohelices of FePd nanorobots are simulated by a molecular dynamics (MD) model where FePd is a paramagnetic shape memory alloy that can exhibit phase transformation accompanied by softening of the nanohelix under an applied magnetic field (H-field). Two designs of FePd nanorobots are used: (i) a FePd cylindrical head connected to a FePd nanohelix tail and (ii) a FePd nanohelix alone. The geometry and dimensions of the FePd robots are taken after the as-processed FePd nanorobots. In the MD simulation, the FePd head and nanohelix are divided into a number of segmented FePd spheres, each having its magnetic moment. The results of the MD model reveal that upon the applied constant magnetic field, the initial gaps (g = 3 nm) between the adjacent turns of the FePd nanohelix are closed, resulting in the total shrinkage (Stot) of 47 nm of the FePd nanorobot. The effects of the applied H-field on Stot are examined by using the MD model and the M-H curve of FePd fitted with Langevin type, resulting in the smaller applied magnetic field leading to the smaller Stot. The results of the MD model provide us with an effective tool in the analysis and design of new nanorobots based on the paramagnetic shape memory alloy of FePd nanohelices that can exert dynamic vibrations on target cells under the oscillating magnetic field.

  4. Parametric Study of ReaxFF Simulation Parameters for Molecular Dynamics Modeling of Reactive Carbon Gases.

    Science.gov (United States)

    Jensen, Benjamin D; Bandyopadhyay, Ananyo; Wise, Kristopher E; Odegard, Gregory M

    2012-09-11

    The development of innovative carbon-based materials can be greatly facilitated by molecular modeling techniques. Although the Reax Force Field (ReaxFF) can be used to simulate the chemical behavior of carbon-based systems, the simulation settings required for accurate predictions have not been fully explored. Using the ReaxFF, molecular dynamics (MD) simulations are used to simulate the chemical behavior of pure carbon and hydrocarbon reactive gases that are involved in the formation of carbon structures such as graphite, buckyballs, amorphous carbon, and carbon nanotubes. It is determined that the maximum simulation time step that can be used in MD simulations with the ReaxFF is dependent on the simulated temperature and selected parameter set, as are the predicted reaction rates. It is also determined that different carbon-based reactive gases react at different rates, and that the predicted equilibrium structures are generally the same for the different ReaxFF parameter sets, except in the case of the predicted formation of large graphitic structures with the Chenoweth parameter set under specific conditions.

  5. Molecular Dynamics Modeling of Carbon Nanotube Composite Fracture Using ReaxFF

    Science.gov (United States)

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

    2016-01-01

    Carbon nanotube (CNT) fiber reinforced composites with specific tensile strengths and moduli approaching those of aerospace grade carbon fiber composites have recently been reported. This achievement was enabled by the emerging availability of high N/tex yarns in kilometer-scale quantities. While the production of this yarn is an impressive advance, its strength is still much lower than that of the individual CNTs comprising the yarn. Closing this gap requires understanding load transfer between CNTs at the nanometer dimensional scale. This work uses reactive molecular dynamics simulations to gain an understanding at the nanometer scale of the key factors that determine CNT nanocomposite mechanical performance, and to place more realistic upper bounds on the target properties. While molecular dynamics simulations using conventional force fields can predict elastic properties, the ReaxFF reactive forcefield can also model fracture behavior because of its ability to accurately describe bond breaking and formation during a simulation. The upper and lower bounds of CNT composite properties are investigated by comparing systems composed of CNTs continuously connected across the periodic boundary with systems composed of finite length CNTs. These lengths, effectively infinite for the continuous tubes and an aspect ratio of 13 for the finite length case, result from practical limitations on the number of atoms that can be included in a simulation. Experimentally measured aspect ratios are typically on the order of 100,000, so the calculated results should represent upper and lower limits on experimental mechanical properties. Finally, the effect of various degrees of covalent crosslinking between the CNTs and amorphous carbon matrix is considered to identify the amount of CNT-matrix covalent bonding that maximizes overall composite properties.

  6. From Molecular Dynamics to Brownian Dynamics

    CERN Document Server

    Erban, Radek

    2014-01-01

    Three coarse-grained molecular dynamics (MD) models are investigated with the aim of developing and analyzing multiscale methods which use MD simulations in parts of the computational domain and (less detailed) Brownian dynamics (BD) simulations in the remainder of the domain. The first MD model is formulated in one spatial dimension. It is based on elastic collisions of heavy molecules (e.g. proteins) with light point particles (e.g. water molecules). Two three-dimensional MD models are then investigated. The obtained results are applied to a simplified model of protein binding to receptors on the cellular membrane. It is shown that modern BD simulators of intracellular processes can be used in the bulk and accurately coupled with a (more detailed) MD model of protein binding which is used close to the membrane.

  7. Extended molecular dynamics and optimized Rouse-Zimm model studies of a short peptide: Various friction approximations

    Science.gov (United States)

    Hu, Yi; Kostov, Konstantin; Perico, Angelo; Smithline, Shepard; Freed, Karl F.

    1995-11-01

    Developing a theory for the long time dynamics of polypeptides requires not only a proper choice of the relevant dynamic variables, but also a meaningful definition of friction coefficients for the individual atoms or groups of atoms in the reduced system. We test various aspects of the optimized Rouse-Zimm model for describing the long time rotational dynamics of a peptide fragment. The necessary equilibrium input information is constructed from a 1 ns molecular dynamics simulation for the solvated peptide by using a parallel Cray version of CHARMm, whose new features are described here. The simulations also provide time autocorrelation functions for comparisons with both theoretical predictions and with experiment. Two atomic friction models (van der Waals radii and accessible surface area) are chosen, and tests are made of the applicability of two combining rules for calculating the group friction coefficients. While the rotational dynamics of the peptide is insensitive to the friction models used, the combining rules are found to impact profoundly upon the theoretical descriptions for the behavior of the peptide dynamics for the reduced descriptions with fewer variables. The calculations study the role of the memory functions, neglected in this dynamical theory, and the interatomic hydrodynamic interactions in constructing the group friction coefficients. While the 1 ns trajectory is longer than customarily used for very complex systems, there are nontrivial influences of the duration of the molecular dynamics trajectory on the description of the dynamics.

  8. Learning probabilistic models of hydrogen bond stability from molecular dynamics simulation trajectories

    KAUST Repository

    Chikalov, Igor

    2011-02-15

    Background: Hydrogen bonds (H-bonds) play a key role in both the formation and stabilization of protein structures. They form and break while a protein deforms, for instance during the transition from a non-functional to a functional state. The intrinsic strength of an individual H-bond has been studied from an energetic viewpoint, but energy alone may not be a very good predictor.Methods: This paper describes inductive learning methods to train protein-independent probabilistic models of H-bond stability from molecular dynamics (MD) simulation trajectories of various proteins. The training data contains 32 input attributes (predictors) that describe an H-bond and its local environment in a conformation c and the output attribute is the probability that the H-bond will be present in an arbitrary conformation of this protein achievable from c within a time duration ?. We model dependence of the output variable on the predictors by a regression tree.Results: Several models are built using 6 MD simulation trajectories containing over 4000 distinct H-bonds (millions of occurrences). Experimental results demonstrate that such models can predict H-bond stability quite well. They perform roughly 20% better than models based on H-bond energy alone. In addition, they can accurately identify a large fraction of the least stable H-bonds in a conformation. In most tests, about 80% of the 10% H-bonds predicted as the least stable are actually among the 10% truly least stable. The important attributes identified during the tree construction are consistent with previous findings.Conclusions: We use inductive learning methods to build protein-independent probabilistic models to study H-bond stability, and demonstrate that the models perform better than H-bond energy alone. 2011 Chikalov et al; licensee BioMed Central Ltd.

  9. A molecular dynamics implementation of the 3D Mercedes-Benz water model

    Science.gov (United States)

    Hynninen, T.; Dias, C. L.; Mkrtchyan, A.; Heinonen, V.; Karttunen, M.; Foster, A. S.; Ala-Nissila, T.

    2012-02-01

    The three-dimensional Mercedes-Benz model was recently introduced to account for the structural and thermodynamic properties of water. It treats water molecules as point-like particles with four dangling bonds in tetrahedral coordination, representing H-bonds of water. Its conceptual simplicity renders the model attractive in studies where complex behaviors emerge from H-bond interactions in water, e.g., the hydrophobic effect. A molecular dynamics (MD) implementation of the model is non-trivial and we outline here the mathematical framework of its force-field. Useful routines written in modern Fortran are also provided. This open source code is free and can easily be modified to account for different physical context. The provided code allows both serial and MPI-parallelized execution. Program summaryProgram title: CASHEW (Coarse Approach Simulator for Hydrogen-bonding Effects in Water) Catalogue identifier: AEKM_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKM_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 20 501 No. of bytes in distributed program, including test data, etc.: 551 044 Distribution format: tar.gz Programming language: Fortran 90 Computer: Program has been tested on desktop workstations and a Cray XT4/XT5 supercomputer. Operating system: Linux, Unix, OS X Has the code been vectorized or parallelized?: The code has been parallelized using MPI. RAM: Depends on size of system, about 5 MB for 1500 molecules. Classification: 7.7 External routines: A random number generator, Mersenne Twister ( http://www.math.sci.hiroshima-u.ac.jp/m-mat/MT/VERSIONS/FORTRAN/mt95.f90), is used. A copy of the code is included in the distribution. Nature of problem: Molecular dynamics simulation of a new geometric water model. Solution method: New force-field for

  10. Three-stage classical molecular dynamics model for simulation of heavy-ion fusion

    Directory of Open Access Journals (Sweden)

    Godre Subodh S.

    2015-01-01

    Full Text Available A three-stage Classical Molecular Dynamics (3S-CMD approach for heavy-ion fusion is developed. In this approach the Classical Rigid-Body Dynamics simulation for heavy-ion collision involving light deformed nucleus is initiated on their Rutherford trajectories at very large initial separation. Collision simulation is then followed by relaxation of the rigid-body constrains for one or both the colliding nuclei at distances close to the barrier when the trajectories of all the nucleons are obtained in a Classical Molecular Dynamics approach. This 3S-CMD approach explicitly takes into account not only the long range Coulomb reorientation of the deformed collision partner but also the internal vibrational excitations of one or both the nuclei at distances close to the barrier. The results of the dynamical simulation for 24Mg+208Pb collision show significant modification of the fusion barrier and calculated fusion cross sections due to internal excitations.

  11. The effect of empirical potential functions on modeling of amorphous carbon using molecular dynamics method

    Energy Technology Data Exchange (ETDEWEB)

    Li, Longqiu, E-mail: longqiuli@gmail.com [School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, 150001 (China); Xu, Ming; Song, Wenping [School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, 150001 (China); Ovcharenko, Andrey [Western Digital Corporation, San Jose, CA (United States); Zhang, Guangyu; Jia, Ding [School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, 150001 (China)

    2013-12-01

    Empirical potentials have a strong effect on the hybridization and structure of amorphous carbon and are of great importance in molecular dynamics (MD) simulations. In this work, amorphous carbon at densities ranging from 2.0 to 3.2 g/cm{sup 3} was modeled by a liquid quenching method using Tersoff, 2nd REBO, and ReaxFF empirical potentials. The hybridization, structure and radial distribution function G(r) of carbon atoms were analyzed as a function of the three potentials mentioned above. The ReaxFF potential is capable to model the change of the structure of amorphous carbon and MD results are in a good agreement with experimental results and density function theory (DFT) at low density of 2.6 g/cm{sup 3} and below. The 2nd REBO potential can be used when amorphous carbon has a very low density of 2.4 g/cm{sup 3} and below. Considering the computational efficiency, the Tersoff potential is recommended to model amorphous carbon at a high density of 2.6 g/cm{sup 3} and above. In addition, the influence of the quenching time on the hybridization content obtained with the three potentials is discussed.

  12. First-principles molecular dynamics modeling of the molten fluoride salt with Cr solute

    Energy Technology Data Exchange (ETDEWEB)

    Nam, H.O.; Bengtson, A.; Vörtler, K.; Saha, S.; Sakidja, R.; Morgan, D., E-mail: ddmorgan@wisc.edu

    2014-06-01

    Fluoride salts and their interactions with metals are of wide interest for the nuclear community. In this work, first-principles molecular dynamics (FPMD) was employed to study both pure molten fluoride salt and fluoride salt with dissolved solute Cr ions (a common corrosion product) at high temperature (823–1423 K). Two types of molten fluoride salts, namely flibe (LiF–BeF{sub 2}) and flinak (LiF–NaF–KF), with the Cr{sup 0}, Cr{sup 2+} and Cr{sup 3+} ions were chosen as a target system for the FPMD modeling. The prediction of thermo-kinetic properties of pure fluoride salt, such as the equilibrium volume, density, bulk modulus, coefficient of thermal expansion, and self-diffusion coefficient, provide useful extensions of existing data and verify the accuracy of the FPMD simulation in modeling of fluoride salts. The FPMD modeling of solute Cr in fluoride salt shows the effect of Cr valence on diffusivity and local structure in the salt.

  13. Guidance to Design Grain Boundary Mobility Experiments with Molecular Dynamics and Phase-Field Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Michael R Tonks; Yongfeng Zhang; S.B. Biner; Paul C Millett; Xianming Bai

    2013-02-01

    Quantitative phase-field modeling can play an important role in designing experiments to measure the grain boundary (GB) mobility. In this work, molecular dynamics (MD) simulation is employed to determine the GB mobility using Cu bicrystals. Two grain configurations are considered: a shrinking circular grain and a half loop grain. The results obtained from the half loop configuration approaches asymptotically to that obtained from the circular configuration with increasing half loop width. We then verify the phase- field model by directly comparing to the MD simulation results, obtaining excellent agreement. Next, this phase-field model is used to predict the behavior in a common experimental setup that utilizes a half loop grain configuration in a bicrystal to measure the GB mobility. With a 3D simulation, we identify the two critical times within the experiments to reach an accurate value of the GB mobility. We use a series of 2D simulations to investigate the impact of the notch angle on these two critical times and we identify an angle of 60? as an optimal value. We also show that if the notch does not have a sharp tip, it may immobilize the GB migration indefinitely.

  14. Homology modeling and molecular dynamics study on Schwanniomyces occidentalis alpha-amylase.

    Science.gov (United States)

    Sefidbakht, Yahya; Ranaei Siadat, Omid; Taheri, Fatemeh

    2017-02-01

    With consumers growing increasingly aware of environmental issues, industries find enzymes as a reasonable alternative over physical conditions and chemical catalysts. Amylases are important hydrolase enzymes, which have been widely used in variety of industrial process such as pharmaceutical, food, and fermentation industries. Among amylases α-Amylase is in maximum demand due to its wide range of applications. The homology modeling study on Schwanniomyces occidentalis amylase (AMY1, UniProt identifier number: P19269) was performed by Modeller using Aspergillus oryzae (6TAA) as the template. The resulting structure was analyzed for validity and subjected to 14 ns of molecular dynamics (MD) simulation trough GROMACS. The validity of obtained model may represent that utilized OPLS force field is suitable for calcium-containing enzymes. DSSP secondary structure and contact map analysis represent the conservation of domain A TIM barrel feature together with calcium ion coordination sphere. Investigating the covariance matrix followed by principle component analyses for the first five eigenvectors of both trajectories indicate a little more flexibility for AMY1 structure. The electrostatic calculation for the final structures shows similar isoelectric point and superimposed buffering zone in the 5-8 pH range.

  15. Infiltration effects on a two-dimensional molecular dynamics model of landslides

    CERN Document Server

    Martelloni, Gianluca

    2012-01-01

    In this paper we propose a two-dimensional (2D) computational model, based on a molecular dynamics (MD) approach, for deep landslides triggered by rainfall. Our model is based on interacting particles or grains and describes the behavior of a fictitious granular material along a slope consisting of a vertical section, i.e. with a wide thickness. The triggering of the landslide is caused by the passing of two conditions: a threshold speed and a condition on the static friction of the particles, the latter based on the Mohr-Coulomb failure criterion (Coulomb 1776; Mohr 1914). The inter-particle interactions are through a potential that, in the absence of suitable experimental data and due to the arbitrariness of the grain dimension is modeled by means of a potential similar to the Lennard-Jones one (Lennard-Jones 1924), i.e., with an attractive and a repulsive part. For the updating of the particle positions we use a MD method which results to be very suitable to simulate this type of systems (Herrmann and Ludi...

  16. Molecular dynamics modeling the synthetic and biological polymers interactions pre-studied via docking

    Science.gov (United States)

    Tsvetkov, Vladimir B.; Serbin, Alexander V.

    2014-06-01

    In previous works we reported the design, synthesis and in vitro evaluations of synthetic anionic polymers modified by alicyclic pendant groups (hydrophobic anchors), as a novel class of inhibitors of the human immunodeficiency virus type 1 ( HIV-1) entry into human cells. Recently, these synthetic polymers interactions with key mediator of HIV-1 entry-fusion, the tri-helix core of the first heptad repeat regions [ HR1]3 of viral envelope protein gp41, were pre-studied via docking in terms of newly formulated algorithm for stepwise approximation from fragments of polymeric backbone and side-group models toward real polymeric chains. In the present article the docking results were verified under molecular dynamics ( MD) modeling. In contrast with limited capabilities of the docking, the MD allowed of using much more large models of the polymeric ligands, considering flexibility of both ligand and target simultaneously. Among the synthesized polymers the dinorbornen anchors containing alternating copolymers of maleic acid were selected as the most representative ligands (possessing the top anti-HIV activity in vitro in correlation with the highest binding energy in the docking). To verify the probability of binding of the polymers with the [HR1]3 in the sites defined via docking, various starting positions of polymer chains were tried. The MD simulations confirmed the main docking-predicted priority for binding sites, and possibilities for axial and belting modes of the ligands-target interactions. Some newly MD-discovered aspects of the ligand's backbone and anchor units dynamic cooperation in binding the viral target clarify mechanisms of the synthetic polymers anti-HIV activity and drug resistance prevention.

  17. Development of a model electronic Hamiltonian for understanding electronic relaxation dynamics of [Fe(bpy){sub 3}]{sup 2+} through molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Iuchi, Satoru; Koga, Nobuaki [Graduate School of Information Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan)

    2015-12-31

    A model electronic Hamiltonian of [Fe(bpy){sub 3}]{sup 2+}, which was recently refined for use in molecular dynamics simulations, is reviewed with some additional results. In particular, the quality of the refined model Hamiltonian is examined in terms of the vibrational frequencies and solvation structures of the lowest singlet and quintet states.

  18. A molecular dynamic model for analyzing concentrations of electrolytes: Fractional molar dependences of microstructure properties

    Science.gov (United States)

    Khalansky, D.; Popova, E.; Gladyshev, P.; Dushanov, E.; Kholmurodov, Kh.

    2014-12-01

    Aqueous electrolyte solutions play an important role in many electrophysical and chemical processes in aerospace technology and industrial applications. As noncovalent interactions, the interactions between ions are crucially important for biomolecular structures as well (protein structure folding, molecular level processes followed by ionic pair correlations, the formation of flexible hydrate shells, and so on). Specifically, ions (cations and anions with the same valence charges) can form stable pairs if their sizes match. The formation of ionic pairs can substantially affect the thermodynamic stabilities of proteins in the alkali salts physiologically present in the human body. Research aims and problems impose severe demands on readjustments of the ionic force fields and potential parameters developed to describe aqueous solutions and electrolytic systems. Ionic solutions and their interaction with biomolecules have been observed for over 100 years [1], but the behavior of such solutions remains poorly studied today. New data obtained in this work deals with parameterization strategies and adjustments for the ionic force fields of the alkali cations and halide anions that should be helpful in biomolecular research. Using molecular dynamics (MD) models, four electrolytic systems (HCl-H2O, LiCl-H2O, NaCl-H2O, and KCl-H2O) are investigated as binary mixtures of water and cations and anions, respectively. The intermolecular interaction parameters are varied for two of the four model electrolytes (HCl-H2O and NaCl-H2O) to simulate the possibility of different ionic shells forming during interaction with water. It is found that varying the potential parameters strongly affects the dynamic and structural characteristics of electrolyte systems. MD simulations are performed in the temperature range of 300 to 600 K with a step of 50 K. MD simulations for all electrolyte models (HCl-H2O, LiCl-H2O, NaCl-H2O, KCl-H2O) are also conducted for different molar fractions of

  19. Secondary Structure Analysis of Native Cellulose by Molecular Dynamics Simulations with Coarse-Grained Model

    Institute of Scientific and Technical Information of China (English)

    Shuai Wu; Hai-yi Zhan; Hong-ming Wang; Yan Ju

    2012-01-01

    The secondary structure of different Ⅰβ cellulose was analyzed by a molecular dynamics simulation with MARTINI coarse-grained force field,where each chain of the cellulose includes 40 D-glucoses units.Calculation gives a satisfied description about the secondary structure of the cellulose.As the chain number increasing,the cellulose becomes the form of a helix,with the diameter of screw growing and spiral rising.Interestingly,the celluloses with chain number N of 4,6,24 and 36 do show right-hand twisting.On the contrast,the celluloses with N of 8,12,16 chains are left-hand twisting.These simulations indicate that the cellulose with chain number larger than 36 will break down to two parts.Besides,the result indicates that 36-chains cellulose model is the most stable among all models.Furthermore,the Lennard-Jones potential determines the secondary structure.In addition,an equation was set up to analyze the twisting structure.

  20. Mechanism for cocaine blocking the transport of dopamine: insights from molecular modeling and dynamics simulations.

    Science.gov (United States)

    Huang, Xiaoqin; Gu, Howard H; Zhan, Chang-Guo

    2009-11-12

    Molecular modeling and dynamics simulations have been performed to study how cocaine inhibits dopamine transporter (DAT) for the transport of dopamine. The computationally determined DAT-ligand binding mode is totally different from the previously proposed overlap binding mode in which cocaine- and dopamine-binding sites are the same (Beuming, T.; et al. Nat. Neurosci. 2008, 11, 780-789). The new cocaine-binding site does not overlap with, but is close to, the dopamine-binding site. Analysis of all results reveals that when cocaine binds to DAT, the initial binding site is likely the one modeled in this study because this binding site can naturally accommodate cocaine. Then cocaine may move to the dopamine-binding site after DAT makes some necessary conformational change and expands the binding site cavity. It has been demonstrated that cocaine may inhibit the transport of dopamine through both blocking the initial DAT-dopamine binding and reducing the kinetic turnover of the transporter following the DAT-dopamine binding. The relative contributions to the phenomenological inhibition of the transport of dopamine from blocking the initial binding and reducing the kinetic turnover can be different in different types of assays. The obtained general structural and mechanistic insights are consistent with available experimental data and could be valuable for guiding future studies toward understanding cocaine's inhibiting of other transporters.

  1. Coupled molecular and cantilever dynamics model for frequency-modulated atomic force microscopy.

    Science.gov (United States)

    Klocke, Michael; Wolf, Dietrich E

    2016-01-01

    A molecular dynamics model is presented, which adds harmonic potentials to the atomic interactions to mimic the elastic properties of an AFM cantilever. It gives new insight into the correlation between the experimentally monitored frequency shift and cantilever damping due to the interaction between tip atoms and scanned surface. Applying the model to ionic crystals with rock salt structure two damping mechanisms are investigated, which occur separately or simultaneously depending on the tip position. These mechanisms are adhesion hysteresis on the one hand and lateral excitations of the cantilever on the other. We find that the short range Lennard-Jones part of the atomic interaction alone is sufficient for changing the predominant mechanism. When the long range ionic interaction is switched off, the two damping mechanisms occur with a completely different pattern, which is explained by the energy landscape for the apex atom of the tip. In this case the adhesion hysteresis is always associated with a distinct lateral displacement of the tip. It is shown how this may lead to a systematic shift between the periodic patterns obtained from the frequency and from the damping signal, respectively.

  2. Coupled molecular and cantilever dynamics model for frequency-modulated atomic force microscopy

    Directory of Open Access Journals (Sweden)

    Michael Klocke

    2016-05-01

    Full Text Available A molecular dynamics model is presented, which adds harmonic potentials to the atomic interactions to mimic the elastic properties of an AFM cantilever. It gives new insight into the correlation between the experimentally monitored frequency shift and cantilever damping due to the interaction between tip atoms and scanned surface. Applying the model to ionic crystals with rock salt structure two damping mechanisms are investigated, which occur separately or simultaneously depending on the tip position. These mechanisms are adhesion hysteresis on the one hand and lateral excitations of the cantilever on the other. We find that the short range Lennard-Jones part of the atomic interaction alone is sufficient for changing the predominant mechanism. When the long range ionic interaction is switched off, the two damping mechanisms occur with a completely different pattern, which is explained by the energy landscape for the apex atom of the tip. In this case the adhesion hysteresis is always associated with a distinct lateral displacement of the tip. It is shown how this may lead to a systematic shift between the periodic patterns obtained from the frequency and from the damping signal, respectively.

  3. Atomistic modeling of metal surfaces under electric fields: direct coupling of electric fields to a molecular dynamics algorithm

    CERN Document Server

    Djurabekova, Flyura; Pohjonen, Aarne; Nordlund, Kai

    2011-01-01

    The effect of electric fields on metal surfaces is fairly well studied, resulting in numerous analytical models developed to understand the mechanisms of ionization of surface atoms observed at very high electric fields, as well as the general behavior of a metal surface in this condition. However, the derivation of analytical models does not include explicitly the structural properties of metals, missing the link between the instantaneous effects owing to the applied field and the consequent response observed in the metal surface as a result of an extended application of an electric field. In the present work, we have developed a concurrent electrodynamic–molecular dynamic model for the dynamical simulation of an electric-field effect and subsequent modification of a metal surface in the framework of an atomistic molecular dynamics (MD) approach. The partial charge induced on the surface atoms by the electric field is assessed by applying the classical Gauss law. The electric forces acting on the partially...

  4. Learning Probabilistic Models of Hydrogen Bond Stability from Molecular Dynamics Simulation Trajectories

    KAUST Repository

    Chikalov, Igor

    2011-04-02

    Hydrogen bonds (H-bonds) play a key role in both the formation and stabilization of protein structures. H-bonds involving atoms from residues that are close to each other in the main-chain sequence stabilize secondary structure elements. H-bonds between atoms from distant residues stabilize a protein’s tertiary structure. However, H-bonds greatly vary in stability. They form and break while a protein deforms. For instance, the transition of a protein from a nonfunctional to a functional state may require some H-bonds to break and others to form. The intrinsic strength of an individual H-bond has been studied from an energetic viewpoint, but energy alone may not be a very good predictor. Other local interactions may reinforce (or weaken) an H-bond. This paper describes inductive learning methods to train a protein-independent probabilistic model of H-bond stability from molecular dynamics (MD) simulation trajectories. The training data describes H-bond occurrences at successive times along these trajectories by the values of attributes called predictors. A trained model is constructed in the form of a regression tree in which each non-leaf node is a Boolean test (split) on a predictor. Each occurrence of an H-bond maps to a path in this tree from the root to a leaf node. Its predicted stability is associated with the leaf node. Experimental results demonstrate that such models can predict H-bond stability quite well. In particular, their performance is roughly 20% better than that of models based on H-bond energy alone. In addition, they can accurately identify a large fraction of the least stable H-bonds in a given conformation. The paper discusses several extensions that may yield further improvements.

  5. Interface between platinum(111) and liquid isopropanol (2-propanol): a model for molecular dynamics studies.

    Science.gov (United States)

    Tarmyshov, Konstantin B; Müller-Plathe, Florian

    2007-02-21

    A molecular dynamics model and its parametrization procedure are devised and used to study adsorption of isopropanol on platinum(111) (Pt(111)) surface in unsaturated and oversaturated coverages regimes. Static and dynamic properties of the interface between Pt(111) and liquid isopropanol are also investigated. The magnitude of the adsorption energy at unsaturated level increases at higher coverages. At the oversaturated coverage (multilayer adsorption) the adsorption energy reduces, which coincides with findings by Panja et al. in their temperature-programed desorption experiment [Surf. Sci. 395, 248 (1998)]. The density analysis showed a strong packing of molecules at the interface followed by a depletion layer and then by an oscillating density profile up to 3 nm. The distribution of individual atom types showed that the first adsorbed layer forms a hydrophobic methyl "brush." This brush then determines the distributions further from the surface. In the second layer methyl and methine groups are closer to the surface and followed by the hydroxyl groups; the third layer has exactly the inverted distribution. The alternating pattern extends up to about 2 nm from the surface. The orientational structure of molecules as a function of distance of molecules is determined by the atom distribution and surprisingly does not depend on the electrostatic or chemical interactions of isopropanol with the metal surface. However, possible formation of hydrogen bonds in the first layer is notably influenced by these interactions. The surface-adsorbate interactions influence the mobility of isopropanol molecules only in the first layer. Mobility in the higher layers is independent of these interactions.

  6. Programming an Interpreter Using Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    C.A. Middelburg

    2007-01-01

    Full Text Available PGA (ProGram Algebra is an algebra of programs which concerns programs in their simplest form: sequences of instructions. Molecular dynamics is a simple model of computation developed in the setting of PGA, which bears on the use of dynamic data structures in programming.We consider the programming of an interpreter for a program notation that is close to existing assembly languages using PGA with the primitives of molecular dynamics as basic instructions. It happens that, although primarily meant for explaining programming language features relating to the use of dynamic data structures, the collection of primitives of molecular dynamics in itself is suited to our programming wants.

  7. Isoscalar giant monopole resonance in Sn isotopes by Coulomb excitations using a quantum molecular dynamics model

    CERN Document Server

    Tao, C; Zhang, G Q; Cao, X G; Fang, D Q; Wang, H W; Xu, J

    2013-01-01

    The isoscalar giant monopole resonance (ISGMR) in Sn isotopes and other nuclei has been investigated by Coulomb excitations in the framework of the isospin-dependent quantum molecular dynamics (IQMD) model. The spectrum of GMR has been calculated by taking the root-mean-square (RMS) radius of a nucleus as its monopole moment. The peak energy, the full width at half maximum (FWHM), and the strength of GMR extracted by a Gaussian fit to the spectrum have been studied. The GMR peak energies for Sn isotopes from the calculations using a mass-number dependent Gaussian wave-packet width $\\sigma_r$ for nucleons are found to be overestimated and show a weak dependence on the mass number compared with the experimental data. However, it has been found that experimental data of the GMR peak energies for $^{40}$Ca, $^{56}$Ni, $^{90}$Zr and $^{208}$Pb as well as Sn isotopes can be nicely reproduced after taking into account the isospin dependence in isotope chains in addition to the mass number dependence of $\\sigma_r$ fo...

  8. Molecular dynamics study of water and water/chlorinated hydrocargon mixtures with polarizable potential models

    Energy Technology Data Exchange (ETDEWEB)

    Dang, L.X. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-12-31

    A series of molecular dynamics simulations were carried out to study water and water/chlorinated hydrocarbon mixtures. The properties of water clusters containing up to six water molecules were evaluated. A prism-like structure is predicted to be lowest in energy for the (H{sub 2}O){sub 6} cluster and a cage-like structure is the second lowest in energy with the energy about 0.2 kcal/mol higher than the prism-like structure. The computed dipole moments of water molecules in clusters indicated that there is a transition from cyclic planar configurations to three dimensional structure networks. The computed thermodynamic properties for the model including the liquid density, the enthalpy of vaporization, as well as the diffusion coefficient at room temperature, are in excellent agreement with experimental values. The computed density profile of the water of liquid/valor interface shows that the interface is not sharp at a microscopic level and has a thickness of 3.2 A at 298 K. The calculated surface tension at room temperature is in reasonably agreement with the corresponding experimental data. The computed average dipole moments of water molecules near the interface are close to their gas phase values. The thermodynamic and structural properties of water/chlorinated hydrocarbon mixtures as a function of mole fraction were evaluated.

  9. Modelling human behaviour in a bumper car ride using molecular dynamics tools: a student project

    Science.gov (United States)

    Buendía, Jorge J.; Lopez, Hector; Sanchis, Guillem; Pardo, Luis Carlos

    2017-05-01

    Amusement parks are excellent laboratories of physics, not only to check physical laws, but also to investigate if those physical laws might also be applied to human behaviour. A group of Physics Engineering students from Universitat Politècnica de Catalunya has investigated if human behaviour, when driving bumper cars, can be modelled using tools borrowed from the analysis of molecular dynamics simulations, such as the radial and angular distribution functions. After acquiring several clips and obtaining the coordinates of the cars, those magnitudes are computed and analysed. Additionally, an analogous hard disks system is simulated to compare its distribution functions to those obtained from the cars’ coordinates. Despite the clear difference between bumper cars and a hard disk-like particle system, the obtained distribution functions are very similar. This suggests that there is no important effect of the individuals in the collective behaviour of the system in terms of structure. The research, performed by the students, has been undertaken in the frame of a motivational project designed to approach the scientific method for university students named FISIDABO. This project offers both the logistical and technical support to undertake the experiments designed by students at the amusement park of Barcelona TIBIDABO and accompanies them all along the scientific process.

  10. Population reversal driven by unrestrained interactions in molecular dynamics simulations: A dialanine model

    Directory of Open Access Journals (Sweden)

    Filippo Pullara

    2015-10-01

    Full Text Available Standard Molecular Dynamics simulations (MD are usually performed under periodic boundary conditions using the well-established “Ewald summation”. This implies that the distance among each element in a given lattice cell and its corresponding element in another cell, as well as their relative orientations, are constant. Consequently, protein-protein interactions between proteins in different cells—important in many biological activities, such as protein cooperativity and physiological/pathological aggregation—are severely restricted, and features driven by protein-protein interactions are lost. The consequences of these restrictions, although conceptually understood and mentioned in the literature, have not been quantitatively studied before. The effect of protein-protein interactions on the free energy landscape of a model system, dialanine, is presented. This simple system features a free energy diagram with well-separated minima. It is found that, in the case of absence of peptide-peptide (p-p interactions, the ψ = 150° dihedral angle determines the most energetically favored conformation (global free-energy minimum. When strong p-p interactions are induced, the global minimum switches to the ψ = 0° conformation. This shows that the free-energy landscape of an individual molecule is dramatically affected by the presence of other freely interacting molecules of its same type. Results of the study suggest how taking into account p-p interactions in MD allows having a more realistic picture of system activity and functional conformations.

  11. A study of internal energy relaxation in shocks using molecular dynamics based models

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zheng, E-mail: zul107@psu.edu; Parsons, Neal, E-mail: neal.parsons@cd-adapco.com [Department of Aerospace Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802 (United States); Levin, Deborah A., E-mail: deblevin@illinois.edu [Department of Aerospace Engineering, University of Illinois Urbana-Champaign, Urbana, Illinois 61801-2935 (United States)

    2015-10-14

    Recent potential energy surfaces (PESs) for the N{sub 2} + N and N{sub 2} + N{sub 2} systems are used in molecular dynamics (MD) to simulate rates of vibrational and rotational relaxations for conditions that occur in hypersonic flows. For both chemical systems, it is found that the rotational relaxation number increases with the translational temperature and decreases as the rotational temperature approaches the translational temperature. The vibrational relaxation number is observed to decrease with translational temperature and approaches the rotational relaxation number in the high temperature region. The rotational and vibrational relaxation numbers are generally larger in the N{sub 2} + N{sub 2} system. MD-quasi-classical trajectory (QCT) with the PESs is also used to calculate the V-T transition cross sections, the collision cross section, and the dissociation cross section for each collision pair. Direct simulation Monte Carlo (DSMC) results for hypersonic flow over a blunt body with the total collision cross section from MD/QCT simulations, Larsen-Borgnakke with new relaxation numbers, and the N{sub 2} dissociation rate from MD/QCT show a profile with a decreased translational temperature and a rotational temperature close to vibrational temperature. The results demonstrate that many of the physical models employed in DSMC should be revised as fundamental potential energy surfaces suitable for high temperature conditions become available.

  12. Modeling Of Blood Vessel Constriction In 2-D Case Using Molecular Dynamics Method

    CERN Document Server

    Rendi, Mohamad; Viridi, Sparisoma

    2013-01-01

    Blood vessel constriction is simulated with particle-based method using a molecular dynamics authoring software known as Molecular Workbench (WM). Blood flow and vessel wall, the only components considered in constructing a blood vessel, are all represented in particle form with interaction potentials: Lennard-Jones potential, push-pull spring potential, and bending spring potential. Influence of medium or blood plasma is accommodated in plasma viscosity through Stokes drag force. It has been observed that pressure p is increased as constriction c is increased. Leakage of blood vessel starts at 80 % constriction, which shows existence of maximum pressure that can be overcome by vessel wall.

  13. Molecular dynamics of β-hairpin models of epigenetic recognition motifs.

    Science.gov (United States)

    Zheng, Xiange; Wu, Chuanjie; Ponder, Jay W; Marshall, Garland R

    2012-09-26

    The conformations and stabilities of the β-hairpin model peptides of Waters (Riemen, A. J.; Waters, M. L. Biochemistry 2009, 48, 1525; Hughes, R. M.; Benshoff, M. L.; Waters, M. L. Chemistry 2007, 13, 5753) have been experimentally characterized as a function of lysine ε-methylation. These models were developed to explore molecular recognition of known epigenetic recognition motifs. This system offered an opportunity to computationally examine the role of cation-π interactions, desolvation of the ε-methylated ammonium groups, and aromatic/aromatic interactions on the observed differences in NMR spectra. AMOEBA, a second-generation force field (Ponder, J. W.; Wu, C.; Ren, P.; Pande, V. S.; Chodera, J. D.; Schnieders, M. J.; Haque, I.; Mobley, D. L.; Lambrecht, D. S.; DiStasio, R. A., Jr.; Head-Gordon, M.; Clark, G. N.; Johnson, M. E.; Head-Gordon, T. J. Phys. Chem. B 2010, 114, 2549), was chosen as it includes both multipole electrostatics and polarizability thought to be essential to accurately characterize such interactions. Independent parametrization of ε-methylated amines was required from which aqueous solvation free energies were estimated and shown to agree with literature values. Molecular dynamics simulations (100 ns) using the derived parameters with model peptides, such as Ac-R-W-V-W-V-N-G-Orn-K(Me)(n)-I-L-Q-NH(2), where n = 0, 1, 2, or 3, were conducted in explicit solvent. Distances between the centers of the indole rings of the two-tryptophan residues, 2 and 4, and the ε-methylated ammonium group on Lys-9 as well as the distance between the N- and C-termini were monitored to estimate the strength and orientation of the cation-π and aromatic/aromatic interactions. In agreement with the experimental data, the stability of the β-hairpin increased significantly with lysine ε-methylation. The ability of MD simulations to reproduce the observed NOEs for the four peptides was further estimated for the monopole-based force fields, AMBER, CHARMM, and

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

    OpenAIRE

    Henry, Bryan R.; Gough, Kathleen M.

    1983-01-01

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

  15. Molecular Dynamics Calculations

    Science.gov (United States)

    1996-01-01

    The development of thermodynamics and statistical mechanics is very important in the history of physics, and it underlines the difficulty in dealing with systems involving many bodies, even if those bodies are identical. Macroscopic systems of atoms typically contain so many particles that it would be virtually impossible to follow the behavior of all of the particles involved. Therefore, the behavior of a complete system can only be described or predicted in statistical ways. Under a grant to the NASA Lewis Research Center, scientists at the Case Western Reserve University have been examining the use of modern computing techniques that may be able to investigate and find the behavior of complete systems that have a large number of particles by tracking each particle individually. This is the study of molecular dynamics. In contrast to Monte Carlo techniques, which incorporate uncertainty from the outset, molecular dynamics calculations are fully deterministic. Although it is still impossible to track, even on high-speed computers, each particle in a system of a trillion trillion particles, it has been found that such systems can be well simulated by calculating the trajectories of a few thousand particles. Modern computers and efficient computing strategies have been used to calculate the behavior of a few physical systems and are now being employed to study important problems such as supersonic flows in the laboratory and in space. In particular, an animated video (available in mpeg format--4.4 MB) was produced by Dr. M.J. Woo, now a National Research Council fellow at Lewis, and the G-VIS laboratory at Lewis. This video shows the behavior of supersonic shocks produced by pistons in enclosed cylinders by following exactly the behavior of thousands of particles. The major assumptions made were that the particles involved were hard spheres and that all collisions with the walls and with other particles were fully elastic. The animated video was voted one of two

  16. Molecular dynamics modelling of nanocarbon cluster properties under conditions close to HE detonation

    Directory of Open Access Journals (Sweden)

    Sapozhnikov F.A.

    2011-01-01

    Full Text Available We use molecular dynamics for modelling properties of carbon nanoclusters. The size of modelled carbon nanoclusters is below 5 nm, which is typical of detonation diamond nanoclusters. We have found their structural changes at P = 0 to be as follows: Diamond → Diamond core + GL-surface → sandwich-type graphite → Graphite-like liquid. In smaller clusters the transformations start at a lower temperature. Adaptive Template Analysis (ATA was used to determine the structures. We studied evaporation properties at temperatures above 5000 K. For clusters of several thousands of atoms, the simple dependence kvap ∼ e−T0/T/N1/3 (T0 is constant is quite good. It has been found out that densities of saturated vapour for clusters containing from 4000 to 8000 atoms are very close at T = 5000 K. The structure of nanoclusters was studied at nonzero pressures set by an argon environment. Calculated results suggest that the patterns for different temperatures are qualitatively similar for three pressures under study (20, 25 and 30 GPa. At T = 1000–1500 K, the initial diamond core is preserved and a thin disordered GL layer is present on the surface. At T = 2000–5000 K, graphite grains form in the sample and a thin layer of liquid is present on its surface. The sample is amorphous at 5500 K and 6000 K. The prevalence of the graphite phase at these pressures seems to come from the absence of long-range interaction in REBO-2002.

  17. High-Performance Modeling of Carbon Dioxide Sequestration by Coupling Reservoir Simulation and Molecular Dynamics

    KAUST Repository

    Bao, Kai

    2015-10-26

    The present work describes a parallel computational framework for carbon dioxide (CO2) sequestration simulation by coupling reservoir simulation and molecular dynamics (MD) on massively parallel high-performance-computing (HPC) systems. In this framework, a parallel reservoir simulator, reservoir-simulation toolbox (RST), solves the flow and transport equations that describe the subsurface flow behavior, whereas the MD simulations are performed to provide the required physical parameters. Technologies from several different fields are used to make this novel coupled system work efficiently. One of the major applications of the framework is the modeling of large-scale CO2 sequestration for long-term storage in subsurface geological formations, such as depleted oil and gas reservoirs and deep saline aquifers, which has been proposed as one of the few attractive and practical solutions to reduce CO2 emissions and address the global-warming threat. Fine grids and accurate prediction of the properties of fluid mixtures under geological conditions are essential for accurate simulations. In this work, CO2 sequestration is presented as a first example for coupling reservoir simulation and MD, although the framework can be extended naturally to the full multiphase multicomponent compositional flow simulation to handle more complicated physical processes in the future. Accuracy and scalability analysis are performed on an IBM BlueGene/P and on an IBM BlueGene/Q, the latest IBM supercomputer. Results show good accuracy of our MD simulations compared with published data, and good scalability is observed with the massively parallel HPC systems. The performance and capacity of the proposed framework are well-demonstrated with several experiments with hundreds of millions to one billion cells. To the best of our knowledge, the present work represents the first attempt to couple reservoir simulation and molecular simulation for large-scale modeling. Because of the complexity of

  18. Molecular dynamics simulation of phase and structural transitions in model lung surfactant mixtures

    Science.gov (United States)

    Duncan, Susan L.

    Lung surfactant (LS) is a complex mixture of lipids and proteins that reduces and regulates the surface tension in the lungs, thereby decreasing the work of breathing. A thorough understanding of LS function is critical to the development and optimization of synthetic surfactants for the treatment of neonatal and adult respiratory distress syndrome. We have utilized coarse-grained (CG) molecular dynamics simulation to study the dynamic, hysteretic changes occurring in the structure and phase of model surfactant mixtures with varying temperature, pressure and composition. In particular, we have studied the effects of the LS components palmitoyloleoylphosphatidylglycerol (POPG), palmitoyloleoylphosphatidylcholine (POPC), palmitic acid (PA), cholesterol, and two surface-active proteins SP-B 1--25 (the 25-residue N-terminal fragment of SP-B), and SP-C on model surfactant monolayers containing the primary lipid component dipalmitoylphosphatidylcholine (DPPC). The results indicate that POPG, POPC, SP-B1--25 and SP-C act as fluidizers and PA and cholesterol act as condensing agents, which change the phase-transition temperature, LC-LE phase distribution, and the extent of hysteresis. To explore the role of LS proteins SP-B and SP-C in storing and redelivering lipid from lipid monolayers during the compression and re-expansion occurring in lungs during breathing, we have simulated 2D-to-3D transitions at the interface. These simulations show that at near-zero surface tension the presence of a fluidizing agent, such as POPG, SP-C, or SP-B 1--25 decreases the monolayers resistance to bending allowing the monolayers to form large undulations and ultimately folds. Another folding mechanism is also observed in monolayers containing peptides, involving the lipid-mediated aggregation of the peptides into a defect, from which the fold can nucleate. The occurrence of folding depends on the hydrophobic character of the peptides; if the number of hydrophobic residues is decreased

  19. 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.

  20. Dynamics of biological water: insights from molecular modeling of light scattering in aqueous trehalose solutions.

    Science.gov (United States)

    Lupi, Laura; Comez, Lucia; Paolantoni, Marco; Fioretto, Daniele; Ladanyi, Branka M

    2012-06-28

    Extended depolarized light scattering (EDLS) measurements have been recently employed to investigate the dynamics of water solvating biological molecules, giving evidence of the presence of two different dynamical regimes among water molecules. An interpretation of EDLS has been proposed that provides an independent estimate of the retardation factor of slowdown with respect to fast water molecules and of the number of solvent molecules affected by this slowing down. Nevertheless this measure is an inherently complex one, due to the collective nature of the physical property probed. In the present work a molecular dynamics (MD) approach has been used to more deeply understand experimental results. Time correlation functions of the collective polarizability anisotropy have been calculated for the prototype disaccharide trehalose in aqueous solutions as a function of concentration. The unique capability of MD to disentangle the contributions to the dynamics arising from solute, solvent, and cross terms between the two allowed us to check the reliability of an interpretation that assumes a spectral separation of water and sugar dynamics, as well as to highlight the very presence of two distinct relaxation processes in water. The two processes have been attributed to the dynamics of bulk and hydration water, respectively. A retardation factor of ~5 and concentration dependent hydration numbers have been observed, in good agreement with experimental results [Paolantoni, M.; et al. J. Phys. Chem. B 2009, 113, 7874-7878].

  1. Multiscale Reactive Molecular Dynamics

    Science.gov (United States)

    2012-08-15

    as a linear combination of several possible bond- ing topologies ( diabatic states) that are coupled to one an- other through the off-diagonal elements...adapts and dynamically identifies bonding topolo- gies to include as the simulation progresses. These bonding topologies form a basis of diabatic ...the original geometric factor. The diabatic correction term, VCORR , used here was labeled in previous MS-EVB models as a repulsive interaction, VREP

  2. Molecular Dynamics and Protein Function

    National Research Council Canada - National Science Library

    M. Karplus; J. Kuriyan; Bruce J. Berne

    2005-01-01

    .... Molecular dynamics simulations provide powerful tools for the exploration of the conformational energy landscape accessible to these molecules, and the rapid increase in computational power coupled...

  3. Molecular Mechanisms of ZnO Nanoparticle Dispersion in Solution: Modeling of Surfactant Association, Electrostatic Shielding and Counter Ion Dynamics.

    Directory of Open Access Journals (Sweden)

    Patrick Duchstein

    Full Text Available Molecular models of 5 nm sized ZnO/Zn(OH2 core-shell nanoparticles in ethanolic solution were derived as scale-up models (based on an earlier model created from ion-by-ion aggregation and self-organization and subjected to mechanistic analyses of surface stabilization by block-copolymers. The latter comprise a poly-methacrylate chain accounting for strong surfactant association to the nanoparticle by hydrogen bonding and salt-bridges. While dangling poly-ethylene oxide chains provide only a limited degree of sterical hindering to nanoparticle agglomeration, the key mechanism of surface stabilization is electrostatic shielding arising from the acrylates and a halo of Na+ counter ions associated to the nanoparticle. Molecular dynamics simulations reveal different solvent shells and distance-dependent mobility of ions and solvent molecules. From this, we provide a molecular rationale of effective particle size, net charge and polarizability of the nanoparticles in solution.

  4. Molecular dynamics modeling of carbon dioxide, water and natural organic matter in Na-hectorite.

    Science.gov (United States)

    Yazaydin, A Ozgur; Bowers, Geoffrey M; Kirkpatrick, R James

    2015-09-28

    Molecular dynamics (MD) modeling of systems containing a Na-exchanged smectite clay (hectorite) and model natural organic matter (NOM) molecules along with pure H2O, pure CO2, or a mixture of H2O and CO2 provides significant new insight into the molecular scale interactions among silicate surfaces, dissolved cations and organic molecules, H2O and CO2 relevant to geological C-sequestration strategies. The simulations for systems containing H2O show the following results; (1) Na(+) does not bridge between NOM molecules and the clay surface at protonation states comparable to near neutral pH conditions. (2) In systems without CO2 the NOM molecules retain charge balancing cations and drift away from the silicate surface. (3) In systems containing both H2O and CO2, the NOM molecules adopt equilibrium positions at the H2O-CO2 interface with the more hydrophilic structural elements facing the H2O and the more hydrophobic ones facing the CO2. In systems with only CO2, NOM and Na(+) ions are pinned to the clay surface with the hydrophilic structural elements of the NOM pointed toward the clay surface. Dynamically, in systems with only CO2, Na(+) diffusion is nearly eliminated, and in systems with a thin water film on the clay surface diffusion perpendicular the surface is greatly reduced relative to the system with bulk water. Energetically, the results for the systems with only H2O show that hydration of the net charge neutral Na-NOM molecule outweighs the sum of its Coulombic and dispersive interactions with the net charge-neutral Na-clay particle and the interactions of the water molecules with the hydrophobic structural elements of the NOM. The aggregation of NOM molecules in solution appears to be driven not by Na(+) bridging between the molecules but by hydrophobic interactions between them. In contrast, for the systems with only CO2 the interaction between the Na-NOM molecules and the CO2 is outweighed by the interaction of NOM with the clay particle. With both H2O

  5. Programming an interpreter using molecular dynamics

    OpenAIRE

    2008-01-01

    PGA (ProGram Algebra) is an algebra of programs which concerns programs in their simplest form: sequences of instructions. Molecular dynamics is a simple model of computation developed in the setting of \\PGA, which bears on the use of dynamic data structures in programming. We consider the programming of an interpreter for a program notation that is close to existing assembly languages using PGA with the primitives of molecular dynamics as basic instructions. It happens that, although primari...

  6. Programming an Interpreter Using Molecular Dynamics

    OpenAIRE

    2007-01-01

    PGA (ProGram Algebra) is an algebra of programs which concerns programs in their simplest form: sequences of instructions. Molecular dynamics is a simple model of computation developed in the setting of PGA, which bears on the use of dynamic data structures in programming.We consider the programming of an interpreter for a program notation that is close to existing assembly languages using PGA with the primitives of molecular dynamics as basic instructions. It happens that, although primarily...

  7. A molecular-dynamics simulation study of diffusion of a single model carbonic chain on a graphite (001) surface.

    Science.gov (United States)

    Yang, Hua; Lu, Zhong-Yuan; Li, Ze-Sheng; Sun, Chia-Chung

    2006-03-01

    Molecular-dynamics simulations have been used to study the diffusion of a short single model carbonic chain on the graphite (001) surface. The calculated diffusion coefficient (D) first increases, then decreases with increasing chain length (N). This abnormal behavior is similar to polymer lateral diffusion at the solid-liquid interface. Furthermore, we have studied the relation between the mean-square gyration radius and N. [Figure: see text].

  8. 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...

  9. Mimicking the action of folding chaperones by Hamiltonian replica-exchange molecular dynamics simulations : Application in the refinement of de novo models

    NARCIS (Netherlands)

    Fan, Hao; Periole, Xavier; Mark, Alan E.

    2012-01-01

    The efficiency of using a variant of Hamiltonian replica-exchange molecular dynamics (Chaperone H-replica-exchange molecular dynamics [CH-REMD]) for the refinement of protein structural models generated de novo is investigated. In CH-REMD, the interaction between the protein and its environment, spe

  10. Quasi-classical model of dynamic molecular structure and non-destructive wavepacket manipulation by ultrashort laser pulses

    CERN Document Server

    Bryan, W A; King, R B; Nemeth, G R A J; Greenwood, J B; Williams, I D; Newell, W R

    2010-01-01

    A quasi-classical model (QCM) of molecular dynamics in intense femtosecond laser fields has been developed, and applied to a study of the effect of an ultrashort `control' pulse on the vibrational motion of a deuterium molecular ion in its ground electronic state. A nonadiabatic treatment accounts for the initial ionization-induced vibrational population caused by an ultrashort `pump' pulse. In the QCM, the nuclei move classically on the molecular potential as it is distorted by the laser-induced Stark shift and transition dipole. The nuclei then adjust to the modified potential, non-destructively shifting the vibrational population and relative phase. This shift has been studied as a function of control pulse parameters. Excellent agreement is observed with predictions of time-dependent quantum simulations, lending confidence to the validity of the model and permitting new observations to be made. The applicability of the QCM to more complex multi-potential energy surface molecules (where a quantum treatment...

  11. Molecular dynamics study of ion capture from water by a model ionophore, tetraprotonated cryptand SC24

    Science.gov (United States)

    Owenson, Brian; Macelroy, Robert D.; Pohorille, Andrew

    1988-01-01

    The molecular dynamics of chloride capture from water by the tetraprotonated cryptand SC24 has been studied for the cases of 19 distances between the criptand and the chloride. The chloride capture is found to be characterized by a rapid cooperative change in the conformation of the cryptand when the Cl(-) begins to enter the ligand and just as it encounters the energy barrier. The conformational transition is associated with a shift of three N-H bonds from the pure endo orientation, such that they point toward the chloride.

  12. Multiscale Modeling using Molecular Dynamics and Dual Domain Material Point Method

    Energy Technology Data Exchange (ETDEWEB)

    Dhakal, Tilak Raj [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division. Fluid Dynamics and Solid Mechanics Group, T-3; Rice Univ., Houston, TX (United States)

    2016-07-07

    For problems involving large material deformation rate, the material deformation time scale can be shorter than the material takes to reach a thermodynamical equilibrium. For such problems, it is difficult to obtain a constitutive relation. History dependency become important because of thermodynamic non-equilibrium. Our goal is to build a multi-scale numerical method which can bypass the need for a constitutive relation. In conclusion, multi-scale simulation method is developed based on the dual domain material point (DDMP). Molecular dynamics (MD) simulation is performed to calculate stress. Since the communication among material points is not necessary, the computation can be done embarrassingly parallel in CPU-GPU platform.

  13. Molecular dynamics study of ion capture from water by a model ionophore, tetraprotonated cryptand SC24

    Science.gov (United States)

    Owenson, Brian; Macelroy, Robert D.; Pohorille, Andrew

    1988-01-01

    The molecular dynamics of chloride capture from water by the tetraprotonated cryptand SC24 has been studied for the cases of 19 distances between the criptand and the chloride. The chloride capture is found to be characterized by a rapid cooperative change in the conformation of the cryptand when the Cl(-) begins to enter the ligand and just as it encounters the energy barrier. The conformational transition is associated with a shift of three N-H bonds from the pure endo orientation, such that they point toward the chloride.

  14. Molecular Dynamics of Lipid Bilayers

    Science.gov (United States)

    1989-08-09

    The aim of this work is to study, by molecular dynamics simulations, the properties of lipid bilayers. We have applied the vectorizable, order-N...fast angle-dependent force/potential algorithms to treat angle bending and torsion. Keywords: Molecular dynamics , Lipid bilayers.

  15. 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...

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

    Directory of Open Access Journals (Sweden)

    T. Hede

    2011-07-01

    Full Text Available Cloud condensation nuclei act as cores for water vapour condensation, and their composition and chemical properties may enhance or depress the ability for droplet growth. 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. The model HULIS compounds investigated in this study are cis-pinonic acid (CPA, pinic acid (PAD and pinonaldehyde (PAL. The structural properties examined show the ability for the model HULIS compounds to aggregate inside the nanoaerosol clusters.

  17. MDplot: Visualise Molecular Dynamics.

    Science.gov (United States)

    Margreitter, Christian; Oostenbrink, Chris

    2017-05-10

    The MDplot package provides plotting functions to allow for automated visualisation of molecular dynamics simulation output. It is especially useful in cases where the plot generation is rather tedious due to complex file formats or when a large number of plots are generated. The graphs that are supported range from those which are standard, such as RMsD/RMsF (root-mean-square deviation and root-mean-square fluctuation, respectively) to less standard, such as thermodynamic integration analysis and hydrogen bond monitoring over time. All told, they address many commonly used analyses. In this article, we set out the MDplot package's functions, give examples of the function calls, and show the associated plots. Plotting and data parsing is separated in all cases, i.e. the respective functions can be used independently. Thus, data manipulation and the integration of additional file formats is fairly easy. Currently, the loading functions support GROMOS, GROMACS, and AMBER file formats. Moreover, we also provide a Bash interface that allows simple embedding of MDplot into Bash scripts as the final analysis step. The package can be obtained in the latest major version from CRAN (https://cran.r-project.org/package=MDplot) or in the most recent version from the project's GitHub page at https://github.com/MDplot/MDplot, where feedback is also most welcome. MDplot is published under the GPL-3 license.

  18. The structure of PX{sub 3} (X = Cl, Br, I) molecular liquids from X-ray diffraction, molecular dynamics simulations, and reverse Monte Carlo modeling

    Energy Technology Data Exchange (ETDEWEB)

    Pothoczki, Szilvia, E-mail: pothoczki.szilvia@wigner.mta.hu; Temleitner, László; Pusztai, László [Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, Hungarian Academy of Sciences, Konkoly-Thege M. út 29-33, 1121 Budapest (Hungary)

    2014-02-07

    Synchrotron X-ray diffraction measurements have been conducted on liquid phosphorus trichloride, tribromide, and triiodide. Molecular Dynamics simulations for these molecular liquids were performed with a dual purpose: (1) to establish whether existing intermolecular potential functions can provide a picture that is consistent with diffraction data and (2) to generate reliable starting configurations for subsequent Reverse Monte Carlo modelling. Structural models (i.e., sets of coordinates of thousands of atoms) that were fully consistent with experimental diffraction information, within errors, have been prepared by means of the Reverse Monte Carlo method. Comparison with reference systems, generated by hard sphere-like Monte Carlo simulations, was also carried out to demonstrate the extent to which simple space filling effects determine the structure of the liquids (and thus, also estimating the information content of measured data). Total scattering structure factors, partial radial distribution functions and orientational correlations as a function of distances between the molecular centres have been calculated from the models. In general, more or less antiparallel arrangements of the primary molecular axes that are found to be the most favourable orientation of two neighbouring molecules. In liquid PBr{sub 3} electrostatic interactions seem to play a more important role in determining intermolecular correlations than in the other two liquids; molecular arrangements in both PCl{sub 3} and PI{sub 3} are largely driven by steric effects.

  19. Perovskite Quantum Dots Modeled Using ab Initio and Replica Exchange Molecular Dynamics

    KAUST Repository

    Buin, Andrei

    2015-06-18

    © 2015 American Chemical Society. Organometal halide perovskites have recently attracted tremendous attention at both the experimental and theoretical levels. Much of this work has been dedicated to bulk material studies, yet recent experimental work has shown the formation of highly efficient quantum-confined nanocrystals with tunable band edges. Here we investigate perovskite quantum dots from theory, predicting an upper bound of the Bohr radius of 45 Å that agrees well with literature values. When the quantum dots are stoichiometric, they are trap-free and have nearly symmetric contributions to confinement from the valence and conduction bands. We further show that surface-associated conduction bandedge states in perovskite nanocrystals lie below the bulk states, which could explain the difference in Urbach tails between mesoporous and planar perovskite films. In addition to conventional molecular dynamics (MD), we implement an enhanced phase-space sampling algorithm, replica exchange molecular dynamics (REMD). We find that in simulation of methylammonium orientation and global minima, REMD outperforms conventional MD. To the best of our knowledge, this is the first REMD implementation for realistic-sized systems in the realm of DFT calculations.

  20. Modeling reactive scattering of F(2P) at a liquid squalane interface: a hybrid QM/MM molecular dynamics study.

    Science.gov (United States)

    Radak, Brian K; Yockel, Scott; Kim, Dongwook; Schatz, George C

    2009-07-01

    To better understand the reactivity of gases with liquid surfaces, experimentalists have recently probed the reactive scattering of atomic fluorine at the surface of liquid squalane (C(30)H(62)). In this paper we further this research by simulating this scattering process at collision energies of 0.5 and 1.0 eV using a hybrid QM/MM molecular dynamics scheme. To model the structure of the liquid surface, classical molecular dynamics calculations were performed utilizing the OPLS-AA force field. During the F + squalane molecular dynamics simulation, QM/MM calculations are performed at every trajectory step by combining the MSINDO semiempirical Hamiltonian with OPLS-AA and using a dynamic partitioning of the atoms in the QM or MM regions via a "seed atom" method. This computational model provides a type of "on-the-fly" direct dynamics applicable to larger scale chemical processes that include the making/breaking of chemical bonds not available in standard force field models. Our results show that H abstraction is the only reactive scattering pathway and that most trajectories result in reactive scattering. Reaction statistics at the squalane surface are discussed, including variation of the results with incident angle and collision energy, and the probability of reaction as a function of carbon atom type, collision depth, and residence time. Product states, including angular distributions and final translational and rovibrational energies, are also considered and found to be significantly affected by the exothermic reaction energy for H abstraction. The vibrational distributions are in good agreement with recent experiments, but the rotational distributions are dominated by a nonthermal component while the experiments, which involve thermal incident energies, show comparable thermal and nonthermal contributions. Results for O + squalane at 1.0 eV, which we also present, show analogous comparisons with experiment, with OH vibrational distributions which are cold and

  1. Modeling of annexin A2-Membrane interactions by molecular dynamics simulations.

    Science.gov (United States)

    Hakobyan, Davit; Gerke, Volker; Heuer, Andreas

    2017-01-01

    The annexins are a family of Ca2+-regulated phospholipid binding proteins that are involved in membrane domain organization and membrane trafficking. Although they are widely studied and crystal structures are available for several soluble annexins their mode of membrane association has never been studied at the molecular level. Here we obtained molecular information on the annexin-membrane interaction that could serve as paradigm for the peripheral membrane association of cytosolic proteins by Molecular Dynamics simulations. We analyzed systems containing the monomeric annexin A2 (AnxA2), a membrane with negatively charged phosphatidylserine (POPS) lipids as well as Ca2+ ions. On the atomic level we identify the AnxA2 orientations and the respective residues which display the strongest interaction with Ca2+ ions and the membrane. The simulation results fully agree with earlier experimental findings concerning the positioning of bound Ca2+ ions. Furthermore, we identify for the first time a significant interaction between lysine residues of the protein and POPS lipids that occurs independently of Ca2+ suggesting that AnxA2-membrane interactions can also occur in a low Ca2+ environment. Finally, by varying Ca2+ concentrations and lipid composition in our simulations we observe a calcium-induced negative curvature of the membrane as well as an AnxA2-induced lipid ordering.

  2. Molecular modeling studies of [6,6,5] Tricyclic Fused Oxazolidinones as FXa inhibitors using 3D-QSAR, Topomer CoMFA, molecular docking and molecular dynamics simulations.

    Science.gov (United States)

    Xu, Cheng; Ren, Yujie

    2015-10-15

    Coagulation factor Xa (Factor Xa, FXa) is a particularly promising target for novel anticoagulant therapy. The first oral factor Xa inhibitor has been approved in the EU and Canada in 2008. In this work, 38 [6,6,5] Tricyclic Fused Oxazolidinones were studied using a combination of molecular modeling techniques including three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, molecular dynamics and Topomer CoMFA (comparative molecular field analysis) were used to build 3D-QSAR models. The results show that the best CoMFA model has q(2)=0.511 and r(2)=0.984, the best CoMSIA (comparative molecular similarity indices analysis) model has q(2)=0.700 and r(2)=0.993 and the Topomer CoMFA analysis has q(2)=0.377 and r(2)=0.886. The results indicated the steric, hydrophobic, H-acceptor and electrostatic fields play key roles in models. Molecular docking and molecular dynamics explored the binding relationship of the ligand and the receptor protein.

  3. 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.

  4. A hydrated ion model of [UO2] 2 + in water: Structure, dynamics, and spectroscopy from classical molecular dynamics

    Science.gov (United States)

    Pérez-Conesa, Sergio; Torrico, Francisco; Martínez, José M.; Pappalardo, Rafael R.; Sánchez Marcos, Enrique

    2016-12-01

    A new ab initio interaction potential based on the hydrated ion concept has been developed to obtain the structure, energetics, and dynamics of the hydration of uranyl in aqueous solution. It is the first force field that explicitly parameterizes the interaction of the uranyl hydrate with bulk water molecules to accurately define the second-shell behavior. The [UO2(H2O)5 ] 2 + presents a first hydration shell U-O average distance of 2.46 Å and a second hydration shell peak at 4.61 Å corresponding to 22 molecules using a coordination number definition based on a multisite solute cavity. The second shell solvent molecules have longer mean residence times than those corresponding to the divalent monatomic cations. The axial regions are relatively de-populated, lacking direct hydrogen bonding to apical oxygens. Angle-solved radial distribution functions as well as the spatial distribution functions show a strong anisotropy in the ion hydration. The [UO2(H2O)5 ] 2 + solvent structure may be regarded as a combination of a conventional second hydration shell in the equatorial and bridge regions, and a clathrate-like low density region in the axial region. Translational diffusion coefficient, hydration enthalpy, power spectra of the main vibrational modes, and the EXAFS spectrum simulated from molecular dynamics trajectories agree fairly well with the experiment.

  5. Modeling of tensile testing on perfect and defective graphenylene nanotubes using molecular dynamics simulations

    Science.gov (United States)

    Rouhi, Saeed

    2017-08-01

    Molecular dynamics simulations are employed here to study the mechanical properties of graphenylene nanotubes (NTs). The effects of different geometrical parameters, such as NT length and diameter, on the behavior of graphenylene NTs under tensile testing are investigated. Moreover, the tensile test is simulated at several temperatures, to obtain the stress-strain curves of both armchair and zigzag graphenylene NTs. It is shown that graphenylene NTs with larger diameter possess larger elastic moduli. The elastic modulus of graphenylene NTs is about one half that of carbon NTs. However, the maximum tolerable stress and strain of the graphenylene NTs decreases with increasing NT diameter. Investigating the effect of vacancy defects on the elastic properties of the graphenylene NTs, it is shown that Young’s modulus of armchair and zigzag graphenylene NTs decreases nonlinearly with increasing defect percentages.

  6. Explicit solvent model for spectral shift of acrolein and simulation with molecular dynamics

    Institute of Scientific and Technical Information of China (English)

    ZHU Quan; LIU Jifeng; FU Kexiang; HAN Keli; LI Xiangyuan

    2006-01-01

    By introducing the concept of spring energy of permanent dipole and taking the conformations of solvent molecules into account, the formulas of electrostatic solvation energy in equilibrium and nonequilibrium are derived from the explicit solvent scheme, with the spatial distribution of the discrete permanent charges and induced dipoles of the solvent molecules involved. The energy change of solute due to the variation of wave function from the case of vacuum to that in solution is estimated by treating the solvent effect as external field in the iteration cycles of the self-consistent field. The expression for spectral shift is deduced and applied to the processes of light absorption and emission in solution. According to the new formulations, the averaged solvent electrostatic potential/molecular dynamics program is modified and adopted to investigate the equilibrium solvation energy of water molecule and spectral shift of acrolein.

  7. Molecular modeling study of CP-690550 derivatives as JAK3 kinase inhibitors through combined 3D-QSAR, molecular docking, and dynamics simulation techniques.

    Science.gov (United States)

    Wang, Jing Li; Cheng, Li Ping; Wang, Tian Chi; Deng, Wei; Wu, Fan Hong

    2017-03-01

    To develop more potent JAK3 kinase inhibitors, a series of CP-690550 derivatives were investigated using combined molecular modeling techniques, such as 3D-QSAR, molecular docking and molecular dynamics (MD). The leave-one-out correlation (q(2)) and non-cross-validated correlation coefficient (r(2)) of the best CoMFA model are 0.715 and 0.992, respectively. The q(2) and r(2) values of the best CoMSIA model are 0.739 and 0.995, respectively. The steric, electrostatic, and hydrophobic fields played important roles in determining the inhibitory activity of CP-690550 derivatives. Some new JAK3 kinase inhibitors were designed. Some of them have better inhibitory activity than the most potent Tofacitinib (CP-690550). Molecular docking was used to identify some key amino acid residues at the active site of JAK3 protein. 10ns MD simulations were successfully performed to confirm the detailed binding mode and validate the rationality of docking results. The calculation of the binding free energies by MMPBSA method gives a good correlation with the predicted biological activity. To our knowledge, this is the first report on MD simulations and free energy calculations for this series of compounds. The combination results of this study will be valuable for the development of potent and novel JAK3 kinase inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Molecular Modeling and Dynamic Simulation of Arabidopsis Thaliana Carotenoid Cleavage Dioxygenase Gene: A Comparison with Bixa orellana and Crocus Sativus.

    Science.gov (United States)

    Priya, R; Sneha, P; Rivera Madrid, Renata; Doss, C George Priya; Singh, Pooja; Siva, Ramamoorthy

    2017-09-01

    Carotenoid cleavage dioxygenase (CCD) gene, ubiquitously found in numerous types of plants, are eminent in synthesizing the various volatile compounds (β-ionone, C13 -norisoprenoid, geranylacetone) known as apocarotenoids. These apocarotenoids have various biological functions such as volatile signals, allelopathic interaction and plant defense. In Arabidopsis genome sequence, four potential CCD genes have been identified namely CCD1, CCD4, CCD7, and CCD8. These four genes give rise to diverse biological functions with almost similar sequence identity. In this investigation, an in silico analysis was proposed to study CCD proteins in Arabidopsis thaliana, aiming at constructing three-dimensional (3D) structure for CCD1 proteins of Bixa orellana and Crocus sativus to observe the structural difference among AtCCD (A. thaliana CCD) proteins. The quality of modeled structures was evaluated using RAMPAGE, PSVS protein validation server and Q Mean server. Finally, we utilised molecular dynamics simulation to identify the stability of the predicted CCD protein structures. The molecular dynamic simulation also revealed that AtCCD4 protein showed lesser stability when compared to other CCD proteins. Overall results from molecular dynamics analysis predicted that BoCCD1, CsCCD1, and AtCCD1 show similar structural characteristics. J. Cell. Biochem. 118: 2712-2721, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Molecular dynamic modeling of CYP51B in complex with azole inhibitors.

    Science.gov (United States)

    Gao, Pan; Cui, Ying-Lu; Wu, Rong-Ling

    2017-05-28

    Cytochrome P450 14α-sterol demethylase (CYP51), the key enzyme in sterol biosynthesis pathway, is an important target protein of cholesterol-lowering agents, antifungal drugs, and herbicides. CYP51B enzyme is one of the CYP51 family members. In the present study, we have chosen four representative inhibitors of CYP51B: diniconazole (Din), fluconazole (Flu), tebuconazole (Teb), and voriconazole (Vor), and launched to investigate the binding features of CYP51B-inhibitor and gating characteristics via molecular docking and molecular dynamics (MD) simulations. The results show that the ranking of binding affinities among these inhibitors is Din > Teb > Vor > Flu. Din shows the strongest binding affinity, whereas Flu shows the weakest binding affinity. More importantly, based on the calculated binding free energy results, we hypothesize that the nonpolar interactions are the most important contributors, and three key residues (Thr77, Ala258, and Lys454) play crucial role in protein-inhibitor binding. Besides, residue Phe180 may play a molecular switch role in the process of the CYP51B-Teb and CYP51B-Vor binding. Additionally, Tunnel analysis results show that the major tunnel of Din, Flu, and Teb is located between helix K, FG loop, and β4 hairpin (Tunnel II).The top ranked possible tunnel (Tunnel II) corresponds to Vor exits through helix K, F and helix J. This study further revealed the CYP51B relevant structural characteristics at the atomic level as well as provided a basis for rational design of new and more efficacious antifungal agents.

  10. Molecular dynamics studies of entangled polymer chains

    NARCIS (Netherlands)

    Bulacu, Monica Iulia

    2008-01-01

    The thesis presents three molecular dynamics studies of polymeric ensembles in which the chain entanglement plays the major role in the internal dynamics of the system. A coarse-grained model is used for representing the polymer chains as strings of beads connected by finite-extensible springs. In a

  11. A thread calculus with molecular dynamics

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2010-01-01

    We present a theory of threads, interleaving of threads, and interaction between threads and services with features of molecular dynamics, a model of computation that bears on computations in which dynamic data structures are involved. Threads can interact with services of which the states consist o

  12. Programming an interpreter using molecular dynamics

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2007-01-01

    PGA (ProGram Algebra) is an algebra of programs which concerns programs in their simplest form: sequences of instructions. Molecular dynamics is a simple model of computation developed in the setting of \\PGA, which bears on the use of dynamic data structures in programming. We consider the programmi

  13. Programming an interpreter using molecular dynamics

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2007-01-01

    PGA (ProGram Algebra) is an algebra of programs which concerns programs in their simplest form: sequences of instructions. Molecular dynamics is a simple model of computation developed in the setting of \\PGA, which bears on the use of dynamic data structures in programming. We consider the

  14. Molecular modeling-driven approach for identification of Janus kinase 1 inhibitors through 3D-QSAR, docking and molecular dynamics simulations.

    Science.gov (United States)

    Itteboina, Ramesh; Ballu, Srilata; Sivan, Sree Kanth; Manga, Vijjulatha

    2017-10-01

    Janus kinase 1 (JAK 1) belongs to the JAK family of intracellular nonreceptor tyrosine kinase. JAK-signal transducer and activator of transcription (JAK-STAT) pathway mediate signaling by cytokines, which control survival, proliferation and differentiation of a variety of cells. Three-dimensional quantitative structure activity relationship (3 D-QSAR), molecular docking and molecular dynamics (MD) methods was carried out on a dataset of Janus kinase 1(JAK 1) inhibitors. Ligands were constructed and docked into the active site of protein using GLIDE 5.6. Best docked poses were selected after analysis for further 3 D-QSAR analysis using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodology. Employing 60 molecules in the training set, 3 D-QSAR models were generate that showed good statistical reliability, which is clearly observed in terms of r(2)ncv and q(2)loo values. The predictive ability of these models was determined using a test set of 25 molecules that gave acceptable predictive correlation (r(2)Pred) values. The key amino acid residues were identified by means of molecular docking, and the stability and rationality of the derived molecular conformations were also validated by MD simulation. The good consonance between the docking results and CoMFA/CoMSIA contour maps provides helpful clues about the reasonable modification of molecules in order to design more efficient JAK 1 inhibitors. The developed models are expected to provide some directives for further synthesis of highly effective JAK 1 inhibitors.

  15. Analysis of proton-induced fragment production cross sections by the Quantum Molecular Dynamics plus Statistical Decay Model

    Energy Technology Data Exchange (ETDEWEB)

    Chiba, Satoshi; Iwamoto, Osamu; Fukahori, Tokio; Niita, Koji; Maruyama, Toshiki; Maruyama, Tomoyuki; Iwamoto, Akira [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-03-01

    The production cross sections of various fragments from proton-induced reactions on {sup 56}Fe and {sup 27}Al have been analyzed by the Quantum Molecular Dynamics (QMD) plus Statistical Decay Model (SDM). It was found that the mass and charge distributions calculated with and without the statistical decay have very different shapes. These results also depend strongly on the impact parameter, showing an importance of the dynamical treatment as realized by the QMD approach. The calculated results were compared with experimental data in the energy region from 50 MeV to 5 GeV. The QMD+SDM calculation could reproduce the production cross sections of the light clusters and intermediate-mass to heavy fragments in a good accuracy. The production cross section of {sup 7}Be was, however, underpredicted by approximately 2 orders of magnitude, showing the necessity of another reaction mechanism not taken into account in the present model. (author)

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

    Directory of Open Access Journals (Sweden)

    Giulia Morra

    2009-03-01

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

  18. Capturing a Dynamic Chaperone-Substrate Interaction Using NMR-Informed Molecular Modeling.

    Science.gov (United States)

    Salmon, Loïc; Ahlstrom, Logan S; Horowitz, Scott; Dickson, Alex; Brooks, Charles L; Bardwell, James C A

    2016-08-10

    Chaperones maintain a healthy proteome by preventing aggregation and by aiding in protein folding. Precisely how chaperones influence the conformational properties of their substrates, however, remains unclear. To achieve a detailed description of dynamic chaperone-substrate interactions, we fused site-specific NMR information with coarse-grained simulations. Our model system is the binding and folding of a chaperone substrate, immunity protein 7 (Im7), with the chaperone Spy. We first used an automated procedure in which NMR chemical shifts inform the construction of system-specific force fields that describe each partner individually. The models of the two binding partners are then combined to perform simulations on the chaperone-substrate complex. The binding simulations show excellent agreement with experimental data from multiple biophysical measurements. Upon binding, Im7 interacts with a mixture of hydrophobic and hydrophilic residues on Spy's surface, causing conformational exchange within Im7 to slow down as Im7 folds. Meanwhile, the motion of Spy's flexible loop region increases, allowing for better interaction with different substrate conformations, and helping offset losses in Im7 conformational dynamics that occur upon binding and folding. Spy then preferentially releases Im7 into a well-folded state. Our strategy has enabled a residue-level description of a dynamic chaperone-substrate interaction, improving our understanding of how chaperones facilitate substrate folding. More broadly, we validate our approach using two other binding partners, showing that this approach provides a general platform from which to investigate other flexible biomolecular complexes through the integration of NMR data with efficient computational models.

  19. A Dynamical Model of Molecular Monolayers: Why Tethers Don't Snap

    Science.gov (United States)

    Mann, Elizabeth K.; Bernoff, Andrew; Alexander, James; Mann, J. Adin

    2005-03-01

    A bola-shaped domain in a Langmuir monolayer at the air/water interface relaxes towards a circular shape under the influence of line tension. The ``tether'' thickens continuously in this process, in marked contrast to the Hele-Shaw and the three-dimensional cases, where hydrodynamic instabilities lead to the tether snapping. A simplified dynamical model allows us use lubrication theory to explain this without incorporating repulsive forces to stabilize the tether in 2D. The model also allows us to give a better estimate of line tensions from the relaxation rate of such monolayer domains. This material is based upon work supported by the National Science Foundation under Grant No.9984304.

  20. A unified electrostatic and cavitation model for first-principles molecular dynamics in solution

    Energy Technology Data Exchange (ETDEWEB)

    Scherlis, D A; Fattebert, J; Gygi, F; Cococcioni, M; Marzari, N

    2005-11-14

    The electrostatic continuum solvent model developed by Fattebert and Gygi is combined with a first-principles formulation of the cavitation energy based on a natural quantum-mechanical definition for the surface of a solute. Despite its simplicity, the cavitation contribution calculated by this approach is found to be in remarkable agreement with that obtained by more complex algorithms relying on a large set of parameters. The model allows for very efficient Car-Parrinello simulations of finite or extended systems in solution, and demonstrates a level of accuracy as good as that of established quantum-chemistry continuum solvent methods. They apply this approach to the study of tetracyanoethylene dimers in dichloromethane, providing valuable structural and dynamical insights on the dimerization phenomenon.

  1. Molecular dynamics modeling of defect formation in many-layer hexagonal boron nitride

    Energy Technology Data Exchange (ETDEWEB)

    Stephani, Kelly A., E-mail: ksteph@illinois.edu [Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Boyd, Iain D. [Department of Aerospace Engineering, University of Michigan, Ann Arbor, MI 48109 (United States)

    2015-12-15

    Molecular dynamics simulations are conducted to examine lattice defect formation in a hexagonal boron nitride lattice by high-energy xenon ion impact. This work seeks to characterize the production of defects which occur under ion irradiation. Lattice defect formation is first examined in single-layer hexagonal boron nitride. Energetic xenon ions over a range of 10 eV–10 keV are used to randomly impact the central lattice at an angle of 90° (orthogonal to the lattice basal plane). The resulting defects are analyzed for 5000 ion impacts, and results are reported for average single and double vacancy formation per impact. A similar study is conducted for a many-layer hexagonal boron nitride lattice, to assess the influence of additional layers in the formation of point defects as a function of incident ion energy. Ion impacts at both 90° and 45° are examined. The defects formed in the top layer of the many-layer lattice are qualitatively similar to the single layer results, but the presence of the bulk lattice is found to reduce the single vacancy probability in the top-most layer. Point defects are prominent in the lattice sub-layers with increasing ion energy. Orthogonal ion impacts are found to cause the most damage, as measured by the number of vacancy defects produced; the number of vacancies increases linearly with energy, while the number of defects in the oblique impact configuration reaches an asymptotic limit with increasing energy.

  2. Calibration of nonlocal strain gradient shell model for buckling analysis of nanotubes using molecular dynamics simulations

    Science.gov (United States)

    Mehralian, Fahimeh; Tadi Beni, Yaghoub; Karimi Zeverdejani, Mehran

    2017-09-01

    The present paper is concerned with the applicability of nonlocal strain gradient theory for axial buckling analysis of nanotubes. The first order shear deformation theory with the von Kármán geometrical nonlinearity is utilized to establish theoretical formulations. The governing equations and boundary conditions are derived using the minimum potential energy principle. As main purpose of this study, the small length scale parameters are calibrated for the axial buckling problem of carbon nanotubes (CNTs) using molecular dynamics (MDs) simulations. Further the influences of different geometrical and material parameters, such as length and thickness ratio as well as small length scale parameters on the buckling response of nanotubes are studied. It is indicated that the effect of small length scale parameters on the critical buckling load becomes more prominent by increasing thickness and decreasing length ratio. Moreover, the calibrated small length scale parameters presented herein would be useful for the purpose of applying the nonlocal strain gradient theory for the analysis of nanotubes. The calibrated nonlocal strain gradient theory presented herein should be useful for researchers who are using the nonlocal strain gradient shell theories for analysis of micro/nanotubes.

  3. Molecular dynamics simulation of benzene

    Science.gov (United States)

    Trumpakaj, Zygmunt; Linde, Bogumił B. J.

    2016-03-01

    Intermolecular potentials and a few models of intermolecular interaction in liquid benzene are tested by Molecular Dynamics (MD) simulations. The repulsive part of the Lennard-Jones 12-6 (LJ 12-6) potential is too hard, which yields incorrect results. The exp-6 potential with a too hard repulsive term is also often used. Therefore, we took an expa-6 potential with a small Gaussian correction plus electrostatic interactions. This allows to modify the curvature of the potential. The MD simulations are carried out in the temperature range 280-352 K under normal pressure and at experimental density. The Rayleigh scattering of depolarized light is used for comparison. The results of MD simulations are comparable with the experimental values.

  4. Development of a model for the rational design of molecular imprinted polymer: Computational approach for combined molecular dynamics/quantum mechanics calculations

    Energy Technology Data Exchange (ETDEWEB)

    Dong Cunku [Department of Chemistry, Harbin Institute of Technology, Harbin 150090 (China); Li Xin, E-mail: lixin@hit.edu.cn [Department of Chemistry, Harbin Institute of Technology, Harbin 150090 (China); Guo Zechong [School of Municipal Environmental Engineering, Harbin Institute of Technology, Harbin 150090 (China); Qi Jingyao, E-mail: jyq@hit.edu.cn [School of Municipal Environmental Engineering, Harbin Institute of Technology, Harbin 150090 (China)

    2009-08-04

    A new rational approach for the preparation of molecularly imprinted polymer (MIP) based on the combination of molecular dynamics (MD) simulations and quantum mechanics (QM) calculations is described in this work. Before performing molecular modeling, a virtual library of functional monomers was created containing forty frequently used monomers. The MD simulations were first conducted to screen the top three monomers from virtual library in each porogen-acetonitrile, chloroform and carbon tetrachloride. QM simulations were then performed with an aim to select the optimum monomer and progen solvent in which the QM simulations were carried out; the monomers giving the highest binding energies were chosen as the candidate to prepare MIP in its corresponding solvent. The acetochlor, a widely used herbicide, was chosen as the target analyte. According to the theoretical calculation results, the MIP with acetochlor as template was prepared by emulsion polymerization method using N,N-methylene bisacrylamide (MBAAM) as functional monomer and divinylbenzene (DVB) as cross-linker in chloroform. The synthesized MIP was then tested by equilibrium-adsorption method, and the MIP demonstrated high removal efficiency to the acetochlor. Mulliken charge distribution and {sup 1}H NMR spectroscopy of the synthesized MIP provided insight on the nature of recognition during the imprinting process probing the governing interactions for selective binding site formation at a molecular level. We think the computer simulation method first proposed in this paper is a novel and reliable method for the design and synthesis of MIP.

  5. The use of two-phase molecular dynamics simulations to determine the phase behavior and critical point of propane molecular models.

    Science.gov (United States)

    Patel, Sonal; Wilding, W Vincent; Rowley, Richard L

    2011-01-14

    Molecular dynamics simulations were performed to determine two-phase configurations of model propane molecules below the critical point and in the near-critical, two-phase region. A postprocessor that uses a Monte Carlo method for determination of volumes attributable to each molecule was used to obtain density histograms of the particles from which the bulk coexisting equilibrium vapor and liquid densities were determined. This method of analyzing coexisting densities in a two-phase simulation is straightforward and can be easily implemented for complex, multisite models. Various degrees of internal flexibility in the propane models have little effect on the coexisting densities at temperatures 40 K or more below the critical point, but internal flexibility (angle bending and bond vibrations) does affect the saturated liquid densities in the near-critical region, changing the critical temperature by approximately 20 K. Shorter cutoffs were also found to affect the phase dome and the location of the critical point.

  6. Simulation of shock-induced melting of Ni using molecular dynamics coupled to a two-temperature model

    Science.gov (United States)

    Koči, L.; Bringa, E. M.; Ivanov, D. S.; Hawreliak, J.; McNaney, J.; Higginbotham, A.; Zhigilei, L. V.; Belonoshko, A. B.; Remington, B. A.; Ahuja, R.

    2006-07-01

    Using nonequilibrium molecular dynamics (MD) simulations we study shock-induced melting in Ni with an embedded atom method (EAM). Dynamic melting is probed by the pair correlation function, and we find a melting lattice temperature of Tmelt=6400±300K for a melting pressure of Pmelt=275±10GPa . When a combined MD+TTM (two-temperature model) approach is used to include electronic heat conduction and electron-phonon coupling, Pmelt and Tmelt change. For a given pressure, the temperature behind the shock decreases due to electronic heat diffusion into the cold, unshocked material. This cooling of the material behind the shock slightly increases the melting pressure compared to simulations without electronic heat conduction and electron-phonon coupling. The decrease in the temperature behind the shock front is enhanced if the electron-phonon coupling is artificially made larger. We also explore the feasibility of using x-ray diffraction to detect melting.

  7. A combination of pharmacophore modeling, atom-based 3D-QSAR, molecular docking and molecular dynamics simulation studies on PDE4 enzyme inhibitors.

    Science.gov (United States)

    Tripuraneni, Naga Srinivas; Azam, Mohammed Afzal

    2016-11-01

    Phosphodiesterases 4 enzyme is an attractive target for the design of anti-inflammatory and bronchodilator agents. In the present study, pharmacophore and atom-based 3D-QSAR studies were carried out for pyrazolopyridine and quinoline derivatives using Schrödinger suite 2014-3. A four-point pharmacophore model was developed using 74 molecules having pIC50 ranging from 10.1 to 4.5. The best four feature model consists of one hydrogen bond acceptor, two aromatic rings, and one hydrophobic group. The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a high correlation coefficient (R(2 )= .9949), cross validation coefficient (Q(2 )= .7291), and Pearson-r (.9107) at six component partial least square factor. The external validation indicated that our QSAR model possessed high predictive power with R(2) value of .88. The generated model was further validated by enrichment studies using the decoy test. Molecular docking, free energy calculation, and molecular dynamics (MD) simulation studies have been performed to explore the putative binding modes of these ligands. A 10-ns MD simulation confirmed the docking results of both stability of the 1XMU-ligand complex and the presumed active conformation. Outcomes of the present study provide insight in designing novel molecules with better PDE4 inhibitory activity.

  8. Molecular characterization of Mtb-OMP decarboxylase by modeling, docking and dynamic studies.

    Science.gov (United States)

    Madhusudana, P; Babajan, B; Chaitanya, M; Anuradha, C M; Shobharani, C; Chikati, Rajasekar; Kumar, Chitta Suresh; Rao, K R S Sambasiva; Poda, Sudhakar

    2012-06-01

    Tuberculosis (TB), the second most deadly disease in the world is caused by Mycobacterium tuberculosis (Mtb). In the present work a unique enzyme of Mtb orotidine 5' monophosphate decarboxylase (Mtb-OMP Decase) is selected as drug target due to its indispensible role in biosynthesis of pyrimidines. The present work is focused on understanding the structural and functional aspects of Mtb-OMP Decase at molecular level. Due to absence of crystal structure, the 3D structure of Mtb-OMP Decase was predicted by MODELLER9V7 using a known structural template 3L52. Energy minimization and refinement of the developed 3D model was carried out with Gromacs 3.2.1 and the optimized homology model was validated by PROCHECK,WHAT-IF and PROSA2003. Further, the surface active site amino acids were quantified by WHAT-IF pocket. The exact binding interactions of the ligands, 6-idiouridine 5' monophosphate and its designed analogues with the receptor Mtb-OMP Decase were predicted by docking analysis with AUTODOCK 4.0. This would be helpful in understanding the blockade mechanism of OMP Decase and provide a candidate lead for the discovery of Mtb-OMP Decase inhibitors, which may bring insights into outcome new therapy to treat drug resistant Mtb.

  9. A hybrid molecular dynamics/fluctuating hydrodynamics method for modelling liquids at multiple scales in space and time

    Energy Technology Data Exchange (ETDEWEB)

    Korotkin, Ivan, E-mail: i.korotkin@qmul.ac.uk; Karabasov, Sergey; Markesteijn, Anton [The School of Engineering and Material Science, Queen Mary University of London, Mile End Road, E1 4NS London (United Kingdom); Nerukh, Dmitry; Scukins, Arturs [Institute of Systems Analytics, Aston University, Birmingham B4 7ET (United Kingdom); Farafonov, Vladimir [Department of Physical Chemistry, V. N. Karazin Kharkiv National University, Svobody Square 4, 61022 Kharkiv (Ukraine); Pavlov, Evgen [Institute of Systems Analytics, Aston University, Birmingham B4 7ET (United Kingdom); Faculty of Physics, Kiev National Taras Shevchenko University, Prospect Acad. Glushkova 4, Kiev 03127 (Ukraine)

    2015-07-07

    A new 3D implementation of a hybrid model based on the analogy with two-phase hydrodynamics has been developed for the simulation of liquids at microscale. The idea of the method is to smoothly combine the atomistic description in the molecular dynamics zone with the Landau-Lifshitz fluctuating hydrodynamics representation in the rest of the system in the framework of macroscopic conservation laws through the use of a single “zoom-in” user-defined function s that has the meaning of a partial concentration in the two-phase analogy model. In comparison with our previous works, the implementation has been extended to full 3D simulations for a range of atomistic models in GROMACS from argon to water in equilibrium conditions with a constant or a spatially variable function s. Preliminary results of simulating the diffusion of a small peptide in water are also reported.

  10. Complete protein-protein association kinetics in atomic detail revealed by molecular dynamics simulations and Markov modelling

    Science.gov (United States)

    Plattner, Nuria; Doerr, Stefan; de Fabritiis, Gianni; Noé, Frank

    2017-10-01

    Protein-protein association is fundamental to many life processes. However, a microscopic model describing the structures and kinetics during association and dissociation is lacking on account of the long lifetimes of associated states, which have prevented efficient sampling by direct molecular dynamics (MD) simulations. Here we demonstrate protein-protein association and dissociation in atomistic resolution for the ribonuclease barnase and its inhibitor barstar by combining adaptive high-throughput MD simulations and hidden Markov modelling. The model reveals experimentally consistent intermediate structures, energetics and kinetics on timescales from microseconds to hours. A variety of flexibly attached intermediates and misbound states funnel down to a transition state and a native basin consisting of the loosely bound near-native state and the tightly bound crystallographic state. These results offer a deeper level of insight into macromolecular recognition and our approach opens the door for understanding and manipulating a wide range of macromolecular association processes.

  11. Challenges in modelling homogeneous catalysis: new answers from ab initio molecular dynamics to the controversy over the Wacker process.

    Science.gov (United States)

    Stirling, András; Nair, Nisanth N; Lledós, Agustí; Ujaque, Gregori

    2014-07-21

    We present here a review of the mechanistic studies of the Wacker process stressing the long controversy about the key reaction steps. We give an overview of the previous experimental and theoretical studies on the topic. Then we describe the importance of the most recent Ab Initio Molecular Dynamics (AIMD) calculations in modelling organometallic reactivity in water. As a prototypical example of homogeneous catalytic reactions, the Wacker process poses serious challenges to modelling. The adequate description of the multiple role of the water solvent is very difficult by using static quantum chemical approaches including cluster and continuum solvent models. In contrast, such reaction systems are suitable for AIMD, and by combining with rare event sampling techniques, the method provides reaction mechanisms and the corresponding free energy profiles. The review also highlights how AIMD has helped to obtain a novel understanding of the mechanism and kinetics of the Wacker process.

  12. Molecular dynamics simulations of the aqueous interface with the [BMI][PF6] ionic liquid: Comparison of different solvent models.

    Science.gov (United States)

    Chevrot, G; Schurhammer, R; Wipff, G

    2006-09-28

    We report a Molecular Dynamics (MD) study of the interface between water and the hygroscopic room temperature Ionic Liquid "IL" [BMI][PF6] (1-butyl-3-methyl-imidazolium hexafluorophosphate), comparing the TIP3P, SPC/E and TIP5P models for water and two IL models where the ions are +/-1 or +/-0.9 charged. A recent MD study (A. Chaumont, R. Schurhammer and G. Wipff, J. Phys. Chem. B, 2005, 109, 18964) showed that using TIP3P water in conjunction with the IL(+/-1) model led to water-IL mixing without forming an interface, whereas a biphasic system could be obtained with the IL(+/-0.9) model. With the TIP5P and SPC/E models, the juxtaposed aqueous and IL phases are found to remain distinct for at least 20 ns. The resulting IL humidity, exaggerated with the IL(+/-1) model, is in better agreement with experiment using the IL(+/-0.9) model. We also report demixing simulations on the "randomly mixed" liquids, using the IL(+/-0.9) model for the ionic liquid. With the three tested water models, the phases separate very slowly ( approximately 20 ns or more) compared to "classical" chloroform-water mixtures (less than 1 ns), leading to biphasic systems similar to those obtained after equilibration of the juxtaposed liquids. The characteristics of the interface (size, polarity, ion orientation, electrostatic potential) are compared with the different models. Possible reasons why, among the three tested water models, the widely-used TIP3P model exaggerates the inter-solvent mixing, are analyzed. The difficulty in computationally and experimentally equilibrating water-IL mixtures is attributed to the slow dynamics and micro-heterogeneity of the IL and to the different states of water in the IL phase.

  13. Molecular modeling study for the design of novel acetyl-CoA carboxylase inhibitors using 3D QSAR, molecular docking and dynamic simulations.

    Science.gov (United States)

    Vyas, Vivek K; Dabasia, Mohini; Qureshi, Gulamnizami; Patel, Palak; Ghate, Manjunath

    2017-07-01

    Acetyl-CoA carboxylase (ACC) enzyme plays an important role in the regulation of biosynthesis and oxidation of fatty acids. ACC is a recognized drug target for the treatment of obesity and diabetes. Combination of ligand and structure-based in silico methods along with activity and toxicity prediction provides best lead compounds in the drug discovery process. In this study, a data-set of 100 ACC inhibitors were used for the development of comparative molecular field analysis (CoMFA) and comparative molecular similarity index matrix analysis (CoMSIA) models. The generated contour maps were used for the design of novel ACC inhibitors. CoMFA and CoMSIA models were used for the predication of activity of designed compounds. In silico toxicity risk prediction study was carried out for the designed compounds. Molecular docking and dynamic simulations studies were performed to know the binding mode of designed compounds with the ACC enzyme. The designed compounds showed interactions with key amino acid residues important for catalysis, and good correlation was observed between binding free energy and inhibition of ACC.

  14. Molecular dynamics simulation of protein adsorption at fluid interfaces: a comparison of all-atom and coarse-grained models.

    Science.gov (United States)

    Euston, Stephen R

    2010-10-11

    The adsorption of LTP at the decane-water interface was modeled using all-atom and coarse-grained (CG) molecular dynamics simulations. The CG model (300 ns simulation, 1200 ns scaled time) generates equilibrium adsorbed conformations in about 12 h, whereas the equivalent 1200 ns simulation would take about 300 days for the all-atom model. In both models the LTP molecule adsorbs with α-helical regions parallel to the interface with an average tilt angle normal to the interface of 73° for the all-atom model and 62° for the CG model. In the all-atom model, the secondary structure of the LTP is conserved upon adsorption. A considerable proportion of the N-terminal loop of LTP can be found in the decane phase for the all-atom model, whereas in the CG model the protein only penetrates as far as the mixed water-decane interfacial region. This difference may arise due to the different schemes used to parametrize force field parameters in the two models.

  15. Exploration of virtual candidates for human HMG-CoA reductase inhibitors using pharmacophore modeling and molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Minky Son

    Full Text Available 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR is a rate-controlling enzyme in the mevalonate pathway which involved in biosynthesis of cholesterol and other isoprenoids. This enzyme catalyzes the conversion of HMG-CoA to mevalonate and is regarded as a drug target to treat hypercholesterolemia. In this study, ten qualitative pharmacophore models were generated based on chemical features in active inhibitors of HMGR. The generated models were validated using a test set. In a validation process, the best hypothesis was selected based on the statistical parameters and used for virtual screening of chemical databases to find novel lead candidates. The screened compounds were sorted by applying drug-like properties. The compounds that satisfied all drug-like properties were used for molecular docking study to identify their binding conformations at active site of HMGR. The final hit compounds were selected based on docking score and binding orientation. The HMGR structures in complex with the hit compounds were subjected to 10 ns molecular dynamics simulations to refine the binding orientation as well as to check the stability of the hits. After simulation, binding modes including hydrogen bonding patterns and molecular interactions with the active site residues were analyzed. In conclusion, four hit compounds with new structural scaffold were suggested as novel and potent HMGR inhibitors.

  16. The structure of molten CuCl: Reverse Monte Carlo modeling with high-energy X-ray diffraction data and molecular dynamics of a polarizable ion model

    Science.gov (United States)

    Alcaraz, Olga; Trullàs, Joaquim; Tahara, Shuta; Kawakita, Yukinobu; Takeda, Shin'ichi

    2016-09-01

    The results of the structural properties of molten copper chloride are reported from high-energy X-ray diffraction measurements, reverse Monte Carlo modeling method, and molecular dynamics simulations using a polarizable ion model. The simulated X-ray structure factor reproduces all trends observed experimentally, in particular the shoulder at around 1 Å-1 related to intermediate range ordering, as well as the partial copper-copper correlations from the reverse Monte Carlo modeling, which cannot be reproduced by using a simple rigid ion model. It is shown that the shoulder comes from intermediate range copper-copper correlations caused by the polarized chlorides.

  17. Molecular modeling and molecular dynamics simulation study of the human Rab9 and RhoBTB3 C-terminus complex

    Science.gov (United States)

    Junaid, Muhammad; Muhseen, Ziyad Tariq; Ullah, Ata; Wadood, Abdul; Liu, Junjun; Zhang, Houjin

    2014-01-01

    Rab9 is required for the transport of mannose 6-phosphate receptors to the trans-Golgi network from late endosomes through the interaction with its effector: RhoBTB3. Earlier research indicates the C-terminus of RhoBTB3 (Rho_Cterm) is used for the interaction with Rab9. We used the homology modeling along with the molecular dynamics (MD) simulation to study the binding pattern of Rho_Cterm and Rab9 at atomic level. Both modeled structures, Rab9 and Rho_Cterm, are of high quality as suggested by the Ramachandran plot and ProCheck. The complex of Rab9-Rho_Cterm was generated by unrestrained pairwise docking using ZDOCK server. The interface of complex is consistent with the previous experimental data. The results of MD simulation indicate that the binding interface is stable along the simulation process. PMID:25670879

  18. Modeling, molecular dynamics, and docking assessment of transcription factor rho: a potential drug target in Brucella melitensis 16M.

    Science.gov (United States)

    Pradeepkiran, Jangampalli Adi; Kumar, Konidala Kranthi; Kumar, Yellapu Nanda; Bhaskar, Matcha

    2015-01-01

    The zoonotic disease brucellosis, a chronic condition in humans affecting renal and cardiac systems and causing osteoarthritis, is caused by Brucella, a genus of Gram-negative, facultative, intracellular pathogens. The mode of transmission and the virulence of the pathogens are still enigmatic. Transcription regulatory elements, such as rho proteins, play an important role in the termination of transcription and/or the selection of genes in Brucella. Adverse effects of the transcription inhibitors play a key role in the non-successive transcription challenges faced by the pathogens. In the investigation presented here, we computationally predicted the transcription termination factor rho (TtFRho) inhibitors against Brucella melitensis 16M via a structure-based method. In view the unknown nature of its crystal structure, we constructed a robust three-dimensional homology model of TtFRho's structure by comparative modeling with the crystal structure of the Escherichia coli TtFRho (Protein Data Bank ID: 1PVO) as a template in MODELLER (v 9.10). The modeled structure was optimized by applying a molecular dynamics simulation for 2 ns with the CHARMM (Chemistry at HARvard Macromolecular Mechanics) 27 force field in NAMD (NAnoscale Molecular Dynamics program; v 2.9) and then evaluated by calculating the stereochemical quality of the protein. The flexible docking for the interaction phenomenon of the template consists of ligand-related inhibitor molecules from the ZINC (ZINC Is Not Commercial) database using a structure-based virtual screening strategy against minimized TtFRho. Docking simulations revealed two inhibitors compounds - ZINC24934545 and ZINC72319544 - that showed high binding affinity among 2,829 drug analogs that bind with key active-site residues; these residues are considered for protein-ligand binding and unbinding pathways via steered molecular dynamics simulations. Arg215 in the model plays an important role in the stability of the protein-ligand complex

  19. Modeling, molecular dynamics, and docking assessment of transcription factor rho: a potential drug target in Brucella melitensis 16M

    Directory of Open Access Journals (Sweden)

    Pradeepkiran JA

    2015-03-01

    Full Text Available Jangampalli Adi Pradeepkiran,1 Konidala Kranthi Kumar,1 Yellapu Nanda Kumar,2 Matcha Bhaskar11Division of Animal Biotechnology, Department of Zoology, Sri Venkateswara University, Tirupati, 2Biomedical Informatics Centre, Vector Control Research Centre, Indian Council of Medical Research, Pondicherry, India Abstract: The zoonotic disease brucellosis, a chronic condition in humans affecting renal and cardiac systems and causing osteoarthritis, is caused by Brucella, a genus of Gram-negative, facultative, intracellular pathogens. The mode of transmission and the virulence of the pathogens are still enigmatic. Transcription regulatory elements, such as rho proteins, play an important role in the termination of transcription and/or the selection of genes in Brucella. Adverse effects of the transcription inhibitors play a key role in the non-successive transcription challenges faced by the pathogens. In the investigation presented here, we computationally predicted the transcription termination factor rho (TtFRho inhibitors against Brucella melitensis 16M via a structure-based method. In view the unknown nature of its crystal structure, we constructed a robust three-dimensional homology model of TtFRho’s structure by comparative modeling with the crystal structure of the Escherichia coli TtFRho (Protein Data Bank ID: 1PVO as a template in MODELLER (v 9.10. The modeled structure was optimized by applying a molecular dynamics simulation for 2 ns with the CHARMM (Chemistry at HARvard Macromolecular Mechanics 27 force field in NAMD (NAnoscale Molecular Dynamics program; v 2.9 and then evaluated by calculating the stereochemical quality of the protein. The flexible docking for the interaction phenomenon of the template consists of ligand-related inhibitor molecules from the ZINC (ZINC Is Not Commercial database using a structure-based virtual screening strategy against minimized TtFRho. Docking simulations revealed two inhibitors compounds – ZINC

  20. Modeling, molecular dynamics, and docking assessment of transcription factor rho: a potential drug target in Brucella melitensis 16M

    Science.gov (United States)

    Pradeepkiran, Jangampalli Adi; Kumar, Konidala Kranthi; Kumar, Yellapu Nanda; Bhaskar, Matcha

    2015-01-01

    The zoonotic disease brucellosis, a chronic condition in humans affecting renal and cardiac systems and causing osteoarthritis, is caused by Brucella, a genus of Gram-negative, facultative, intracellular pathogens. The mode of transmission and the virulence of the pathogens are still enigmatic. Transcription regulatory elements, such as rho proteins, play an important role in the termination of transcription and/or the selection of genes in Brucella. Adverse effects of the transcription inhibitors play a key role in the non-successive transcription challenges faced by the pathogens. In the investigation presented here, we computationally predicted the transcription termination factor rho (TtFRho) inhibitors against Brucella melitensis 16M via a structure-based method. In view the unknown nature of its crystal structure, we constructed a robust three-dimensional homology model of TtFRho’s structure by comparative modeling with the crystal structure of the Escherichia coli TtFRho (Protein Data Bank ID: 1PVO) as a template in MODELLER (v 9.10). The modeled structure was optimized by applying a molecular dynamics simulation for 2 ns with the CHARMM (Chemistry at HARvard Macromolecular Mechanics) 27 force field in NAMD (NAnoscale Molecular Dynamics program; v 2.9) and then evaluated by calculating the stereochemical quality of the protein. The flexible docking for the interaction phenomenon of the template consists of ligand-related inhibitor molecules from the ZINC (ZINC Is Not Commercial) database using a structure-based virtual screening strategy against minimized TtFRho. Docking simulations revealed two inhibitors compounds – ZINC24934545 and ZINC72319544 – that showed high binding affinity among 2,829 drug analogs that bind with key active-site residues; these residues are considered for protein-ligand binding and unbinding pathways via steered molecular dynamics simulations. Arg215 in the model plays an important role in the stability of the protein

  1. Towards a Discrete Element Method (DEM) for modeling anisotropic, nano- and colloidal scale particles in Molecular Dynamics (MD)

    Science.gov (United States)

    Marson, Ryan; Spellings, Matthew; Anderson, Joshua; Glotzer, Sharon

    2014-03-01

    Faceted shapes, such as polyhedra, are commonly created in experimental systems of nanoscale, colloidal, and granular particles. Many interesting physical phenomena, like crystalline nucleation and growth, vacancy motion, and glassy dynamics, are challenging to model in these systems because they require detailed dynamical information at the individual particle level. Within the granular materials community the Discrete Element Method has been used extensively to model systems of anisotropic particles under gravity, with friction. We report the first implementation of DEM MD intended for thermodynamic nanoscale simulation. Our method is implemented in parallel on the GPU within the HOOMD-Blue framework. By decomposing the force calculation into its components, this implementation can take advantage of massive data parallelism, enabling optimal use of the GPU for even relatively small systems while achieving a speedup of 60 times over a single CPU core. This method is a natural extension of classical molecular dynamics into the realm of faceted particles, and allows simulation of disparate size scales ranging from the nanoscale to granular particulates, all within the same framework.

  2. Molecular dynamics simulation of pyridine

    Science.gov (United States)

    Trumpakaj, Zygmunt; Linde, Bogumił

    2015-04-01

    Molecular Dynamics (MD) simulations are used for the investigation of molecular motions in pyridine in the temperature range 20-480 K under normal pressure. The results obtained are analyzed within the frame of the Mori Zwanzig memory function formalism. An analytical approximation of the first memory function K(t) is applied to predict some dependences on temperature. Experimental results of the Rayleigh scattering of depolarized light from liquid pyridine are used as the main base for the comparison.

  3. Efficient dynamic molecular simulation using QSAR model to know inhibition activity in breast cancer medicine

    Science.gov (United States)

    Zharifah, A.; Kusumowardani, E.; Saputro, A.; Sarwinda, D.

    2017-07-01

    According to data from GLOBOCAN (IARC) at 2012, breast cancer was the highest rated of new cancer case by 43.3 % (after controlled by age), with mortality rated as high as 12.9 %. Oncology is a major field which focusing on improving the development of drug and therapeutics cancer in pharmaceutical and biotechnology companies. Nowadays, many researchers lead to computational chemistry and bioinformatic for pharmacophore generation. A pharmacophore describes as a group of atoms in the molecule which is considered to be responsible for a pharmacological action. Prediction of biological function from chemical structure in silico modeling reduces the use of chemical reagents so the risk of environmental pollution decreased. In this research, we proposed QSAR model to analyze the composition of cancer drugs which assumed to be homogenous in character and treatment. Atomic interactions which analyzed are learned through parameters such as log p as descriptors hydrophobic, n_poinas descriptor contour strength and molecular structure, and also various concentrations inhibitor (micromolar and nanomolar) from NCBI drugs bank. The differences inhibitor activity was observed by the presence of IC 50 residues value from inhibitor substances at various concentration. Then, we got a general overview of the state of safety for drug stability seen from its IC 50 value. In our study, we also compared between micromolar and nanomolar inhibitor effect from QSAR model results. The QSAR model analysis shows that the drug concentration with nanomolar is better than micromolar, related with the content of inhibitor substances concentration. This QSAR model got the equation: Log 1/IC50 = (0.284) (±0.195) logP + (0.02) (±0.012) n_poin + (-0.005) (±0.083) Inhibition10.2nanoM + (0.1) (±0.079) Inhibition30.5nanoM + (-0.016) (±0.045) Inhibition91.5nanoM + (-2.572) (±1.570) (n = 13; r = 0.813; r2 = 0.660; s = 0.764; F = 2.720; q2 = 0.660).

  4. Insights into the structure and inhibition of Giardia intestinalis arginine deiminase: homology modeling, docking, and molecular dynamics studies.

    Science.gov (United States)

    Trejo-Soto, Pedro Josué; Aguayo-Ortiz, Rodrigo; Yépez-Mulia, Lilián; Hernández-Campos, Alicia; Medina-Franco, José Luis; Castillo, Rafael

    2016-01-01

    Giardia intestinalis arginine deiminase (GiADI) is an important metabolic enzyme involved in the energy production and defense of this protozoan parasite. The lack of this enzyme in the human host makes GiADI an attractive target for drug design against G. intestinalis. One approach in the design of inhibitors of GiADI could be computer-assisted studies of its crystal structure, such as docking; however, the required crystallographic structure of the enzyme still remains unresolved. Because of its relevance, in this work, we present a three-dimensional structure of GiADI obtained from its amino acid sequence using the homology modeling approximation. Furthermore, we present an approximation of the most stable dimeric structure of GiADI identified through molecular dynamics simulation studies. An in silico analysis of druggability using the structure of GiADI was carried out in order to know if it is a good target for design and optimization of selective inhibitors. Potential GiADI inhibitors were identified by docking of a set of 3196 commercial and 19 in-house benzimidazole derivatives, and molecular dynamics simulation studies were used to evaluate the stability of the ligand-enzyme complexes.

  5. Molecular dynamics simulations of the dynamic and energetic properties of alkali and halide ions using water-model-specific ion parameters.

    Science.gov (United States)

    Joung, In Suk; Cheatham, Thomas E

    2009-10-01

    The dynamic and energetic properties of the alkali and halide ions were calculated using molecular dynamics (MD) and free energy simulations with various different water and ion force fields including our recently developed water-model-specific ion parameters. The properties calculated were activity coefficients, diffusion coefficients, residence times of atomic pairs, association constants, and solubility. Through calculation of these properties, we can assess the validity and range of applicability of the simple pair potential models and better understand their limitations. Due to extreme computational demands, the activity coefficients were only calculated for a subset of the models. The results qualitatively agree with experiment. Calculated diffusion coefficients and residence times between cation-anion, water-cation, and water-anion showed differences depending on the choice of water and ion force field used. The calculated solubilities of the alkali-halide salts were generally lower than the true solubility of the salts. However, for both the TIP4P(EW) and SPC/E water-model-specific ion parameters, solubility was reasonably well-reproduced. Finally, the correlations among the various properties led to the following conclusions: (1) The reliability of the ion force fields is significantly affected by the specific choice of water model. (2) Ion-ion interactions are very important to accurately simulate the properties, especially solubility. (3) The SPC/E and TIP4P(EW) water-model-specific ion force fields are preferred for simulation in high salt environments compared to the other ion force fields.

  6. Random Matrix Theory in molecular dynamics analysis.

    Science.gov (United States)

    Palese, Luigi Leonardo

    2015-01-01

    It is well known that, in some situations, principal component analysis (PCA) carried out on molecular dynamics data results in the appearance of cosine-shaped low index projections. Because this is reminiscent of the results obtained by performing PCA on a multidimensional Brownian dynamics, it has been suggested that short-time protein dynamics is essentially nothing more than a noisy signal. Here we use Random Matrix Theory to analyze a series of short-time molecular dynamics experiments which are specifically designed to be simulations with high cosine content. We use as a model system the protein apoCox17, a mitochondrial copper chaperone. Spectral analysis on correlation matrices allows to easily differentiate random correlations, simply deriving from the finite length of the process, from non-random signals reflecting the intrinsic system properties. Our results clearly show that protein dynamics is not really Brownian also in presence of the cosine-shaped low index projections on principal axes.

  7. Modeling of amorphous SiCxO6/5 by classical molecular dynamics and first principles calculations

    Science.gov (United States)

    Liao, Ningbo; Zhang, Miao; Zhou, Hongming; Xue, Wei

    2017-02-01

    Polymer-derived silicon oxycarbide (SiCO) presents excellent performance for high temperature and lithium-ion battery applications. Current experiments have provided some information on nano-structure of SiCO, while it is very challenging for experiments to take further insight into the molecular structure and its relationship with properties of materials. In this work, molecular dynamics (MD) based on empirical potential and first principle calculation were combined to investigate amorphous SiCxO6/5 ceramics. The amorphous structures of SiCO containing silicon-centered mix bond tetrahedrons and free carbon were successfully reproduced. The calculated radial distribution, angular distribution and Young’s modulus were validated by current experimental data, and more details on molecular structure were discussed. The change in the slope of Young’s modulus is related to the glass transition temperature of the material. The proposed modeling approach can be used to predict the properties of SiCO with different compositions.

  8. Modelling (1 0 0) hydrogen-induced platelets in silicon with a multi-scale molecular dynamics approach

    Energy Technology Data Exchange (ETDEWEB)

    Moras, G. [Department of Physics, King' s College London, Strand, London WC2R 2LS (United Kingdom)], E-mail: gianpietro.moras@kcl.ac.uk; Colombi Ciacchi, L. [Fraunhofer Institut fuer Werkstoffmechanik, Woehlerstrasse 11, 79108 Freiburg (Germany); Institut fuer Zuverlaessigkeit von Bauteilen und Systemen, University of Karlsruhe, Kaiserstrasse 12, 76131 Karlsruhe (Germany); Csanyi, G. [Department of Engineering, Centre for Micromechanics, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ (United Kingdom); De Vita, A. [Department of Physics, King' s College London, Strand, London WC2R 2LS (United Kingdom); INFM-DEMOCRITOS National Simulation Centre and Centre of Excellence for Nanostructured Materials (CENMAT), University of Trieste (Italy)

    2007-12-15

    We introduce a multiscale molecular dynamics (MD) approach to study the thermal evolution of (1 0 0) hydrogen-induced platelets (HIPs) in silicon. The HIPs are modeled by {approx}10 nm long planar defects in a periodically repeated crystalline model system containing {approx}25,000 silicon atoms. The initial defect models are created either by cleavage of atomic planes or by planar assemblies of vacancies, and are stabilized by saturating the resulting surface dangling bonds with hydrogen atoms. The time evolution of the defects is studied by finite-temperature MD using the 'Learn On The Fly' (LOTF) technique. This hybrid scheme allows us to perform accurate density-functional-tight-binding (DFTB) force calculations only on the chemically reactive platelet zone, while the surrounding silicon crystal is described by the Stillinger-Weber (SW) classical potential. Reliable dynamical trajectories are obtained by choosing the DFTB zone in a way which minimizes the errors on the atomic forces.

  9. Dynamic molecular graphs: "hopping" structures.

    Science.gov (United States)

    Cortés-Guzmán, Fernando; Rocha-Rinza, Tomas; Guevara-Vela, José Manuel; Cuevas, Gabriel; Gómez, Rosa María

    2014-05-05

    This work aims to contribute to the discussion about the suitability of bond paths and bond-critical points as indicators of chemical bonding defined within the theoretical framework of the quantum theory of atoms in molecules. For this purpose, we consider the temporal evolution of the molecular structure of [Fe{C(CH2 )3 }(CO)3 ] throughout Born-Oppenheimer molecular dynamics (BOMD), which illustrates the changing behaviour of the molecular graph (MG) of an electronic system. Several MGs with significant lifespans are observed across the BOMD simulations. The bond paths between the trimethylenemethane and the metallic core are uninterruptedly formed and broken. This situation is reminiscent of a "hopping" ligand over the iron atom. The molecular graph wherein the bonding between trimethylenemethane and the iron atom takes place only by means of the tertiary carbon atom has the longest lifespan of all the considered structures, which is consistent with the MG found by X-ray diffraction experiments and quantum chemical calculations. In contrast, the η(4) complex predicted by molecular-orbital theory has an extremely brief lifetime. The lifespan of different molecular structures is related to bond descriptors on the basis of the topology of the electron density such as the ellipticities at the FeCH2 bond-critical points and electron delocalisation indices. This work also proposes the concept of a dynamic molecular graph composed of the different structures found throughout the BOMD trajectories in analogy to a resonance hybrid of Lewis structures. It is our hope that the notion of dynamic molecular graphs will prove useful in the discussion of electronic systems, in particular for those in which analysis on the basis of static structures leads to controversial conclusions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Optical dynamics of molecular aggregates

    NARCIS (Netherlands)

    de Boer, Steven

    2006-01-01

    The subject of this thesis is the spectroscopy and dynamics of molecular aggregates in amorphous matrices. Aggregates of three different molecules were studied. The molecules are depicted in Fig. (1.1). Supersaturated solutions of these molecules show aggregate formation. Aggregation is a process si

  11. Homology modeling, molecular dynamics and atomic level interaction study of snake venom 5' nucleotidase.

    Science.gov (United States)

    Arafat, A Syed Yasir; Arun, A; Ilamathi, M; Asha, J; Sivashankari, P R; D'Souza, Cletus J M; Sivaramakrishnan, V; Dhananjaya, B L

    2014-03-01

    5' Nucleotidase (5' NUC) is a ubiquitously distributed enzyme known to be present in snake venoms (SV) that is responsible primarily for causing dysregulation of physiological homeostasis in humans by inducing anticoagulant effects and by inhibiting platelet aggregation. It is also known to act synergistically with other toxins to exert a more pronounced anti-coagulant effect during envenomation. Its structural and functional role is not yet ascertained clearly. The 3D structure of snake venom 5' nucleotidase (SV-5' NUC) is not yet known and was predicted by us for the first time using a comparative homology modeling approach using Demansia vestigiata protein sequence. The accuracy and stability of the predicted SV-5' NUC structure were validated using several computational approaches. Key interactions of SV-5' NUC were studied using experimental studies/molecular docking analysis of the inhibitors vanillin, vanillic acid and maltol. All these inhibitors were found to dock favorably following pharmacologically relevant absorption, distribution, metabolism and excretion (ADME) profiles. Further, atomic level docking interaction studies using inhibitors of the SV-5' NUC active site revealed amino acid residues Y65 and T72 as important for inhibitor-(SV-5' NUC) interactions. Our in silico analysis is in good agreement with experimental inhibition results of SV-5' NUC with vanillin, vanillic acid and maltol. The present study should therefore play a guiding role in the experimental design of new SV-5' NUC inhibitors for snake bite management. We also identified a few pharmacophoric features essential for SV-5' NUC inhibitory activity that can be utilized further for the discovery of putative anti-venom agents of therapeutic value for snake bite management.

  12. Structural insights into human microsomal epoxide hydrolase by combined homology modeling, molecular dynamics simulations, and molecular docking calculations.

    Science.gov (United States)

    Saenz-Méndez, Patricia; Katz, Aline; Pérez-Kempner, María Lucía; Ventura, Oscar N; Vázquez, Marta

    2017-04-01

    A new homology model of human microsomal epoxide hydrolase was derived based on multiple templates. The model obtained was fully evaluated, including MD simulations and ensemble-based docking, showing that the quality of the structure is better than that of only previously known model. Particularly, a catalytic triad was clearly identified, in agreement with the experimental information available. Analysis of intermediates in the enzymatic mechanism led to the identification of key residues for substrate binding, stereoselectivity, and intermediate stabilization during the reaction. In particular, we have confirmed the role of the oxyanion hole and the conserved motif (HGXP) in epoxide hydrolases, in excellent agreement with known experimental and computational data on similar systems. The model obtained is the first one that fully agrees with all the experimental observations on the system. Proteins 2017; 85:720-730. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Modeling sorption and diffusion of organic sorbate in hexadecyltrimethylammonium-modified clay nanopores - a molecular dynamics simulation study.

    Science.gov (United States)

    Zhao, Qian; Burns, Susan E

    2013-03-19

    Organoclays are highly sorptive engineered materials that can be used as amendments in barrier systems or geosynthetic liners. The performance of confining and isolating the nonpolar organic contaminants by those barrier/lining systems is essentially controlled by the process of organic contaminant mass transport in nanopores of organoclays. In this article, we use molecular dynamics (MD) simulations to study the sorption and diffusion of organic sorbates in interlayers of sodium montmorillonite and hexadecyltrimethylammonium (HDTMA(+))-modified montmorillonite clays. Simulated system consisted of the clay framework, interlayer organic cation, water, and organic sorbate. Their interactions were addressed by the combined force field of ClayFF, constant-valence force field, and SPC water model. Simulation results indicated that in HDTMA coated clay nanopores, diffusion of nonpolar species benzene was slowed because they were subjected to influence of both the pore wall and the HDTMA surfactant. This suggested the nonpolar organic compound diffusion in organophilic clays can be affected by molecular size of diffusive species, clay pore size, and organic surfactant loading. Additionally, a model that connected the diffusion rate of organic compounds in the bulk organoclay matrix with macropores and nanopores was established. The impact of intercalated organic cations on the diffusion dominated mass transport of organic compounds yielded insight into the prediction of the apparent diffusion behavior of organic compounds in organic-modified clays.

  14. A rain induced landslide 3D model based on molecular dynamics with fractal and fractional water diffusion

    CERN Document Server

    Martelloni, Gianluca; Guarino, Alessio

    2016-01-01

    We present a three-dimensional model, based on cohesive spherical particles, of rain-induced landslides. The rainwater infiltration into the soil follow the either the fractional or the fractal diffusion equations. We solve analytically the fractal diffusion partial differential equation (PDE) with particular boundary conditions to simulate a rainfall event. Then, for the PDE, we developed a numerical integration scheme that we integrate with MD (Molecular Dynamics) algorithm for the triggering and propagation of the simulated landslide. Therefore we test the numerical integration scheme of fractal diffusion equation with the analytical solution. We adopt the fractal diffusion equation in term of gravimetric water content that we use as input of triggering scheme based on Mohr-Coulomb limit-equilibrium criterion, adapted to particle level. Moreover, taking into account an interacting force Lennard-Jones inspired, we use a standard MD algorithm to update particle positions and velocities. Then we present resul...

  15. Glass Formation of n-Butanol: Coarse-grained Molecular Dynamics Simulations Using Gay-Berne Potential Model

    Institute of Scientific and Technical Information of China (English)

    Gui-long Xie; Yong-hong Zhang; Shi-ping Huang

    2012-01-01

    Using coarse-grained molecular dynamics simulations based on Gay-Berne potential model,we have simulated the cooling process of liquid n-butanol.A new set of GB parameters are obtained by fitting the results of density functional theory calculations.The simulations are carried out in the range of 290-50 K with temperature decrements of 10 K.The cooling characteristics are determined on the basis of the variations of the density,the potential energy and orientational order parameter with temperature,whose slopes all show discontinuity.Both the radial distribution function curves and the second-rank orientational correlation function curves exhibit splitting in the second peak.Using the discontinuous change of these thermodynamic and structure properties,we obtain the glass transition at an estimate of temperature Tg=120±10 K,which is in good agreement with experimental results 110±1 K.

  16. Molecular dynamics simulation of impact test

    Energy Technology Data Exchange (ETDEWEB)

    Akahoshi, Y. [Kyushu Inst. of Tech., Kitakyushu, Fukuoka (Japan); Schmauder, S.; Ludwig, M. [Stuttgart Univ. (Germany). Staatliche Materialpruefungsanstalt

    1998-11-01

    This paper describes an impact test by molecular dynamics (MD) simulation to evaluate embrittlement of bcc Fe at different temperatures. A new impact test model is developed for MD simulation. The typical fracture behaviors show transition from brittle to ductile fracture, and a history of the impact loads also demonstrates its transition. We conclude that the impact test by MD could be feasible. (orig.)

  17. 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.

  18. 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

  19. Exploring the interaction of SV2A with racetams using homology modelling, molecular dynamics and site-directed mutagenesis.

    Science.gov (United States)

    Lee, Joanna; Daniels, Veronique; Sands, Zara A; Lebon, Florence; Shi, Jiye; Biggin, Philip C

    2015-01-01

    The putative Major Facilitator Superfamily (MFS) transporter, SV2A, is the target for levetiracetam (LEV), which is a successful anti-epileptic drug. Furthermore, SV2A knock out mice display a severe seizure phenotype and die after a few weeks. Despite this, the mode of action of LEV is not known at the molecular level. It would be extremely desirable to understand this more fully in order to aid the design of improved anti-epileptic compounds. Since there is no structure for SV2A, homology modelling can provide insight into the ligand-binding site. However, it is not a trivial process to build such models, since SV2A has low sequence identity to those MFS transporters whose structures are known. A further level of complexity is added by the fact that it is not known which conformational state of the receptor LEV binds to, as multiple conformational states have been inferred by tomography and ligand binding assays or indeed, if binding is exclusive to a single state. Here, we explore models of both the inward and outward facing conformational states of SV2A (according to the alternating access mechanism for MFS transporters). We use a sequence conservation analysis to help guide the homology modelling process and generate the models, which we assess further with Molecular Dynamics (MD). By comparing the MD results in conjunction with docking and simulation of a LEV-analogue used in radioligand binding assays, we were able to suggest further residues that line the binding pocket. These were confirmed experimentally. In particular, mutation of D670 leads to a complete loss of binding. The results shed light on the way LEV analogues may interact with SV2A and may help with the on-going design of improved anti-epileptic compounds.

  20. Exploring the interaction of SV2A with racetams using homology modelling, molecular dynamics and site-directed mutagenesis.

    Directory of Open Access Journals (Sweden)

    Joanna Lee

    Full Text Available The putative Major Facilitator Superfamily (MFS transporter, SV2A, is the target for levetiracetam (LEV, which is a successful anti-epileptic drug. Furthermore, SV2A knock out mice display a severe seizure phenotype and die after a few weeks. Despite this, the mode of action of LEV is not known at the molecular level. It would be extremely desirable to understand this more fully in order to aid the design of improved anti-epileptic compounds. Since there is no structure for SV2A, homology modelling can provide insight into the ligand-binding site. However, it is not a trivial process to build such models, since SV2A has low sequence identity to those MFS transporters whose structures are known. A further level of complexity is added by the fact that it is not known which conformational state of the receptor LEV binds to, as multiple conformational states have been inferred by tomography and ligand binding assays or indeed, if binding is exclusive to a single state. Here, we explore models of both the inward and outward facing conformational states of SV2A (according to the alternating access mechanism for MFS transporters. We use a sequence conservation analysis to help guide the homology modelling process and generate the models, which we assess further with Molecular Dynamics (MD. By comparing the MD results in conjunction with docking and simulation of a LEV-analogue used in radioligand binding assays, we were able to suggest further residues that line the binding pocket. These were confirmed experimentally. In particular, mutation of D670 leads to a complete loss of binding. The results shed light on the way LEV analogues may interact with SV2A and may help with the on-going design of improved anti-epileptic compounds.

  1. Molecular Dynamic Simulation and Inhibitor Prediction of Cysteine Synthase Structured Model as a Potential Drug Target for Trichomoniasis

    Directory of Open Access Journals (Sweden)

    Satendra Singh

    2013-01-01

    Full Text Available In our presented research, we made an attempt to predict the 3D model for cysteine synthase (A2GMG5_TRIVA using homology-modeling approaches. To investigate deeper into the predicted structure, we further performed a molecular dynamics simulation for 10 ns and calculated several supporting analysis for structural properties such as RMSF, radius of gyration, and the total energy calculation to support the predicted structured model of cysteine synthase. The present findings led us to conclude that the proposed model is stereochemically stable. The overall PROCHECK G factor for the homology-modeled structure was −0.04. On the basis of the virtual screening for cysteine synthase against the NCI subset II molecule, we present the molecule 1-N, 4-N-bis [3-(1H-benzimidazol-2-yl phenyl] benzene-1,4-dicarboxamide (ZINC01690699 having the minimum energy score (−13.0 Kcal/Mol and a log P value of 6 as a potential inhibitory molecule used to inhibit the growth of T. vaginalis infection.

  2. Molecular dynamic simulation and inhibitor prediction of cysteine synthase structured model as a potential drug target for trichomoniasis.

    Science.gov (United States)

    Singh, Satendra; Sablok, Gaurav; Farmer, Rohit; Singh, Atul Kumar; Gautam, Budhayash; Kumar, Sunil

    2013-01-01

    In our presented research, we made an attempt to predict the 3D model for cysteine synthase (A2GMG5_TRIVA) using homology-modeling approaches. To investigate deeper into the predicted structure, we further performed a molecular dynamics simulation for 10 ns and calculated several supporting analysis for structural properties such as RMSF, radius of gyration, and the total energy calculation to support the predicted structured model of cysteine synthase. The present findings led us to conclude that the proposed model is stereochemically stable. The overall PROCHECK G factor for the homology-modeled structure was -0.04. On the basis of the virtual screening for cysteine synthase against the NCI subset II molecule, we present the molecule 1-N, 4-N-bis [3-(1H-benzimidazol-2-yl) phenyl] benzene-1,4-dicarboxamide (ZINC01690699) having the minimum energy score (-13.0 Kcal/Mol) and a log P value of 6 as a potential inhibitory molecule used to inhibit the growth of T. vaginalis infection.

  3. Theory of bi-molecular association dynamics in 2D for accurate model and experimental parameterization of binding rates.

    Science.gov (United States)

    Yogurtcu, Osman N; Johnson, Margaret E

    2015-08-28

    The dynamics of association between diffusing and reacting molecular species are routinely quantified using simple rate-equation kinetics that assume both well-mixed concentrations of species and a single rate constant for parameterizing the binding rate. In two-dimensions (2D), however, even when systems are well-mixed, the assumption of a single characteristic rate constant for describing association is not generally accurate, due to the properties of diffusional searching in dimensions d ≤ 2. Establishing rigorous bounds for discriminating between 2D reactive systems that will be accurately described by rate equations with a single rate constant, and those that will not, is critical for both modeling and experimentally parameterizing binding reactions restricted to surfaces such as cellular membranes. We show here that in regimes of intrinsic reaction rate (ka) and diffusion (D) parameters ka/D > 0.05, a single rate constant cannot be fit to the dynamics of concentrations of associating species independently of the initial conditions. Instead, a more sophisticated multi-parametric description than rate-equations is necessary to robustly characterize bimolecular reactions from experiment. Our quantitative bounds derive from our new analysis of 2D rate-behavior predicted from Smoluchowski theory. Using a recently developed single particle reaction-diffusion algorithm we extend here to 2D, we are able to test and validate the predictions of Smoluchowski theory and several other theories of reversible reaction dynamics in 2D for the first time. Finally, our results also mean that simulations of reactive systems in 2D using rate equations must be undertaken with caution when reactions have ka/D > 0.05, regardless of the simulation volume. We introduce here a simple formula for an adaptive concentration dependent rate constant for these chemical kinetics simulations which improves on existing formulas to better capture non-equilibrium reaction dynamics from dilute

  4. Grand canonical Molecular Dynamics Simulations

    CERN Document Server

    Fritsch, S; Junghans, C; Ciccotti, G; Site, L Delle; Kremer, K

    2011-01-01

    For simulation studies of (macro-) molecular liquids it would be of significant interest to be able to adjust/increase the level of resolution within one region of space, while allowing for the free exchange of molecules between (open) regions of different resolution/representation. In the present work we generalize the adaptive resolution idea in terms of a generalized Grand Canonical approach. This provides a robust framework for truly open Molecular Dynamics systems. We apply the method to liquid water at ambient conditions.

  5. A quantum-classical approach to the molecular dynamics of butatriene cation with a realistic model Hamiltonian.

    Science.gov (United States)

    Sardar, Subhankar; Paul, Amit Kumar; Mondal, Padmabati; Sarkar, Biplab; Adhikari, Satrajit

    2008-11-14

    We are investigating the molecular dynamics of the butatriene cation after excitation from the ground state (X(2)B(2g)) to the first excited electronic state (A(2)B(2u)) by using the time-dependent discrete variable representation (TDDVR) method. The investigation is being carried out with a realistic 18-mode model Hamiltonian consisting of all the vibrational degrees of freedom of the butatriene molecule. First, we perform the simulation on a basic five mode model, and then by including additional thirteen modes as bath on the basic model. This sequential inclusion of bath modes demonstrates the effect of so called weak modes on the subsystem, where the calculations of energy and population transfer from the basic model to the bath quantify the same effect. The spectral profile obtained by using the TDDVR approach shows reasonably good agreement with the results calculated by the quantum mechanical approach/experimental measurement. It appears that the TDDVR approach for those large systems where quantum mechanical description is needed in a restricted region, is a good compromise between accuracy and speed.

  6. Evaluation of reptation-based modeling of entangled polymeric fluids including chain rotation via nonequilibrium molecular dynamics simulation

    Science.gov (United States)

    Nafar Sefiddashti, Mohammad Hadi; Edwards, Brian J.; Khomami, Bamin

    2017-08-01

    Recent simulation results of a moderately entangled linear polyethylene C700H1402 liquid have confirmed prior simulation and experimental evidence that individual polymer molecules experience periodic rotation and retraction cycles under steady shear flow at high Weissenberg number. With this insight, theoreticians have begun to grapple with this additional complicating physical phenomenon that needs to be incorporated into rheological models to help explain the data under conditions of high shear. In this paper we examine these recent efforts by using nonequilibrium molecular dynamics simulations to provide insight into the requisite theoretical variables and their assigned evolution equations to evaluate the capability of these tube-based models to predict accurately the simulated data sets. This analysis reveals that the primary variables used in tube models to impart a conceptual basis to the theory, namely, the tube orientation tensor and the tube stretch, remain fundamental system properties even far away from equilibrium; however, the theory describing their evolution under flow is not well suited to quantitative prediction. Furthermore, it is demonstrated that key system properties, such as the entanglement number and disengagement time, should play a more significant role in model development since these quantities can change dramatically under flow, particularly at high Weissenberg number where the chain rotation and retraction cycles dominate the system physics.

  7. Chirikov criterion of resonance overlapping for the model of molecular dynamics

    CERN Document Server

    Guzev, M A

    2012-01-01

    The chaotic dynamics in a cell of particles' chain interacting by means of Lennard-Jones potential is considered. Chirikov criterion of resonance over- lapping is used as the condition of chaos. The asymptotic representation for this function at low and high energies is obtained for the function corresponding to the criterion.

  8. Efficient 3D Kinetic Monte Carlo Method for Modeling of Molecular Structure and Dynamics

    DEFF Research Database (Denmark)

    Panshenskov, Mikhail; Solov'yov, Ilia; Solov'yov, Andrey V.

    2014-01-01

    Self-assembly of molecular systems is an important and general problem that intertwines physics, chemistry, biology, and material sciences. Through understanding of the physical principles of self-organization, it often becomes feasible to control the process and to obtain complex structures with...... the kinetic Monte Carlo approach in a three-dimensional space. We describe the computational side of the developed code, discuss its efficiency, and apply it for studying an exemplary system....

  9. Molecular dynamics simulation of ribosome jam

    KAUST Repository

    Matsumoto, Shigenori

    2011-09-01

    We propose a coarse-grained molecular dynamics model of ribosome molecules to study the dependence of translation process on environmental parameters. We found the model exhibits traffic jam property, which is consistent with an ASEP model. We estimated the influence of the temperature and concentration of molecules on the hopping probability used in the ASEP model. Our model can also treat environmental effects on the translation process that cannot be explained by such cellular automaton models. © 2010 Elsevier B.V. All rights reserved.

  10. Homology modeling and molecular dynamics simulation of the HIF2α degradation-related HIF2α-VHL complex.

    Science.gov (United States)

    Dong, Xiaotian; Su, Xiaoru; Yu, Jiong; Liu, Jingqi; Shi, Xiaowei; Pan, Qiaoling; Yang, Jinfeng; Chen, Jiajia; Li, Lanjuan; Cao, Hongcui

    2017-01-01

    Hypoxia-inducible factor 2 alpha (HIF2α), prolyl hydroxylase domain protein 2 (PHD2), and the von Hippel Lindau tumor suppressor protein (pVHL) are three principal proteins in the oxygen-sensing pathway. Under normoxic conditions, a conserved proline in HIF2α is hydroxylated by PHD2 in an oxygen-dependent manner, and then pVHL binds and promotes the degradation of HIF2α. However, the crystal structure of the HIF2α-pVHL complex has not yet been established, and this has limited research on the interaction between HIF and pVHL. Here, we constructed a structural model of a 23-residue HIF2α peptide (528-550)-pVHL-ElonginB-ElonginC complex by using homology modeling and molecular dynamics simulations. We also applied these methods to HIF2α mutants (HYP531PRO, F540L, A530 V, A530T, and G537R) to reveal structural defects that explain how these mutations weaken the interaction with pVHL. Homology modeling and molecular dynamics simulations were used to construct a three-dimensional (3D) structural model of the HIF2α-VHL complex. Subsequently, MolProbity, an active validation tool, was used to analyze the reliability of the model. Molecular mechanics energies combined with the generalized Born and surface area continuum solvation (MM-GBSA) and solvated interaction energy (SIE) methods were used to calculate the binding free energy between HIF2a and pVHL, and the stability of the simulation system was evaluated by using root mean square deviation (RMSD) analysis. We also determined the secondary structure of the system by using the definition of secondary structure of proteins (DSSP) algorithm. Finally, we investigated the structural significance of specific point mutations known to have clinical implications. We established a reliable structural model of the HIF2α-pVHL complex, which is similar to the crystal structure of HIF1α in 1LQB. Furthermore, we compared the structural model of the HIF2α-pVHL complex and the HIF2α (HYP531P, F540L, A530V, A530T, and G537

  11. Molecular Dynamics Simulation Study of Parallel Telomeric DNA Quadruplexes at Different Ionic Strengths: Evaluation of Water and Ion Models.

    Science.gov (United States)

    Rebič, Matúš; Laaksonen, Aatto; Šponer, Jiří; Uličný, Jozef; Mocci, Francesca

    2016-08-04

    Most molecular dynamics (MD) simulations of DNA quadruplexes have been performed under minimal salt conditions using the Åqvist potential parameters for the cation with the TIP3P water model. Recently, this combination of parameters has been reported to be problematic for the stability of quadruplex DNA, especially caused by the ion interactions inside or near the quadruplex channel. Here, we verify how the choice of ion parameters and water model can affect the quadruplex structural stability and the interactions with the ions outside the channel. We have performed a series of MD simulations of the human full-parallel telomeric quadruplex by neutralizing its negative charge with K(+) ions. Three combinations of different cation potential parameters and water models have been used: (a) Åqvist ion parameters, TIP3P water model; (b) Joung and Cheatham ion parameters, TIP3P water model; and (c) Joung and Cheatham ion parameters, TIP4Pew water model. For the combinations (b) and (c), the effect of the ionic strength has been evaluated by adding increasing amounts of KCl salt (50, 100, and 200 mM). Two independent simulations using the Åqvist parameters with the TIP3P model show that this combination is clearly less suited for the studied quadruplex with K(+) as counterions. In both simulations, one ion escapes from the channel, followed by significant deformation of the structure, leading to deviating conformation compared to that in the reference crystallographic data. For the other combinations of ion and water potentials, no tendency is observed for the channel ions to escape from the quadruplex channel. In addition, the internal mobility of the three loops, torsion angles, and counterion affinity have been investigated at varied salt concentrations. In summary, the selection of ion and water models is crucial as it can affect both the structure and dynamics as well as the interactions of the quadruplex with its counterions. The results obtained with the TIP4Pew

  12. Available Instruments for Analyzing Molecular Dynamics Trajectories.

    Science.gov (United States)

    Likhachev, I V; Balabaev, N K; Galzitskaya, O V

    2016-01-01

    Molecular dynamics trajectories are the result of molecular dynamics simulations. Trajectories are sequential snapshots of simulated molecular system which represents atomic coordinates at specific time periods. Based on the definition, in a text format trajectory files are characterized by their simplicity and uselessness. To obtain information from such files, special programs and information processing techniques are applied: from molecular dynamics animation to finding characteristics along the trajectory (versus time). In this review, we describe different programs for processing molecular dynamics trajectories. The performance of these programs, usefulness for analyses of molecular dynamics trajectories, strong and weak aspects are discussed.

  13. Modeling surface motion effects in N2 dissociation on W(110): Ab initio molecular dynamics calculations and generalized Langevin oscillator model

    Science.gov (United States)

    Nattino, Francesco; Galparsoro, Oihana; Costanzo, Francesca; Díez Muiño, Ricardo; Alducin, Maite; Kroes, Geert-Jan

    2016-06-01

    Accurately modeling surface temperature and surface motion effects is necessary to study molecule-surface reactions in which the energy dissipation to surface phonons can largely affect the observables of interest. We present here a critical comparison of two methods that allow to model such effects, namely, the ab initio molecular dynamics (AIMD) method and the generalized Langevin oscillator (GLO) model, using the dissociation of N2 on W(110) as a benchmark. AIMD is highly accurate as the surface atoms are explicitly part of the dynamics, but this advantage comes with a large computational cost. The GLO model is much more computationally convenient, but accounts for lattice motion effects in a very approximate way. Results show that, despite its simplicity, the GLO model is able to capture the physics of the system to a large extent, returning dissociation probabilities which are in better agreement with AIMD than static-surface results. Furthermore, the GLO model and the AIMD method predict very similar energy transfer to the lattice degrees of freedom in the non-reactive events, and similar dissociation dynamics.

  14. Dynamical Non-Equilibrium Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Giovanni Ciccotti

    2013-12-01

    Full Text Available In this review, we discuss the Dynamical approach to Non-Equilibrium Molecular Dynamics (D-NEMD, which extends stationary NEMD to time-dependent situations, be they responses or relaxations. Based on the original Onsager regression hypothesis, implemented in the nineteen-seventies by Ciccotti, Jacucci and MacDonald, the approach permits one to separate the problem of dynamical evolution from the problem of sampling the initial condition. D-NEMD provides the theoretical framework to compute time-dependent macroscopic dynamical behaviors by averaging on a large sample of non-equilibrium trajectories starting from an ensemble of initial conditions generated from a suitable (equilibrium or non-equilibrium distribution at time zero. We also discuss how to generate a large class of initial distributions. The same approach applies also to the calculation of the rate constants of activated processes. The range of problems treatable by this method is illustrated by discussing applications to a few key hydrodynamic processes (the “classical” flow under shear, the formation of convective cells and the relaxation of an interface between two immiscible liquids.

  15. Coupled molecular dynamics-Monte Carlo model to study the role of chemical processes during laser ablation of polymeric materials.

    Science.gov (United States)

    Prasad, Manish; Conforti, Patrick F; Garrison, Barbara J

    2007-08-28

    The coarse grained chemical reaction model is enhanced to build a molecular dynamics (MD) simulation framework with an embedded Monte Carlo (MC) based reaction scheme. The MC scheme utilizes predetermined reaction chemistry, energetics, and rate kinetics of materials to incorporate chemical reactions occurring in a substrate into the MD simulation. The kinetics information is utilized to set the probabilities for the types of reactions to perform based on radical survival times and reaction rates. Implementing a reaction involves changing the reactants species types which alters their interaction potentials and thus produces the required energy change. We discuss the application of this method to study the initiation of ultraviolet laser ablation in poly(methyl methacrylate). The use of this scheme enables the modeling of all possible photoexcitation pathways in the polymer. It also permits a direct study of the role of thermal, mechanical, and chemical processes that can set off ablation. We demonstrate that the role of laser induced heating, thermomechanical stresses, pressure wave formation and relaxation, and thermochemical decomposition of the polymer substrate can be investigated directly by suitably choosing the potential energy and chemical reaction energy landscape. The results highlight the usefulness of such a modeling approach by showing that various processes in polymer ablation are intricately linked leading to the transformation of the substrate and its ejection. The method, in principle, can be utilized to study systems where chemical reactions are expected to play a dominant role or interact strongly with other physical processes.

  16. Exploration of Novel Inhibitors for Class I Histone Deacetylase Isoforms by QSAR Modeling and Molecular Dynamics Simulation Assays.

    Directory of Open Access Journals (Sweden)

    Zainab Noor

    Full Text Available Histone deacetylases (HDAC are metal-dependent enzymes and considered as important targets for cell functioning. Particularly, higher expression of class I HDACs is common in the onset of multiple malignancies which results in deregulation of many target genes involved in cell growth, differentiation and survival. Although substantial attempts have been made to control the irregular functioning of HDACs by employing various inhibitors with high sensitivity towards transformed cells, limited success has been achieved in epigenetic cancer therapy. Here in this study, we used ligand-based pharmacophore and 2-dimensional quantitative structure activity relationship (QSAR modeling approaches for targeting class I HDAC isoforms. Pharmacophore models were generated by taking into account the known IC50 values and experimental energy scores with extensive validations. The QSAR model having an external R2 value of 0.93 was employed for virtual screening of compound libraries. 10 potential lead compounds (C1-C10 were short-listed having strong binding affinities for HDACs, out of which 2 compounds (C8 and C9 were able to interact with all members of class I HDACs. The potential binding modes of HDAC2 and HDAC8 to C8 were explored through molecular dynamics simulations. Overall, bioactivity and ligand efficiency (binding energy/non-hydrogen atoms profiles suggested that proposed hits may be more effective inhibitors for cancer therapy.

  17. Molecular Dynamics for Dense Matter

    CERN Document Server

    Maruyama, Toshiki; Chiba, Satoshi

    2012-01-01

    We review a molecular dynamics method for nucleon many-body systems called the quantum molecular dynamics (QMD) and our studies using this method. These studies address the structure and the dynamics of nuclear matter relevant to the neutron star crusts, supernova cores, and heavy-ion collisions. A key advantage of QMD is that we can study dynamical processes of nucleon many-body systems without any assumptions on the nuclear structure. First we focus on the inhomogeneous structures of low-density nuclear matter consisting not only of spherical nuclei but also of nuclear "pasta", i.e., rod-like and slab-like nuclei. We show that the pasta phases can appear in the ground and equilibrium states of nuclear matter without assuming nuclear shape. Next we show our simulation of compression of nuclear matter which corresponds to the collapsing stage of supernovae. With increase of density, a crystalline solid of spherical nuclei change to a triangular lattice of rods by connecting neighboring nuclei. Finally, we dis...

  18. Multiscale coupling of molecular dynamics and peridynamics

    Science.gov (United States)

    Tong, Qi; Li, Shaofan

    2016-10-01

    We propose a multiscale computational model to couple molecular dynamics and peridynamics. The multiscale coupling model is based on a previously developed multiscale micromorphic molecular dynamics (MMMD) theory, which has three dynamics equations at three different scales, namely, microscale, mesoscale, and macroscale. In the proposed multiscale coupling approach, we divide the simulation domain into atomistic region and macroscale region. Molecular dynamics is used to simulate atom motions in atomistic region, and peridynamics is used to simulate macroscale material point motions in macroscale region, and both methods are nonlocal particle methods. A transition zone is introduced as a messenger to pass the information between the two regions or scales. We employ the "supercell" developed in the MMMD theory as the transition element, which is named as the adaptive multiscale element due to its ability of passing information from different scales, because the adaptive multiscale element can realize both top-down and bottom-up communications. We introduce the Cauchy-Born rule based stress evaluation into state-based peridynamics formulation to formulate atomistic-enriched constitutive relations. To mitigate the issue of wave reflection on the interface, a filter is constructed by switching on and off the MMMD dynamic equations at different scales. Benchmark tests of one-dimensional (1-D) and two-dimensional (2-D) wave propagations from atomistic region to macro region are presented. The mechanical wave can transit through the interface smoothly without spurious wave deflections, and the filtering process is proven to be efficient.

  19. Exploration of Novel Inhibitors for Bruton’s Tyrosine Kinase by 3D QSAR Modeling and Molecular Dynamics Simulation

    Science.gov (United States)

    Choi, Light; Woo Lee, Keun

    2016-01-01

    Bruton’s tyrosine kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase which is expressed in most of the hematopoietic cells and plays an important role in many cellular signaling pathways. B cell malignancies are dependent on BCR signaling, thus making BTK an efficient therapeutic target. Over the last few years, significant efforts have been made in order to develop BTK inhibitors to treat B-cell malignancies, and autoimmunity or allergy/hypersensitivity but limited success has been achieved. Here in this study, 3D QSAR pharmacophore models were generated for Btk based on known IC50 values and experimental energy scores with extensive validations. The five features pharmacophore model, Hypo1, includes one hydrogen bond acceptor lipid, one hydrogen bond donor, and three hydrophobic features, which has the highest correlation coefficient (0.98), cost difference (112.87), and low RMS (1.68). It was further validated by the Fisher’s randomization method and test set. The well validated Hypo1 was used as a 3D query to search novel Btk inhibitors with different chemical scaffold using high throughput virtual screening technique. The screened compounds were further sorted by applying ADMET properties, Lipinski’s rule of five and molecular docking studies to refine the retrieved hits. Furthermore, molecular dynamic simulation was employed to study the stability of docked conformation and to investigate the binding interactions in detail. Several important hydrogen bonds with Btk were revealed, which includes the gatekeeper residues Glu475 and Met 477 at the hinge region. Overall, this study suggests that the proposed hits may be more effective inhibitors for cancer and autoimmune therapy. PMID:26784025

  20. Exploration of Novel Inhibitors for Bruton's Tyrosine Kinase by 3D QSAR Modeling and Molecular Dynamics Simulation.

    Directory of Open Access Journals (Sweden)

    Rohit Bavi

    Full Text Available Bruton's tyrosine kinase (BTK is a cytoplasmic, non-receptor tyrosine kinase which is expressed in most of the hematopoietic cells and plays an important role in many cellular signaling pathways. B cell malignancies are dependent on BCR signaling, thus making BTK an efficient therapeutic target. Over the last few years, significant efforts have been made in order to develop BTK inhibitors to treat B-cell malignancies, and autoimmunity or allergy/hypersensitivity but limited success has been achieved. Here in this study, 3D QSAR pharmacophore models were generated for Btk based on known IC50 values and experimental energy scores with extensive validations. The five features pharmacophore model, Hypo1, includes one hydrogen bond acceptor lipid, one hydrogen bond donor, and three hydrophobic features, which has the highest correlation coefficient (0.98, cost difference (112.87, and low RMS (1.68. It was further validated by the Fisher's randomization method and test set. The well validated Hypo1 was used as a 3D query to search novel Btk inhibitors with different chemical scaffold using high throughput virtual screening technique. The screened compounds were further sorted by applying ADMET properties, Lipinski's rule of five and molecular docking studies to refine the retrieved hits. Furthermore, molecular dynamic simulation was employed to study the stability of docked conformation and to investigate the binding interactions in detail. Several important hydrogen bonds with Btk were revealed, which includes the gatekeeper residues Glu475 and Met 477 at the hinge region. Overall, this study suggests that the proposed hits may be more effective inhibitors for cancer and autoimmune therapy.

  1. Exploration of Novel Inhibitors for Bruton's Tyrosine Kinase by 3D QSAR Modeling and Molecular Dynamics Simulation.

    Science.gov (United States)

    Bavi, Rohit; Kumar, Raj; Choi, Light; Woo Lee, Keun

    2016-01-01

    Bruton's tyrosine kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase which is expressed in most of the hematopoietic cells and plays an important role in many cellular signaling pathways. B cell malignancies are dependent on BCR signaling, thus making BTK an efficient therapeutic target. Over the last few years, significant efforts have been made in order to develop BTK inhibitors to treat B-cell malignancies, and autoimmunity or allergy/hypersensitivity but limited success has been achieved. Here in this study, 3D QSAR pharmacophore models were generated for Btk based on known IC50 values and experimental energy scores with extensive validations. The five features pharmacophore model, Hypo1, includes one hydrogen bond acceptor lipid, one hydrogen bond donor, and three hydrophobic features, which has the highest correlation coefficient (0.98), cost difference (112.87), and low RMS (1.68). It was further validated by the Fisher's randomization method and test set. The well validated Hypo1 was used as a 3D query to search novel Btk inhibitors with different chemical scaffold using high throughput virtual screening technique. The screened compounds were further sorted by applying ADMET properties, Lipinski's rule of five and molecular docking studies to refine the retrieved hits. Furthermore, molecular dynamic simulation was employed to study the stability of docked conformation and to investigate the binding interactions in detail. Several important hydrogen bonds with Btk were revealed, which includes the gatekeeper residues Glu475 and Met 477 at the hinge region. Overall, this study suggests that the proposed hits may be more effective inhibitors for cancer and autoimmune therapy.

  2. Computationally Efficient Multiconfigurational Reactive Molecular Dynamics.

    Science.gov (United States)

    Yamashita, Takefumi; Peng, Yuxing; Knight, Chris; Voth, Gregory A

    2012-12-11

    It is a computationally demanding task to explicitly simulate the electronic degrees of freedom in a system to observe the chemical transformations of interest, while at the same time sampling the time and length scales required to converge statistical properties and thus reduce artifacts due to initial conditions, finite-size effects, and limited sampling. One solution that significantly reduces the computational expense consists of molecular models in which effective interactions between particles govern the dynamics of the system. If the interaction potentials in these models are developed to reproduce calculated properties from electronic structure calculations and/or ab initio molecular dynamics simulations, then one can calculate accurate properties at a fraction of the computational cost. Multiconfigurational algorithms model the system as a linear combination of several chemical bonding topologies to simulate chemical reactions, also sometimes referred to as "multistate". These algorithms typically utilize energy and force calculations already found in popular molecular dynamics software packages, thus facilitating their implementation without significant changes to the structure of the code. However, the evaluation of energies and forces for several bonding topologies per simulation step can lead to poor computational efficiency if redundancy is not efficiently removed, particularly with respect to the calculation of long-ranged Coulombic interactions. This paper presents accurate approximations (effective long-range interaction and resulting hybrid methods) and multiple-program parallelization strategies for the efficient calculation of electrostatic interactions in reactive molecular simulations.

  3. Microscopic dynamical description of proton-induced fission with the Constrained Molecular Dynamics (CoMD) Model

    CERN Document Server

    Vonta, N; Veselsky, M; Bonasera, A

    2015-01-01

    The microscopic description of nuclear fission still remains a topic of intense basic research. Un- derstanding nuclear fission, apart from a theoretical point of view, is of practical importance for energy production and the transmutation of nuclear waste. In nuclear astrophysics, fission sets the upper limit to the nucleosynthesis of heavy elements via the r-process. In this work we initiated a systematic study of intermediate energy proton-induced fission using the Constrained Molecu- lar Dynamics (CoMD) code. The CoMD code implements an effective interaction with a nuclear matter compressibility of K=200 (soft EOS) with several forms of the density dependence of the nucleon-nucleon symmetry potential. Moreover, a constraint is imposed in the phase-space occu- pation for each nucleon restoring the Pauli principle at each time step of the collision. A proper choice of the surface parameter of the effective interaction has been made to describe fission. In this work, we present results of fission calculation...

  4. Structural insight into tetrameric hTRPV1 from homology modeling, molecular docking, molecular dynamics simulation, virtual screening, and bioassay validations.

    Science.gov (United States)

    Feng, Zhiwei; Pearce, Larry V; Xu, Xiaomeng; Yang, Xiaole; Yang, Peng; Blumberg, Peter M; Xie, Xiang-Qun

    2015-03-23

    The transient receptor potential vanilloid type 1 (TRPV1) is a heat-activated cation channel protein, which contributes to inflammation, acute and persistent pain. Antagonists of human TRPV1 (hTRPV1) represent a novel therapeutic approach for the treatment of pain. Developing various antagonists of hTRPV1, however, has been hindered by the unavailability of a 3D structure of hTRPV1. Recently, the 3D structures of rat TRPV1 (rTRPV1) in the presence and absence of ligand have been reported as determined by cryo-EM. rTRPV1 shares 85.7% sequence identity with hTRPV1. In the present work, we constructed and reported the 3D homology tetramer model of hTRPV1 based on the cryo-EM structures of rTRPV1. Molecular dynamics (MD) simulations, energy minimizations, and prescreen were applied to select and validate the best model of hTRPV1. The predicted binding pocket of hTRPV1 consists of two adjacent monomers subunits, which were congruent with the experimental rTRPV1 data and the cyro-EM structures of rTRPV1. The detailed interactions between hTRPV1 and its antagonists or agonists were characterized by molecular docking, which helped us to identify the important residues. Conformational changes of hTRPV1 upon antagonist/agonist binding were also explored by MD simulation. The different movements of compounds led to the different conformational changes of monomers in hTRPV1, indicating that TRPV1 works in a concerted way, resembling some other channel proteins such as aquaporins. We observed that the selective filter was open when hTRPV1 bound with an agonist during MD simulation. For the lower gate of hTRPV1, we observed large similarities between hTRPV1 bound with antagonist and with agonist. A five-point pharmacophore model based on several antagonists was established, and the structural model was used to screen in silico for new antagonists for hTRPV1. By using the 3D TRPV1 structural model above, the pilot in silico screening has begun to yield promising hits with

  5. Variations in calcite growth kinetics with surface topography: molecular dynamics simulations and process-based growth kinetics modelling

    NARCIS (Netherlands)

    Wolthers, M.; Di Tommaso, D.; Du, Zhimei; de Leeuw, Nora H.

    2013-01-01

    It is generally accepted that cation dehydration is the rate-limiting step to crystal growth from aqueous solution. Here we employ classical molecular dynamics simulations to show that the water exchange frequency at structurally distinct calcium sites in the calcite surface varies by about two orde

  6. Molecular dynamics simulations of cyclosporin A: The crystal structure and dynamic modelling of a structure in apolar solution based on NMR data

    Science.gov (United States)

    Lautz, J.; Kessler, H.; Kaptein, R.; van Gunsteren, W. F.

    1987-10-01

    The conformation of the immunosuppressive drug cyclosporin A (CPA), both in apolar solution and in crystalline state, has been studied by computer simulation techniques. Three molecular dynamics (MD) simulations have been performed: one modelling the crystal structure and two modelling the structure in apolar solution, using a restrained MD approach in which data from nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy are taken into account. The simulation of the crystalline state (MDC) concerns a system of 4 unit cells containing 16 cyclosporin A molecules and 22 water molecules, which is simulated using crystalline periodic boundary conditions. The simulations modelling the apolar solvent conformation (MDS) concern one isolated cyclosporin A molecule. In these simulations an extra term in the interatomic potential function is used, which forces the molecule to satisfy a set of 57 atom-atom distance constraints originating from nuclear Overhauser effects (NOEs) obtained from NMR spectroscopy and one distance constraint deduced from IR spectroscopy. From a comparison of the results of the crystal simulation to those of the X-ray experiment in terms of structure, atomic fluctuations, hydrogen bond pattern, etc., it is concluded that the force field that is used yields an adequate representation of crystalline cyclosporin A. Secondly, it is shown that the dynamic modelling technique that is used to obtain a structure in a polar solution from NMR distance information works well. Starting from initial conformations which have a root mean square difference of 0.14 nm both distance restrained MD simulations converge to the same final solution structure. A comparison of the crystal structure of cyclosporin A and the one in apolar solution shows that there are significant differences. The overall difference in atomic positions is 0.09 nm for the Cx atoms and 0.17 nm for all atoms. In apolar solution, the molecule is slightly more bent and the side chains of 1

  7. Modelling the local atomic structure of molybdenum in nuclear waste glasses with ab initio molecular dynamics simulations.

    Science.gov (United States)

    Konstantinou, Konstantinos; Sushko, Peter V; Duffy, Dorothy M

    2016-09-21

    The nature of chemical bonding of molybdenum in high level nuclear waste glasses has been elucidated by ab initio molecular dynamics simulations. Two compositions, (SiO2)57.5-(B2O3)10-(Na2O)15-(CaO)15-(MoO3)2.5 and (SiO2)57.3-(B2O3)20-(Na2O)6.8-(Li2O)13.4-(MoO3)2.5, were considered in order to investigate the effect of ionic and covalent components on the glass structure and the formation of the crystallisation precursors (Na2MoO4 and CaMoO4). The coordination environments of Mo cations and the corresponding bond lengths calculated from our model are in excellent agreement with experimental observations. The analysis of the first coordination shell reveals two different types of molybdenum host matrix bonds in the lithium sodium borosilicate glass. Based on the structural data and the bond valence model, we demonstrate that the Mo cation can be found in a redox state and the molybdate tetrahedron can be connected with the borosilicate network in a way that inhibits the formation of crystalline molybdates. These results significantly extend our understanding of bonding in Mo-containing nuclear waste glasses and demonstrate that tailoring the glass composition to specific heavy metal constituents can facilitate incorporation of heavy metals at high concentrations.

  8. Molecular Dynamics Modeling of the Effect of Axial and Transverse Compression on the Residual Tensile Properties of Ballistic Fiber

    Directory of Open Access Journals (Sweden)

    Sanjib C. Chowdhury

    2017-02-01

    Full Text Available Ballistic impact induces multiaxial loading on Kevlar® and polyethylene fibers used in protective armor systems. The influence of multiaxial loading on fiber failure is not well understood. Experiments show reduction in the tensile strength of these fibers after axial and transverse compression. In this paper, we use molecular dynamics (MD simulations to explain and develop a fundamental understanding of this experimental observation since the property reduction mechanism evolves from the atomistic level. An all-atom MD method is used where bonded and non-bonded atomic interactions are described through a state-of-the-art reactive force field. Monotonic tension simulations in three principal directions of the models are conducted to determine the anisotropic elastic and strength properties. Then the models are subjected to multi-axial loads—axial compression, followed by axial tension and transverse compression, followed by axial tension. MD simulation results indicate that pre-compression distorts the crystal structure, inducing preloading of the covalent bonds and resulting in lower tensile properties.

  9. Model-free methods of analyzing domain motions in proteins from simulation : A comparison of normal mode analysis and molecular dynamics simulation of lysozyme

    NARCIS (Netherlands)

    Hayward, S; Kitao, A; Berendsen, HJC

    1997-01-01

    Model-free methods are introduced to determine quantities pertaining to protein domain motions from normal mode analyses and molecular dynamics simulations, For the normal mode analysis, the methods are based on the assumption that in low frequency modes, domain motions can be well approximated by m

  10. Molecular Biodynamers : Dynamic Covalent Analogues of Biopolymers

    NARCIS (Netherlands)

    Liu, Yun; Lehn, Jean-Marie; Hirsch, Anna K H

    2017-01-01

    Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and

  11. Molecular Biodynamers : Dynamic Covalent Analogues of Biopolymers

    NARCIS (Netherlands)

    Liu, Yun; Lehn, Jean-Marie; Hirsch, Anna K H

    2017-01-01

    Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and

  12. Matching a surface complexation model with ab initio molecular dynamics: montmorillonite case

    Energy Technology Data Exchange (ETDEWEB)

    Kulik, D.A.; Churakov, S.V. [Paul Scherrer Institute, Nuclear Energy and Safety Dpt., Lab. for Waste Management, CH-5232 Villigen PSI (Switzerland)

    2005-07-01

    Speciation modelling of sorption on mineral-water interfaces is performed with help of surface complexation models (SCM), suitable for diluted suspensions that seem to reach adsorption equilibrium within laboratory times. Electrostatic SCMs need several input parameters even for a relatively simple oxide mineral surface. Moreover, the electrolyte ion adsorption constants in triple layer (TL) or basic Stern (BS) models depend on the inner layer capacitance density Cl, but clear physical understanding of this parameter is missing so far. SCMs can fit acidimetric or metal titration data well at quite different combinations of input parameters, and this fact casts doubt on any interpretation of fitted parameter values in terms of microscopic physicochemical mechanisms. The problem is even deeper in SCMs for clay minerals like montmorillonite having at least two surface types: the edges exposing different (aluminol and silanol) functional groups, and the basal siloxane planes with permanent charge and ion exchange. A feasible way to overcome the caveat of SCMs is seen nowadays in relying on crystallographic data and ab initio calculations to restrict the EDL setup, species stoichiometries, and input parameter values when constructing the adsorption model. The aim of this contribution is to discuss how recent advances in sample surface characterization an d in quantum-chemistry calculations for pyrophyllite can help in putting together a multi-site-surface electrostatic SCM for montmorillonite implemented in GEM approach. The quality of macroscopic model fits is checked against the titration data. (authors)

  13. A polarizable model of water for molecular dynamics simulations of biomolecules

    Science.gov (United States)

    Lamoureux, Guillaume; Harder, Edward; Vorobyov, Igor V.; Roux, Benoît; MacKerell, Alexander D.

    2006-01-01

    The SWM4-DP polarizable water model [G. Lamoureux, A.D. MacKerell, Jr., B. Roux, J. Chem. Phys. 119 (2003) 5185], based on classical Drude oscillators, is re-optimized for negatively charged Drude particles. The new model, called SWM4-NDP, will be incorporated into a polarizable biomolecular force field currently in development. It is calibrated to reproduce important properties of the neat liquid at room temperature and pressure: vaporization enthalpy, density, static dielectric constant and self-diffusion constant. In this Letter, we also show that it yields the correct liquid shear viscosity and free energy of hydration.

  14. Scalable molecular dynamics with NAMD.

    Science.gov (United States)

    Phillips, James C; Braun, Rosemary; Wang, Wei; Gumbart, James; Tajkhorshid, Emad; Villa, Elizabeth; Chipot, Christophe; Skeel, Robert D; Kalé, Laxmikant; Schulten, Klaus

    2005-12-01

    NAMD is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD scales to hundreds of processors on high-end parallel platforms, as well as tens of processors on low-cost commodity clusters, and also runs on individual desktop and laptop computers. NAMD works with AMBER and CHARMM potential functions, parameters, and file formats. This article, directed to novices as well as experts, first introduces concepts and methods used in the NAMD program, describing the classical molecular dynamics force field, equations of motion, and integration methods along with the efficient electrostatics evaluation algorithms employed and temperature and pressure controls used. Features for steering the simulation across barriers and for calculating both alchemical and conformational free energy differences are presented. The motivations for and a roadmap to the internal design of NAMD, implemented in C++ and based on Charm++ parallel objects, are outlined. The factors affecting the serial and parallel performance of a simulation are discussed. Finally, typical NAMD use is illustrated with representative applications to a small, a medium, and a large biomolecular system, highlighting particular features of NAMD, for example, the Tcl scripting language. The article also provides a list of the key features of NAMD and discusses the benefits of combining NAMD with the molecular graphics/sequence analysis software VMD and the grid computing/collaboratory software BioCoRE. NAMD is distributed free of charge with source code at www.ks.uiuc.edu. (c) 2005 Wiley Periodicals, Inc.

  15. Rheology via nonequilibrium molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Hoover, W.G.

    1982-10-01

    The equilibrium molecular dynamics formulated by Newton, Lagrange, and Hamilton has been modified in order to simulate rheologial molecular flows with fast computers. This modified Nonequilibrium Molecular Dynamics (NEMD) has been applied to fluid and solid deformations, under both homogeneous and shock conditions, as well as to the transport of heat. The irreversible heating associated with dissipation could be controlled by carrying out isothermal NEMD calculations. The new isothermal NEMD equations of motion are consistent with Gauss' 1829 Least-Constraint principle as well as certain microscopic equilibrium and nonequilibrium statistical formulations due to Gibbs and Boltzmann. Application of isothermal NEMD revealed high-frequency and high-strain-rate behavior for simple fluids which resembled the behavior of polymer solutions and melts at lower frequencies and strain rates. For solids NEMD produces plastic flows consistent with experimental observations at much lower strain rates. The new nonequilibrium methods also suggest novel formulations of thermodynamics in nonequilibrium systems and shed light on the failure of the Principle of Material Frame Indifference.

  16. Molecular Exchange Dynamics in Block Copolymer Micelles

    Science.gov (United States)

    Bates, Frank; Lu, Jie; Choi, Soohyung; Lodge, Timothy

    2012-02-01

    Poly(styrene-b-ethylene propylene) (PS-PEP) diblock copolymers were mixed with squalane (C30H62) at 1% by weight resulting in the formation of spherical micelles. The structure and dynamics of molecular exchange were characterized by synchrotron small-angle x-ray scattering (SAXS) and time resolved small-angle neutron scattering (TR-SANS), respectively, between 100 C and 160 C. TR-SANS measurements were performed with solutions initially containing deuterium labeled micelle cores and normal cores dispersed in a contrast matched squalane. Monitoring the reduction in scattering intensity as a function of time at various temperatures revealed molecular exchange dynamics highly sensitive to the core molecular weight and molecular weight distribution. Time-temperature superposition of data acquired at different temperatures produced a single master curve for all the mixtures. Experiments conducted with isotopically labeled micelle cores, each formed from two different but relatively mondisperse PS blocks, confirmed a simple dynamical model based on first order kinetics and core Rouse single chain relaxation. These findings demonstrate a dramatic transition to nonergodicity with increasing micelle core molecular weight and confirm the origins of the logarithmic exchange kinetics in such systems.

  17. Dynamic Maintenance and Visualization of Molecular Surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Bajaj, C L; Pascucci, V; Shamir, A; Holt, R J; Netravali, A N

    2004-12-16

    Molecular surface computations are often necessary in order to perform synthetic drug design. A critical step in this process is the computation and update of an exact boundary representation for the molecular surface (e.g. the Lee-Richards surface). In this paper they introduce efficient techniques for computing a molecular surface boundary representation as a set of NURBS (non-uniform rational B-splines) patches. This representation introduces for molecules the same geometric data structure used in the solid modeling community and enables immediate access to a wide range of modeling operations and techniques. Furthermore, this allows the use of any general solid modeling or visualization system as a molecular modeling interface. However, using such a representation in a molecular modeling environment raises several efficiency and update constraints, especially in a dynamic setting. For example, changes in the probe radius result in both geometric and topological changes to the set of patches. The techniques provide the option of trading accuracy of the representation for the efficiency of the computation, while still tracking the changes in the set of patches. In particular, they discuss two main classes of dynamic updates: one that keeps the topology of the molecular configuration fixed, and a more complicated case where the topology may be updated continuously. In general the generated output surface is represented in a format that can be loaded into standard solid modeling systems. It can also be directly triangulated or rendered, possibly at different levels of resolution, by a standard graphics library such as OpenGL without any additional effort.

  18. Homology modeling, molecular dynamics, e-pharmacophore mapping and docking study of Chikungunya virus nsP2 protease.

    Science.gov (United States)

    Singh, Kh Dhanachandra; Kirubakaran, Palani; Nagarajan, Shanthi; Sakkiah, Sugunadevi; Muthusamy, Karthikeyan; Velmurgan, Devadasan; Jeyakanthan, Jeyaraman

    2012-01-01

    To date, no suitable vaccine or specific antiviral drug is available to treat Chikungunya viral (CHIKV) fever. Hence, it is essential to identify drug candidates that could potentially impede CHIKV infection. Here, we present the development of a homology model of nsP2 protein based on the crystal structure of the nsP2 protein of Venezuelan equine encephalitis virus (VEEV). The protein modeled was optimized using molecular dynamics simulation; the junction peptides of a nonstructural protein complex were then docked in order to investigate the possible protein-protein interactions between nsP2 and the proteins cleaved by nsP2. The modeling studies conducted shed light on the binding modes, and the critical interactions with the peptides provide insight into the chemical features needed to inhibit the CHIK virus infection. Energy-optimized pharmacophore mapping was performed using the junction peptides. Based on the results, we propose the pharmacophore features that must be present in an inhibitor of nsP2 protease. The resulting pharmacophore model contained an aromatic ring, a hydrophobic and three hydrogen-bond donor sites. Using these pharmacophore features, we screened a large public library of compounds (Asinex, Maybridge, TOSLab, Binding Database) to find a potential ligand that could inhibit the nsP2 protein. The compounds that yielded a fitness score of more than 1.0 were further subjected to Glide HTVS and Glide XP. Here, we report the best four compounds based on their docking scores; these compounds have IDs of 27943, 21362, ASN 01107557 and ASN 01541696. We propose that these compounds could bind to the active site of nsP2 protease and inhibit this enzyme. Furthermore, the backbone structural scaffolds of these four lead compounds could serve as building blocks when designing drug-like molecules for the treatment of Chikungunya viral fever.

  19. Comparative modeling and molecular dynamics suggest high carboxylase activity of the Cyanobium sp. CACIAM14 RbcL protein.

    Science.gov (United States)

    Siqueira, Andrei Santos; Lima, Alex Ranieri Jerônimo; Dall'Agnol, Leonardo Teixeira; de Azevedo, Juliana Simão Nina; da Silva Gonçalves Vianez, João Lídio; Gonçalves, Evonnildo Costa

    2016-03-01

    Rubisco catalyzes the first step reaction in the carbon fixation pathway, bonding atmospheric CO2/O2 to ribulose 1,5-bisphosphate; it is therefore considered one of the most important enzymes in the biosphere. Genetic modifications to increase the carboxylase activity of rubisco are a subject of great interest to agronomy and biotechnology, since this could increase the productivity of biomass in plants, algae and cyanobacteria and give better yields in crops and biofuel production. Thus, the aim of this study was to characterize in silico the catalytic domain of the rubisco large subunit (rbcL gene) of Cyanobium sp. CACIAM14, and identify target sites to improve enzyme affinity for ribulose 1,5-bisphosphate. A three-dimensional model was built using MODELLER 9.14, molecular dynamics was used to generate a 100 ns trajectory by AMBER12, and the binding free energy was calculated using MM-PBSA, MM-GBSA and SIE methods with alanine scanning. The model obtained showed characteristics of form-I rubisco, with 15 beta sheets and 19 alpha helices, and maintained the highly conserved catalytic site encompassing residues Lys175, Lys177, Lys201, Asp203, and Glu204. The binding free energy of the enzyme-substrate complexation of Cyanobium sp. CACIAM14 showed values around -10 kcal mol(-1) using the SIE method. The most important residues for the interaction with ribulose 1,5-bisphosphate were Arg295 followed by Lys334. The generated model was successfully validated, remaining stable during the whole simulation, and demonstrated characteristics of enzymes with high carboxylase activity. The binding analysis revealed candidates for directed mutagenesis sites to improve rubisco's affinity.

  20. Atomic dynamics of alumina melt: A molecular dynamics simulation study

    Directory of Open Access Journals (Sweden)

    S.Jahn

    2008-03-01

    Full Text Available The atomic dynamics of Al2O3 melt are studied by molecular dynamics simulation. The particle interactions are described by an advanced ionic interaction model that includes polarization effects and ionic shape deformations. The model has been shown to reproduce accurately the static structure factors S(Q from neutron and x-ray diffraction and the dynamic structure factor S(Q,ω from inelastic x-ray scattering. Analysis of the partial dynamic structure factors shows inelastic features in the spectra up to momentum transfers, Q, close to the principal peaks of partial static structure factors. The broadening of the Brillouin line widths is discussed in terms of a frequency dependent viscosity η(ω.

  1. Dynamics and Thermodynamics of Molecular Machines

    DEFF Research Database (Denmark)

    Golubeva, Natalia

    2014-01-01

    Molecular machines, or molecular motors, are small biophysical devices that perform a variety of essential metabolic processes such as DNA replication, protein synthesis and intracellular transport. Typically, these machines operate by converting chemical energy into motion and mechanical work. Due...... to their microscopic size, molecular motors are governed by principles fundamentally different from those describing the operation of man-made motors such as car engines. In this dissertation the dynamic and thermodynamic properties of molecular machines are studied using the tools of nonequilibrium statistical...... of the important trade-off between power output and efficiency. Steric motor-motor interactions are shown to play an important thermodynamic role by enhancing the EMP as compared to the noninteracting case. Remarkably, the enhancement occurs at biologically relevant parameters. Finally, a generic model of motor...

  2. Homology modeling, molecular dynamics, and virtual screening of NorA efflux pump inhibitors of Staphylococcus aureus

    Science.gov (United States)

    Bhaskar, Baki Vijaya; Babu, Tirumalasetty Muni Chandra; Reddy, Netala Vasudeva; Rajendra, Wudayagiri

    2016-01-01

    Emerging drug resistance in clinical isolates of Staphylococcus aureus might be implicated to the overexpression of NorA efflux pump which is capable of extruding numerous structurally diverse compounds. However, NorA efflux pump is considered as a potential drug target for the development of efflux pump inhibitors. In the present study, NorA model was constructed based on the crystal structure of glycerol-3-phosphate transporter (PDBID: 1PW4). Molecular dynamics (MD) simulation was performed using NAMD2.7 for NorA which is embedded in the hydrated lipid bilayer. Structural design of NorA unveils amino (N)- and carboxyl (C)-terminal domains which are connected by long cytoplasmic loop. N and C domains are composed of six transmembrane α-helices (TM) which exhibits pseudo-twofold symmetry and possess voluminous substrate binding cavity between TM helices. Molecular docking of reserpine, totarol, ferruginol, salvin, thioxanthene, phenothiazine, omeprazole, verapamil, nalidixic acid, ciprofloxacin, levofloxacin, and acridine to NorA found that all the molecules were bound at the large hydrophobic cleft and indicated significant interactions with the key residues. In addition, structure-based virtual screening was employed which indicates that 14 potent novel lead molecules such as CID58685302, CID58685367, CID5799283, CID5578487, CID60028372, ZINC12196383, ZINC72140751, ZINC72137843, ZINC39227983, ZINC43742707, ZINC12196375, ZINC66166948, ZINC39228014, and ZINC14616160 have highest binding affinity for NorA. These lead molecules displayed considerable pharmacological properties as evidenced by Lipinski rule of five and prophecy of toxicity risk assessment. Thus, the present study will be helpful in designing and synthesis of a novel class of NorA efflux pump inhibitors that restore the susceptibilities of drug compounds. PMID:27757014

  3. Molecular dynamics study of lipid bilayers modeling the plasma membranes of normal murine thymocytes and leukemic GRSL cells.

    Science.gov (United States)

    Andoh, Yoshimichi; Okazaki, Susumu; Ueoka, Ryuichi

    2013-04-01

    Molecular dynamics (MD) calculations for the plasma membranes of normal murine thymocytes and thymus-derived leukemic GRSL cells in water have been performed under physiological isothermal-isobaric conditions (310.15K and 1 atm) to investigate changes in membrane properties induced by canceration. The model membranes used in our calculations for normal and leukemic thymocytes comprised 23 and 25 kinds of lipids, respectively, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, lysophospholipids, and cholesterol. The mole fractions of the lipids adopted here were based on previously published experimental values. Our calculations clearly showed that the membrane area was increased in leukemic cells, and that the isothermal area compressibility of the leukemic plasma membranes was double that of normal cells. The calculated membranes of leukemic cells were thus considerably bulkier and softer in the lateral direction compared with those of normal cells. The tilt angle of the cholesterol and the conformation of the phospholipid fatty acid tails both showed a lower level of order in leukemic cell membranes compared with normal cell membranes. The lateral radial distribution function of the lipids also showed a more disordered structure in leukemic cell membranes than in normal cell membranes. These observations all show that, for the present thymocytes, the lateral structure of the membrane is considerably disordered by canceration. Furthermore, the calculated lateral self-diffusion coefficient of the lipid molecules in leukemic cell membranes was almost double that in normal cell membranes. The calculated rotational and wobbling autocorrelation functions also indicated that the molecular motion of the lipids was enhanced in leukemic cell membranes. Thus, here we have demonstrated that the membranes of thymocyte leukemic cells are more disordered and more fluid than normal cell membranes.

  4. Adsorption of Synthetic Cationic Polymers on Model Phospholipid Membranes: Insight from Atomic-Scale Molecular Dynamics Simulations.

    Science.gov (United States)

    Kostritskii, Andrei Yu; Kondinskaia, Diana A; Nesterenko, Alexey M; Gurtovenko, Andrey A

    2016-10-11

    Although synthetic cationic polymers represent a promising class of effective antibacterial agents, the molecular mechanisms behind their antimicrobial activity remain poorly understood. To this end, we employ atomic-scale molecular dynamics simulations to explore adsorption of several linear cationic polymers of different chemical structure and protonation (polyallylamine (PAA), polyethylenimine (PEI), polyvinylamine (PVA), and poly-l-lysine (PLL)) on model bacterial membranes (4:1 mixture of zwitterionic phosphatidylethanolamine (PE) and anionic phosphatidylglycerol (PG) lipids). Overall, our findings show that binding of polycations to the anionic membrane surface effectively neutralizes its charge, leading to the reorientation of water molecules close to the lipid/water interface and to the partial release of counterions to the water phase. In certain cases, one has even an overcharging of the membrane, which was shown to be a cooperative effect of polymer charges and lipid counterions. Protonated amine groups of polycations are found to interact preferably with head groups of anionic lipids, giving rise to formation of hydrogen bonds and to a noticeable lateral immobilization of the lipids. While all the above findings are mostly defined by the overall charge of a polymer, we found that the polymer architecture also matters. In particular, PVA and PEI are able to accumulate anionic PG lipids on the membrane surface, leading to lipid segregation. In turn, PLL whose charge twice exceeds charges of PVA/PEI does not induce such lipid segregation due to its considerably less compact architecture and relatively long side chains. We also show that partitioning of a polycation into the lipid/water interface is an interplay between its protonation level (the overall charge) and hydrophobicity of the backbone. Therefore, a possible strategy in creating highly efficient antimicrobial polymeric agents could be in tuning these polycation's properties through proper

  5. Better, Cheaper, Faster Molecular Dynamics

    Science.gov (United States)

    Pohorille, Andrew; DeVincenzi, Donald L. (Technical Monitor)

    2001-01-01

    Recent, revolutionary progress in genomics and structural, molecular and cellular biology has created new opportunities for molecular-level computer simulations of biological systems by providing vast amounts of data that require interpretation. These opportunities are further enhanced by the increasing availability of massively parallel computers. For many problems, the method of choice is classical molecular dynamics (iterative solving of Newton's equations of motion). It focuses on two main objectives. One is to calculate the relative stability of different states of the system. A typical problem that has' such an objective is computer-aided drug design. Another common objective is to describe evolution of the system towards a low energy (possibly the global minimum energy), "native" state. Perhaps the best example of such a problem is protein folding. Both types of problems share the same difficulty. Often, different states of the system are separated by high energy barriers, which implies that transitions between these states are rare events. This, in turn, can greatly impede exploration of phase space. In some instances this can lead to "quasi non-ergodicity", whereby a part of phase space is inaccessible on time scales of the simulation. To overcome this difficulty and to extend molecular dynamics to "biological" time scales (millisecond or longer) new physical formulations and new algorithmic developments are required. To be efficient they should account for natural limitations of multi-processor computer architecture. I will present work along these lines done in my group. In particular, I will focus on a new approach to calculating the free energies (stability) of different states and to overcoming "the curse of rare events". I will also discuss algorithmic improvements to multiple time step methods and to the treatment of slowly decaying, log-ranged, electrostatic effects.

  6. Evaluation of protein-protein docking model structures using all-atom molecular dynamics simulations combined with the solution theory in the energy representation.

    Science.gov (United States)

    Takemura, Kazuhiro; Guo, Hao; Sakuraba, Shun; Matubayasi, Nobuyuki; Kitao, Akio

    2012-12-07

    We propose a method to evaluate binding free energy differences among distinct protein-protein complex model structures through all-atom molecular dynamics simulations in explicit water using the solution theory in the energy representation. Complex model structures are generated from a pair of monomeric structures using the rigid-body docking program ZDOCK. After structure refinement by side chain optimization and all-atom molecular dynamics simulations in explicit water, complex models are evaluated based on the sum of their conformational and solvation free energies, the latter calculated from the energy distribution functions obtained from relatively short molecular dynamics simulations of the complex in water and of pure water based on the solution theory in the energy representation. We examined protein-protein complex model structures of two protein-protein complex systems, bovine trypsin/CMTI-1 squash inhibitor (PDB ID: 1PPE) and RNase SA/barstar (PDB ID: 1AY7), for which both complex and monomer structures were determined experimentally. For each system, we calculated the energies for the crystal complex structure and twelve generated model structures including the model most similar to the crystal structure and very different from it. In both systems, the sum of the conformational and solvation free energies tended to be lower for the structure similar to the crystal. We concluded that our energy calculation method is useful for selecting low energy complex models similar to the crystal structure from among a set of generated models.

  7. Thermodynamic properties and shear viscosity over entropy density ratio of nuclear fireball in a quantum-molecular dynamics model

    CERN Document Server

    Zhou, C L; Fang, D Q; Zhang, G Q

    2013-01-01

    Thermodynamic and transport properties of nuclear fireball created in the central region of heavy-ion collisions below 200 MeV/nucleon are investigated within the isospin-dependent quantum molecular dynamic (IQMD) model. These properties include time evolutions of the density, temperature, chemical potential, entropy density ($s$) and shear viscosity ($\\eta$) as well as density and temperature dependencies of the ratio of shear viscosity over entropy density ($\\eta/s$) etc. Based on the shear viscosity parametrization developed by Danilewicz and entropy density which is obtained by a generalized hot Thomas Fermi formalism, the ratio of shear viscosity over entropy density is calculated in the whole collision process as well as in the freeze-out stage. With the collision goes on, a transient minimal $\\eta/s$ with the value around 5/$4\\pi$ occurs in the largest compression stage. While, the relationship of $\\eta/s$ to tempertaure ($T$) in the freeze-out stage displays a local minimum which is about 9-10 times $...

  8. Similarities and differences of serotonin and its precursors in their interactions with model membranes studied by molecular dynamics simulation

    Science.gov (United States)

    Wood, Irene; Martini, M. Florencia; Pickholz, Mónica

    2013-08-01

    In this work, we report a molecular dynamics (MD) simulations study of relevant biological molecules as serotonin (neutral and protonated) and its precursors, tryptophan and 5-hydroxy-tryptophan, in a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline (POPC). The simulations were carried out at the fluid lamellar phase of POPC at constant pressure and temperature conditions. Two guest molecules of each type were initially placed at the water phase. We have analyzed, the main localization, preferential orientation and specific interactions of the guest molecules within the bilayer. During the simulation run, the four molecules were preferentially found at the water-lipid interphase. We found that the interactions that stabilized the systems are essentially hydrogen bonds, salt bridges and cation-π. None of the guest molecules have access to the hydrophobic region of the bilayer. Besides, zwitterionic molecules have access to the water phase, while protonated serotonin is anchored in the interphase. Even taking into account that these simulations were done using a model membrane, our results suggest that the studied molecules could not cross the blood brain barrier by diffusion. These results are in good agreement with works that show that serotonin and Trp do not cross the BBB by simple diffusion.

  9. Finite-size effects in molecular dynamics simulations: Static structure factor and compressibility. II. Application to a model krypton fluid

    Science.gov (United States)

    Salacuse, J. J.; Denton, A. R.; Egelstaff, P. A.; Tau, M.; Reatto, L.

    1996-03-01

    The method described in the preceding paper [J. J. Salacuse, A. R. Denton, and P. A. Egelstaff, preceding paper, Phys. Rev. E 53, 2382 (1996)] for computing the static structure factor S(Q) of a bulk fluid is used to analyze molecular dynamics computer simulation data for a model krypton fluid whose atoms interact via a truncated Aziz pair potential. Simulations have been carried out for two system sizes of N=706 and 2048 particles and two thermodynamic states, described by a common reduced temperature T*=1.51 and reduced densities ρ*=0.25 and 0.4. Results presented include the N-particle radial distribution function gN(r) and the bulk static structure factor S(Q). In addition we calculate the direct correlation function c(r) from the full S(Q). In comparison with corresponding predictions of the modified hypernetted chain theory, the results are generally in excellent agreement at all r and Q, to within random statistical errors in the simulation data.

  10. Lipid-assisted protein transport: A diffusion-reaction model supported by kinetic experiments and molecular dynamics simulations

    Science.gov (United States)

    La Rosa, Carmelo; Scalisi, Silvia; Lolicato, Fabio; Pannuzzo, Martina; Raudino, Antonio

    2016-05-01

    The protein transport inside a cell is a complex phenomenon that goes through several difficult steps. The facilitated transport requires sophisticated machineries involving protein assemblies. In this work, we developed a diffusion-reaction model to simulate co-transport kinetics of proteins and lipids. We assume the following: (a) there is always a small lipid concentration of order of the Critical Micellar Concentration (CMC) in equilibrium with the membrane; (b) the binding of lipids to proteins modulates the hydrophobicity of the complexes and, therefore, their ability to interact and merge with the bilayer; and (c) some lipids leave the bilayer to replenish those bound to proteins. The model leads to a pair of integral equations for the time-evolution of the adsorbed proteins in the lipid bilayer. Relationships between transport kinetics, CMC, and lipid-protein binding constants were found. Under particular conditions, a perturbation analysis suggests the onset of kinks in the protein adsorption kinetics. To validate our model, we performed leakage measurements of vesicles composed by either high or low CMC lipids interacting with Islet Amyloid PolyPeptide (IAPP) and Aβ (1-40) used as sample proteins. Since the lipid-protein complex stoichiometry is not easily accessible, molecular dynamics simulations were performed using monomeric IAPP interacting with an increasing number of phospholipids. Main results are the following: (a) 1:1 lipid-protein complexes generally show a faster insertion rate proportional to the complex hydrophobicity and inversely related to lipid CMC; (b) on increasing the number of bound lipids, the protein insertion rate decreases; and (c) at slow lipids desorption rate, the lipid-assisted proteins transport might exhibit a discontinuous behavior and does non-linearly depend on protein concentration.

  11. Uncertainty in a Markov state model with missing states and rates: Application to a room temperature kinetic model obtained using high temperature molecular dynamics.

    Science.gov (United States)

    Chatterjee, Abhijit; Bhattacharya, Swati

    2015-09-21

    Several studies in the past have generated Markov State Models (MSMs), i.e., kinetic models, of biomolecular systems by post-analyzing long standard molecular dynamics (MD) calculations at the temperature of interest and focusing on the maximally ergodic subset of states. Questions related to goodness of these models, namely, importance of the missing states and kinetic pathways, and the time for which the kinetic model is valid, are generally left unanswered. We show that similar questions arise when we generate a room-temperature MSM (denoted MSM-A) for solvated alanine dipeptide using state-constrained MD calculations at higher temperatures and Arrhenius relation — the main advantage of such a procedure being a speed-up of several thousand times over standard MD-based MSM building procedures. Bounds for rate constants calculated using probability theory from state-constrained MD at room temperature help validate MSM-A. However, bounds for pathways possibly missing in MSM-A show that alternate kinetic models exist that produce the same dynamical behaviour at short time scales as MSM-A but diverge later. Even in the worst case scenario, MSM-A is found to be valid longer than the time required to generate it. Concepts introduced here can be straightforwardly extended to other MSM building techniques.

  12. Thermodynamic properties of Fe-S alloys from molecular dynamics modeling: Implications for the lunar fluid core

    Science.gov (United States)

    Kuskov, Oleg L.; Belashchenko, David K.

    2016-09-01

    Density and sound velocity of Fe-S liquids for the P-T parameters of the lunar core have not been constrained well. From the analysis of seismic wave travel time, Weber et al. (2011) proposed that the lunar core is composed of iron alloyed with ⩽6 wt% of light elements, such as S. A controversial issue in models of planetary core composition concerns whether Fe-S liquids under high pressure - temperature conditions provide sound velocity and density data, which match the seismic model. Here we report the results of molecular dynamics (MD) simulations of iron-sulfur alloys based on Embedded Atom Model (EAM). The results of calculations include caloric, thermal and elastic properties of Fe-S alloys at concentrations of sulfur 0-18 at.%, temperatures up to 2500 K and pressures up to 14 GPa. The effect of sulfur on the elastic properties of Fe-rich melts is most evident in the notably decreased density with added S content. In the MD simulation, the density and bulk modulus KT of liquid Fe-S decrease with increasing sulfur content, while the bulk modulus KS decreases as a whole but has some fluctuations with increasing sulfur content. The sound velocity increases with increasing pressure, but depends weakly on temperature and the concentration of sulfur. For a fluid Fe-S core of the Moon (∼5 GPa/2000 K) with 6-16 at.% S (3.5-10 wt%), the sound velocity and density may be estimated at the level of 4000 m s-1 and 6.25-7.0 g cm-3. Comparison of thermodynamic calculations with the results of interpretation of seismic observations shows good agreement of P-wave velocities in the liquid outer core, while the core density does not match the seismic models. At such concentrations of sulfur and a density by 20-35% higher than the model seismic density, a radius for the fluid outer core should be less than about 330 km found by Weber et al. because at the specified mass and moment of inertia values of the Moon an increase of the core density leads to a decrease of the core

  13. Molecular dynamics of interface rupture

    Science.gov (United States)

    Koplik, Joel; Banavar, Jayanth R.

    1993-01-01

    Several situations have been studied in which a fluid-vapor or fluid-fluid interface ruptures, using molecular dynamics simulations of 3000 to 20,000 Lennard-Jones molecules in three dimensions. The cases studied are the Rayleigh instability of a liquid thread, the burst of a liquid drop immersed in a second liquid undergoing shear, and the rupture of a liquid sheet in an extensional flow. The late stages of the rupture process involve the gradual withdrawal of molecules from a thinning neck, or the appearance and growth of holes in a sheet. In all cases, it is found that despite the small size of the systems studied, tens of angstroms, the dynamics is in at least qualitative accord with the behavior expected from continuum calculations, and in some cases the agreement is to within tens of percent. Remarkably, this agreement occurs even though the Eulerian velocity and stress fields are essentially unmeasurable - dominated by thermal noise. The limitations and prospects for such molecular simulation techniques are assessed.

  14. Molecular dynamics of interface rupture

    Science.gov (United States)

    Koplik, Joel; Banavar, Jayanth R.

    1993-01-01

    Several situations have been studied in which a fluid-vapor or fluid-fluid interface ruptures, using molecular dynamics simulations of 3000 to 20,000 Lennard-Jones molecules in three dimensions. The cases studied are the Rayleigh instability of a liquid thread, the burst of a liquid drop immersed in a second liquid undergoing shear, and the rupture of a liquid sheet in an extensional flow. The late stages of the rupture process involve the gradual withdrawal of molecules from a thinning neck, or the appearance and growth of holes in a sheet. In all cases, it is found that despite the small size of the systems studied, tens of angstroms, the dynamics is in at least qualitative accord with the behavior expected from continuum calculations, and in some cases the agreement is to within tens of percent. Remarkably, this agreement occurs even though the Eulerian velocity and stress fields are essentially unmeasurable - dominated by thermal noise. The limitations and prospects for such molecular simulation techniques are assessed.

  15. 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.

  16. Study of clathrate hydrates via equilibrium molecular-dynamics simulation employing polarisable and non-polarisable, rigid and flexible water models

    Science.gov (United States)

    Burnham, Christian J.; English, Niall J.

    2016-04-01

    Equilibrium molecular-dynamics (MD) simulations have been performed on metastable sI and sII polymorphs of empty hydrate lattices, in addition to liquid water and ice Ih. The non-polarisable TIP4P-2005, simple point charge model (SPC), and polarisable Thole-type models (TTM): TTM2, TTM3, and TTM4 water models were used in order to survey the differences between models and to see what differences can be expected when polarisability is incorporated. Rigid and flexible variants were used of each model to gauge the effects of flexibility. Power spectra are calculated and compared to density-of-states spectra inferred from inelastic neutron scattering (INS) measurements. Thermodynamic properties were also calculated, as well as molecular-dipole distributions. It was concluded that TTM models offer optimal fidelity vis-à-vis INS spectra, together with thermodynamic properties, with the flexible TTM2 model offering optimal placement of vibrational modes.

  17. Enhanced Sampling of an Atomic Model with Hybrid Nonequilibrium Molecular Dynamics-Monte Carlo Simulations Guided by a Coarse-Grained Model.

    Science.gov (United States)

    Chen, Yunjie; Roux, Benoît

    2015-08-11

    Molecular dynamics (MD) trajectories based on a classical equation of motion provide a straightforward, albeit somewhat inefficient approach, to explore and sample the configurational space of a complex molecular system. While a broad range of techniques can be used to accelerate and enhance the sampling efficiency of classical simulations, only algorithms that are consistent with the Boltzmann equilibrium distribution yield a proper statistical mechanical computational framework. Here, a multiscale hybrid algorithm relying simultaneously on all-atom fine-grained (FG) and coarse-grained (CG) representations of a system is designed to improve sampling efficiency by combining the strength of nonequilibrium molecular dynamics (neMD) and Metropolis Monte Carlo (MC). This CG-guided hybrid neMD-MC algorithm comprises six steps: (1) a FG configuration of an atomic system is dynamically propagated for some period of time using equilibrium MD; (2) the resulting FG configuration is mapped onto a simplified CG model; (3) the CG model is propagated for a brief time interval to yield a new CG configuration; (4) the resulting CG configuration is used as a target to guide the evolution of the FG system; (5) the FG configuration (from step 1) is driven via a nonequilibrium MD (neMD) simulation toward the CG target; (6) the resulting FG configuration at the end of the neMD trajectory is then accepted or rejected according to a Metropolis criterion before returning to step 1. A symmetric two-ends momentum reversal prescription is used for the neMD trajectories of the FG system to guarantee that the CG-guided hybrid neMD-MC algorithm obeys microscopic detailed balance and rigorously yields the equilibrium Boltzmann distribution. The enhanced sampling achieved with the method is illustrated with a model system with hindered diffusion and explicit-solvent peptide simulations. Illustrative tests indicate that the method can yield a speedup of about 80 times for the model system and up

  18. Molecular dynamics simulations of classical stopping power.

    Science.gov (United States)

    Grabowski, Paul E; Surh, Michael P; Richards, David F; Graziani, Frank R; Murillo, Michael S

    2013-11-22

    Molecular dynamics can provide very accurate tests of classical kinetic theory; for example, unambiguous comparisons can be made for classical particles interacting via a repulsive 1/r potential. The plasma stopping power problem, of great interest in its own right, provides an especially stringent test of a velocity-dependent transport property. We have performed large-scale (~10(4)-10(6) particles) molecular dynamics simulations of charged-particle stopping in a classical electron gas that span the weak to moderately strong intratarget coupling regimes. Projectile-target coupling is varied with projectile charge and velocity. Comparisons are made with disparate kinetic theories (both Boltzmann and Lenard-Balescu classes) and fully convergent theories to establish regimes of validity. We extend these various stopping models to improve agreement with the MD data and provide a useful fit to our results.

  19. 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

  20. Molecular dynamics studies of aromatic hydrocarbon liquids

    Energy Technology Data Exchange (ETDEWEB)

    McLaughlin, E.; Gupta, S.

    1990-01-01

    This project mainly involves a molecular dynamics and Monte Carlo study of the effect of molecular shape on thermophysical properties of bulk fluids with an emphasis on the aromatic hydrocarbon liquids. In this regard we have studied the modeling, simulation methodologies, and predictive and correlating methods for thermodynamic properties of fluids of nonspherical molecules. In connection with modeling we have studied the use of anisotropic site-site potentials, through a modification of the Gay-Berne Gaussian overlap potential, to successfully model the aromatic rings after adding the necessary electrostatic moments. We have also shown these interaction sites should be located at the geometric centers of the chemical groups. In connection with predictive methods, we have shown two perturbation type theories to work well for fluids modeled using one-center anisotropic potentials and the possibility exists for extending these to anisotropic site-site models. In connection with correlation methods, we have studied, through simulations, the effect of molecular shape on the attraction term in the generalized van der Waals equation of state for fluids of nonspherical molecules and proposed a possible form which is to be studied further. We have successfully studied the vector and parallel processing aspects of molecular simulations for fluids of nonspherical molecules.

  1. Discovery of a regioselectivity switch in nitrating P450s guided by molecular dynamics simulations and Markov models

    Science.gov (United States)

    Dodani, Sheel C.; Kiss, Gert; Cahn, Jackson K. B.; Su, Ye; Pande, Vijay S.; Arnold, Frances H.

    2016-05-01

    The dynamic motions of protein structural elements, particularly flexible loops, are intimately linked with diverse aspects of enzyme catalysis. Engineering of these loop regions can alter protein stability, substrate binding and even dramatically impact enzyme function. When these flexible regions are unresolvable structurally, computational reconstruction in combination with large-scale molecular dynamics simulations can be used to guide the engineering strategy. Here we present a collaborative approach that consists of both experiment and computation and led to the discovery of a single mutation in the F/G loop of the nitrating cytochrome P450 TxtE that simultaneously controls loop dynamics and completely shifts the enzyme's regioselectivity from the C4 to the C5 position of L-tryptophan. Furthermore, we find that this loop mutation is naturally present in a subset of homologous nitrating P450s and confirm that these uncharacterized enzymes exclusively produce 5-nitro-L-tryptophan, a previously unknown biosynthetic intermediate.

  2. Interplay Between Non-adiabatic Dynamics and Frenkel Exciton Transfer in Molecular Aggregates: Formulation and Application to a Perylene Bismide Model

    CERN Document Server

    Schröter, M

    2013-01-01

    The quantum dynamics of linear molecular aggregates in the presence of S0-S1 and S0-S2 transitions is investigated putting emphasis on the interplay between local non-adiabatic S2 to S1 deactivation and Frenkel exciton transfer. The theoretical approach combines aspects of the linear vibronic coupling and Frenkel exciton models. Dynamics calculations are performed for the absorption spectrum and the electronic state populations using the multiconfiguration time-dependent Hartree approach. As an application perylene bisimde J-type dimer and trimer aggregates are considered, including four tuning and one coupling mode per monomer. This leads to a dynamical model comprising up to 7 electronic states and 15 vibrational modes. The unknown non-adiabatic coupling strength is treated as a parameter that is chosen in accordance with available absorption spectra. This leaves some flexibility that can be limited by the clearly distinguishable population dynamics.

  3. Molecular Dynamics and Picosecond Vibrational Spectra.

    Science.gov (United States)

    1980-07-01

    and Identify by block number) molecular dynamics picosecond infra-red spectra crmputer simulation vibrational spectra array processor linear rcsponse...that for molecular dynamics theoretical computation is now long enough, to significantly overlap. This overlap of theory and experiment can, at least...to discover these microscopic atomic trajectories, i.e. the molecular dynamics of solution processes, we must be able to both theoretically compute

  4. Molecular Dynamics in the Vacuum Ultraviolet

    Science.gov (United States)

    1989-01-30

    CLASSIFICATION OF THIS PAGE COMPLETED PROJECT SUMMARY TITLE: Molecular dynamics in the Vacuum Ultraviolet PRINCIPAL INVESTIGATOR: Paul L. Houston...DTIC TAB 0 Unannounced 0 By Distr ibution I Availability Codes Avail and I or Dist Special I Molecular Dynamics In the Vacuum Ultraviolet Final Technical...Further development of tunable vacuum ultraviolet sources has opened wide areas of molecular dynamics for study. Completed Research Photodissociation of

  5. Brownian motion from molecular dynamics

    CERN Document Server

    Shin, Hyun Kyung; Talkner, Peter; Lee, Eok Kyun

    2010-01-01

    Brownian motion of single particles with various masses M and diameters D is studied by molecular dynamics simulations. Besides the momentum auto-correlation function of the Brownian particle the memory function and the fluctuating force which enter the generalized Langevin equation of the Brownian particle are determined and their dependence on mass and diameter are investigated for two different fluid densities. Deviations of the fluctuating force distribution from a Gaussian form are observed for small particle diameters. For heavy particles the deviations of the fluctuating force from the total force acting on the Brownian particle decrease linearly with the mass ratio m/M where m denotes the mass of a fluid particle.

  6. Theoretical Concepts in Molecular Photodissociation Dynamics

    DEFF Research Database (Denmark)

    Henriksen, Niels Engholm

    1995-01-01

    This chapter contains sections titled: Introduction Quantum Dynamics of Molecular Photofragmentation The Total Reaction Probability Final Product Distributions Time-Independent Approach, Stationary Scattering States Gaussian Wave Packet Dynamics Wigner Phase Space Representation The Diatomic...

  7. Studying the Impact of Modified Saccharides on the Molecular Dynamics and Crystallization Tendencies of Model API Nifedipine.

    Science.gov (United States)

    Kaminska, E; Tarnacka, M; Wlodarczyk, P; Jurkiewicz, K; Kolodziejczyk, K; Dulski, M; Haznar-Garbacz, D; Hawelek, L; Kaminski, K; Wlodarczyk, A; Paluch, M

    2015-08-03

    Molecular dynamics of pure nifedipine and its solid dispersions with modified carbohydrates as well as the crystallization kinetics of active pharmaceutical ingredient (API) above and below the glass transition temperature were studied in detail by means of broadband dielectric spectroscopy (BDS), differential scanning calorimetry (DSC), and X-ray diffraction method. It was found that the activation barrier of crystallization increases in molecular dispersions composed of acetylated disaccharides, whereas it slightly decreases in those consisting of modified monocarbohydrates for the experiments carried out above the glass transition temperature. As shown by molecular dynamics simulations it can be related to the strength, character, and structure of intermolecular interactions between API and saccharides, which vary dependently on the excipient. Long-term physical stability studies showed that, in solid dispersions consisting of acetylated maltose and acetylated sucrose, the crystallization of nifedipine is dramatically slowed down, although it is still observable for a low concentration of excipients. With increasing content of modified carbohydrates, the crystallization of API becomes completely suppressed. This is most likely due to additional barriers relating to the intermolecular interactions and diffusion of nifedipine that must be overcome to trigger the crystallization process.

  8. Molecular dynamics of membrane proteins.

    Energy Technology Data Exchange (ETDEWEB)

    Woolf, Thomas B. (Johns Hopkins University School of Medicine, Baltimore, MD); Crozier, Paul Stewart; Stevens, Mark Jackson

    2004-10-01

    Understanding the dynamics of the membrane protein rhodopsin will have broad implications for other membrane proteins and cellular signaling processes. Rhodopsin (Rho) is a light activated G-protein coupled receptor (GPCR). When activated by ligands, GPCRs bind and activate G-proteins residing within the cell and begin a signaling cascade that results in the cell's response to external stimuli. More than 50% of all current drugs are targeted toward G-proteins. Rho is the prototypical member of the class A GPCR superfamily. Understanding the activation of Rho and its interaction with its Gprotein can therefore lead to a wider understanding of the mechanisms of GPCR activation and G-protein activation. Understanding the dark to light transition of Rho is fully analogous to the general ligand binding and activation problem for GPCRs. This transition is dependent on the lipid environment. The effect of lipids on membrane protein activity in general has had little attention, but evidence is beginning to show a significant role for lipids in membrane protein activity. Using the LAMMPS program and simulation methods benchmarked under the IBIG program, we perform a variety of allatom molecular dynamics simulations of membrane proteins.

  9. Cluster adsorption on amorphous and crystalline surfaces - A molecular dynamics study of model Pt on Cu and model Pd on Pt

    Science.gov (United States)

    Garofalini, S. H.; Halicioglu, T.; Pound, G. M.

    1981-01-01

    Molecular dynamics was used to study the structure, dispersion and short-time behavior of ten-atom clusters adsorbed onto amorphous and crystalline substrates, in which the cluster atoms differed from the substrate atoms. Two adatom-substrate model systems were chosen; one, in which the interaction energy between adatom pairs was greater than that between substrate pairs, and the other, in which the reverse was true. At relatively low temperature ranges, increased dispersion of cluster atoms occurred: (a) on the amorphous substrate as compared to the FCC(100) surface, (b) with increasing reduced temperature, and (c) with adatom-substrate interaction energy stronger than adatom-adatom interaction. Two-dimensional clusters (rafts) on the FCC(100) surface displayed migration of edge atoms only, indicating a mechanism for the cluster rotation and shape changes found in experimental studies.

  10. Control-volume representation of molecular dynamics.

    Science.gov (United States)

    Smith, E R; Heyes, D M; Dini, D; Zaki, T A

    2012-05-01

    A molecular dynamics (MD) parallel to the control volume (CV) formulation of fluid mechanics is developed by integrating the formulas of Irving and Kirkwood [J. Chem. Phys. 18, 817 (1950)] over a finite cubic volume of molecular dimensions. The Lagrangian molecular system is expressed in terms of an Eulerian CV, which yields an equivalent to Reynolds' transport theorem for the discrete system. This approach casts the dynamics of the molecular system into a form that can be readily compared to the continuum equations. The MD equations of motion are reinterpreted in terms of a Lagrangian-to-control-volume (LCV) conversion function ϑ(i) for each molecule i. The LCV function and its spatial derivatives are used to express fluxes and relevant forces across the control surfaces. The relationship between the local pressures computed using the volume average [Lutsko, J. Appl. Phys. 64, 1152 (1988)] techniques and the method of planes [Todd et al., Phys. Rev. E 52, 1627 (1995)] emerges naturally from the treatment. Numerical experiments using the MD CV method are reported for equilibrium and nonequilibrium (start-up Couette flow) model liquids, which demonstrate the advantages of the formulation. The CV formulation of the MD is shown to be exactly conservative and is, therefore, ideally suited to obtain macroscopic properties from a discrete system.

  11. Molecular dynamics and reverse Monte Carlo modeling of scheelite-type AWO4 (A = Ca, Sr, Ba) W L 3-edge EXAFS spectra

    Science.gov (United States)

    Kalinko, Aleksandr; Bauer, Matthias; Timoshenko, Janis; Kuzmin, Alexei

    2016-11-01

    Classical molecular dynamics (MD) and reverse Monte Carlo methods coupled with ab initio multiple-scattering extended x-ray absorption fine structure (EXAFS) calculations were used for modeling of scheelite-type AWO4 (A = Ca, Sr, Ba) W L 3-edge EXAFS spectra. The two theoretical approaches are complementary and allowed us to perform analysis of full EXAFS spectra. Both methods reproduce well the structure and dynamics of tungstates in the outer coordination shells, however the classical MD simulations underestimate the W-O bond MSRD due to a neglect of quantum zero-point-motion. The thermal vibration amplitudes, correlation effects and anisotropy of the tungstate structure were also estimated.

  12. 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

  13. Modelling the local atomic structure of molybdenum in nuclear waste glasses with ab initio molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2016-01-01

    The nature of chemical bonding of molybdenum in high level nuclear waste glasses has been elucidated by ab initio molecular dynamics simulations. Two compositions, (SiO2)57.5 – (B2O3)10 – (Na2O)15 – (CaO)15 – (MoO3)2.5 and (SiO2)57.3 – (B2O3)20 – (Na2O)6.8 – (Li2O)13.4 – (MoO3)2.5 , were considered in order to investigate the effect of ionic and covalent components on the glass structure and the formation of the crystallisation precursors (Na2MoO4 and CaMoO4). The coordination environments of Mo cations and the corresponding bond lengths calculated from our model are in excellent agreement with experimental observations. The analysis of the first coordination shell reveals two different types of molybdenum host matrix bonds in the lithium sodium borosilicate glass. Based on the structural data and the bond valence model, we demonstrate that the Mo cation can be found in a redox state and the molybdate tetrahedron can be connected with the borosilicate network in a way that inhibits the formation of crystalline molybdates. These results significantly extend our understanding of bonding in Mo-containing nuclear waste glasses and demonstrate that tailoring the glass composition to specific heavy metal constituents can facilitate incorporation of heavy metals at high concentrations. K.K. was supported through the Impact Studentship scheme at UCL co-funded by the IHI Corporation and UCL. P.V.S. thanks the Royal Society, which supported preliminary work on this project, and the Laboratory Directed Research and Development program at PNNL, a multiprogram national laboratory operated by Battelle for the U.S. Department of Energy. Via our membership of the UK's HEC Materials Chemistry Consortium, which is funded by EPSRC (EP/L000202), this work used the ARCHER UK National Supercomputing Service (http://www.archer.ac.uk).

  14. Quantum dynamical simulation of non-adiabatic proton transfers in aqueous solution methodology, molecular models and applications

    CERN Document Server

    Billeter, S R

    1998-01-01

    This thesis describes the methodology of quantum dynamical (QD) simulation of proton transfers in aqueous solutions, its implementation in the simulation program QDGROMOS and its application to protonated water and aqueous solutions of acetic acid. QDGROMOS is based on the GROMOS96 molecular dynamics (MD) program package. Many of the solutions to partial problems such as the representation of the quantum state, the solution of the time-dependent Schrodinger equation, the forces from the quantum subsystem, the time-ordering of the propagations and the correlations between the subsystems, are complementary. In chapter 1, various numerical propagation algorithms for solving the time-dependent Schrodinger equation under the influence of a constant Hamilton operator are compared against each other, mainly in one dimension. A Chebysheff series expansion and the expansion in terms of eigenstates of the Hamilton operator were found to be most stable. Chapter 2 describes the theory, the methods and the algorithms of Q...

  15. Molecular dynamics simulations of double-stranded DNA in an explicit solvent model with the zero-dipole summation method.

    Directory of Open Access Journals (Sweden)

    Takamasa Arakawa

    Full Text Available Molecular dynamics (MD simulations of a double-stranded DNA with explicit water and small ions were performed with the zero-dipole summation (ZD method, which was recently developed as one of the non-Ewald methods. Double-stranded DNA is highly charged and polar, with phosphate groups in its backbone and their counterions, and thus precise treatment for the long-range electrostatic interactions is always required to maintain the stable and native double-stranded form. A simple truncation method deforms it profoundly. On the contrary, the ZD method, which considers the neutralities of charges and dipoles in a truncated subset, well reproduced the electrostatic energies of the DNA system calculated by the Ewald method. The MD simulations using the ZD method provided a stable DNA system, with similar structures and dynamic properties to those produced by the conventional Particle mesh Ewald method.

  16. Generative models of conformational dynamics.

    Science.gov (United States)

    Langmead, Christopher James

    2014-01-01

    Atomistic simulations of the conformational dynamics of proteins can be performed using either Molecular Dynamics or Monte Carlo procedures. The ensembles of three-dimensional structures produced during simulation can be analyzed in a number of ways to elucidate the thermodynamic and kinetic properties of the system. The goal of this chapter is to review both traditional and emerging methods for learning generative models from atomistic simulation data. Here, the term 'generative' refers to a model of the joint probability distribution over the behaviors of the constituent atoms. In the context of molecular modeling, generative models reveal the correlation structure between the atoms, and may be used to predict how the system will respond to structural perturbations. We begin by discussing traditional methods, which produce multivariate Gaussian models. We then discuss GAMELAN (GRAPHICAL MODELS OF ENERGY LANDSCAPES), which produces generative models of complex, non-Gaussian conformational dynamics (e.g., allostery, binding, folding, etc.) from long timescale simulation data.

  17. Nonequilibrium molecular dynamics simulations of the thermal conductivity of water: a systematic investigation of the SPC/E and TIP4P/2005 models.

    Science.gov (United States)

    Römer, Frank; Lervik, Anders; Bresme, Fernando

    2012-08-21

    We report an extensive nonequilibrium molecular dynamics investigation of the thermal conductivity of water using two of the most accurate rigid nonpolarizable empirical models available, SPC/E and TIP4P/2005. Our study covers liquid and supercritical states. Both models predict the anomalous increase of the thermal conductivity with temperature and the thermal conductivity maximum, hence confirming their ability to reproduce the complex anomalous behaviour of water. The performance of the models strongly depends on the thermodynamic state investigated, and best agreement with experiment is obtained for states close to the liquid coexistence line and at high densities and temperatures. Considering the simplicity of these two models the overall agreement with experiments is remarkable. Our results show that explicit polarizability and molecular flexibility are not needed to reproduce the anomalous heat conduction of water.

  18. Capillary dynamics driven by molecular self-layering.

    Science.gov (United States)

    Wu, Pingkeng; Nikolov, Alex; Wasan, Darsh

    2017-02-10

    Capillary dynamics is a ubiquitous everyday phenomenon. It has practical applications in diverse fields, including ink-jet printing, lab-on-a-chip, biotechnology, and coating. Understanding capillary dynamics requires essential knowledge on the molecular level of how fluid molecules interact with a solid substrate (the wall). Recent studies conducted with the surface force apparatus (SFA), atomic force microscope (AFM), and statistical mechanics simulation revealed that molecules/nanoparticles confined into the film/wall surfaces tend to self-layer into 2D layer/s and even 2D in-layer with increased confinement and fluid volume fraction. Here, the capillary rise dynamics of simple molecular fluids in cylindrical capillary is explained by the molecular self-layering model. The proposed model considers the role of the molecular shape on self-layering and its effect on the molecularly thin film viscosity in regards to the advancing (dynamic) contact angle. The model was tested to explain the capillary rise dynamics of fluids of spherical, cylindrical, and disk shape molecules in borosilicate glass capillaries. The good agreement between the capillary rise data and SFA data from the literature for simple fluid self-layering shows the validity of the present model. The present model provides new insights into the design of many applications where dynamic wetting is important because it reveals the significant impact of molecular self-layering close to the wall on dynamic wetting.

  19. Molecular dynamics in cytochrome c oxidase Moessbauer spectra deconvolution

    Energy Technology Data Exchange (ETDEWEB)

    Bossis, Fabrizio [Department of Medical Biochemistry, Medical Biology and Medical Physics (DIBIFIM), University of Bari ' Aldo Moro' , Bari (Italy); Palese, Luigi L., E-mail: palese@biochem.uniba.it [Department of Medical Biochemistry, Medical Biology and Medical Physics (DIBIFIM), University of Bari ' Aldo Moro' , Bari (Italy)

    2011-01-07

    Research highlights: {yields} Cytochrome c oxidase molecular dynamics serve to predict Moessbauer lineshape widths. {yields} Half height widths are used in modeling of Lorentzian doublets. {yields} Such spectral deconvolutions are useful in detecting the enzyme intermediates. -- Abstract: In this work low temperature molecular dynamics simulations of cytochrome c oxidase are used to predict an experimentally observable, namely Moessbauer spectra width. Predicted lineshapes are used to model Lorentzian doublets, with which published cytochrome c oxidase Moessbauer spectra were simulated. Molecular dynamics imposed constraints to spectral lineshapes permit to obtain useful information, like the presence of multiple chemical species in the binuclear center of cytochrome c oxidase. Moreover, a benchmark of quality for molecular dynamic simulations can be obtained. Despite the overwhelming importance of dynamics in electron-proton transfer systems, limited work has been devoted to unravel how much realistic are molecular dynamics simulations results. In this work, molecular dynamics based predictions are found to be in good agreement with published experimental spectra, showing that we can confidently rely on actual simulations. Molecular dynamics based deconvolution of Moessbauer spectra will lead to a renewed interest for application of this approach in bioenergetics.

  20. Molecular dynamics simulations of T-2410 and T-2429 HIV fusion inhibitors interacting with model membranes: Insight into peptide behavior, structure and dynamics.

    Science.gov (United States)

    Mavioso, I C V C; de Andrade, V C R; Palace Carvalho, A J; Martins do Canto, A M T

    2017-09-01

    T-2410 and T-2429 are HIV fusion inhibitor peptides (FI) designed to present a higher efficiency even against HIV strains that developed resistance against other FIs. Similar peptides were shown to interact with model membranes both in the liquid disordered phase and in the liquid ordered state. Those results indicated that such interaction is important to function and could be correlated with their effectiveness. Extensive molecular dynamics simulations were carried out to investigate the interactions between both T-2410 and T-2429 with bilayers of pure 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and a mixture of POPC/cholesterol (Chol) (1:1). It was observed that both peptides interact strongly with both membrane systems, especially with the POPC/Chol systems, where these peptides show the highest number of H-bonds observed so far. T-2410 and T-2429 showed higher extent of interaction with bilayers when compared to T-20 or T-1249 in previous studies. This is most notable in POPC/Chol membranes where, although able to form H-bonds with Chol, they do so to a lesser extent than T-1249 does, the latter being the only FI peptide so far that was observed to form H-bonds with Chol. This behavior suggests that interaction of FI peptides with rigid Chol rich membranes may not be as dependent from peptide/Chol H-bond formation as previous results of T-1249 behavior led to believe. As in other similar peptides, the higher ability to interact with membranes shown by T-2410 and T2429 is probably correlated with its higher inhibitory efficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Towards better modelling of drug-loading in solid lipid nanoparticles: Molecular dynamics, docking experiments and Gaussian Processes machine learning.

    Science.gov (United States)

    Hathout, Rania M; Metwally, Abdelkader A

    2016-11-01

    This study represents one of the series applying computer-oriented processes and tools in digging for information, analysing data and finally extracting correlations and meaningful outcomes. In this context, binding energies could be used to model and predict the mass of loaded drugs in solid lipid nanoparticles after molecular docking of literature-gathered drugs using MOE® software package on molecularly simulated tripalmitin matrices using GROMACS®. Consequently, Gaussian processes as a supervised machine learning artificial intelligence technique were used to correlate the drugs' descriptors (e.g. M.W., xLogP, TPSA and fragment complexity) with their molecular docking binding energies. Lower percentage bias was obtained compared to previous studies which allows the accurate estimation of the loaded mass of any drug in the investigated solid lipid nanoparticles by just projecting its chemical structure to its main features (descriptors). Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Improvising 5-HT7R homology model for design of high affinity ligands: model validation with docking, embrace minimization, MM-GBSA, and molecular dynamic simulations.

    Science.gov (United States)

    Jha, Preeti; Chaturvedi, Shubhra; Swastika; Pal, Sunil; Jain, Nidhi; Mishra, Anil K

    2017-08-09

    The subtype, 5-HT7R has been implicated in neurological disorders and presents itself as a promising target for antidepressant drugs. Design of targeted selective ligands, require a sound knowledge of 3D-receptor structure. In absence of receptor structure, structure-based design of targeted ligands relies on generation of 5-HT7R homology model. In this study, the impact of template choice, alignment, and model building methods on the homology model of 5-HT7R is addressed. The compactness and model quality due to the presence of cholesterol (lipidic receptor) have also been observed. The results suggest good stereochemical quality of the final model. Ramachandran Plot Analysis indicated more than 97.5% amino acid residues in the favorable region. The overall quality factor was 91.8% using ERRAT. The Z-score for backbone confirmation and packing quality were -1.248 and -1.427, respectively, using WHATCHECK. The RMS Z-score for side chain planarity was .711. Other validation results for the final model include binding site analysis in which Asp162, Val163, Phe343, Phe344, Arg350, Arg367, and Leu370 conserved residues were found in the active site, correlation coefficient of .82 in ligand-based screening and .85 in embrace minimization. Further, the model showed good correlation for agonist and antagonist in docking ([Formula: see text] ≈ .76, [Formula: see text] ≈ .82), embrace minimization ([Formula: see text] ≈ .73, [Formula: see text] ≈ .72), and MM-GBSA ([Formula: see text] ≈ .69, [Formula: see text] ≈ .75) studies. The model was subjected to Molecular Dynamics (MD) simulation of 20 ns both in ligand-free and ligand-bound receptor (agonist and antagonist) system in order to assess its stability.

  3. Application of optimal prediction to molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Barber, IV, John Letherman [Univ. of California, Berkeley, CA (United States)

    2004-12-01

    Optimal prediction is a general system reduction technique for large sets of differential equations. In this method, which was devised by Chorin, Hald, Kast, Kupferman, and Levy, a projection operator formalism is used to construct a smaller system of equations governing the dynamics of a subset of the original degrees of freedom. This reduced system consists of an effective Hamiltonian dynamics, augmented by an integral memory term and a random noise term. Molecular dynamics is a method for simulating large systems of interacting fluid particles. In this thesis, I construct a formalism for applying optimal prediction to molecular dynamics, producing reduced systems from which the properties of the original system can be recovered. These reduced systems require significantly less computational time than the original system. I initially consider first-order optimal prediction, in which the memory and noise terms are neglected. I construct a pair approximation to the renormalized potential, and ignore three-particle and higher interactions. This produces a reduced system that correctly reproduces static properties of the original system, such as energy and pressure, at low-to-moderate densities. However, it fails to capture dynamical quantities, such as autocorrelation functions. I next derive a short-memory approximation, in which the memory term is represented as a linear frictional force with configuration-dependent coefficients. This allows the use of a Fokker-Planck equation to show that, in this regime, the noise is δ-correlated in time. This linear friction model reproduces not only the static properties of the original system, but also the autocorrelation functions of dynamical variables.

  4. Implementing peridynamics within a molecular dynamics code.

    Energy Technology Data Exchange (ETDEWEB)

    Lehoucq, Richard B.; Silling, Stewart Andrew; Plimpton, Steven James; Parks, Michael L.

    2007-12-01

    Peridynamics (PD) is a continuum theory that employs a nonlocal model to describe material properties. In this context, nonlocal means that continuum points separated by a finite distance may exert force upon each other. A meshless method results when PD is discretized with material behavior approximated as a collection of interacting particles. This paper describes how PD can be implemented within a molecular dynamics (MD) framework, and provides details of an efficient implementation. This adds a computational mechanics capability to an MD code, enabling simulations at mesoscopic or even macroscopic length and time scales.

  5. Exchange frequency in replica exchange molecular dynamics

    Science.gov (United States)

    Sindhikara, Daniel; Meng, Yilin; Roitberg, Adrian E.

    2008-01-01

    The effect of the exchange-attempt frequency on sampling efficiency is studied in replica exchange molecular dynamics (REMD). We show that sampling efficiency increases with increasing exchange-attempt frequency. This conclusion is contrary to a commonly expressed view in REMD. Five peptides (1-21 residues long) are studied with a spectrum of exchange-attempt rates. Convergence rates are gauged by comparing ensemble properties between fixed length test REMD simulations and longer reference simulations. To show the fundamental correlation between exchange frequency and convergence time, a simple model is designed and studied, displaying the same basic behavior of much more complex systems.

  6. Extension of Isospin Dependent Quantum Molecular Dynamics

    Institute of Scientific and Technical Information of China (English)

    FengZhaoqing; ZhangFengshou; LiWenfei; JinGenming

    2003-01-01

    Isospin dependent molecular dynamics (IQMD) has been used with success for studying isospin effects in heavy ion collisions at intermediate energies[1,2]. However, this model meets difficulty to study heavy ion collisions at low energies near Coulomb barrier since unsuitable dealing with the deformation, such as surface term induced by deformation during approaching projectile and target, which is not important at high energies, and it results in the calculated cross sections with IQMD which are much smaller than the experimental data at low energies. In this report, we propose a new method in which the surface term in the mean field is included in a proper way, the switch function method.

  7. Development of the Hamiltonian molecular dynamics (HMD) model: A first-principles, relativistic description of nucleus-nucleus interactions at medium energy

    Science.gov (United States)

    Zapp, Edward Neal

    Simulation of energetic, colliding nuclear systems at energies between 100 AMeV and 5 AGeV has utility in fields as diverse as the design and construction of fundamental particle physics experiments, patient treatment by radiation exposure, and in the protection of astronaut crews from the risks of exposure to natural radiation sources during spaceflight. Descriptions of these colliding systems which are derived from theoretical principles are necessary in order to provide confidence in describing systems outside the scope of existing data, which is sparse. The system size and velocity dictate descriptions which include both special relativistic and quantum effects, and the currently incomplete state of understanding with respect to the basic processes at work within nuclear matter dictate that any description will exist at some level of approximation. Models commonly found in the literature employ approximations to theory which lead to simulation results which demonstrate departure from fundamental physical principles, most notably conservation of system energy. The HMD (Hamiltonian Molecular Dynamics) mode is developed as a phase-space description of colliding nuclear system on the level of hadrons, inclusive of the necessary quantum and relativistic elements. Evaluation of model simulations shows that the HMD model shows the necessary conservations throughout system simulation. HMD model predictions are compared to both the RQMD (Relativistic Quantum Molecular Dynamics) and JQMD (Jaeri-Quantum Molecular Dynamics) codes, both commonly employed for the purpose of simulating nucleus-nucleus collisions. Comparison is also provided between all three codes and measurement. The HMD model is shown to perform well in light of both measurement and model calculation, while providing for a physically self-consistent description of the system throughout.

  8. Molecular dynamics in high electric fields

    Science.gov (United States)

    Apostol, M.; Cune, L. C.

    2016-06-01

    Molecular rotation spectra, generated by the coupling of the molecular electric-dipole moments to an external time-dependent electric field, are discussed in a few particular conditions which can be of some experimental interest. First, the spherical-pendulum molecular model is reviewed, with the aim of introducing an approximate method which consists in the separation of the azimuthal and zenithal motions. Second, rotation spectra are considered in the presence of a static electric field. Two particular cases are analyzed, corresponding to strong and weak fields. In both cases the classical motion of the dipoles consists of rotations and vibrations about equilibrium positions; this motion may exhibit parametric resonances. For strong fields a large macroscopic electric polarization may appear. This situation may be relevant for polar matter (like pyroelectrics, ferroelectrics), or for heavy impurities embedded in a polar solid. The dipolar interaction is analyzed in polar condensed matter, where it is shown that new polarization modes appear for a spontaneous macroscopic electric polarization (these modes are tentatively called "dipolons"); one of the polarization modes is related to parametric resonances. The extension of these considerations to magnetic dipoles is briefly discussed. The treatment is extended to strong electric fields which oscillate with a high frequency, as those provided by high-power lasers. It is shown that the effect of such fields on molecular dynamics is governed by a much weaker, effective, renormalized, static electric field.

  9. Molecular modeling of the structure and dynamics of the interlayer species of ZnAlCl layered double hydroxide.

    Science.gov (United States)

    Pisson, J; Morel, J P; Morel-Desrosiers, N; Taviot-Guého, C; Malfreyt, P

    2008-07-03

    Molecular dynamics simulations of the ZnAl layered double hydroxide containing interlayer chloride anions have been performed in the NpT and Np(zz)T statistical ensembles for metal Zn/Al ratios of 2 and 3. We have monitored the interlayer spacing as a function of the number of intercalated water molecules for each statistical ensemble. We have studied how these profiles are affected by the method of calculation of the charges of the hydroxide layer atoms. Diffusion coefficients of the interlayer water molecules have been calculated for different Zn/Al ratios. The calculation of the chemical potential of the interlayer water molecules has been carried out for three amounts of interlayer water molecules. The calculation showed a qualitative agreement with the bulk water chemical potential within a range of interlayer water molecule contents.

  10. Modelling self trapping and trap mutation in tungsten using DFT and Molecular Dynamics with an empirical potential based on DFT

    Energy Technology Data Exchange (ETDEWEB)

    Boisse, J. [Unité Matériaux et Transformations, UMET, UMR 8207, Université de Lille 1, F-59655 Villeneuve d’Ascq (France); Laboratoire d’Energétique et de Mécanique Théorique et Appliquée, LEMTA, UMR 7563, Université de Lorraine, F-54504 Vandoeuvre-lès-Nancy (France); Domain, C. [Unité Matériaux et Transformations, UMET, UMR 8207, Université de Lille 1, F-59655 Villeneuve d’Ascq (France); EDF-R and D, Département MMC, Les Renardières, F-77250 Moret sur Loing (France); Becquart, C.S., E-mail: Charlotte.becquart@univ-lille1.fr [Unité Matériaux et Transformations, UMET, UMR 8207, Université de Lille 1, F-59655 Villeneuve d’Ascq (France)

    2014-12-15

    Density Functional Theory calculations and Molecular Dynamics with a recently developed potential for W–He were used to evaluate the thermal stability of helium–vacancy clusters (nHe.mv) as well as pure interstitial helium clusters in tungsten. The stability of such objects results from a competitive process between thermal emission of vacancies, self interstitial atoms (SIAs) and helium, depending on the helium-to-vacancy ratio in mixed clusters or helium number in pure interstitial helium clusters. We investigated in particular the thermodynamics and kinetics of self trapping and trap mutation, i.e. the emission of one SIA along with the creation of one vacancy from a vacancy–helium or pure helium object.

  11. Molecular modeling and molecular dynamic simulation of the effects of variants in the TGFBR2 kinase domain as a paradigm for interpretation of variants obtained by next generation sequencing.

    Science.gov (United States)

    Zimmermann, Michael T; Urrutia, Raul; Oliver, Gavin R; Blackburn, Patrick R; Cousin, Margot A; Bozeck, Nicole J; Klee, Eric W

    2017-01-01

    Variants in the TGFBR2 kinase domain cause several human diseases and can increase propensity for cancer. The widespread application of next generation sequencing within the setting of Individualized Medicine (IM) is increasing the rate at which TGFBR2 kinase domain variants are being identified. However, their clinical relevance is often uncertain. Consequently, we sought to evaluate the use of molecular modeling and molecular dynamics (MD) simulations for assessing the potential impact of variants within this domain. We documented the structural differences revealed by these models across 57 variants using independent MD simulations for each. Our simulations revealed various mechanisms by which variants may lead to functional alteration; some are revealed energetically, while others structurally or dynamically. We found that the ATP binding site and activation loop dynamics may be affected by variants at positions throughout the structure. This prediction cannot be made from the linear sequence alone. We present our structure-based analyses alongside those obtained using several commonly used genomics-based predictive algorithms. We believe the further mechanistic information revealed by molecular modeling will be useful in guiding the examination of clinically observed variants throughout the exome, as well as those likely to be discovered in the near future by clinical tests leveraging next-generation sequencing through IM efforts.

  12. Thermally driven molecular linear motors - A molecular dynamics study

    DEFF Research Database (Denmark)

    Zambrano, Harvey A; Walther, Jens Honore; Jaffe, Richard Lawrence

    2009-01-01

    We conduct molecular dynamics simulations of a molecular linear motor consisting of coaxial carbon nanotubes with a long outer carbon nanotube confining and guiding the motion of an inner short, capsule-like nanotube. The simulations indicate that the motion of the capsule can be controlled...

  13. Analysis of Time Reversible Born-Oppenheimer Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Lin Lin

    2013-12-01

    Full Text Available We analyze the time reversible Born-Oppenheimer molecular dynamics (TRBOMD scheme, which preserves the time reversibility of the Born-Oppenheimer molecular dynamics even with non-convergent self-consistent field iteration. In the linear response regime, we derive the stability condition, as well as the accuracy of TRBOMD for computing physical properties, such as the phonon frequency obtained from the molecular dynamics simulation. We connect and compare TRBOMD with Car-Parrinello molecular dynamics in terms of accuracy and stability. We further discuss the accuracy of TRBOMD beyond the linear response regime for non-equilibrium dynamics of nuclei. Our results are demonstrated through numerical experiments using a simplified one-dimensional model for Kohn-Sham density functional theory.

  14. Nuclear quantum effect on hydrogen adsorption site of zeolite-templated carbon model using path integral molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kimichi, E-mail: ki-suzuki@aist.go.jp [Research Institute for Nanosystem, National Institute of Advanced Industrial Science and Technology, Chuo-2, 1-1-1, Umezono, Tsukuba, Ibaraki 305-8568 (Japan); Kayanuma, Megumi [Institut de Chimie, UMR 7177 CNRS/Universite de Strasbourg, 4 rue Blaise Pascal 67000, Strasbourg (France); Tachikawa, Masanori [Quantum Chemistry Division, Graduate School of Science, Yokohama-city University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027 (Japan); Ogawa, Hiroshi [Research Institute for Nanosystem, National Institute of Advanced Industrial Science and Technology, Chuo-2, 1-1-1, Umezono, Tsukuba, Ibaraki 305-8568 (Japan); Nishihara, Hirotomo; Kyotani, Takashi [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); Nagashima, Umpei [Research Institute for Nanosystem, National Institute of Advanced Industrial Science and Technology, Chuo-2, 1-1-1, Umezono, Tsukuba, Ibaraki 305-8568 (Japan)

    2011-09-15

    Research highlights: > The stable hydrogen adsorption sites on C{sub 36}H{sub 12} were evaluated at 300 K using path integral molecular dynamics. > In the static MO calculation and conventional MD simulation, five stable adsorption sites of hydrogen atom were found. > In path integral simulation, only four stable adsorption sites were obtained. > The thermal and nuclear quantum effects are key role to settle the hydrogen adsorption sites on carbon materials. - Abstract: To settle the hydrogen adsorption sites on buckybowl C{sub 36}H{sub 12}, which is picked up from zeolite-templated carbon (ZTC), we have performed path integral molecular dynamics (PIMD) simulation including thermal and nuclear quantum fluctuations under semi-empirical PM3 method. In the static PM3 calculation and classical simulation the five stable adsorption sites of hydrogen atom are optimized inside a buckybowl C{sub 36}H{sub 12}, which are labeled as {alpha}-, {beta}{sub 1}-, {beta}{sub 2}-, {gamma}-, and {delta}-carbons from edge to innermost carbon. In PIMD simulation, meanwhile, stable adsorption site is not appeared on {delta}-carbon, but on only {alpha}-, {beta}{sub 1}-, {beta}{sub 2}-, and {gamma}-carbons. This result is due to the fact that the adsorbed hydrogen atom can easily go over the barrier for hydrogen transferring from {delta}- to {beta}{sub 1}-carbons by thermal and nuclear quantum fluctuations. The thermal and nuclear quantum effects are key role to settle the hydrogen adsorption sites on carbon materials.

  15. The role of the deformational entropy in the miscibility of polymer blends investigated using a hybrid statistical mechanics and molecular dynamics model.

    Science.gov (United States)

    Madkour, Tarek M; Salem, Sarah A; Miller, Stephen A

    2013-04-28

    To fully understand the thermodynamic nature of polymer blends and accurately predict their miscibility on a microscopic level, a hybrid model employing both statistical mechanics and molecular dynamics techniques was developed to effectively predict the total free energy of mixing. The statistical mechanics principles were used to derive an expression for the deformational entropy of the chains in the polymeric blends that could be evaluated from molecular dynamics trajectories. Evaluation of the entropy loss due to the deformation of the polymer chains in the case of coiling as a result of the repulsive interactions between the blend components or in the case of swelling due to the attractive interactions between the polymeric segments predicted a negative value for the deformational entropy resulting in a decrease in the overall entropy change upon mixing. Molecular dynamics methods were then used to evaluate the enthalpy of mixing, entropy of mixing, the loss in entropy due to the deformation of the polymeric chains upon mixing and the total free energy change for a series of polar and non-polar, poly(glycolic acid), PGA, polymer blends.

  16. Modeling the tetraphenylalanine-PEG hybrid amphiphile: from DFT calculations on the peptide to molecular dynamics simulations on the conjugate.

    Science.gov (United States)

    Zanuy, David; Hamley, Ian W; Alemán, Carlos

    2011-07-21

    The conformational properties of the hybrid amphiphile formed by the conjugation of a hydrophobic peptide with four phenylalanine (Phe) residues and hydrophilic poly(ethylene glycol), have been investigated using quantum mechanical calculations and atomistic molecular dynamics simulations. The intrinsic conformational preferences of the peptide were examined using the building-up search procedure combined with B3LYP/6-31G(d) geometry optimizations, which led to the identification of 78, 78, and 92 minimum energy structures for the peptides containing one, two, and four Phe residues. These peptides tend to adopt regular organizations involving turn-like motifs that define ribbon or helical-like arrangements. Furthermore, calculations indicate that backbone···side chain interactions involving the N-H of the amide groups and the π clouds of the aromatic rings play a crucial role in Phe-containing peptides. On the other hand, MD simulations on the complete amphiphile in aqueous solution showed that the polymer fragment rapidly unfolds maximizing the contacts with the polar solvent, even though the hydrophobic peptide reduce the number of waters of hydration with respect to an individual polymer chain of equivalent molecular weight. In spite of the small effect of the peptide in the hydrodynamic properties of the polymer, we conclude that the two counterparts of the amphiphile tend to organize as independent modules.

  17. Analysing the Effect of Mutation on Protein Function and Discovering Potential Inhibitors of CDK4: Molecular Modelling and Dynamics Studies.

    Directory of Open Access Journals (Sweden)

    Nagasundaram N

    Full Text Available The cyclin-dependent kinase 4 (CDK4-cyclin D1 complex plays a crucial role in the transition from the G1 phase to S phase of the cell cycle. Among the CDKs, CDK4 is one of the genes most frequently affected by somatic genetic variations that are associated with various forms of cancer. Thus, because the abnormal function of the CDK4-cyclin D1 protein complex might play a vital role in causing cancer, CDK4 can be considered a genetically validated therapeutic target. In this study, we used a systematic, integrated computational approach to identify deleterious nsSNPs and predict their effects on protein-protein (CDK4-cyclin D1 and protein-ligand (CDK4-flavopiridol interactions. This analysis resulted in the identification of possible inhibitors of mutant CDK4 proteins that bind the conformations induced by deleterious nsSNPs. Using computational prediction methods, we identified five nsSNPs as highly deleterious: R24C, Y180H, A205T, R210P, and R246C. From molecular docking and molecular dynamic studies, we observed that these deleterious nsSNPs affected CDK4-cyclin D1 and CDK4-flavopiridol interactions. Furthermore, in a virtual screening approach, the drug 5_7_DIHYDROXY_ 2_ (3_4_5_TRI HYDROXYPHENYL _4H_CHROMEN_ 4_ONE displayed good binding affinity for proteins with the mutations R24C or R246C, the drug diosmin displayed good binding affinity for the protein with the mutation Y180H, and the drug rutin displayed good binding affinity for proteins with the mutations A205T and R210P. Overall, this computational investigation of the CDK4 gene highlights the link between genetic variation and biological phenomena in human cancer and aids in the discovery of molecularly targeted therapies for personalized treatment.

  18. The dynamical role of the central molecular ring within the framework of a seven-component Galaxy model

    Science.gov (United States)

    Simin, A. A.; Fridman, A. M.; Haud, U. A.

    1991-09-01

    A Galaxy model in which the surface density of the gas component has a sharp (two orders of magnitude) jump in the region of the outer radius of the molecular ring is constructed on the basis of observational data. This model is used to calculate the contributions of each population to the model curve of Galactic rotation. The value of the dimensionless increment of hydrodynamical instability for the gas component, being much less than 1, coincides with a similar magnitude for the same gas in the gravity field of the entire Galaxy. It is concluded that the unstable gas component of the Galaxy lies near the limit of the hydrodynamical instability, which is in accordance with the Le Chatelier principle. The stellar populations of the Galaxy probably do not affect the generation of the spiral structure in the gaseous component.

  19. The Computer Simulation of Liquids by Molecular Dynamics.

    Science.gov (United States)

    Smith, W.

    1987-01-01

    Proposes a mathematical computer model for the behavior of liquids using the classical dynamic principles of Sir Isaac Newton and the molecular dynamics method invented by other scientists. Concludes that other applications will be successful using supercomputers to go beyond simple Newtonian physics. (CW)

  20. The investigation of nucleation rate and Johnson–Mehl–Avrami model of Pt–Pd alloy using molecular dynamics simulation during heat treatment processes

    Energy Technology Data Exchange (ETDEWEB)

    Celik, Fatih Ahmet, E-mail: facelik@beu.edu.tr

    2015-05-25

    Highlights: • The Avrami exponent increases with increasing annealing temperature. • Recrystallization occurrence is most likely at low temperatures. • Heat of fusion and critical nucleus radius are evaluated from the MD calculations. - Abstract: In this work, molecular dynamics simulation is carried out to investigate the crystallization kinetics at low cooling rate during solidification and at different annealing temperature from amorphous phase during annealing of Pt–Pd (Pt{sub 50}–Pd{sub 50}) model alloy system. The interfacial free energies, critical nucleus radius, total free energy from high temperatures to low temperatures during solidification of alloy system are also determined by molecular dynamics. At the same time, in order to define the nucleation rate, it is suggested a model based on nucleation theory. The local atomic bonded pairs and short range order properties in the model alloy have been analyzed using Honeycutt–Andersen (HA) method. The kinetic of the crystallization is described by Johnson, Mehl and Avrami (JMA) model, which has been analyzed with MD method by using the crystalline-type bonded pairs during annealing process. The results demonstrated that the crystal kinetics is very important to understand the process of homogenous nucleation formation and also, the results are consistent with the classical nucleation theory.

  1. Dynamical processes in atomic and molecular physics

    CERN Document Server

    Ogurtsov, Gennadi

    2012-01-01

    Atomic and molecular physics underlie a basis for our knowledge of fundamental processes in nature and technology and in such applications as solid state physics, chemistry and biology. In recent years, atomic and molecular physics has undergone a revolutionary change due to great achievements in computing and experimental techniques. As a result, it has become possible to obtain information both on atomic and molecular characteristics and on dynamics of atomic and molecular processes. This e-book highlights the present state of investigations in the field of atomic and molecular physics. Rece

  2. Coarse-grained protein molecular dynamics simulations

    Science.gov (United States)

    Derreumaux, Philippe; Mousseau, Normand

    2007-01-01

    A limiting factor in biological science is the time-scale gap between experimental and computational trajectories. At this point, all-atom explicit solvent molecular dynamics (MD) are clearly too expensive to explore long-range protein motions and extract accurate thermodynamics of proteins in isolated or multimeric forms. To reach the appropriate time scale, we must then resort to coarse graining. Here we couple the coarse-grained OPEP model, which has already been used with activated methods, to MD simulations. Two test cases are studied: the stability of three proteins around their experimental structures and the aggregation mechanisms of the Alzheimer's Aβ16-22 peptides. We find that coarse-grained isolated proteins are stable at room temperature within 50ns time scale. Based on two 220ns trajectories starting from disordered chains, we find that four Aβ16-22 peptides can form a three-stranded β sheet. We also demonstrate that the reptation move of one chain over the others, first observed using the activation-relaxation technique, is a kinetically important mechanism during aggregation. These results show that MD-OPEP is a particularly appropriate tool to study qualitatively the dynamics of long biological processes and the thermodynamics of molecular assemblies.

  3. 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.

  4. A Classical Approach in Simple Nuclear Fusion Reaction 1H2 + 1H3 using Two-Dimension Granular Molecular Dynamics Model

    CERN Document Server

    Viridi, Sparisoma; Waris, Abdul; Perkasa, Yudha Satya

    2011-01-01

    Molecular dynamics in 2-D accompanied by granular model provides an opportunity to investigate binding between nuclei particles and its properties that arises during collision in a fusion reaction. A fully classical approach is used to observe the influence of initial angle of nucleus orientation to the product yielded by the reaction. As an example, a simplest fusion reaction between 1H2 and 1H3 is observed. Several products of the fusion reaction have been obtained, even the unreported ones, including temporary 2He4 nucleus.

  5. Paramaterization of a coarse-grained model for linear alkylbenzene sulfonate surfactants and molecular dynamics studies of their self-assembly in aqueous solution

    Science.gov (United States)

    He, Xibing; Shinoda, Wataru; DeVane, Russell; Anderson, Kelly L.; Klein, Michael L.

    2010-02-01

    A coarse-grained (CG) forcefield for linear alkylbenzene sulfonates (LAS) was systematically parameterized. Thermodynamic data from experiments and structural data obtained from all-atom molecular dynamics were used as targets to parameterize CG potentials for the bonded and non-bonded interactions. The added computational efficiency permits one to employ computer simulation to probe the self-assembly of LAS aqueous solutions into different morphologies starting from a random configuration. The present CG model is shown to accurately reproduce the phase behavior of solutions of pure isomers of sodium dodecylbenzene sulfonate, despite the fact that phase behavior was not directly taken into account in the forcefield parameterization.

  6. Molecular Dynamics Simulations of Simple Liquids

    Science.gov (United States)

    Speer, Owner F.; Wengerter, Brian C.; Taylor, Ramona S.

    2004-01-01

    An experiment, in which students were given the opportunity to perform molecular dynamics simulations on a series of molecular liquids using the Amber suite of programs, is presented. They were introduced to both physical theories underlying classical mechanics simulations and to the atom-atom pair distribution function.

  7. Molecular Dynamics Simulations of Simple Liquids

    Science.gov (United States)

    Speer, Owner F.; Wengerter, Brian C.; Taylor, Ramona S.

    2004-01-01

    An experiment, in which students were given the opportunity to perform molecular dynamics simulations on a series of molecular liquids using the Amber suite of programs, is presented. They were introduced to both physical theories underlying classical mechanics simulations and to the atom-atom pair distribution function.

  8. Molecular dynamics study of force acting on a model nano particle immersed in fluid with temperature gradient: Effect of interaction potential

    Science.gov (United States)

    Tsuji, Tetsuro; Iseki, Hirotaka; Hanasaki, Itsuo; Kawano, Satoyuki

    2016-11-01

    Thermophoresis of a nano particle in a fluid is investigated using molecular dynamics simulation. In order to elucidate effective factors on the characteristics of thermophoresis, simple models for both the fluid and the nano particle are considered, namely, the surrounding fluid consists of Lennard-Jones (LJ) particles and the model nano particle is a cluster consisting of several tens of LJ particles. Interaction between the fluid particle and the model nano particle is described by the LJ interaction potential or repulsive interaction potential with the Lorentz-Berthelot mixing rule. As a preliminary result, the effect of mass on thermophoretic force acting on the model nano particle is investigated for both interaction potentials.

  9. Use of Molecular Dynamics for the Refinement of an Electrostatic Model for the In Silico Design of a Polymer Antidote for the Anticoagulant Fondaparinux

    Directory of Open Access Journals (Sweden)

    Adriana Cajiao

    2013-01-01

    Full Text Available Molecular dynamics (MD simulations results are herein incorporated into an electrostatic model used to determine the structure of an effective polymer-based antidote to the anticoagulant fondaparinux. In silico data for the polymer or its cationic binding groups has not, up to now, been available, and experimental data on the structure of the polymer-fondaparinux complex is extremely limited. Consequently, the task of optimizing the polymer structure is a daunting challenge. MD simulations provided a means to gain microscopic information on the interactions of the binding groups and fondaparinux that would have otherwise been inaccessible. This was used to refine the electrostatic model and improve the quantitative model predictions of binding affinity. Once refined, the model provided guidelines to improve electrostatic forces between candidate polymers and fondaparinux in order to increase association rate constants.

  10. Molecular Dynamic Screening Sesquiterpenoid Pogostemon Herba as Suggested Cyclooxygenase Inhibitor.

    Science.gov (United States)

    Raharjo, Sentot Joko; Kikuchi, Takeshi

    2016-10-01

    Virtual molecular dynamic sesquiterpenoid Pogostemon Herba (CID56928117, CID94275, CID107152, and CID519743) have screening as cyclooxygenase (COX-1/COX-2) selective inhibitor. Molecular interaction studies sesquiterpenoid compounds with COX-1 and COX-2 were using the molecular docking tools by Hex 8.0 and interactions were further visualized using by Discovery Studio Client 3.5 software tool and Virtual Molecular Dynamic 1.9.1 software. The binding energy calculation of molecular dynamic interaction was calculated by AMBER12 software. The analysis of the sesquiterpenoid compounds showed that CID56928117, CID94275, CID107152, and CID519743 have suggested as inhibitor of COX-1 and COX-2. Collectively, the scoring binding energy calculation (with PBSA Model Solvent) sesquiterpenoid compounds: CID519743 had suggested as candidate for non-selective inhibitor; CID56928117 and CID94275 had suggested as candidate for a selective COX-1 inhibitor; and CID107152 had suggested as candidate for a selective COX-2 inhibitor.

  11. "The molecule's the thing:" the promise of molecular modeling and dynamic simulations in aiding the prioritization and interpretation of genomic testing results.

    Science.gov (United States)

    Oliver, Gavin R; Zimmermann, Michael T; Klee, Eric W; Urrutia, Raul A

    2016-01-01

    Clinical genomics is now a reality and lies at the heart of individualized medicine efforts. The success of these approaches is evidenced by the increasing volume of publications that report causal links between genomic variants and disease. In spite of early success, clinical genomics currently faces significant challenges in establishing the relevance of the majority of variants identified by next generation sequencing tests. Indeed, the majority of mutations identified are harbored by proteins whose functions remain elusive. Herein we describe the current scenario in genomic testing and in particular the burden of variants of uncertain significance (VUSs). We highlight a role for molecular modeling and molecular dynamic simulations as tools that can significantly increase the yield of information to aid in the evaluation of pathogenicity. Though the application of these methodologies to the interpretation of variants identified by genomic testing is not yet widespread, we predict that an increase in their use will significantly benefit the mission of clinical genomics for individualized medicine.

  12. Structure and energetics of model amphiphilic molecules at the water liquid-vapor interface - A molecular dynamics study

    Science.gov (United States)

    Pohorille, Andrew; Benjamin, Ilan

    1993-01-01

    A molecular dynamics study of adsorption of p-n-pentylphenol at infinite dilution at the water liquid-vapor interface is reported. The calculated free energy of adsorption is -8.8 +/- 0.7 kcal/mol, in good agreement with the experimental value of -7.3 kcal/mol. The transition between the interfacial region and the bulk solution is sharp and well-defined by energetic, conformational, and orientational criteria. At the water surface, the phenol head group is mostly immersed in aqueous solvent. The most frequent orientation of the hydrocarbon tail is parallel to the interface, due to dispersion interactions with the water surface. This arrangement of the phenol ring and the alkyl chain requires that the chain exhibits a kink. As the polar head group is being moved into the solvent, the chain length increases and the tail becomes increasingly aligned toward the surface normal, such that the nonpolar part of the molecule exposed to water is minimized. The same effect was achieved when phenol was replaced by a more polar head group, phenolate.

  13. Structure and energetics of model amphiphilic molecules at the water liquid-vapor interface - A molecular dynamics study

    Science.gov (United States)

    Pohorille, Andrew; Benjamin, Ilan

    1993-01-01

    A molecular dynamics study of adsorption of p-n-pentylphenol at infinite dilution at the water liquid-vapor interface is reported. The calculated free energy of adsorption is -8.8 +/- 0.7 kcal/mol, in good agreement with the experimental value of -7.3 kcal/mol. The transition between the interfacial region and the bulk solution is sharp and well-defined by energetic, conformational, and orientational criteria. At the water surface, the phenol head group is mostly immersed in aqueous solvent. The most frequent orientation of the hydrocarbon tail is parallel to the interface, due to dispersion interactions with the water surface. This arrangement of the phenol ring and the alkyl chain requires that the chain exhibits a kink. As the polar head group is being moved into the solvent, the chain length increases and the tail becomes increasingly aligned toward the surface normal, such that the nonpolar part of the molecule exposed to water is minimized. The same effect was achieved when phenol was replaced by a more polar head group, phenolate.

  14. Capturing intracellular pH dynamics by coupling its molecular mechanisms within a fully tractable mathematical model.

    Directory of Open Access Journals (Sweden)

    Yann Bouret

    Full Text Available We describe the construction of a fully tractable mathematical model for intracellular pH. This work is based on coupling the kinetic equations depicting the molecular mechanisms for pumps, transporters and chemical reactions, which determine this parameter in eukaryotic cells. Thus, our system also calculates the membrane potential and the cytosolic ionic composition. Such a model required the development of a novel algebraic method that couples differential equations for slow relaxation processes to steady-state equations for fast chemical reactions. Compared to classical heuristic approaches based on fitted curves and ad hoc constants, this yields significant improvements. This model is mathematically self-consistent and allows for the first time to establish analytical solutions for steady-state pH and a reduced differential equation for pH regulation. Because of its modular structure, it can integrate any additional mechanism that will directly or indirectly affect pH. In addition, it provides mathematical clarifications for widely observed biological phenomena such as overshooting in regulatory loops. Finally, instead of including a limited set of experimental results to fit our model, we show examples of numerical calculations that are extremely consistent with the wide body of intracellular pH experimental measurements gathered by different groups in many different cellular systems.

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

    Science.gov (United States)

    Nowroozi, Amin; Shahlaei, Mohsen

    2017-02-01

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

  16. Osmosis : a molecular dynamics computer simulation study

    Science.gov (United States)

    Lion, Thomas

    Osmosis is a phenomenon of critical importance in a variety of processes ranging from the transport of ions across cell membranes and the regulation of blood salt levels by the kidneys to the desalination of water and the production of clean energy using potential osmotic power plants. However, despite its importance and over one hundred years of study, there is an ongoing confusion concerning the nature of the microscopic dynamics of the solvent particles in their transfer across the membrane. In this thesis the microscopic dynamical processes underlying osmotic pressure and concentration gradients are investigated using molecular dynamics (MD) simulations. I first present a new derivation for the local pressure that can be used for determining osmotic pressure gradients. Using this result, the steady-state osmotic pressure is studied in a minimal model for an osmotic system and the steady-state density gradients are explained using a simple mechanistic hopping model for the solvent particles. The simulation setup is then modified, allowing us to explore the timescales involved in the relaxation dynamics of the system in the period preceding the steady state. Further consideration is also given to the relative roles of diffusive and non-diffusive solvent transport in this period. Finally, in a novel modification to the classic osmosis experiment, the solute particles are driven out-of-equilibrium by the input of energy. The effect of this modification on the osmotic pressure and the osmotic ow is studied and we find that active solute particles can cause reverse osmosis to occur. The possibility of defining a new "osmotic effective temperature" is also considered and compared to the results of diffusive and kinetic temperatures..

  17. Dynamic Latent Classification Model

    DEFF Research Database (Denmark)

    Zhong, Shengtong; Martínez, Ana M.; Nielsen, Thomas Dyhre

    as possible. Motivated by this problem setting, we propose a generative model for dynamic classification in continuous domains. At each time point the model can be seen as combining a naive Bayes model with a mixture of factor analyzers (FA). The latent variables of the FA are used to capture the dynamics...... in the process as well as modeling dependences between attributes....

  18. HOMOLOGY MODELING AND MOLECULAR DYNAMICS STUDIES OF EC1 DOMAIN OF VE-CADHERIN TO ELUCIDATE DOCKING INTERACTION WITH CADHERIN-DERIVED PEPTIDE

    Directory of Open Access Journals (Sweden)

    Vivitri Dewi Prasasty

    2014-01-01

    Full Text Available VE-cadherin is a protein in the cadherin family that is found at the adherens junctions of the microvessel endothelial cells of the Blood-Brain Barrier (BBB. It is recognized as the homotypic cell adhesion molecules and there is limited structural information on how VE-cadherins mediate cell-cell adhesion. It has been shown that the EC1 domain of cadherins is important for the homophilic interactions for cell-cell adhesion. Therefore, the aims of this study are to model the structure of the EC1 domain of VE-cadherin, study its molecular dynamics properties and evaluate its interactions with cadherin peptides. In this study, the sequence alignment between EC1 domain of VE-cadherin and the template protein were conducted by CLUSTALW2 platform. The SWISS-MODEL platform performed the homology modeling of the EC1 domain of VE-cadherin structure. Structural refinement was done by using KOBAMIN. Some validation analysis platforms also were conducted included PROCHECK, VERIFY3D, ERRAT and MOLPROBITY to check the allowed residues region in Ramachandran Plot (RP and the quality of the structure. The most favored region was found 95.5% in RP value and overall model structure quality is 71.34%. Molecular Dynamics (MD was run under CABS-FLEX to determine the flexibility of the residue index. The RMSD value of MD is 1.5Å per residue index. Eventually, molecular docking by AUTODOCK VINA was conducted to investigate protein-ligand interaction. From docking, it is found that the affinity energy is -4.8 kcal/mol which has the most favorable binding of EC1 domain with the peptide.

  19. Molecular Dynamics Simulation of Amyloid Beta Dimer Formation

    CERN Document Server

    Urbanc, B; Ding, F; Sammond, D; Khare, S; Buldyrev, S V; Stanley, H E; Dokholyan, N V

    2004-01-01

    Recent experiments with amyloid-beta (Abeta) peptide suggest that formation of toxic oligomers may be an important contribution to the onset of Alzheimer's disease. The toxicity of Abeta oligomers depends on their structure, which is governed by assembly dynamics. Due to limitations of current experimental techniques, a detailed knowledge of oligomer structure at the atomic level is missing. We introduce a molecular dynamics approach to study Abeta dimer formation: (1) we use discrete molecular dynamics simulations of a coarse-grained model to identify a variety of dimer conformations, and (2) we employ all-atom molecular mechanics simulations to estimate the thermodynamic stability of all dimer conformations. Our simulations of a coarse-grained Abeta peptide model predicts ten different planar beta-strand dimer conformations. We then estimate the free energies of all dimer conformations in all-atom molecular mechanics simulations with explicit water. We compare the free energies of Abeta(1-42) and Abeta(1-40...

  20. Structural dynamics of Casein Kinase I (CKI) from malarial parasite Plasmodium falciparum (Isolate 3D7): Insights from theoretical modelling and molecular simulations.

    Science.gov (United States)

    Dehury, Budheswar; Behera, Santosh Kumar; Mahapatra, Namita

    2017-01-01

    The protein kinases (PKs), belonging to serine/threonine kinase (STKs), are important drug targets for a wide spectrum of diseases in human. Among protein kinases, the Casein Kinases (CKs) are vastly expanded in various organisms, where, the malarial parasite Plasmodium falciparum possesses a single member i.e., PfCKI, which can phosphorylate various proteins in parasite extracts in vitro condition. But, the structure-function relationship of PfCKI and dynamics of ATP binding is yet to be understood. Henceforth, an attempt was made to study the dynamics, stability, and ATP binding mechanisms of PfCKI through computational modelling, docking, molecular dynamics (MD) simulations, and MM/PBSA binding free energy estimation. Bi-lobed catalytic domain of PfCKI shares a high degree of secondary structure topology with CKI domains of rice, human, and mouse indicating co-evolution of these kinases. Molecular docking study revealed that ATP binds to the active site where the glycine-rich ATP-binding motif (G16-X-G18-X-X-G21) along with few conserved residues plays a crucial role maintaining stability of the complex. Structural superposition of PfCKI with close structural homologs depicted that the location and length of important loops are different, indicating the dynamic properties of these loops among CKIs, which is consistent with principal component analysis (PCA). PCA displayed that the overall global motion of ATP-bound form is comparatively higher than that of apo form. The present study provides insights into the structural features of PfCKI, which could contribute towards further understanding of related protein structures, dynamics of catalysis and phosphorylation mechanism in these important STKs from malarial parasite in near future.

  1. Molecular Dynamics Studies of Matrix Metalloproteases.

    Science.gov (United States)

    Díaz, Natalia; Suárez, Dimas

    2017-01-01

    Matrix metalloproteases are multidomain enzymes with a remarkable proteolytic activity located in the extracellular environment. Their catalytic activity and structural properties have been intensively studied during the last few decades using both experimental and theoretical approaches, but many open questions still remain. Extensive molecular dynamics simulations enable the sampling of the configurational space of a molecular system, thus contributing to the characterization of the structure, dynamics, and ligand binding properties of a particular MMP. Based on previous computational experience, we provide in this chapter technical and methodological guidelines that may be useful to and stimulate other researchers to perform molecular dynamics simulations to help address unresolved questions concerning the molecular mode of action of MMPs.

  2. Integrating Pharmacophore into Membrane Molecular Dynamics Simulations to Improve Homology Modeling of G Protein-coupled Receptors with Ligand Selectivity: A2A Adenosine Receptor as an Example.

    Science.gov (United States)

    Zeng, Lingxiao; Guan, Mengxin; Jin, Hongwei; Liu, Zhenming; Zhang, Liangren

    2015-12-01

    Homology modeling has been applied to fill in the gap in experimental G protein-coupled receptors structure determination. However, achievement of G protein-coupled receptors homology models with ligand selectivity remains challenging due to structural diversity of G protein-coupled receptors. In this work, we propose a novel strategy by integrating pharmacophore and membrane molecular dynamics (MD) simulations to improve homology modeling of G protein-coupled receptors with ligand selectivity. To validate this integrated strategy, the A2A adenosine receptor (A2A AR), whose structures in both active and inactive states have been established, has been chosen as an example. We performed blind predictions of the active-state A2A AR structure based on the inactive-state structure and compared the performance of different refinement strategies. The blind prediction model combined with the integrated strategy identified ligand-receptor interactions and conformational changes of key structural elements related to the activation of A2 A AR, including (i) the movements of intracellular ends of TM3 and TM5/TM6; (ii) the opening of ionic lock; (iii) the movements of binding site residues. The integrated strategy of pharmacophore with molecular dynamics simulations can aid in the optimization in the identification of side chain conformations in receptor models. This strategy can be further investigated in homology modeling and expand its applicability to other G protein-coupled receptor modeling, which should aid in the discovery of more effective and selective G protein-coupled receptor ligands. © 2015 John Wiley & Sons A/S.

  3. Exploring the Origin of Differential Binding Affinities of Human Tubulin Isotypes αβII, αβIII and αβIV for DAMA-Colchicine Using Homology Modelling, Molecular Docking and Molecular Dynamics Simulations.

    Science.gov (United States)

    Kumbhar, Bajarang Vasant; Borogaon, Anubhaw; Panda, Dulal; Kunwar, Ambarish

    2016-01-01

    Tubulin isotypes are found to play an important role in regulating microtubule dynamics. The isotype composition is also thought to contribute in the development of drug resistance as tubulin isotypes show differential binding affinities for various anti-cancer agents. Tubulin isotypes αβII, αβIII and αβIV show differential binding affinity for colchicine. However, the origin of differential binding affinity is not well understood at the molecular level. Here, we investigate the origin of differential binding affinity of a colchicine analogue N-deacetyl-N-(2-mercaptoacetyl)-colchicine (DAMA-colchicine) for human αβII, αβIII and αβIV isotypes, employing sequence analysis, homology modeling, molecular docking, molecular dynamics simulation and MM-GBSA binding free energy calculations. The sequence analysis study shows that the residue compositions are different in the colchicine binding pocket of αβII and αβIII, whereas no such difference is present in αβIV tubulin isotypes. Further, the molecular docking and molecular dynamics simulations results show that residue differences present at the colchicine binding pocket weaken the bonding interactions and the correct binding of DAMA-colchicine at the interface of αβII and αβIII tubulin isotypes. Post molecular dynamics simulation analysis suggests that these residue variations affect the structure and dynamics of αβII and αβIII tubulin isotypes, which in turn affect the binding of DAMA-colchicine. Further, the binding free-energy calculation shows that αβIV tubulin isotype has the highest binding free-energy and αβIII has the lowest binding free-energy for DAMA-colchicine. The order of binding free-energy for DAMA-colchicine is αβIV ≃ αβII > αβIII. Thus, our computational approaches provide an insight into the effect of residue variations on differential binding of αβII, αβIII and αβIV tubulin isotypes with DAMA-colchicine and may help to design new analogues with higher

  4. Exploring the Origin of Differential Binding Affinities of Human Tubulin Isotypes αβII, αβIII and αβIV for DAMA-Colchicine Using Homology Modelling, Molecular Docking and Molecular Dynamics Simulations.

    Directory of Open Access Journals (Sweden)

    Bajarang Vasant Kumbhar

    Full Text Available Tubulin isotypes are found to play an important role in regulating microtubule dynamics. The isotype composition is also thought to contribute in the development of drug resistance as tubulin isotypes show differential binding affinities for various anti-cancer agents. Tubulin isotypes αβII, αβIII and αβIV show differential binding affinity for colchicine. However, the origin of differential binding affinity is not well understood at the molecular level. Here, we investigate the origin of differential binding affinity of a colchicine analogue N-deacetyl-N-(2-mercaptoacetyl-colchicine (DAMA-colchicine for human αβII, αβIII and αβIV isotypes, employing sequence analysis, homology modeling, molecular docking, molecular dynamics simulation and MM-GBSA binding free energy calculations. The sequence analysis study shows that the residue compositions are different in the colchicine binding pocket of αβII and αβIII, whereas no such difference is present in αβIV tubulin isotypes. Further, the molecular docking and molecular dynamics simulations results show that residue differences present at the colchicine binding pocket weaken the bonding interactions and the correct binding of DAMA-colchicine at the interface of αβII and αβIII tubulin isotypes. Post molecular dynamics simulation analysis suggests that these residue variations affect the structure and dynamics of αβII and αβIII tubulin isotypes, which in turn affect the binding of DAMA-colchicine. Further, the binding free-energy calculation shows that αβIV tubulin isotype has the highest binding free-energy and αβIII has the lowest binding free-energy for DAMA-colchicine. The order of binding free-energy for DAMA-colchicine is αβIV ≃ αβII >> αβIII. Thus, our computational approaches provide an insight into the effect of residue variations on differential binding of αβII, αβIII and αβIV tubulin isotypes with DAMA-colchicine and may help to design new

  5. Dynamic molecular crystals with switchable physical properties.

    Science.gov (United States)

    Sato, Osamu

    2016-06-21

    The development of molecular materials whose physical properties can be controlled by external stimuli - such as light, electric field, temperature, and pressure - has recently attracted much attention owing to their potential applications in molecular devices. There are a number of ways to alter the physical properties of crystalline materials. These include the modulation of the spin and redox states of the crystal's components, or the incorporation within the crystalline lattice of tunable molecules that exhibit stimuli-induced changes in their molecular structure. A switching behaviour can also be induced by changing the molecular orientation of the crystal's components, even in cases where the overall molecular structure is not affected. Controlling intermolecular interactions within a molecular material is also an effective tool to modulate its physical properties. This Review discusses recent advances in the development of such stimuli-responsive, switchable crystalline compounds - referred to here as dynamic molecular crystals - and suggests how different approaches can serve to prepare functional materials.

  6. Molecular Dynamics Simulations for Predicting Surface Wetting

    Directory of Open Access Journals (Sweden)

    Jing Chen

    2014-06-01

    Full Text Available The investigation of wetting of a solid surface by a liquid provides important insights; the contact angle of a liquid droplet on a surface provides a quantitative measurement of this interaction and the degree of attraction or repulsion of that liquid type by the solid surface. Molecular dynamics (MD simulations are a useful way to examine the behavior of liquids on solid surfaces on a nanometer scale. Thus, we surveyed the state of this field, beginning with the fundamentals of wetting calculations to an examination of the different MD methodologies used. We highlighted some of the advantages and disadvantages of the simulations, and look to the future of computer modeling to understand wetting and other liquid-solid interaction phenomena.

  7. The 2011 Dynamics of Molecular Collisions Conference

    Energy Technology Data Exchange (ETDEWEB)

    Nesbitt, David J. [JILA, NIST

    2011-07-11

    Yuan T. Lee & Professor George Schatz. Professor Lee’s research has been based on the development & use of advanced chemical kinetics & molecular beams to investigate & manipulate the behavior of fundamental chemical reactions. Lee’s work has been recognized by many awards, including the Nobel Prize for Chemistry in 1986, as well as Sloan Fellow, Dreyfus Scholar, Fellowship in the American Academy of Arts & Sciences, Fellowship in the American Physical Society, Guggenheim Fellow, Member National Academy of Sciences, Member Academia Sinica, E.O. Lawrence Award, Miller Professor, Berkeley, Fairchild Distinguished Scholar, Harrison Howe Award, Peter Debye Award, & the National Medal of Science. Lee also has served as the President of the Academia Sinica in Taiwan (ROC). Professor Schatz’s research group is interested in using theory & computation to describe physical phenomena in a broad range of applications relevant to chemistry, physics, biology & engineering. Among the types of applications that we interested are: optical properties of nanoparticles & nanoparticle assemblies; using theory to model polymer properties; DNA structure, thermodynamics & dynamics; modeling self assembly & nanopatterning; & gas phase reaction dynamics. Among his many awards & distinctions have been appointment as an Alfred P. Sloan Research Fellow, Camille & Henry Dreyfus Teacher-Scholar, the Fresenius Award, Fellow of the American Physical Society, the Max Planck Research Award, Fellowship in the American Association for the Advancement of Science, & election to the International Academy of Quantum Molecular Sciences & the American Academy of Arts & Sciences. Dr Schatz is also lauded for his highly successful work as Editor for the Journal of Physical Chemistry. We requested $10,000 from DOE in support of this meeting. The money was distributed widely among the student & post doctoral fellows & some used to attract the very best scientists in the field. The organizers were committed

  8. Modeling of the hEP1 receptor based on the crystallographic structure of β2-adrenergic receptor and its assessment with docking studies and molecular dynamics simulation

    Directory of Open Access Journals (Sweden)

    B Zare

    2009-12-01

    Full Text Available "nIntroduction: The human EP1 (hEP1 prostanoid receptor is a G-Protein Coupled Receptor (GPCR which plays important physiological roles in some systems in the body like cardiovascular and immune systems and could be a very important target for drug design. "nMaterials and methods: To understand the molecular structure of hEP1 receptor, a homology model of the receptor was constructed from the 2.4 Å resolution crystal structure of human β2-adrenergic receptor (PDB code: 2RH1, using three different sequence alignments. The model including PGE2 inside the active site was subjected to molecular dynamics simulation. Docking studies were performed for PGE2 and 10 prostanoid analogs in the active site of the modeled receptor. Results and Discussion: The structure of modeled receptor remained stable during the 10 nanosecond(ns simulation. In the docking simulations a correlation of r2=0.74 was observed between the Ki values and the docking scores of the prostanoid compounds. The structure which was modeled in the present study can be used in the structure-based drug design, helping the rational design of novel ligands for the hEP1 receptor. "n "n 

  9. 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...

  10. Study of PEGylated lipid layers as a model for PEGylated liposome surfaces: molecular dynamics simulation and Langmuir monolayer studies.

    Science.gov (United States)

    Stepniewski, Michał; Pasenkiewicz-Gierula, Marta; Róg, Tomasz; Danne, Reinis; Orlowski, Adam; Karttunen, Mikko; Urtti, Arto; Yliperttula, Marjo; Vuorimaa, Elina; Bunker, Alex

    2011-06-21

    We have combined Langmuir monolayer film experiments and all-atom molecular dynamics (MD) simulation of a bilayer to study the surface structure of a PEGylated liposome and its interaction with the ionic environment present under physiological conditions. Lipids that form both gel and liquid-crystalline membranes have been used in our study. By varying the salt concentration in the Langmuir film experiment and including salt at the physiological level in the simulation, we have studied the effect of salt ions present in the blood plasma on the structure of the poly(ethylene glycol) (PEG) layer. We have also studied the interaction between the PEG layer and the lipid bilayer in both the liquid-crystalline and gel states. The MD simulation shows two clear results: (a) The Na(+) ions form close interactions with the PEG oxygens, with the PEG chains forming loops around them and (b) PEG penetrates the lipid core of the membrane for the case of a liquid-crystalline membrane but is excluded from the tighter structure of the gel membrane. The Langmuir monolayer results indicate that the salt concentration affects the PEGylated lipid system, and these results can be interpreted in a fashion that is in agreement with the results of our MD simulation. We conclude that the currently accepted picture of the PEG surface layer acting as a generic neutral hydrophilic polymer entirely outside the membrane, with its effect explained through steric interactions, is not sufficient. The phenomena we have observed may affect both the interaction between the liposome and bloodstream proteins and the liquid-crystalline-gel transition and is thus relevant to nanotechnological drug delivery device design.

  11. Exciton dynamics in molecular aggregates

    NARCIS (Netherlands)

    Augulis, R.; Pugžlys, A.; Loosdrecht, P.H.M. van; Pugzlys, A

    2006-01-01

    The fundamental aspects of exciton dynamics in double-wall cylindrical aggregates of cyanine dyes are studied by means of frequency resolved femtosecond pump-probe spectroscopy. The collective excitations of the aggregates, resulting from intermolecular dipole-dipole interactions have the characteri

  12. Exciton dynamics in molecular aggregates

    NARCIS (Netherlands)

    Augulis, R.; Pugžlys, A.; Loosdrecht, P.H.M. van; Pugzlys, A

    2006-01-01

    The fundamental aspects of exciton dynamics in double-wall cylindrical aggregates of cyanine dyes are studied by means of frequency resolved femtosecond pump-probe spectroscopy. The collective excitations of the aggregates, resulting from intermolecular dipole-dipole interactions have the

  13. A quantum molecular dynamics study of aqueous solvation dynamics

    Science.gov (United States)

    Videla, Pablo E.; Rossky, Peter J.; Laria, D.

    2013-10-01

    Ring polymer molecular dynamics experiments have been carried out to examine effects derived from nuclear quantum fluctuations at ambient conditions on equilibrium and non-equilibrium dynamical characteristics of charge solvation by a popular simple, rigid, water model, SPC/E, and for a more recent, and flexible, q-TIP4P/F model, to examine the generality of conclusions. In particular, we have recorded the relaxation of the solvent energy gap following instantaneous, ±e charge jumps in an initially uncharged Lennard-Jones-like solute. In both charge cases, quantum effects are reflected in sharper decays at the initial stages of the relaxation, which produce up to a ˜20% reduction in the characteristic timescales describing the solvation processes. For anionic solvation, the magnitude of polarization fluctuations controlling the extent of the water proton localization in the first solvation shell is somewhat more marked than for cations, bringing the quantum solvation process closer to the classical case. Effects on the solvation response from the explicit incorporation of flexibility in the water Hamiltonian are also examined. Predictions from linear response theories for the overall relaxation profile and for the corresponding characteristic timescales are reasonably accurate for the solvation of cations, whereas we find that they are much less satisfactory for the anionic case.

  14. Temperature dependence of the microscopic structure and density anomaly of the SPC/E and TIP4P-Ew water models. Molecular dynamics simulation results

    Directory of Open Access Journals (Sweden)

    E. Galicia-Andrés

    2015-03-01

    Full Text Available We have investigated temperature trends of the microscopic structure of the SPC/E and TIP4P-Ew water models in terms of the pair distribution functions, coordination numbers, the average number of hydrogen bonds, the distribution of bonding states of a single molecule as well as the angular distribution of molecules by using the constant pressure molecular dynamics simulations. The evolution of the structure is put in correspondence with the dependence of water density on high temperatures down to the region of temperatures where the system becomes supercooled. It is shown that the fraction of molecules with three and four bonds determine the maximum density for both models. Moreover, the temperature dependence of the dielectric constant is obtained and analyzed.

  15. Liouville-von Neumann molecular dynamics

    Science.gov (United States)

    Jakowski, Jacek; Morokuma, Keiji

    2009-06-01

    We present a novel first principles molecular dynamics scheme, called Liouville-von Neumann molecular dynamics, based on Liouville-von Neumann equation for density matrices propagation and Magnus expansion of the time-evolution operator. The scheme combines formally accurate quantum propagation of electrons represented via density matrices and a classical propagation of nuclei. The method requires a few iterations per each time step where the Fock operator is formed and von Neumann equation is integrated. The algorithm (a) is free of constraint and fictitious parameters, (b) avoids diagonalization of the Fock operator, and (c) can be used in the case of fractional occupation as in metallic systems. The algorithm is very stable, and has a very good conservation of energy even in cases when a good quality conventional Born-Oppenheimer molecular dynamics trajectories is difficult to obtain. Test simulations include initial phase of fullerene formation from gaseous C2 and retinal system.

  16. Advances in molecular vibrations and collision dynamics molecular clusters

    CERN Document Server

    Bacic, Zatko

    1998-01-01

    This volume focuses on molecular clusters, bound by van der Waals interactions and hydrogen bonds. Twelve chapters review a wide range of recent theoretical and experimental advances in the areas of cluster vibrations, spectroscopy, and reaction dynamics. The authors are leading experts, who have made significant contributions to these topics.The first chapter describes exciting results and new insights in the solvent effects on the short-time photo fragmentation dynamics of small molecules, obtained by combining heteroclusters with femtosecond laser excitation. The second is on theoretical work on effects of single solvent (argon) atom on the photodissociation dynamics of the solute H2O molecule. The next two chapters cover experimental and theoretical aspects of the energetics and vibrations of small clusters. Chapter 5 describes diffusion quantum Monte Carlo calculations and non additive three-body potential terms in molecular clusters. The next six chapters deal with hydrogen-bonded clusters, refle...

  17. Binding sensitivity of adefovir to the polymerase from different genotypes of HBV: molecular modeling,docking and dynamics simulation studies

    Institute of Scientific and Technical Information of China (English)

    Jing LI; Yun DU; Xian LIU; Qian-cheng SHEN; Ai-long HUANG; Ming-yue ZHENG; Xiao-min LUO; Hua-liang JIANG

    2013-01-01

    Aim: To investigate the molecular mechanisms underlying the influence of DNA polymerase from different genotypes of hepatitis B virus (HBV) on the binding affinity of adefovir (ADV).Methods: Computational approaches,including homology modeling,docking,MD simulation and MM/PBSA free energy analyses were used.Results: Sequence analyses revealed that residue 238 near the binding pocket was not only a polymorphic site but also a genotypespecific site (His238 in genotype B; Asn238 in genotype C).The calculated binding free-energy supported the hypothesis that the polymerase from HBV genotype C was more sensitive to ADV than that from genotype B.By using MD simulation trajectory analysis,binding free energy decomposition and alanine scanning,some energy variation in the residues around the binding pocket was observed.Both the alanine mutations at residues 236 and 238 led to an increase of the energy difference between genotypes C and B (△△Gc-B),suggesting that these residues contributed to the genotype-associated antiviral variability with regard to the interaction with ADV.Conclusion: The results support the hypothesis that the HBV genotype C polymerase is more sensitive to ADV than that from genotype B.Moreover,residue N236 and the polymorphic site 238 play important roles in contributing to the higher sensitivity of genotype C over B in the interaction with ADV.

  18. Molecular-dynamic study of liquid ethylenediamine

    Science.gov (United States)

    Balabaev, N. K.; Kraevskii, S. V.; Rodnikova, M. N.; Solonina, I. A.

    2016-10-01

    Models of liquid ethylenediamine (ED) are built using the molecular dynamics approach at temperatures of 293-363 K and a size of 1000 molecules in a basic cell as a cuboid. The structural and dynamic characteristics of liquid ED versus temperature are derived. The gauche conformation of the ED molecule that is characteristic of the gas phase is shown to transition easily into the trans conformation of the molecules in the liquid. NH···N hydrogen bonds are analyzed in liquid ED. The number of H-bonds per ED molecule is found to vary from 5.02 at 293 K to 3.86 at 363 K. The lifetimes in the range of the temperatures and dissociation activation energy for several H-bonds in liquid ED are found to range from 0.574 to 4.524 ps at 293 K; the activation energies are 8.8 kJ/mol for 50% of the H-bonds and 16.3 kJ/mol for 6.25% of them. A weaker and more mobile spatial grid of H-bonds in liquid ED is observed, compared to data calculated earlier for monoethanolamine.

  19. A molecular dynamics approach to barrodiffusion

    Science.gov (United States)

    Cooley, James; Marciante, Mathieu; Murillo, Michael

    2016-10-01

    Unexpected phenomena in the reaction rates for Inertial Confinement Fusion (ICF) capsules have led to a renewed interest in the thermo-dynamically driven diffusion process for the past 10 years, often described collectively as barodiffusion. In the current context, barodiffusion would manifest as a process that separates ions of differing mass and charge ratios due to pressure and temperature gradients set-up through shock structures in the capsule core. Barrodiffusion includes additional mass transfer terms that account for the irreversible transport of species due to gradients in the system, both thermodynamic and electric e.g, i = - ρD [ ∇c +kp ∇ln(pi) +kT(i) ∇ln(Ti) +kt(e) ∇ln(Te) +eke/Ti ∇ϕ ] . Several groups have attacked this phenomena using continuum scale models and supplemented with kinetic theory to derive coefficients for the different diffusion terms based on assumptions about the collisional processes. In contrast, we have applied a molecular dynamics (MD) simulation to this system to gain a first-principle understanding of the rate kinetics and to assess the accuracy of the differin

  20. Mimicking the action of folding chaperones by Hamiltonian replica-exchange molecular dynamics simulations: application in the refinement of de novo models.

    Science.gov (United States)

    Fan, Hao; Periole, Xavier; Mark, Alan E

    2012-07-01

    The efficiency of using a variant of Hamiltonian replica-exchange molecular dynamics (Chaperone H-replica-exchange molecular dynamics [CH-REMD]) for the refinement of protein structural models generated de novo is investigated. In CH-REMD, the interaction between the protein and its environment, specifically, the electrostatic interaction between the protein and the solvating water, is varied leading to cycles of partial unfolding and refolding mimicking some aspects of folding chaperones. In 10 of the 15 cases examined, the CH-REMD approach sampled structures in which the root-mean-square deviation (RMSD) of secondary structure elements (SSE-RMSD) with respect to the experimental structure was more than 1.0 Å lower than the initial de novo model. In 14 of the 15 cases, the improvement was more than 0.5 Å. The ability of three different statistical potentials to identify near-native conformations was also examined. Little correlation between the SSE-RMSD of the sampled structures with respect to the experimental structure and any of the scoring functions tested was found. The most effective scoring function tested was the DFIRE potential. Using the DFIRE potential, the SSE-RMSD of the best scoring structures was on average 0.3 Å lower than the initial model. Overall the work demonstrates that targeted enhanced-sampling techniques such as CH-REMD can lead to the systematic refinement of protein structural models generated de novo but that improved potentials for the identification of near-native structures are still needed.

  1. 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.

  2. Theory and application of quantum molecular dynamics

    CERN Document Server

    Zeng Hui Zhang, John

    1999-01-01

    This book provides a detailed presentation of modern quantum theories for treating the reaction dynamics of small molecular systems. Its main focus is on the recent development of successful quantum dynamics theories and computational methods for studying the molecular reactive scattering process, with specific applications given in detail for a number of benchmark chemical reaction systems in the gas phase and the gas surface. In contrast to traditional books on collision in physics focusing on abstract theory for nonreactive scattering, this book deals with both the development and the appli

  3. Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers

    Science.gov (United States)

    2017-01-01

    Conspectus Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition

  4. Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers.

    Science.gov (United States)

    Liu, Yun; Lehn, Jean-Marie; Hirsch, Anna K H

    2017-02-21

    Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition, molecular

  5. Molecular Scale Dynamics of Large Ring Polymers

    Science.gov (United States)

    Gooßen, S.; Brás, A. R.; Krutyeva, M.; Sharp, M.; Falus, P.; Feoktystov, A.; Gasser, U.; Pyckhout-Hintzen, W.; Wischnewski, A.; Richter, D.

    2014-10-01

    We present neutron scattering data on the structure and dynamics of melts from polyethylene oxide rings with molecular weights up to ten times the entanglement mass of the linear counterpart. The data reveal a very compact conformation displaying a structure approaching a mass fractal, as hypothesized by recent simulation work. The dynamics is characterized by a fast Rouse relaxation of subunits (loops) and a slower dynamics displaying a lattice animal-like loop displacement. The loop size is an intrinsic property of the ring architecture and is independent of molecular weight. This is the first experimental observation of the space-time evolution of segmental motion in ring polymers illustrating the dynamic consequences of their topology that is unique among all polymeric systems of any other known architecture.

  6. Molecular dynamic simulations of ocular tablet dissolution.

    Science.gov (United States)

    Ru, Qian; Fadda, Hala M; Li, Chung; Paul, Daniel; Khaw, Peng T; Brocchini, Steve; Zloh, Mire

    2013-11-25

    Small tablets for implantation into the subconjunctival space in the eye are being developed to inhibit scarring after glaucoma filtration surgery (GFS). There is a need to evaluate drug dissolution at the molecular level to determine how the chemical structure of the active may correlate with dissolution in the nonsink conditions of the conjunctival space. We conducted molecular dynamics simulations to study the dissolution process of tablets derived from two drugs that can inhibit fibrosis after GFS, 5-fluorouracil (5-FU) and the matrix metalloprotease inhibitor (MMPi), ilomastat. The dissolution was simulated in the presence of simple point charge (SPC) water molecules, and the liquid turnover of the aqueous humor in the subconjunctival space was simulated by removal of the dissolved drug molecules at regular intervals and replacement by new water molecules. At the end of the simulation, the total molecular solvent accessible surface area of 5-FU tablets increased by 60 times more than that of ilomastat as a result of tablet swelling and release of molecules into solution. The tablet dissolution pattern shown in our molecular dynamic simulations tends to correlate with experimental release profiles. This work indicates that a series of molecular dynamic simulations can be used to predict the influence of the molecular properties of a drug on its dissolution profile and could be useful during preformulation where sufficient amounts of the drug are not always available to perform dissolution studies.

  7. Molecular dynamics of protein A and a WW domain with a united-residue model including hydrodynamic interaction

    Science.gov (United States)

    Lipska, Agnieszka G.; Seidman, Steven R.; Sieradzan, Adam K.; Giełdoń, Artur; Liwo, Adam; Scheraga, Harold A.

    2016-05-01

    The folding of the N-terminal part of the B-domain of staphylococcal protein A (PDB ID: 1BDD, a 46-residue three-α-helix bundle) and the formin-binding protein 28 WW domain (PDB ID: 1E0L, a 37-residue three-stranded anti-parallel β protein) was studied by means of Langevin dynamics with the coarse-grained UNRES force field to assess the influence of hydrodynamic interactions on protein-folding pathways and kinetics. The unfolded, intermediate, and native-like structures were identified by cluster analysis, and multi-exponential functions were fitted to the time dependence of the fractions of native and intermediate structures, respectively, to determine bulk kinetics. It was found that introducing hydrodynamic interactions slows down both the formation of an intermediate state and the transition from the collapsed structures to the final native-like structures by creating multiple kinetic traps. Therefore, introducing hydrodynamic interactions considerably slows the folding, as opposed to the results obtained from earlier studies with the use of Gō-like models.

  8. Quaternary association in -prism I fold plant lectins: Insights from X-ray crystallography, modelling and molecular dynamics

    Indian Academy of Sciences (India)

    Alok Sharma; Mamannamana Vijayan

    2011-12-01

    Dimeric banana lectin and calsepa, tetrameric artocarpin and octameric heltuba are mannose-specific -prism I fold lectins of nearly the same tertiary structure. MD simulations on individual subunits and the oligomers provide insights into the changes in the structure brought about in the protomers on oligomerization, including swapping of the N-terminal stretch in one instance. The regions that undergo changes also tend to exhibit dynamic flexibility during MD simulations. The internal symmetries of individual oligomers are substantially retained during the calculations. Energy minimization and simulations were also carried out on models using all possible oligomers by employing the four different protomers. The unique dimerization pattern observed in calsepa could be traced to unique substitutions in a peptide stretch involved in dimerization. The impossibility of a specific mode of oligomerization involving a particular protomer is often expressed in terms of unacceptable steric contacts or dissociation of the oligomer during simulations. The calculations also led to a rationale for the observation of a heltuba tetramer in solution although the lectin exists as an octamer in the crystal, in addition to providing insights into relations among evolution, oligomerization and ligand binding.

  9. Neutron Star Crust and Molecular Dynamics Simulation

    CERN Document Server

    Horowitz, C J; Schneider, A; Berry, D K

    2011-01-01

    In this book chapter we review plasma crystals in the laboratory, in the interior of white dwarf stars, and in the crust of neutron stars. We describe a molecular dynamics formalism and show results for many neutron star crust properties including phase separation upon freezing, diffusion, breaking strain, shear viscosity and dynamics response of nuclear pasta. We end with a summary and discuss open questions and challenges for the future.

  10. Molecular Dynamics Simulations of Polyelectrolyte Solutions

    Science.gov (United States)

    Dobrynin, Andrey

    2014-03-01

    Polyelectrolytes are polymers with ionizable groups. In polar solvents, these groups dissociate releasing counterions into solution and leaving uncompensated charges on the polymer backbone. Examples of polyelectrolytes include biopolymers such as DNA and RNA, and synthetic polymers such as poly(styrene sulfonate) and poly(acrylic acids). In this talk I will discuss recent molecular dynamics simulations of static and dynamic properties of polyelectrolyte solutions. These simulations show that in dilute and semidilute polyelectrolyte solutions the electrostatic induced chain persistence length scales with the solution ionic strength as I - 1 / 2. This dependence of the chain persistence length is due to counterion condensation on the polymer backbone. In dilute polyelectrolyte solutions the chain size decreases with increasing the salt concentration as R ~ I- 1 / 5. This is in agreement with the scaling of the chain persistence length on the solution ionic strength, lp ~ I- 1 / 2. In semidilute solution regime at low salt concentrations the chain size decreases with increasing polymer concentration, R ~ cp-1 / 4 . While at high salt concentrations one observes a weaker dependence of the chain size on the solution ionic strength, R ~ I- 1 / 8. Analysis of the simulation data throughout the studied salt and polymer concentration ranges shows that there exist general scaling relations between multiple quantities X (I) in salt solutions and corresponding quantities X (I0) in salt-free solutions, X (I) = X (I0) (I /I0) β . The exponent β = -1/2 for chain persistence length lp , β = 1/4 for solution correlation length, β = -1/5 and β = -1/8 for chain size R in dilute and semidilute solution regimes respectively. Furthermore, the analysis of the spectrum and of the relaxation times of Rouse modes confirms existence of the single length scale (correlation length) that controls both static and dynamic properties of semidilute polyelectrolyte solutions. These findings

  11. Insights from molecular dynamics simulations: structural basis for the V567D mutation-induced instability of zebrafish alpha-dystroglycan and comparison with the murine model.

    Directory of Open Access Journals (Sweden)

    Davide Pirolli

    Full Text Available A missense amino acid mutation of valine to aspartic acid in 567 position of alpha-dystroglycan (DG, identified in dag1-mutated zebrafish, results in a reduced transcription and a complete absence of the protein. Lacking experimental structural data for zebrafish DG domains, the detailed mechanism for the observed mutation-induced destabilization of the DG complex and membrane damage, remained unclear. With the aim to contribute to a better clarification of the structure-function relationships featuring the DG complex, three-dimensional structural models of wild-type and mutant (V567D C-terminal domain of alpha-DG from zebrafish were constructed by a template-based modelling approach. We then ran extensive molecular dynamics (MD simulations to reveal the structural and dynamic properties of the C-terminal domain and to evaluate the effect of the single mutation on alpha-DG stability. A comparative study has been also carried out on our previously generated model of murine alpha-DG C-terminal domain including the I591D mutation, which is topologically equivalent to the V567D mutation found in zebrafish. Trajectories from MD simulations were analyzed in detail, revealing extensive structural disorder involving multiple beta-strands in the mutated variant of the zebrafish protein whereas local effects have been detected in the murine protein. A biochemical analysis of the murine alpha-DG mutant I591D confirmed a pronounced instability of the protein. Taken together, the computational and biochemical analysis suggest that the V567D/I591D mutation, belonging to the G beta-strand, plays a key role in inducing a destabilization of the alpha-DG C-terminal Ig-like domain that could possibly affect and propagate to the entire DG complex. The structural features herein identified may be of crucial help to understand the molecular basis of primary dystroglycanopathies.

  12. Catalysis and communication in dynamic molecular networks

    NARCIS (Netherlands)

    Fanlo Virgos, Hugo

    2015-01-01

    The interactions of a Dynamic Combinatorial Library (DCL) of molecules with specific targets leads to composition changes of the library which can reveal potential guests and / or catalysts. In this thesis some chemical systems have been proposed to achieve a certain level of molecular complexity

  13. Hydrogen bonding and induced dipole moments in water: predictions from the Gaussian charge polarizable model and Car-Parrinello molecular dynamics.

    Science.gov (United States)

    Dyer, Peter J; Cummings, Peter T

    2006-10-14

    We compare a new classical water model, which features Gaussian charges and polarizability (GCPM) with ab initio Car-Parrinello molecular dynamics (CPMD) simulations. We compare the total dipole moment, the total dipole moment distribution, and degree of hydrogen bonding at ambient to supercritical conditions. We also compared the total dipole moment calculated from both the electron density (partitioning the electron density among molecules based on a zero electron flux condition), and from the center of localized Wannier function centers (WFCs). Compared to CPMD, we found that GCPM overpredicts the dipole moment derived by partitioning the electron density and underpredicts that obtained from the WFCs, but exhibits similar trends and distribution of values. We also found that GCPM predicted similar degrees of hydrogen bonding compared to CPMD and has a similar structure.

  14. A model for the shuttle motions of puerarin and daidzin inside the cavity of β-cyclodextrin in aqueous acetic acid: insights from molecular dynamics simulations.

    Science.gov (United States)

    Zhang, Haiyang; Feng, Wei; Li, Cong; Lv, Yongqin; Tan, Tianwei

    2012-01-01

    Acetic acid acts as one component of the mobile phase to influence separation of puerarin from daidzin when using β-cyclodextrin-substituted media. In this work considering an explicit acetic acid solution, host-guest complexes of β-cyclodextrin (β-CD) with puerarin and daidzin were investigated by molecular dynamics simulations. Computational results indicate different shuttle motions of puerarin and daidzin inside the cavity of β-CD. A model detailing the shuttle motion was constructed, and the relationships between shuttle depth and guest rotation angles, hydrogen bonds, and host-guest interaction energies were analyzed. The results can be used to explain the chromatographic retention mechanisms of puerarin and daidzin with β-CD, and to explore the complexity of host-guest interactions involving β-CD.

  15. The isovector/isoscalar ratio for the imaginary part of the medium-energy nucleon optical model potential studied by the quantum molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Chiba, Satoshi; Niita, Koji; Fukahori, Tokio; Maruyama, Tomoyuki; Maruyama, Toshiki; Iwamoto, Akira [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-05-01

    Energy dependence of the ratio of the isovector and isoscalar strengths in the imaginary part of the nucleon optical model potential at the medium energy range was extracted from an analysis of proton and neutron induced total reaction cross sections on {sup 11}Li with a theoretical framework called quantum molecular dynamics (QMD). The isovector/isoscalar ratio was found to be about 0.8 at 100 MeV, and decreased almost linearly in log(E) to 0 at several hundred MeV. This result was consistent with an estimate at lower energy, and was also in good accord with the values used by Kozack and Madland for the analysis of nucleon + {sup 208}Pb reactions. (author)

  16. Investigation of the Binding Site of CCR2 using 4-Azetidinyl-1-aryl-cyclohexane Derivatives: A Membrane Modeling and Molecular Dynamics Study

    Energy Technology Data Exchange (ETDEWEB)

    Kothandan, Gugan; Gadhe, Changdev G.; Cho, Seung Joo [Chosun Univ., Gwangju (Korea, Republic of)

    2013-11-15

    Chemokine receptor (CCR2) is a G protein-coupled receptor that contains seven transmembrane helices. Recent pharmaceutical research has focused on the antagonism of CCR2 and candidate drugs are currently undergoing clinical studies for the treatment of diseases like arthritis, multiple sclerosis, and type 2 diabetes. In this study, we analyzed the time dependent behavior of CCR2 docked with a potent 4-azetidinyl-1-aryl-cyclohexane (4AAC) derivative using molecular dynamics simulations (MDS) for 20 nanoseconds (ns). Homology modeling of CCR2 was performed and the 4AAC derivative was docked into this binding site. The docked model of selected conformations was then utilized to study the dynamic behavior of the 4AAC enzyme complexes inside lipid membrane. MDS of CCR2-16b of 4AAC complexes allowed us to refine the system since binding of an inhibitor to a receptor is a dynamic process and identify stable structures and better binding modes. Structure activity relationships (SAR) for 4AAC derivatives were investigated and reasons for the activities were determined. Probable binding pose for some CCR2 antagonists were determined from the perspectives of binding site. Initial modeling showed that Tyr49, Trp98, Ser101, Glu291, and additional residues are crucial for 4AAC binding, but MDS analysis showed that Ser101 may not be vital. 4AAC moved away from Ser101 and the hydrogen bonding between 4AAC and Ser101 vanished. The results of this study provide useful information regarding the structure-based drug design of CCR2 antagonists and additionally suggest key residues for further study by mutagenesis.

  17. Models for Dynamic Applications

    DEFF Research Database (Denmark)

    2011-01-01

    be applied to formulate, analyse and solve these dynamic problems and how in the case of the fuel cell problem the model consists of coupledmeso and micro scale models. It is shown how data flows are handled between the models and how the solution is obtained within the modelling environment....

  18. Molecular dynamics computer simulation of permeation in solids

    Energy Technology Data Exchange (ETDEWEB)

    Pohl, P.I.; Heffelfinger, G.S.; Fisler, D.K.; Ford, D.M. [Sandia National Labs., Albuquerque, NM (United States)

    1997-12-31

    In this work the authors simulate permeation of gases and cations in solid models using molecular mechanics and a dual control volume grand canonical molecular dynamics technique. The molecular sieving nature of microporous zeolites are discussed and compared with that for amorphous silica made by sol-gel methods. One mesoporous and one microporous membrane model are tested with Lennard-Jones gases corresponding to He, H{sub 2}, Ar and CH{sub 4}. The mesoporous membrane model clearly follows a Knudsen diffusion mechanism, while the microporous model having a hard-sphere cutoff pore diameter of {approximately}3.4 {angstrom} demonstrates molecular sieving of the methane ({sigma} = 3.8 {angstrom}) but anomalous behavior for Ar ({sigma} = 3.4 {angstrom}). Preliminary results of Ca{sup +} diffusion in calcite and He/H{sub 2} diffusion in polyisobutylene are also presented.

  19. Modelling of nuclear glasses by classical and ab initio molecular dynamics; Modelisation de verres intervenant dans le conditionnement des dechets radioactifs par dynamiques moleculaires classique et ab initio

    Energy Technology Data Exchange (ETDEWEB)

    Ganster, P

    2004-10-15

    A calcium aluminosilicate glass of molar composition 67 % SiO{sub 2} - 12 % Al{sub 2}O{sub 3} - 21 % CaO was modelled by classical and ab initio molecular dynamics. The size effect study in classical MD shows that the systems of 100 atoms are more ordered than the larger ones. These effects are mainly due to the 3-body terms in the empirical potentials. Nevertheless, these effects are small and the structures generated are in agreement with experimental data. In such kind of glass, we denote an aluminium avoidance and an excess of non bridging oxygens which can be compensated by tri coordinated oxygens. When the dynamics of systems of 100 and 200 atoms is followed by ab initio MD, some local arrangements occurs (bond length, angular distributions). Thus, more realistic vibrational properties are obtained in ab initio MD. The modelling of thin films shows that aluminium atoms extend to the most external part of the surface and they are all tri-coordinated. Calcium atoms are set in the sub layer part of the surface and they produce a depolymerization of the network. In classical MD, tri-coordinated aluminium atoms produce an important electric field above the surface. With non bridging oxygens, they constitute attractive sites for single water molecules. (author)

  20. Nanoscale deicing by molecular dynamics simulation

    Science.gov (United States)

    Xiao, Senbo; He, Jianying; Zhang, Zhiliang

    2016-07-01

    Deicing is important to human activities in low-temperature circumstances, and is critical for combating the damage caused by excessive accumulation of ice. The aim of creating anti-icing materials, surfaces and applications relies on the understanding of fundamental nanoscale ice adhesion mechanics. Here in this study, we employ all-atom modeling and molecular dynamics simulation to investigate ice adhesion. We apply force to detach and shear nano-sized ice cubes for probing the determinants of atomistic adhesion mechanics, and at the same time investigate the mechanical effect of a sandwiched aqueous water layer between ice and substrates. We observe that high interfacial energy restricts ice mobility and increases both ice detaching and shearing stresses. We quantify up to a 60% decrease in ice adhesion strength by an aqueous water layer, and provide atomistic details that support previous experimental studies. Our results contribute quantitative comparison of nanoscale adhesion strength of ice on hydrophobic and hydrophilic surfaces, and supply for the first time theoretical references for understanding the mechanics at the atomistic origins of macroscale ice adhesion.Deicing is important to human activities in low-temperature circumstances, and is critical for combating the damage caused by excessive accumulation of ice. The aim of creating anti-icing materials, surfaces and applications relies on the understanding of fundamental nanoscale ice adhesion mechanics. Here in this study, we employ all-atom modeling and molecular dynamics simulation to investigate ice adhesion. We apply force to detach and shear nano-sized ice cubes for probing the determinants of atomistic adhesion mechanics, and at the same time investigate the mechanical effect of a sandwiched aqueous water layer between ice and substrates. We observe that high interfacial energy restricts ice mobility and increases both ice detaching and shearing stresses. We quantify up to a 60% decrease in ice

  1. MDMovie: a molecular dynamics viewing tool.

    Science.gov (United States)

    Greenberg, J P

    1996-10-01

    The graphics program MDMovie (Molecular Dynamics Movie), written in C using IRIS GL graphics library calls, is designed to facilitate the visualization and interpretation of empirical force field data. MDMovie was created and initially adapted in accord with the needs of physical chemists and thereafter became an expandable analysis tool. Capabilities include the display of chemical structure, animation of molecular dynamics and Monte Carlo trajectories, and the visual representation of various vector and scalar dynamical properties. In addition to being a research tool, MDMovie has features for creating presentation videos and hardcopy output. A library is also available for linking to Fortran simulation codes running on a remote machine and connecting to MDMovie via a socket connection. MDMovie continues to be an ongoing research project and new features are actively being added in collaboration with various research groups. Future plans include porting to OpenGL and the design of an XII-based user interface.

  2. 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

  3. State-to-state dynamics of molecular energy transfer

    Energy Technology Data Exchange (ETDEWEB)

    Gentry, W.R.; Giese, C.F. [Univ. of Minnesota, Minneapolis (United States)

    1993-12-01

    The goal of this research program is to elucidate the elementary dynamical mechanisms of vibrational and rotational energy transfer between molecules, at a quantum-state resolved level of detail. Molecular beam techniques are used to isolate individual molecular collisions, and to control the kinetic energy of collision. Lasers are used both to prepare specific quantum states prior to collision by stimulated-emission pumping (SEP), and to measure the distribution of quantum states in the collision products by laser-induced fluorescence (LIF). The results are interpreted in terms of dynamical models, which may be cast in a classical, semiclassical or quantum mechanical framework, as appropriate.

  4. Improved Angle Potentials for Coarse-Grained Molecular Dynamics Simulations

    NARCIS (Netherlands)

    Bulacu, Monica; Goga, Nicolae; Zhao, Wei; Rossi, Giulia; Monticelli, Luca; Periole, Xavier; Tieleman, D. Peter; Marrink, Siewert J.

    2013-01-01

    Potentials routinely used in atomistic molecular dynamics simulations are not always suitable for modeling systems at coarse-grained resolution. For example, in the calculation of traditional torsion angle potentials, numerical instability is often encountered in the case of very flexible molecules.

  5. Nonlinear dynamics of zigzag molecular chains (in Russian)

    DEFF Research Database (Denmark)

    Savin, A. V.; Manevitsch, L. I.; Christiansen, Peter Leth;

    1999-01-01

    Nonlinear, collective, soliton type excitations in zigzag molecular chains are analyzed. It is shown that the nonlinear dynamics of a chain dramatically changes in passing from the one-dimensional linear chain to the more realistic planar zigzag model-due, in particular, to the geometry-dependent...

  6. Benchmark of Schemes for Multiscale Molecular Dynamics Simulations

    NARCIS (Netherlands)

    Goga, N.; Melo, M. N.; Rzepiela, A. J.; de Vries, Alex; Hadar, A.; Marrink, S. J.; Berendsen, Herman

    2015-01-01

    In multiscale molecular dynamics simulations the accuracy of detailed models is combined with the efficiency of a reduced representation. For several applications - namely those of sampling enhancement - it is desirable to combine fine-grained (FG) and coarse-grained (CG) approaches into a single hy

  7. A MOLECULAR-DYNAMICS STUDY OF LECITHIN MONOLAYERS

    NARCIS (Netherlands)

    AHLSTROM, P; BERENDSEN, HJC

    1993-01-01

    Two monolayers of didecanoyllecithin at the air-water interface have been studied using molecular dynamics simulations. The model system consisted of two monolayers of 42 lecithin molecules each separated by a roughly 4 nm thick slab of SPC water. The area per lecithin molecule was 0.78 nm(2)

  8. Combined molecular dynamics-spin dynamics simulations of bcc iron

    Energy Technology Data Exchange (ETDEWEB)

    Perera, Meewanage Dilina N [ORNL; Yin, Junqi [ORNL; Landau, David P [University of Georgia, Athens, GA; Nicholson, Don M [ORNL; Stocks, George Malcolm [ORNL; Eisenbach, Markus [ORNL; Brown, Greg [ORNL

    2014-01-01

    Using a classical model that treats translational and spin degrees of freedom on an equal footing, we study phonon-magnon interactions in BCC iron with combined molecular and spin dynamics methods. The atomic interactions are modeled via an empirical many-body potential while spin dependent interactions are established through a Hamiltonian of the Heisenberg form with a distance dependent magnetic exchange interaction obtained from first principles electronic structure calculations. The temporal evolution of translational and spin degrees of freedom was determined by numerically solving the coupled equations of motion, using an algorithm based on the second order Suzuki-Trotter decomposition of the exponential operators. By calculating Fourier transforms of space- and time-displaced correlation functions, we demonstrate that the the presence of lattice vibrations leads to noticeable softening and damping of spin wave modes. As a result of the interplay between lattice and spin subsystems, we also observe additional longitudinal spin wave excitations, with frequencies which coincide with that of the longitudinal lattice vibrations.

  9. Sphere-to-Rod Transitions of Nonionic Surfactant Micelles in Aqueous Solution Modeled by Molecular Dynamics Simulations

    NARCIS (Netherlands)

    Velinova, Maria; Sengupta, Durba; Tadjer, Alia V.; Marrink, Siewert-Jan

    2011-01-01

    Control of the size and agglomeration of micellar systems is important for pharmaceutical applications such as drug delivery. Although shape-related transitions in surfactant solutions are studied experimentally, their molecular mechanisms are still not well understood. In this study, we use coarse-

  10. GPR17: Molecular modeling and dynamics studies of the 3-D structure and purinergic ligand binding features in comparison with P2Y receptors

    Directory of Open Access Journals (Sweden)

    Ranghino Graziella

    2008-06-01

    Full Text Available Abstract Background GPR17 is a G-protein-coupled receptor located at intermediate phylogenetic position between two distinct receptor families: the P2Y and CysLT receptors for extracellular nucleotides and cysteinyl-LTs, respectively. We previously showed that GPR17 can indeed respond to both classes of endogenous ligands and to synthetic compounds active at the above receptor families, thus representing the first fully characterized non-peptide "hybrid" GPCR. In a rat brain focal ischemia model, the selective in vivo knock down of GPR17 by anti-sense technology or P2Y/CysLT antagonists reduced progression of ischemic damage, thus highlighting GPR17 as a novel therapeutic target for stroke. Elucidation of the structure of GPR17 and of ligand binding mechanisms are the necessary steps to obtain selective and potent drugs for this new potential target. On this basis, a 3-D molecular model of GPR17 embedded in a solvated phospholipid bilayer and refined by molecular dynamics simulations has been the first aim of this study. To explore the binding mode of the "purinergic" component of the receptor, the endogenous agonist UDP and two P2Y receptor antagonists demonstrated to be active on GPR17 (MRS2179 and cangrelor were then modeled on the receptor. Results Molecular dynamics simulations suggest that GPR17 nucleotide binding pocket is similar to that described for the other P2Y receptors, although only one of the three basic residues that have been typically involved in ligand recognition is conserved (Arg255. The binding pocket is enclosed between the helical bundle and covered at the top by EL2. Driving interactions are H-bonds and salt bridges between the 6.55 and 6.52 residues and the phosphate moieties of the ligands. An "accessory" binding site in a region formed by the EL2, EL3 and the Nt was also found. Conclusion Nucleotide binding to GPR17 occurs on the same receptor regions identified for already known P2Y receptors. Agonist

  11. Dynamical quenching of tunneling in molecular magnets

    Energy Technology Data Exchange (ETDEWEB)

    José Santander, María, E-mail: maria.jose.noemi@gmail.com [Recursos Educativos Quántica, Santiago (Chile); Departamento de Física, Universidad de Santiago de Chile and CEDENNA, Avda. Ecuador 3493, Santiago (Chile); Nunez, Alvaro S., E-mail: alnunez@dfi.uchile.cl [Departamento de Física, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Casilla 487-3, Santiago (Chile); Roldán-Molina, A. [Instituto de Física, Pontificia Universidad Católica de Valparaíso, Avenida Universidad 330, Curauma, Valparaíso (Chile); Troncoso, Roberto E., E-mail: r.troncoso.c@gmail.com [Centro para el Desarrollo de la Nanociencia y la Nanotecnología, CEDENNA, Avda. Ecuador 3493, Santiago 9170124 (Chile); Departamento de Física, Universidad Técnica Federico Santa María, Avenida España 1680, Valparaíso (Chile)

    2015-12-15

    It is shown that a single molecular magnet placed in a rapidly oscillating magnetic field displays the phenomenon of quenching of tunneling processes. The results open a way to manipulate the quantum states of molecular magnets by means of radiation in the terahertz range. Our analysis separates the time evolution into slow and fast components thereby obtaining an effective theory for the slow dynamics. This effective theory presents quenching of the tunnel effect, in particular, stands out its difference with the so-called coherent destruction of tunneling. We support our prediction with numerical evidence based on an exact solution of Schrödinger's equation. - Highlights: • Single molecular magnets under rapidly oscillating magnetic fields is studied. • It is shown that this system displays the quenching of tunneling processes. • Our findings provide a control of quantum molecular magnets via terahertz radiation.

  12. Homology modeling and molecular dynamics simulation of N-myristoyltransferase from protozoan parasites: active site characterization and insights into rational inhibitor design

    Science.gov (United States)

    Sheng, Chunquan; Ji, Haitao; Miao, Zhenyuan; Che, Xiaoyin; Yao, Jianzhong; Wang, Wenya; Dong, Guoqiang; Guo, Wei; Lü, Jiaguo; Zhang, Wannian

    2009-06-01

    Myristoyl-CoA:protein N-myristoyltransferase (NMT) is a cytosolic monomeric enzyme that catalyzes the transfer of the myristoyl group from myristoyl-CoA to the N-terminal glycine of a number of eukaryotic cellular and viral proteins. Recent experimental data suggest NMT from parasites could be a promising new target for the design of novel antiparasitic agents with new mode of action. However, the active site topology and inhibitor specificity of these enzymes remain unclear. In this study, three-dimensional models of NMT from Plasmodium falciparum (PfNMT), Leishmania major (LmNMT) and Trypanosoma brucei (TbNMT) were constructed on the basis of the crystal structures of fungal NMTs using homology modeling method. The models were further refined by energy minimization and molecular dynamics simulations. The active sites of PfNMT, LmNMT and TbNMT were characterized by multiple copy simultaneous search (MCSS). MCSS functional maps reveal that PfNMT, LmNMT and TbNMT share a similar active site topology, which is defined by two hydrophobic pockets, a hydrogen-bonding (HB) pocket, a negatively-charged HB pocket and a positively-charged HB pocket. Flexible docking approaches were then employed to dock known inhibitors into the active site of PfNMT. The binding mode, structure-activity relationships and selectivity of inhibitors were investigated in detail. From the results of molecular modeling, the active site architecture and certain key residues responsible for inhibitor binding were identified, which provided insights for the design of novel inhibitors of parasitic NMTs.

  13. 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

  14. 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

  15. Exploring 3D structure of human gonadotropin hormone receptor at antagonist state using homology modeling, molecular dynamic simulation, and cross-docking studies.

    Science.gov (United States)

    Sakhteman, Amirhossein; Khoddami, Minasadat; Negahdaripour, Manica; Mehdizadeh, Arash; Tatar, Mohsen; Ghasemi, Younes

    2016-09-01

    Human gonadotropin hormone receptor, a G-protein coupled receptor, is the target of many medications used in fertility disorders. Obtaining more structural information about the receptor could be useful in many studies related to drug design. In this study, the structure of human gonadotropin receptor was subjected to homology modeling studies and molecular dynamic simulation within a DPPC lipid bilayer for 100 ns. Several frames were thereafter extracted from simulation trajectories representing the receptor at different states. In order to find a proper model of the receptor at the antagonist state, all frames were subjected to cross-docking studies of some antagonists with known experimental values (Ki). Frame 194 revealed a reasonable correlation between docking calculated energy scores and experimental activity values (|r| = 0.91). The obtained correlation was validated by means of SSLR and showed the presence of no chance correlation for the obtained model. Different structural features reported for the receptor, such as two disulfide bridges and ionic lock between GLU90 and LYS 121 were also investigated in the final model.

  16. Tracing the molecular basis of transcriptional dynamics in noisy data by using an experiment based mathematical model

    NARCIS (Netherlands)

    Rybakova, K.N.; Tomaszewska, A.; Mourik, van S.; Blom, Joke; Westerhoff, H.V.; Carlberg, C.; Bruggeman, F.J.

    2015-01-01

    Changes in transcription factor levels, epigenetic status, splicing kinetics and mRNA degradation can each contribute to changes in the mRNA dynamics of a gene. We present a novel method to identify which of these processes is changed in cells in response to external signals or as a result of a dise

  17. Tracing the molecular basis of transcriptional dynamics in noisy data by using an experiment-based mathematical model

    NARCIS (Netherlands)

    Rybakova, K.N.; Tomaszewska, A.; Mourik, S. van; Blom, J.G.; Westerhoff, H.V.; Carlberg, C.; Bruggeman, F.J.

    2014-01-01

    Changes in transcription factor levels, epigenetic status, splicing kinetics and mRNA degradation can each contribute to changes in the mRNA dynamics of a gene. We present a novel method to identify which of these processes is changed in cells in response to external signals or as a result of a dise

  18. Tracing the molecular basis of transcriptional dynamics in noisy data by using an experiment-based mathematical model

    NARCIS (Netherlands)

    K.N. Rybakova; A. Tomaszewska; S. van Mourik; J. Blom; H.V. Westerhoff; C. Carlberg; F.J. Bruggeman

    2015-01-01

    Changes in transcription factor levels, epigenetic status, splicing kinetics and mRNA degradation can each contribute to changes in the mRNA dynamics of a gene. We present a novel method to identify which of these processes is changed in cells in response to external signals or as a result of a dise

  19. “The molecule’s the thing:” the promise of molecular modeling and dynamic simulations in aiding the prioritization and interpretation of genomic testing results

    Science.gov (United States)

    Oliver, Gavin R.; Zimmermann, Michael T.; Klee, Eric W.; Urrutia, Raul A.

    2016-01-01

    Clinical genomics is now a reality and lies at the heart of individualized medicine efforts. The success of these approaches is evidenced by the increasing volume of publications that report causal links between genomic variants and disease. In spite of early success, clinical genomics currently faces significant challenges in establishing the relevance of the majority of variants identified by next generation sequencing tests. Indeed, the majority of mutations identified are harbored by proteins whose functions remain elusive. Herein we describe the current scenario in genomic testing and in particular the burden of variants of uncertain significance (VUSs). We highlight a role for molecular modeling and molecular dynamic simulations as tools that can significantly increase the yield of information to aid in the evaluation of pathogenicity. Though the application of these methodologies to the interpretation of variants identified by genomic testing is not yet widespread, we predict that an increase in their use will significantly benefit the mission of clinical genomics for individualized medicine. PMID:27408685

  20. Scattering Density Profile Model of POPG Bilayers as Determined by Molecular Dynamics Simulations and Small-Angle Neutron and X-ray Scattering Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Kucerka, Norbert [Canadian Neutron Beam Centre and Comelius University (Slovakia); Holland, B [University of Guelph; Gray, C.G [University of Guelph; Tomberli, B [Brandon University; Katsaras, John [ORNL

    2012-01-01

    We combine molecular dynamics (MD) simulations and experiment, both small-angle neutron (SANS) and small-angle X-ray scattering (SAXS), to determine the precise structure of bilayers composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG), a lipid commonly encountered in bacterial membranes. Experiment and simulation are used to develop a one-dimensional scattering density profile (SDP) model suitable for the analysis of experimental data. The joint refinement of such data (i.e., SANS and SAXS) results in the area per lipid that is then used in the fixed-area simulations. In the final step, the direct comparison of simulated-to-experimental data gives rise to the detailed structure of POPG bilayers. From these studies we conclude that POPG s molecular area is 66.0 +/- 1.3 ^2, its overall bilayer thickness is 36.7 +/- 0.7 , and its hydrocarbon region thickness is 27.9 ( 0.6 , assuming a simulated value of 1203 ^3 for the total lipid volume.

  1. Thermodynamic, dynamic and solvational properties of PDEδ binding to farnesylated cystein: a model study for uncovering the molecular mechanism of PDEδ interaction with prenylated proteins.

    Science.gov (United States)

    Suladze, S; Ismail, S; Winter, R

    2014-01-30

    The protein PDEδ is an important solubilizing factor for several prenylated proteins including the Ras subfamily members. The binding occurs mainly through the farnesyl anchor of Ras proteins, which is recognized by a hydrophobic pocket of PDEδ. In this study, we carried out a detailed study of the thermodynamic and solvational properties of PDEδ binding to farnesyl-cystein, which serves as a model for PDEδ association to prenylated proteins. Using various biophysical approaches in conjunction with theoretical considerations, we show here that binding of the largely hydrophobic ligand surprisingly has enthalpy-driven signature, and the entropy change is largely controlled by the fine balance between the hydrational and conformational terms. Moreover, binding of PDEδ to farnesyl-cystein is accompanied by an increase in thermal stability, the release of about 150 water molecules from the interacting species, a decrease in solvent accessible surface area, and a marked decrease of the volume fluctuations and hence dynamics of the protein. Altogether, our results shed more light on the molecular mechanism of PDEδ interaction with prenylated Ras proteins, which is also prerequisite for an optimization of the structure-based molecular design of drugs against Ras related diseases and for understanding the multitude of biological functions of PDEδ.

  2. Nanoscale deicing by molecular dynamics simulation.

    Science.gov (United States)

    Xiao, Senbo; He, Jianying; Zhang, Zhiliang

    2016-08-14

    Deicing is important to human activities in low-temperature circumstances, and is critical for combating the damage caused by excessive accumulation of ice. The aim of creating anti-icing materials, surfaces and applications relies on the understanding of fundamental nanoscale ice adhesion mechanics. Here in this study, we employ all-atom modeling and molecular dynamics simulation to investigate ice adhesion. We apply force to detach and shear nano-sized ice cubes for probing the determinants of atomistic adhesion mechanics, and at the same time investigate the mechanical effect of a sandwiched aqueous water layer between ice and substrates. We observe that high interfacial energy restricts ice mobility and increases both ice detaching and shearing stresses. We quantify up to a 60% decrease in ice adhesion strength by an aqueous water layer, and provide atomistic details that support previous experimental studies. Our results contribute quantitative comparison of nanoscale adhesion strength of ice on hydrophobic and hydrophilic surfaces, and supply for the first time theoretical references for understanding the mechanics at the atomistic origins of macroscale ice adhesion.

  3. MOLECULAR DYNAMIC SIMULATION OF PEPTIDE POLYELECTROLYTES

    Directory of Open Access Journals (Sweden)

    I. M. Neelov

    2014-07-01

    Full Text Available The paper deals with investigation of the conformational properties of some charged homopolypeptides in dilute aqueous solutions by computer simulation. A method of molecular dynamics for the full-atomic models of polyaspartic acid and polylysine with explicit account of water and counter-ions is used for this purpose. For systems containing these polypeptides we calculated time trajectories and the size, shape, distribution functions and time correlation functions of inertia radius and the distances between the ends of peptide chains. We have also calculated the solvatation characteristics of considered polyelectrolytes. We have found out that polyaspartic acid in dilute aqueous solution has more compact structure and more spherical shape than polylysine. We have shown that these differences are due to different interaction between the polypeptides and water molecules (in particular, the quality and quantity of hydrogen bonds formed by these peptides with water, and the difference in an amount of ion pairs formed by the charged groups of the peptides and counter-ions. The obtained results should be taken into account for elaboration of new products based on the investigated peptides and their usage in various industrial and biomedical applications.

  4. Molecular dynamics simulations of vibrated granular gases.

    Science.gov (United States)

    Barrat, Alain; Trizac, Emmanuel

    2002-11-01

    We present molecular dynamics simulations of monodisperse or bidisperse inelastic granular gases driven by vibrating walls, in two dimensions (without gravity). Because of the energy injection at the boundaries, a situation often met experimentally, density and temperature fields display heterogeneous profiles in the direction perpendicular to the walls. A general equation of state for an arbitrary mixture of fluidized inelastic hard spheres is derived and successfully tested against numerical data. Single-particle velocity distribution functions with non-Gaussian features are also obtained, and the influence of various parameters (inelasticity coefficients, density, etc.) are analyzed. The validity of a recently proposed random restitution coefficient model is assessed through the study of projected collisions onto the direction perpendicular to that of energy injection. For the binary mixture, the nonequipartition of translational kinetic energy is studied and compared both to experimental data and to the case of homogeneous energy injection ("stochastic thermostat"). The rescaled velocity distribution functions are found to be very similar for both species.

  5. Molecular dynamics simulation of flow in pores

    Science.gov (United States)

    Blömer, Jan

    2001-08-01

    The gaseous flow in nano-scale pores is of wide interest for many today's industrial applications, e.g., in microelectronics, nano-mechanical devices (Knudsen compressor) and reaction and adsorption at porous surfaces. This can be seen from a variety of papers of recent RGD Symposia. Furthermore it is possible to separate gases by porous membranes. Although the fundamental problem of all these applications is same, namely the important role of the gas-surface interaction in such small structures, we will primarily concentrate on the separation of different gas species by porous membranes. These membranes are typically very robust (temperature, chemical resistance) because they are made from ceramics which offers new application fields. Porous flow can roughly be divided in several flow regimes by the Knudsen number: From viscous flow to Knudsen diffusion to surface diffusion and up to capillary condensation. A Molecular Dynamics (MD) model for the gas as well as the surface is formulated to investigate the interaction of gas atoms or molecules with internal degrees of freedom and the pore. The MD method seems to be well suited to study these phenomena because it can deal with the high density and the many-body-interactions, which occur during the multilayer adsorption and condensation at the surface, although it is clear that it is limited to a small physical space because of its high computational consumption.

  6. Dynamic assembly of molecularly imprinted polymer nanoparticles.

    Science.gov (United States)

    Gong, Haiyue; Hajizadeh, Solmaz; Jiang, Lingdong; Ma, Huiting; Ye, Lei

    2017-09-11

    Manipulation of specific binding and recycling of materials are two important aspects for practical applications of molecularly imprinted polymers. In this work, we developed a new approach to control the dynamic assembly of molecularly imprinted nanoparticles by surface functionalization. Molecularly imprinted polymer nanoparticles with a well-controlled core-shell structure were synthesized using precipitation polymerization. The specific binding sites were created in the core during the first step imprinting reaction. In the second polymerization step, epoxide groups were introduced into the particle shell to act asan intermediate linker to immobilize phenylboronic acids, as well as to introduce cis-diol structures on surface. The imprinted polymer nanoparticles modified with boronic acid and cis-diol structures maintained high molecular binding specificity, and the nanoparticles could be induced to form dynamic particle aggregation that responded to pH variation and chemical stimuli. The possibility of modulating molecular binding and nanoparticle assembly in a mutually independent fashion can be exploited in a number of applications where repeated use of precious nanoparticles is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Dynamic term structure models

    DEFF Research Database (Denmark)

    Andreasen, Martin Møller; Meldrum, Andrew

    This paper studies whether dynamic term structure models for US nominal bond yields should enforce the zero lower bound by a quadratic policy rate or a shadow rate specification. We address the question by estimating quadratic term structure models (QTSMs) and shadow rate models with at most four...

  8. Molecular dynamics analysis on impact behavior of carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Seifoori, Sajjad, E-mail: sajjad.seifoori@vru.ac.ir

    2015-01-30

    Graphical abstract: - Highlights: • We present an analytical solution of impact based on two degree of freedom model. • The accuracy is verified by Molecular dynamics simulations. • The effects of the small-size effects on the dynamic deflections are investigated. • The relative motion is also accounted that is due to local indentation. - Abstract: Dynamic analysis of impact of a nanoparticle on carbon nanotubes is investigated based on two degree of freedom model. The accuracy and stability of the present methods are verified by molecular dynamics (MD) simulations. The effect of different types of boundary condition on the maximum dynamic deflections is studied for zigzag and armchair SWCNTs with various aspect ratios (length/diameter). Besides, the influences of velocity of impactor on the dynamic deflections are studied. It is shown that the dynamic behavior on the armchair and zigzag single-walled carbon nanotubes are almost similar. Finally, by making use of the above MD simulation and theoretical results some insight has been obtained about the dynamic characteristics of the impact problems of nanobeam structures. Nonlocal Timoshenko beam models TBT2 should be employed for an accurate prediction of the dynamic deflection rather than nonlocal Euler–Bernoulli beam models EBT2 which ignores the effects of transverse shear deformation and rotary inertia that is especially significant for short beams. The results from nonlocal EBT2 and TBT2 models demonstrated good agreement with MD simulation. The EBT2 and TBT2 models also account for the relative motion between the nanoparticle and the nanobeam that is due to local indentation as can be seen in MD simulation.

  9. Dependence of the atomic level Green-Kubo stress correlation function on wavevector and frequency: molecular dynamics results from a model liquid.

    Science.gov (United States)

    Levashov, V A

    2014-09-28

    We report on a further investigation of a new method that can be used to address vibrational dynamics and propagation of stress waves in liquids. The method is based on the decomposition of the macroscopic Green-Kubo stress correlation function into the atomic level stress correlation functions. This decomposition, as was demonstrated previously for a model liquid studied in molecular dynamics simulations, reveals the presence of stress waves propagating over large distances and a structure that resembles the pair density function. In this paper, by performing the Fourier transforms of the atomic level stress correlation functions, we elucidate how the lifetimes of the stress waves and the ranges of their propagation depend on their frequency, wavevector, and temperature. These results relate frequency and wavevector dependence of the generalized viscosity to the character of propagation of the shear stress waves. In particular, the results suggest that an increase in the value of the frequency dependent viscosity at low frequencies with decrease of temperature is related to the increase in the ranges of propagation of the stress waves of the corresponding low frequencies. We found that the ranges of propagation of the shear stress waves of frequencies less than half of the Einstein frequency extend well beyond the nearest neighbor shell even above the melting temperature. The results also show that the crossover from quasilocalized to propagating behavior occurs at frequencies usually associated with the Boson peak.

  10. Prediction of EPR Spectra of Lyotropic Liquid Crystals using a Combination of Molecular Dynamics Simulations and the Model-Free Approach.

    Science.gov (United States)

    Prior, Christopher; Oganesyan, Vasily S

    2017-09-21

    We report the first application of fully atomistic molecular dynamics (MD) simulations to the prediction of the motional electron paramagnetic resonance (EPR) spectra of lyotropic liquid crystals in different aggregation states doped with a paramagnetic spin probe. The purpose of this study is twofold. First, given that EPR spectra are highly sensitive to the motions and order of the spin probes doped within lyotropic aggregates, simulation of EPR line shapes from the results of MD modelling provides an ultimate test bed for the force fields currently employed to model such systems. Second, the EPR line shapes are simulated using the motional parameters extracted from MD trajectories using the Model-Free (MF) approach. Thus a combined MD-EPR methodology allowed us to test directly the validity of the application of the MF approach to systems with multi-component molecular motions. All-atom MD simulations using the General AMBER Force Field (GAFF) have been performed on sodium dodecyl sulfate (SDS) and dodecyltrimethylammonium chloride (DTAC) liquid crystals. The resulting MD trajectories were used to predict and interpret the EPR spectra of pre-micellar, micellar, rod and lamellar aggregates. The predicted EPR spectra demonstrate good agreement with most of experimental line shapes thus confirming the validity of both the force fields employed and the MF approach for the studied systems. At the same time simulation results confirm that GAFF tends to overestimate the packing and the order of the carbonyl chains of the surfactant molecules. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. EXAFS, ab Initio Molecular Dynamics, and NICIS Spectroscopy Studies on an Organic Dye Model at the Dye-Sensitized Solar Cell Photoelectrode Interface.

    Science.gov (United States)

    Liu, Peng; Johansson, Viktor; Trilaksana, Herri; Rosdahl, Jan; Andersson, Gunther G; Kloo, Lars

    2017-06-14

    The organization of dye molecules in the dye layer adsorbed on the semiconductor substrate in dye-sensitized solar cells has been studied using a combination of theoretical methods and experimental techniques. The model system is based on the simple D-π-A dye L0, which has been chemically modified by substituting the acceptor group CN with Br (L0Br) to offer better X-ray contrast. Experimental EXAFS data based on the Br K-edge backscattering show no obvious difference between dye-sensitized titania powder and titania film samples, thus allowing model systems to be based on powder slurries. Ab initio molecular dynamic (aiMD) calculations have been performed to extract less biased information from the experimental EXASF data. Using the aiMD calculation as input, the EXAFS structural models can be generated a priori that match the experimental data. Our study shows that the L0Br dye adsorbs in the trans-L0Br configuration and that adsorption involves both a proximity to other L0Br dye molecules and the titanium atoms in the TiO2 substrate. These results indicate direct coordination of the dye molecules to the TiO2 surface in contrast to previous results on metal-organic dyes. The molecular coverage of L0Br on mesoporous TiO2 was also estimated using NICIS spectroscopy. The NICISS results emphasized that the L0Br dye on nanoporous titania mainly forms monolayers with a small contribution of multilayer coverage.

  12. G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations

    DEFF Research Database (Denmark)

    Ísberg, Vignir; Balle, Thomas; Sander, Tommy

    2011-01-01

    A 5-HT(2A) receptor model was constructed by homology modeling based on the ß(2)-adrenergic receptor and the G protein-bound opsin crystal structures. The 5-HT(2A) receptor model was transferred into an active conformation by an agonist ligand and a G(aq) peptide in four subsequent steered...

  13. Molecular Dynamics Simulation of a Coarse Grained Model of Tetra-PEG Gel with Monomers of 5 and 9 particles

    Science.gov (United States)

    Ogawa, Shizuka; Waide, Sayaka; Takasu, Masako; Miyakawa, Takeshi; Morikawa, Ryota; Sakai, Takamasa; Chung, Ung-il

    We study the early process of gelation using our model of 5 particles and 9 particles in a monomer. We compare our models and obtain slower reaction for model of 9 particles. We also study the effect of random force and obtain slower reaction with random force but more extended structure.

  14. Isobaric yield ratio difference between the 140 $A$ MeV $^{58, 64}$Ni + $^{9}$Be reactions studied by antisymmetric molecular dynamics model

    CERN Document Server

    Qiao, C Y; Ma, C W; Zhang, Y L; Wang, S S

    2015-01-01

    \\item[Background] The isobaric yield ratio difference (IBD) method is found to be sensitive to the density difference of neutron-rich nucleus induced reaction around the Fermi energy. \\item[Purpose] An investigation is performed to study the IBD results in the transport model. \\item[Methods] The antisymmetric molecular dynamics (AMD) model plus the sequential decay model GEMINI are adopted to simulate the 140$A$ MeV $^{58, 64}$Ni + $^{9}$Be reactions. A relative small coalescence radius R$_c =$ 2.5 fm is used for the phase space at $t =$ 500 fm/c to form the hot fragment. Two limitations on the impact parameter ($b1 = 0 - 2$ fm and $b2 = 0 - 9$ fm) are used to study the effect of central collisions in IBD. \\item[Results] The isobaric yield ratios (IYRs) for the large--$A$ fragments are found to be suppressed in the symmetric reaction. The IBD results for fragments with neutron-excess $I = $ 0 and 1 are obtained. A small difference is found in the IBDs with the $b1$ and $b2$ limitations in the AMD simulated re...

  15. Molecular dynamics modeling the synthetic and biological polymers interactions pre-studied via docking: anchors modified polyanions interference with the HIV-1 fusion mediator.

    Science.gov (United States)

    Tsvetkov, Vladimir B; Serbin, Alexander V

    2014-06-01

    In previous works we reported the design, synthesis and in vitro evaluations of synthetic anionic polymers modified by alicyclic pendant groups (hydrophobic anchors), as a novel class of inhibitors of the human immunodeficiency virus type 1 (HIV-1) entry into human cells. Recently, these synthetic polymers interactions with key mediator of HIV-1 entry-fusion, the tri-helix core of the first heptad repeat regions [HR1]3 of viral envelope protein gp41, were pre-studied via docking in terms of newly formulated algorithm for stepwise approximation from fragments of polymeric backbone and side-group models toward real polymeric chains. In the present article the docking results were verified under molecular dynamics (MD) modeling. In contrast with limited capabilities of the docking, the MD allowed of using much more large models of the polymeric ligands, considering flexibility of both ligand and target simultaneously. Among the synthesized polymers the dinorbornen anchors containing alternating copolymers of maleic acid were selected as the most representative ligands (possessing the top anti-HIV activity in vitro in correlation with the highest binding energy in the docking). To verify the probability of binding of the polymers with the [HR1]3 in the sites defined via docking, various starting positions of polymer chains were tried. The MD simulations confirmed the main docking-predicted priority for binding sites, and possibilities for axial and belting modes of the ligands-target interactions. Some newly MD-discovered aspects of the ligand's backbone and anchor units dynamic cooperation in binding the viral target clarify mechanisms of the synthetic polymers anti-HIV activity and drug resistance prevention.

  16. 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...

  17. Characterization of Rare Events in Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Carsten Hartmann

    2013-12-01

    Full Text Available A good deal of molecular dynamics simulations aims at predicting and quantifying rare events, such as the folding of a protein or a phase transition. Simulating rare events is often prohibitive, especially if the equations of motion are high-dimensional, as is the case in molecular dynamics. Various algorithms have been proposed for efficiently computing mean first passage times, transition rates or reaction pathways. This article surveys and discusses recent developments in the field of rare event simulation and outlines a new approach that combines ideas from optimal control and statistical mechanics. The optimal control approach described in detail resembles the use of Jarzynski’s equality for free energy calculations, but with an optimized protocol that speeds up the sampling, while (theoretically giving variance-free estimators of the rare events statistics. We illustrate the new approach with two numerical examples and discuss its relation to existing methods.

  18. Kinetic distance and kinetic maps from molecular dynamics simulation

    CERN Document Server

    Noe, Frank

    2015-01-01

    Characterizing macromolecular kinetics from molecular dynamics (MD) simulations requires a distance metric that can distinguish slowly-interconverting states. Here we build upon diffusion map theory and define a kinetic distance for irreducible Markov processes that quantifies how slowly molecular conformations interconvert. The kinetic distance can be computed given a model that approximates the eigenvalues and eigenvectors (reaction coordinates) of the MD Markov operator. Here we employ the time-lagged independent component analysis (TICA). The TICA components can be scaled to provide a kinetic map in which the Euclidean distance corresponds to the kinetic distance. As a result, the question of how many TICA dimensions should be kept in a dimensionality reduction approach becomes obsolete, and one parameter less needs to be specified in the kinetic model construction. We demonstrate the approach using TICA and Markov state model (MSM) analyses for illustrative models, protein conformation dynamics in bovine...

  19. Study of Nanowires Using Molecular Dynamics Simulations

    OpenAIRE

    Monk, Joshua D

    2007-01-01

    In this dissertation I present computational studies that focus on the unique characteristics of metallic nanowires. We generated virtual nanowires of nanocrystalline nickel (nc-Ni) and single crystalline silver (Ag) in order to investigate particular nanoscale effects. Three-dimensional atomistic molecular dynamics studies were performed for each sample using the super computer System X located at Virginia Tech. Thermal grain growth simulations were performed on 4 nm grain size nc-Ni by o...

  20. Molecular crowding and protein enzymatic dynamics.

    Science.gov (United States)

    Echeverria, Carlos; Kapral, Raymond

    2012-05-21

    The effects of molecular crowding on the enzymatic conformational dynamics and transport properties of adenylate kinase are investigated. This tridomain protein undergoes large scale hinge motions in the course of its enzymatic cycle and serves as prototype for the study of crowding effects on the cyclic conformational dynamics of proteins. The study is carried out at a mesoscopic level where both the protein and the solvent in which it is dissolved are treated in a coarse grained fashion. The amino acid residues in the protein are represented by a network of beads and the solvent dynamics is described by multiparticle collision dynamics that includes effects due to hydrodynamic interactions. The system is crowded by a stationary random array of hard spherical objects. Protein enzymatic dynamics is investigated as a function of the obstacle volume fraction and size. In addition, for comparison, results are presented for a modification of the dynamics that suppresses hydrodynamic interactions. Consistent with expectations, simulations of the dynamics show that the protein prefers a closed conformation for high volume fractions. This effect becomes more pronounced as the obstacle radius decreases for a given volume fraction since the average void size in the obstacle array is smaller for smaller radii. At high volume fractions for small obstacle radii, the average enzymatic cycle time and characteristic times of internal conformational motions of the protein deviate substantially from their values in solution or in systems with small density of obstacles. The transport properties of the protein are strongly affected by molecular crowding. Diffusive motion adopts a subdiffusive character and the effective diffusion coefficients can change by more than an order of magnitude. The orientational relaxation time of the protein is also significantly altered by crowding.

  1. Monoamine transporters: Insights from molecular dynamics simulations

    Directory of Open Access Journals (Sweden)

    Julie eGrouleff

    2015-10-01

    Full Text Available The human monoamine transporters facilitate the reuptake of the neurotransmitters serotonin, dopamine, and norepinephrine from the synaptic cleft. Imbalance in monoaminergic neurotransmission is linked to various diseases including major depression, attention deficit hyperactivity disorder, schizophrenia and Parkinson’s disease. Inhibition of the monoamine transporters is thus an important strategy for treatment of such diseases. The monoamine transporters are sodium-coupled transport proteins belonging to the neurotransmitter/Na+ symporter (NSS family, and the publication of the first high-resolution structure of a NSS family member, the bacterial leucine transporter LeuT, in 2005, proved to be a major stepping stone for understanding this family of transporters. Structural data allows for the use of computational methods to study the monoamine transporters, which in turn has led to a number of important discoveries. The process of substrate translocation across the membrane is an intrinsically dynamic process. Molecular dynamics simulations, which can provide atomistic details of molecular motion on ns to ms timescales, are therefore well-suited for studying transport processes. In this review, we outline how molecular dynamics simulations have provided insight into the large scale motions associated with transport of the neurotransmitters, as well as the presence of external and internal gates, the coupling between ion and substrate transport, and differences in the conformational changes induced by substrates and inhibitors.

  2. Bead-Fourier path integral molecular dynamics

    Science.gov (United States)

    Ivanov, Sergei D.; Lyubartsev, Alexander P.; Laaksonen, Aatto

    2003-06-01

    Molecular dynamics formulation of Bead-Fourier path integral method for simulation of quantum systems at finite temperatures is presented. Within this scheme, both the bead coordinates and Fourier coefficients, defining the path representing the quantum particle, are treated as generalized coordinates with corresponding generalized momenta and masses. Introduction of the Fourier harmonics together with the center-of-mass thermostating scheme is shown to remove the ergodicity problem, known to pose serious difficulties in standard path integral molecular dynamics simulations. The method is tested for quantum harmonic oscillator and hydrogen atom (Coulombic potential). The simulation results are compared with the exact analytical solutions available for both these systems. Convergence of the results with respect to the number of beads and Fourier harmonics is analyzed. It was shown that addition of a few Fourier harmonics already improves the simulation results substantially, even for a relatively small number of beads. The proposed Bead-Fourier path integral molecular dynamics is a reliable and efficient alternative to simulations of quantum systems.

  3. Monoamine transporters: insights from molecular dynamics simulations

    Science.gov (United States)

    Grouleff, Julie; Ladefoged, Lucy Kate; Koldsø, Heidi; Schiøtt, Birgit

    2015-01-01

    The human monoamine transporters (MATs) facilitate the reuptake of the neurotransmitters serotonin, dopamine, and norepinephrine from the synaptic cleft. Imbalance in monoaminergic neurotransmission is linked to various diseases including major depression, attention deficit hyperactivity disorder, schizophrenia, and Parkinson’s disease. Inhibition of the MATs is thus an important strategy for treatment of such diseases. The MATs are sodium-coupled transport proteins belonging to the neurotransmitter/Na+ symporter (NSS) family, and the publication of the first high-resolution structure of a NSS family member, the bacterial leucine transporter LeuT, in 2005, proved to be a major stepping stone for understanding this family of transporters. Structural data allows for the use of computational methods to study the MATs, which in turn has led to a number of important discoveries. The process of substrate translocation across the membrane is an intrinsically dynamic process. Molecular dynamics simulations, which can provide atomistic details of molecular motion on ns to ms timescales, are therefore well-suited for studying transport processes. In this review, we outline how molecular dynamics simulations have provided insight into the large scale motions associated with transport of the neurotransmitters, as well as the presence of external and internal gates, the coupling between ion and substrate transport, and differences in the conformational changes induced by substrates and inhibitors. PMID:26528185

  4. Nonequilibrium molecular dynamics theory, algorithms and applications

    CERN Document Server

    Todd, Billy D

    2017-01-01

    Written by two specialists with over twenty-five years of experience in the field, this valuable text presents a wide range of topics within the growing field of nonequilibrium molecular dynamics (NEMD). It introduces theories which are fundamental to the field - namely, nonequilibrium statistical mechanics and nonequilibrium thermodynamics - and provides state-of-the-art algorithms and advice for designing reliable NEMD code, as well as examining applications for both atomic and molecular fluids. It discusses homogenous and inhomogenous flows and pays considerable attention to highly confined fluids, such as nanofluidics. In addition to statistical mechanics and thermodynamics, the book covers the themes of temperature and thermodynamic fluxes and their computation, the theory and algorithms for homogenous shear and elongational flows, response theory and its applications, heat and mass transport algorithms, applications in molecular rheology, highly confined fluids (nanofluidics), the phenomenon of slip and...

  5. Optimizing legacy molecular dynamics software with directive-based offload

    Science.gov (United States)

    Michael Brown, W.; Carrillo, Jan-Michael Y.; Gavhane, Nitin; Thakkar, Foram M.; Plimpton, Steven J.

    2015-10-01

    Directive-based programming models are one solution for exploiting many-core coprocessors to increase simulation rates in molecular dynamics. They offer the potential to reduce code complexity with offload models that can selectively target computations to run on the CPU, the coprocessor, or both. In this paper, we describe modifications to the LAMMPS molecular dynamics code to enable concurrent calculations on a CPU and coprocessor. We demonstrate that standard molecular dynamics algorithms can run efficiently on both the CPU and an x86-based coprocessor using the same subroutines. As a consequence, we demonstrate that code optimizations for the coprocessor also result in speedups on the CPU; in extreme cases up to 4.7X. We provide results for LAMMPS benchmarks and for production molecular dynamics simulations using the Stampede hybrid supercomputer with both Intel® Xeon Phi™ coprocessors and NVIDIA GPUs. The optimizations presented have increased simulation rates by over 2X for organic molecules and over 7X for liquid crystals on Stampede. The optimizations are available as part of the "Intel package" supplied with LAMMPS.

  6. Simulational nanoengineering: Molecular dynamics implementation of an atomistic Stirling engine

    Science.gov (United States)

    Rapaport, D. C.

    2009-04-01

    A nanoscale-sized Stirling engine with an atomistic working fluid has been modeled using molecular dynamics simulation. The design includes heat exchangers based on thermostats, pistons attached to a flywheel under load, and a regenerator. Key aspects of the behavior, including the time-dependent flows, are described. The model is shown to be capable of stable operation while producing net work at a moderate level of efficiency.

  7. Mesoscopic Dynamics of Biopolymers and Protein Molecular Machines

    Science.gov (United States)

    Kapral, Raymond

    2013-03-01

    The dynamics of biopolymers in solution and in crowded molecular environments, which mimic some features of the interior of a biochemical cell, will be discussed. In particular, the dynamics of protein machines that utilize chemical energy to effect cyclic conformational changes to carry out their catalytic functions will be described. The investigation of the dynamics of such complex systems requires knowledge of the time evolution on physically relevant long distance and time scales. This often necessitates a coarse grained or mesoscopic treatment of the dynamics. A hybrid particle-based mesoscopic dynamical method, which combines molecular dynamics for a coarse-grain model of the proteins with multiparticle collision dynamics for the solvent, will be described and utilized to study the dynamics of such systems. See, C. Echeverria, Y. Togashi, A. S. Mikhailov, and R. Kapral, Phys. Chem. Chem. Phys 13, 10527 (2011); C. Echeverria and R. Kapral, Phys. Chem. Chem. Phys., 14, 6755 (2012); J. M. Schofield, P. Inder and R. Kapral, J. Chem. Phys. 136, 205101 (2012). Work was supported in part by a grant from the Natural Sciences and Engineering Research Council of Canada.

  8. Para-(benzoyl)-phenylalanine as a potential inhibitor against LpxC of Leptospira spp.: homology modeling, docking, and molecular dynamics study.

    Science.gov (United States)

    Pradhan, Dibyabhaba; Priyadarshini, Vani; Munikumar, Manne; Swargam, Sandeep; Umamaheswari, Amineni; Bitla, Aparna

    2014-01-01

    Leptospira interrogans, a Gram-negative bacterial pathogen is the main cause of human leptospirosis. Lipid A is a highly immunoreactive endotoxic center of lipopolysaccharide (LPS) that anchors LPS into the outer membrane of Leptospira. Discovery of compounds inhibiting lipid-A biosynthetic pathway would be promising for dissolving the structural integrity of membrane leading to cell lysis and death of Leptospira. LpxC, a unique enzyme of lipid-A biosynthetic pathway was identified as common drug target of Leptospira. Herein, homology modeling, docking, and molecular dynamics (MD) simulations were employed to discover potential inhibitors of LpxC. A reliable tertiary structure of LpxC in complex with inhibitor BB-78485 was constructed in Modeller 9v8. A data-set of BB-78485 structural analogs were docked with LpxC in Maestro v9.2 virtual screening workflow, which implements three stage Glide docking protocol. Twelve lead molecules with better XP Gscore compared to BB-78485 were proposed as potential inhibitors of LpxC. Para-(benzoyl)-phenylalanine - that showed lowest XP Gscore (-10.35 kcal/mol) - was predicted to have best binding affinity towards LpxC. MD simulations were performed for LpxC and para-(benzoyl)-phenylalanine docking complex in Desmond v3.0. Trajectory analysis showed the docking complex and inter-molecular interactions was stable throughout the entire production part of MD simulations. The results indicate para-(benzoyl)-phenylalanine as a potent drug molecule against leptospirosis. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:10.

  9. Application of Parallel Processing to the Investigation of Supercritical Droplet Evaporation and Combustion Using Molecular Dynamics

    Science.gov (United States)

    2007-11-02

    Molecular dynamics (MD) implemented on parallel processors was used to model supercritical droplet phenomena occurring in combustion devices. The use...of molecular dynamics allows the modeling of supercritical phenomena without an a priori knowledge of the equation of state or transport properties

  10. Discrete dynamical models

    CERN Document Server

    Salinelli, Ernesto

    2014-01-01

    This book provides an introduction to the analysis of discrete dynamical systems. The content is presented by an unitary approach that blends the perspective of mathematical modeling together with the ones of several discipline as Mathematical Analysis, Linear Algebra, Numerical Analysis, Systems Theory and Probability. After a preliminary discussion of several models, the main tools for the study of linear and non-linear scalar dynamical systems are presented, paying particular attention to the stability analysis. Linear difference equations are studied in detail and an elementary introduction of Z and Discrete Fourier Transform is presented. A whole chapter is devoted to the study of bifurcations and chaotic dynamics. One-step vector-valued dynamical systems are the subject of three chapters, where the reader can find the applications to positive systems, Markov chains, networks and search engines. The book is addressed mainly to students in Mathematics, Engineering, Physics, Chemistry, Biology and Economic...

  11. Synthesis, characterization and molecular modelling of a novel dipyridamole supramolecule - X-ray structure, quantum mechanics and molecular dynamics study to comprehend the hydrogen bond structure-activity relationship

    Science.gov (United States)

    Vepuri, Suresh B.; Devarajegowda, H. C.; Soliman, Mahmoud E.

    2016-02-01

    Hydrochloride salt formation for Active Pharmaceutical Ingredients (APIs) is the primary choice to impart aqueous solubility and to promote dissolution. Dipyridamole (DIP) is a cardiovascular drug which is practically insoluble in water. We discovered a new form of DIP called as dipyridamole hydrochloride trihydrate (DIPHT), which was prepared by an unusual method of reacting the DIP with hydrated hydrochloric acid (HCl) that was liberated in situ by the reaction of ferric chloride with water. The liberated HCl was consumed as reagent in situ by the scavenger (API) and was converted to a hydrochloride trihydrate. The product was characterized by FTIR, mass spectroscopy, PXRD and DSC. Supramolecular structure of this novel DIPHT was revealed by single crystal XRD. A sustained intramolecular hydrogen bond alliance was found in DIP and the DIPHT. Stability of this hydrogen bond was further evaluated by means of molecular modelling studies. We performed electron calculations using quantum mechanics (QM) on both the base and salt structures to compare their geometry and molecular orbital energy levels. Molecular Dynamics (MD) simulations were also conducted in explicit solvent models to provide more insights into the hydrogen bond strength and conformational preferences of the base and salt structure. Together with QM and MD, we were able to explain the influence of hydrogen bonds on proton uptake activity of DIP and stability of DIP and DIPHT. DIPHT which can dissolve faster than DIP in water may enhance the dissolution and bioavailability of the drug. As the current drug development research is shifting to repurpose the existing drugs in order to subside the untoward risks in new drug development, we believe that DIPHT with its intrinsic aqueous solubility could bring more application for DIP and generate interest within the pharmaceutical industry.

  12. Molecular dynamics simulations of magnetized dusty plasmas

    Science.gov (United States)

    Piel, Alexander; Reichstein, Torben; Wilms, Jochen

    2012-10-01

    The combination of the electric field that confines a dust cloud with a static magnetic field generally leads to a rotation of the dust cloud. In weak magnetic fields, the Hall component of the ion flow exerts a drag force that sets the dust in rotation. We have performed detailed molecular-dynamics simulations of the dynamics of torus-shaped dust clouds in anodic plasmas. The stationary flow [1] is characterized by a shell structure in the laminar dust flow and by the spontaneous formation of a shear-flow around a stationary vortex. Here we present new results on dynamic phenomena, among them fluctuations due to a Kelvin-Helmholtz instability in the shear-flow. The simulations are compared with experimental results. [4pt] [1] T. Reichstein, A. Piel, Phys. Plasmas 18, 083705 (2011)

  13. 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.

  14. A Method for Combining Experimentation and Molecular Dynamics Simulation to Improve Cohesive Zone Models for Metallic Microstructures

    Science.gov (United States)

    Hochhalter, J. D.; Glaessgen, E. H.; Ingraffea, A. R.; Aquino, W. A.

    2009-01-01

    Fracture processes within a material begin at the nanometer length scale at which the formation, propagation, and interaction of fundamental damage mechanisms occur. Physics-based modeling of these atomic processes quickly becomes computationally intractable as the system size increases. Thus, a multiscale modeling method, based on the aggregation of fundamental damage processes occurring at the nanoscale within a cohesive zone model, is under development and will enable computationally feasible and physically meaningful microscale fracture simulation in polycrystalline metals. This method employs atomistic simulation to provide an optimization loop with an initial prediction of a cohesive zone model (CZM). This initial CZM is then applied at the crack front region within a finite element model. The optimization procedure iterates upon the CZM until the finite element model acceptably reproduces the near-crack-front displacement fields obtained from experimental observation. With this approach, a comparison can be made between the original CZM predicted by atomistic simulation and the converged CZM that is based on experimental observation. Comparison of the two CZMs gives insight into how atomistic simulation scales.

  15. Modeling dynamic swarms

    KAUST Repository

    Ghanem, Bernard

    2013-01-01

    This paper proposes the problem of modeling video sequences of dynamic swarms (DSs). We define a DS as a large layout of stochastically repetitive spatial configurations of dynamic objects (swarm elements) whose motions exhibit local spatiotemporal interdependency and stationarity, i.e., the motions are similar in any small spatiotemporal neighborhood. Examples of DS abound in nature, e.g., herds of animals and flocks of birds. To capture the local spatiotemporal properties of the DS, we present a probabilistic model that learns both the spatial layout of swarm elements (based on low-level image segmentation) and their joint dynamics that are modeled as linear transformations. To this end, a spatiotemporal neighborhood is associated with each swarm element, in which local stationarity is enforced both spatially and temporally. We assume that the prior on the swarm dynamics is distributed according to an MRF in both space and time. Embedding this model in a MAP framework, we iterate between learning the spatial layout of the swarm and its dynamics. We learn the swarm transformations using ICM, which iterates between estimating these transformations and updating their distribution in the spatiotemporal neighborhoods. We demonstrate the validity of our method by conducting experiments on real and synthetic video sequences. Real sequences of birds, geese, robot swarms, and pedestrians evaluate the applicability of our model to real world data. © 2012 Elsevier Inc. All rights reserved.

  16. Water dynamics in protein hydration shells: the molecular origins of the dynamical perturbation.

    Science.gov (United States)

    Fogarty, Aoife C; Laage, Damien

    2014-07-17

    Protein hydration shell dynamics play an important role in biochemical processes including protein folding, enzyme function, and molecular recognition. We present here a comparison of the reorientation dynamics of individual water molecules within the hydration shell of a series of globular proteins: acetylcholinesterase, subtilisin Carlsberg, lysozyme, and ubiquitin. Molecular dynamics simulations and analytical models are used to access site-resolved information on hydration shell dynamics and to elucidate the molecular origins of the dynamical perturbation of hydration shell water relative to bulk water. We show that all four proteins have very similar hydration shell dynamics, despite their wide range of sizes and functions, and differing secondary structures. We demonstrate that this arises from the similar local surface topology and surface chemical composition of the four proteins, and that such local factors alone are sufficient to rationalize the hydration shell dynamics. We propose that these conclusions can be generalized to a wide range of globular proteins. We also show that protein conformational fluctuations induce a dynamical heterogeneity within the hydration layer. We finally address the effect of confinement on hydration shell dynamics via a site-resolved analysis and connect our results to experiments via the calculation of two-dimensional infrared spectra.

  17. Development of a molecular-dynamics-based cluster-heat-capacity model for study of homogeneous condensation in supersonic water-vapor expansions.

    Science.gov (United States)

    Borner, Arnaud; Li, Zheng; Levin, Deborah A

    2013-02-14

    Supersonic expansions to vacuum produce clusters of sufficiently small size that properties such as heat capacities and latent heat of evaporation cannot be described by bulk vapor thermodynamic values. In this work the Monte-Carlo Canonical-Ensemble (MCCE) method was used to provide potential energies and constant-volume heat capacities for small water clusters. The cluster structures obtained using the well-known simple point charge model were found to agree well with earlier simulations using more rigorous potentials. The MCCE results were used as the starting point for molecular dynamics simulations of the evaporation rate as a function of cluster temperature and size which were found to agree with unimolecular dissociation theory and classical nucleation theory. The heat capacities and latent heat obtained from the MCCE simulations were used in direct-simulation Monte-Carlo of two experiments that measured Rayleigh scattering and terminal dimer mole fraction of supersonic water-jet expansions. Water-cluster temperature and size were found to be influenced by the use of kinetic rather than thermodynamic heat-capacity and latent-heat values as well as the nucleation model.

  18. A Molecular Dynamics simulation of Hugoniot curves of HMX using ReaxFF and its application in SPH modeling of macroscale terminal effects

    Science.gov (United States)

    Liu, Gui-Rong; Wang, Gangyu; Peng, Qing; de, Suvranu

    2015-06-01

    HMX is a widely used high explosive. Hugoniot curve is a valuable tool for analyzing the equations of state, and is of importance for all energetic materials including HMX. The Hugoniot curves serve as one of the key character in continuum modeling of high explosives. It can be obtained from experimental measurements, and recently also from computational studies. In this study, the Hugoniot curve of HMX is calculated using a multi-scale shock technique via Molecular Dynamics (MD) simulations, where the reactive force field ReaxFF is obtained from Quantum Mechanics calculations and tailored for HMX. It is found that our MD Hugoniot curve of HMX from the optimized ReaxFF potential agree well with experiments. The MD Hugoniot curve of HMX is also incorporated in our in-house Smoothed Particle Hydrodynamics (SPH) code for the modeling of the macro-scale explosive behaviors of HMX explosives and HMX cased in a 3D cylinder. The authors would like to acknowledge the generous financial support from the Defense Threat Reduction Agency (DTRA) Grant HDTRA1-13-1-0025.

  19. In-silico screening for DNA-dependent protein kinase (DNA-PK) inhibitors: Combined homology modeling, docking, molecular dynamic study followed by biological investigation.

    Science.gov (United States)

    Tarazi, Hamadeh; Saleh, Ekram; El-Awady, Raafat

    2016-10-01

    DNA-dependent protein kinase (DNA-PK) is a key enzyme in non-homologous DNA end joining (NHEJ) repair pathway. The targeted inhibition of such enzyme would furnish a valuable option for cancer treatment. In this study we report the development of validation of enzyme homology model, and the subsequent use of this model to perform docking-based virtual screening against a database of FDA-approved drugs. The nominated highest ranking hits (Praziquantel and Dutasteride) were subjected to biological investigation. Additionally, molecular dynamic study was carried-out for binding mode exploration. Results of the biological evaluation revealed that both compounds inhibit the DNA-PK enzymatic activity at relatively high concentration levels with an IC50 of 17.3μM for praziquantel and >20μM for dutasteride. Furthermore, both agents enhanced the anti-proliferative effects of doxorubicin and cisplatin on breast cancer (MCF7) and lung cancer (A549) cell lines. This result indicates that these two hits are good candidate as DNA-PK inhibitors and worth further structural modifications to enhance their enzyme inhibitory effects. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Exploring the structure-solubility relationship of asphaltene models in toluene, heptane, and amphiphiles using a molecular dynamic atomistic methodology.

    Science.gov (United States)

    Aray, Yosslen; Hernández-Bravo, Raiza; Parra, José G; Rodríguez, Jesús; Coll, David S

    2011-10-27

    The solubility parameters, δ, of several asphaltene models were calculated by mean of an atomistic NPT ensemble. Continental and archipelago models were explored. A relationship between the solubility parameter and the molecule structure was determined. In general, increase of the fused-rings number forming the aromatic core and the numbers of heteroatoms such as oxygen, nitrogen, and sulfur produces an increase of the solubility parameter, while increases of the numbers and length of the aliphatic chains yield a systematic decrease of this parameter. Molecules with large total carbon atom number at the tails, n(c), and small aromatic ring number, n(r), exhibit the biggest values of δ, while molecules with small n(c) and large n(r) show the smallest δ values. A good polynomial correlation δ = 5.967(n(r)/n(c)) - 3.062(n(r)/n(c))(2) + 0.507(n(r)/n(c))(3) + 16.593 with R(2) = 0.965 was found. The solubilities of the asphaltene models in toluene, heptane, and amphiphiles were studied using the Scatchard-Hildebrand and the Hansen sphere methodologies. Generally, there is a large affinity between the archipelago model and amphiphiles containing large aliphatic tails and no aromatic rings, while continental models show high affinity for amphiphiles containing an aromatic ring and small aliphatic chains.

  1. A comparison of molecular dynamics results for two models of nanoparticles with fixed and mobile ligands in two-dimensions

    Science.gov (United States)

    Baran, Ł.; Sokołowski, S.

    2017-02-01

    We compare the results of simulations of models of nanoparticles in two dimensions. Nanoparticles are built of central, big circle (core) with 4 ligands attached to it. The models differ by the mobility of the ligands and by ligand-core interactions. We evaluated liquid-vapor phase diagrams, as well as structural and thermodynamic properties at supercritical temperatures. In order to characterize the orientational ordering in the systems with mobile ligands, we use the concept of mass dipole. Moreover, we propose the application of the theoretical approximation for evaluation of the core-core pair correlation functions.

  2. Watching coherent molecular structural dynamics during photoreaction: beyond kinetic description

    CERN Document Server

    Lemke, Henrik T; Hartsock, Robert; van Driel, Tim Brandt; Chollet, Matthieu; Glownia, J M; Song, Sanghoon; Zhu, Diling; Pace, Elisabetta; Nielsen, Martin M; Benfatto, Maurizio; Gaffney, Kelly J; Collet, Eric; Cammarata, Marco

    2015-01-01

    A deep understanding of molecular photo-transformations occurring is challenging because of the complex interaction between electronic and nuclear structure. The initially excited electronic energy dissipates into electronic and structural reconfigurations often in less than a billionth of a second. Molecular dynamics induced by photoexcitation have been very successfully studied with femtosecond optical spectroscopies, but electronic and nuclear dynamics are often very difficult to disentangle. X-ray based spectroscopies can reduce the ambiguity between theoretical models and experimental data, but it is only with the recent development of bright ultrafast X-ray sources, that key information during transient molecular processes can be obtained on their intrinsic timescale. We use Free Electron Laser (FEL) based time-resolved X-ray Absorption Near Edge Structure (XANES) measurements around the Iron K-edge of a spin crossover prototypical compound. We reveal its transformation from the ligand-located electroni...

  3. Orbital free molecular dynamics; Approche sans orbitale des plasmas denses

    Energy Technology Data Exchange (ETDEWEB)

    Lambert, F

    2007-08-15

    The microscopic properties of hot and dense plasmas stay a field essentially studied thanks to classical theories like the One Component Plasma, models which rely on free parameters, particularly ionization. In order to investigate these systems, we have used, in this PhD work, a semi-classical model, without free parameters, that is based on coupling consistently classical molecular dynamics for the nuclei and orbital free density functional theory for the electrons. The electronic fluid is represented by a free energy entirely determined by the local density. This approximation was validated by a comparison with an ab initio technique, quantum molecular dynamics. This one is identical to the previous except for the description of the free energy that depends on a quantum-independent-particle model. Orbital free molecular dynamics was then used to compute equation of state of boron and iron plasmas in the hot and dense regime. Furthermore, comparisons with classical theories were performed on structural and dynamical properties. Finally, equation of state and transport coefficients mixing laws were studied by direct simulation of a plasma composed of deuterium and copper. (author)

  4. Spectroscopic and dynamic properties of arachidonoyl serotonin- β-lactoglobulin complex: A molecular modeling and chemometric study.

    Science.gov (United States)

    Gholami, Samira; Bordbar, Abdol-Khalegh; Akvan, Nadia

    2016-09-01

    UV-Vis absorption data of β-lactoglobulin (BLG) and arachidonoyl serotonin (AA-5HT) in BLG complex were examined and analyzed using chemometrics method. Analysis of the spectral data matrices by using the multivariate curve resolution-alternating least squares (MCR-ALS) algorithm resulted to the pure concentration calculation and spectral profiles resolution of the chemical constituents and the values of (6.433±0.019)×10(4)M(-1), (4.532±0.007)×10(4)M(-1), (3.364±0.010)×10(4)M(-1) and (2.977±0.013)×10(4)M(-1) as estimated equilibrium constants at 288, 293, 298 and 303K, respectively. The number of chemical constituents involved in the interaction which was extracted by PCA method were free and bound BLG. The spontaneity of the binding process and critical role of hydrogen bonding and van der Waals interactions in stabilizing protein-ligand complex have been designated by negative values of Gibbs free energy, entropy and enthalpy changes. Molecular docking study showed that AA-5HT binds to Val(41), Leu(39), Leu(54), Ile(71), Phe(82), Asn(90), Val(92), Phe(105), Met(107), Glu(108) with the free binding energy of -37.478kJ/mol. Computational studies predicted that in spite of serotonin (5HT) which anchors to the outer surface of BLG by hydrogen bonds, AA-5HT is situated in the calyx pose and stayed there during the entire time of simulation. This binding is accompanying with no apparent influence on secondary structure and partially destabilization of tertiary structure of BLG which pointed the suitability of this protein as drug carrier for AA-5HT.

  5. The dopamine D2 receptor dimer and its interaction with homobivalent antagonists: homology modeling, docking and molecular dynamics.

    Science.gov (United States)

    Kaczor, Agnieszka A; Jörg, Manuela; Capuano, Ben

    2016-09-01

    In order to apply structure-based drug design techniques to G protein-coupled receptor complexes, it is essential to model their 3D structure and to identify regions that are suitable for selective drug binding. For this purpose, we have developed and tested a multi-component protocol to model the inactive conformation of the dopamine D2 receptor dimer, suitable for interaction with homobivalent antagonists. Our approach was based on protein-protein docking, applying the Rosetta software to obtain populations of dimers as present in membranes with all the main possible interfaces. Consensus scoring based on the values and frequencies of best interfaces regarding four scoring parameters, Rosetta interface score, interface area, free energy of binding and energy of hydrogen bond interactions indicated that the best scored dimer model possesses a TM4-TM5-TM7-TM1 interface, which is in agreement with experimental data. This model was used to study interactions of the previously published dopamine D2 receptor homobivalent antagonists based on clozapine,1,4-disubstituted aromatic piperidines/piperazines and arylamidoalkyl substituted phenylpiperazine pharmacophores. It was found that the homobivalent antagonists stabilize the receptor-inactive conformation by maintaining the ionic lock interaction, and change the dimer interface by disrupting a set of hydrogen bonds and maintaining water- and ligand-mediated hydrogen bonds in the extracellular and intracellular part of the interface. Graphical Abstract Structure of the final model of the dopamine D2 receptor homodimer, indicating the distancebetween Tyr37 and Tyr 5.42 in the apo form (left) and in the complex with the ligand (right).

  6. Dynamic causal modelling revisited.

    Science.gov (United States)

    Friston, K J; Preller, Katrin H; Mathys, Chris; Cagnan, Hayriye; Heinzle, Jakob; Razi, Adeel; Zeidman, Peter

    2017-02-17

    This paper revisits the dynamic causal modelling of fMRI timeseries by replacing the usual (Taylor) approximation to neuronal dynamics with a neural mass model of the canonical microcircuit. This provides a generative or dynamic causal model of laminar specific responses that can generate haemodynamic and electrophysiological measurements. In principle, this allows the fusion of haemodynamic and (event related or induced) electrophysiological responses. Furthermore, it enables Bayesian model comparison of competing hypotheses about physiologically plausible synaptic effects; for example, does attentional modulation act on superficial or deep pyramidal cells - or both? In this technical note, we describe the resulting dynamic causal model and provide an illustrative application to the attention to visual motion dataset used in previous papers. Our focus here is on how to answer long-standing questions in fMRI; for example, do haemodynamic responses reflect extrinsic (afferent) input from distant cortical regions, or do they reflect intrinsic (recurrent) neuronal activity? To what extent do inhibitory interneurons contribute to neurovascular coupling? What is the relationship between haemodynamic responses and the frequency of induced neuronal activity? This paper does not pretend to answer these questions; rather it shows how they can be addressed using neural mass models of fMRI timeseries. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. 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.

  8. Insight into the intermolecular recognition mechanism between Keap1 and IKKβ combining homology modelling, protein-protein docking, molecular dynamics simulations and virtual alanine mutation.

    Directory of Open Access Journals (Sweden)

    Zheng-Yu Jiang

    Full Text Available Degradation of certain proteins through the ubiquitin-proteasome pathway is a common strategy taken by the key modulators responsible for stress responses. Kelch-like ECH-associated protein-1(Keap1, a substrate adaptor component of the Cullin3 (Cul3-based ubiquitin E3 ligase complex, mediates the ubiquitination of two key modulators, NF-E2-related factor 2 (Nrf2 and IκB kinase β (IKKβ, which are involved in the redox control of gene transcription. However, compared to the Keap1-Nrf2 protein-protein interaction (PPI, the intermolecular recognition mechanism of Keap1 and IKKβ has been poorly investigated. In order to explore the binding pattern between Keap1 and IKKβ, the PPI model of Keap1 and IKKβ was investigated. The structure of human IKKβ was constructed by means of the homology modeling method and using reported crystal structure of Xenopus laevis IKKβ as the template. A protein-protein docking method was applied to develop the Keap1-IKKβ complex model. After the refinement and visual analysis of docked proteins, the chosen pose was further optimized through molecular dynamics simulations. The resulting structure was utilized to conduct the virtual alanine mutation for the exploration of hot-spots significant for the intermolecular interaction. Overall, our results provided structural insights into the PPI model of Keap1-IKKβ and suggest that the substrate specificity of Keap1 depend on the interaction with the key tyrosines, namely Tyr525, Tyr574 and Tyr334. The study presented in the current project may be useful to design molecules that selectively modulate Keap1. The selective recognition mechanism of Keap1 with IKKβ or Nrf2 will be helpful to further know the crosstalk between NF-κB and Nrf2 signaling.

  9. Insight into the intermolecular recognition mechanism between Keap1 and IKKβ combining homology modelling, protein-protein docking, molecular dynamics simulations and virtual alanine mutation.

    Science.gov (United States)

    Jiang, Zheng-Yu; Chu, Hong-Xi; Xi, Mei-Yang; Yang, Ting-Ting; Jia, Jian-Min; Huang, Jing-Jie; Guo, Xiao-Ke; Zhang, Xiao-Jin; You, Qi-Dong; Sun, Hao-Peng

    2013-01-01

    Degradation of certain proteins through the ubiquitin-proteasome pathway is a common strategy taken by the key modulators responsible for stress responses. Kelch-like ECH-associated protein-1(Keap1), a substrate adaptor component of the Cullin3 (Cul3)-based ubiquitin E3 ligase complex, mediates the ubiquitination of two key modulators, NF-E2-related factor 2 (Nrf2) and IκB kinase β (IKKβ), which are involved in the redox control of gene transcription. However, compared to the Keap1-Nrf2 protein-protein interaction (PPI), the intermolecular recognition mechanism of Keap1 and IKKβ has been poorly investigated. In order to explore the binding pattern between Keap1 and IKKβ, the PPI model of Keap1 and IKKβ was investigated. The structure of human IKKβ was constructed by means of the homology modeling method and using reported crystal structure of Xenopus laevis IKKβ as the template. A protein-protein docking method was applied to develop the Keap1-IKKβ complex model. After the refinement and visual analysis of docked proteins, the chosen pose was further optimized through molecular dynamics simulations. The resulting structure was utilized to conduct the virtual alanine mutation for the exploration of hot-spots significant for the intermolecular interaction. Overall, our results provided structural insights into the PPI model of Keap1-IKKβ and suggest that the substrate specificity of Keap1 depend on the interaction with the key tyrosines, namely Tyr525, Tyr574 and Tyr334. The study presented in the current project may be useful to design molecules that selectively modulate Keap1. The selective recognition mechanism of Keap1 with IKKβ or Nrf2 will be helpful to further know the crosstalk between NF-κB and Nrf2 signaling.

  10. Nano-tribology through molecular dynamics simulations

    Institute of Scientific and Technical Information of China (English)

    WANG; Hui(

    2001-01-01

    [1]Burkert, U., Allinger, N. L., Molecular Mechanics, York: Maple Press Company, 1982.[2]Daw, M. S. , Baskes, M. I., Embedded-atom method: derivation and application to impurities, surface and other defects in metals, Phys. Rev. B, 1984, 29: 6443-6453.[3]Frenke, D., Smit, B., Understanding Molecular Simulation, San Diego: Academic Press, 1996, 60-67, 125-140.[4]Granick, S., Motions and relaxation of confined liquids, Science, 1991, 253: 1374-1379.[5]Koplik, J., Banavar, J., Willemsen, J., Molecular dynamics of Poisewulle flow and moving contact line, Phys. Rev.Lett., 1988, 60: 1282-1285.[6]Hu, Y. Z., Wang, H., Guo, Y. et al., Simulation of lubricant rheology in thin film lubrication, Part I: simulation of Poiseuille flow, Wear, 1996, 196: 243-259.[7]Zou, K., Li, Z. J, Leng, Y. S. et al. , Surface force apparatus and its application in the study of solid contacts, Chinese Science Bulletin, 1999, 44: 268-271.[8]Stevens, M. , Mondello, M., Grest, G. et al. , Comparison of shear flow of hexadecane in a confined geometry and in bulk,J. Chem. Phys., 1997, 106: 7303-7314.[9]Huang, P., Luo, J. B., Wen, S. Z., Theoretical study on the lubrication failure for tthe lubricants with a limiting shear stress, Tribology International, 1999, 32: 421-426.[10]Ryckaert, J. P. , Bellemans. , A molecular dynamics of alkanes, Faraday Soc. , 1978, 66: 95-106.[11]Wang, H. , Hu, Y. Z., A molecular dynamics study on slip phenomenon at solid-liquid interface, in Proceedings of tthe First AICT, Beijing: Tsinghua University Press, 1998, 295-299.[12]Landman, U., Luedtke, W., Burnham, N. et al., Mechanisms and dynamics of adhesion, nanoindentation, and fracture, Science, 1990, 248: 454-461.[13]Leng, Y. S., Hu, Y. Z., Zheng, L. Q., Adhesive contact of flat-ended wedges: theory and computer experiments, Journal of Tribology, 1999, 121: 128-132.

  11. Structures and autocorrelation functions of liquid Al and Mg modelled via Lennard-Jones potential from molecular dynamics simulation

    Indian Academy of Sciences (India)

    G A Adebayo; O Akinlade; L A Hussain

    2005-02-01

    The structures and autocorrelation functions of Al and Mg in the liquid state are investigated through the pair distribution function (), the diffusion coefficients as well as the shear viscosity via the Green{Kubo and Einstein relations. From the structure and the Enskog relation we determined the frequency of collisions of atoms in the first shell of () in the systems. We also discovered that the packing fraction of Lennard-Jones liquids should be approximately half the reduced density value. This approximation is accurate to within 99%. The temperature dependence of the pair distribution function and the atomic mean square displacement are investigated by performing simulations at various experimental temperatures and corresponding densities. The structures of the systems are affected by temperature via movements of atoms in the first minimum of (). The Lennard-Jones model shows that density dependence of the shear viscosity is in agreement with what is expected of simple liquids in the range of investigated temperatures and densities. In the gas limit, the Stoke-Einstein relation = B/2 is grossly overestimated by Lennard-Jones model. This could not be attributed to defficiencies in the model, as other investigators using first principle method could not obtain the gas limit of the Stoke-Einstein relation.

  12. Molecular dynamics simulations on PGLa using NMR orientational constraints.

    Science.gov (United States)

    Sternberg, Ulrich; Witter, Raiker

    2015-11-01

    NMR data obtained by solid state NMR from anisotropic samples are used as orientational constraints in molecular dynamics simulations for determining the structure and dynamics of the PGLa peptide within a membrane environment. For the simulation the recently developed molecular dynamics with orientational constraints technique (MDOC) is used. This method introduces orientation dependent pseudo-forces into the COSMOS-NMR force field. Acting during a molecular dynamics simulation these forces drive molecular rotations, re-orientations and folding in such a way that the motional time-averages of the tensorial NMR properties are consistent with the experimentally measured NMR parameters. This MDOC strategy does not depend on the initial choice of atomic coordinates, and is in principle suitable for any flexible and mobile kind of molecule; and it is of course possible to account for flexible parts of peptides or their side-chains. MDOC has been applied to the antimicrobial peptide PGLa and a related dimer model. With these simulations it was possible to reproduce most NMR parameters within the experimental error bounds. The alignment, conformation and order parameters of the membrane-bound molecule and its dimer were directly derived with MDOC from the NMR data. Furthermore, this new approach yielded for the first time the distribution of segmental orientations with respect to the membrane and the order parameter tensors of the dimer systems. It was demonstrated the deuterium splittings measured at the peptide to lipid ratio of 1/50 are consistent with a membrane spanning orientation of the peptide.

  13. Clustering molecular dynamics trajectories for optimizing docking experiments.

    Science.gov (United States)

    De Paris, Renata; Quevedo, Christian V; Ruiz, Duncan D; Norberto de Souza, Osmar; Barros, Rodrigo C

    2015-01-01

    Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR) model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand.

  14. Molecular dynamics simulations on PGLa using NMR orientational constraints

    Energy Technology Data Exchange (ETDEWEB)

    Sternberg, Ulrich, E-mail: ulrich.sternberg@partner.kit.edu; Witter, Raiker [Tallinn University of Technology, Technomedicum (Estonia)

    2015-11-15

    NMR data obtained by solid state NMR from anisotropic samples are used as orientational constraints in molecular dynamics simulations for determining the structure and dynamics of the PGLa peptide within a membrane environment. For the simulation the recently developed molecular dynamics with orientational constraints technique (MDOC) is used. This method introduces orientation dependent pseudo-forces into the COSMOS-NMR force field. Acting during a molecular dynamics simulation these forces drive molecular rotations, re-orientations and folding in such a way that the motional time-averages of the tensorial NMR properties are consistent with the experimentally measured NMR parameters. This MDOC strategy does not depend on the initial choice of atomic coordinates, and is in principle suitable for any flexible and mobile kind of molecule; and it is of course possible to account for flexible parts of peptides or their side-chains. MDOC has been applied to the antimicrobial peptide PGLa and a related dimer model. With these simulations it was possible to reproduce most NMR parameters within the experimental error bounds. The alignment, conformation and order parameters of the membrane-bound molecule and its dimer were directly derived with MDOC from the NMR data. Furthermore, this new approach yielded for the first time the distribution of segmental orientations with respect to the membrane and the order parameter tensors of the dimer systems. It was demonstrated the deuterium splittings measured at the peptide to lipid ratio of 1/50 are consistent with a membrane spanning orientation of the peptide.

  15. Clustering Molecular Dynamics Trajectories for Optimizing Docking Experiments

    Directory of Open Access Journals (Sweden)

    Renata De Paris

    2015-01-01

    Full Text Available Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand.

  16. Molecular Dynamic Screening Sesquiterpenoid Pogostemon Herba as Suggested Cyclooxygenase Inhibitor

    Science.gov (United States)

    Raharjo, Sentot Joko; Kikuchi, Takeshi

    2016-01-01

    Objective: Virtual molecular dynamic sesquiterpenoid Pogostemon Herba (CID56928117, CID94275, CID107152, and CID519743) have screening as cyclooxygenase (COX-1/COX-2) selective inhibitor. Methods: Molecular interaction studies sesquiterpenoid compounds with COX-1 and COX-2 were using the molecular docking tools by Hex 8.0 and interactions were further visualized using by Discovery Studio Client 3.5 software tool and Virtual Molecular Dynamic 1.9.1 software. The binding energy calculation of molecular dynamic interaction was calculated by AMBER12 software. Result: The analysis of the sesquiterpenoid compounds showed that CID56928117, CID94275, CID107152, and CID519743 have suggested as inhibitor of COX-1 and COX-2. Conclusion: Collectively, the scoring binding energy calculation (with PBSA Model Solvent) sesquiterpenoid compounds: CID519743 had suggested as candidate for non-selective inhibitor; CID56928117 and CID94275 had suggested as candidate for a selective COX-1 inhibitor; and CID107152 had suggested as candidate for a selective COX-2 inhibitor. PMID:28077888

  17. 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.

  18. HTMD: High-Throughput Molecular Dynamics for Molecular Discovery.

    Science.gov (United States)

    Doerr, S; Harvey, M J; Noé, Frank; De Fabritiis, G

    2016-04-12

    Recent advances in molecular simulations have allowed scientists to investigate slower biological processes than ever before. Together with these advances came an explosion of data that has transformed a traditionally computing-bound into a data-bound problem. Here, we present HTMD, a programmable, extensible platform written in Python that aims to solve the data generation and analysis problem as well as increase reproducibility by providing a complete workspace for simulation-based discovery. So far, HTMD includes system building for CHARMM and AMBER force fields, projection methods, clustering, molecular simulation production, adaptive sampling, an Amazon cloud interface, Markov state models, and visualization. As a result, a single, short HTMD script can lead from a PDB structure to useful quantities such as relaxation time scales, equilibrium populations, metastable conformations, and kinetic rates. In this paper, we focus on the adaptive sampling and Markov state modeling features.