Enhanced sampling techniques in molecular dynamics simulations of biological systems.

PubMed

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

2015-05-01

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

Achieving Rigorous Accelerated Conformational Sampling in Explicit Solvent.

PubMed

Doshi, Urmi; Hamelberg, Donald

2014-04-03

Molecular dynamics simulations can provide valuable atomistic insights into biomolecular function. However, the accuracy of molecular simulations on general-purpose computers depends on the time scale of the events of interest. Advanced simulation methods, such as accelerated molecular dynamics, have shown tremendous promise in sampling the conformational dynamics of biomolecules, where standard molecular dynamics simulations are nonergodic. Here we present a sampling method based on accelerated molecular dynamics in which rotatable dihedral angles and nonbonded interactions are boosted separately. This method (RaMD-db) is a different implementation of the dual-boost accelerated molecular dynamics, introduced earlier. The advantage is that this method speeds up sampling of the conformational space of biomolecules in explicit solvent, as the degrees of freedom most relevant for conformational transitions are accelerated. We tested RaMD-db on one of the most difficult sampling problems - protein folding. Starting from fully extended polypeptide chains, two fast folding α-helical proteins (Trpcage and the double mutant of C-terminal fragment of Villin headpiece) and a designed β-hairpin (Chignolin) were completely folded to their native structures in very short simulation time. Multiple folding/unfolding transitions could be observed in a single trajectory. Our results show that RaMD-db is a promisingly fast and efficient sampling method for conformational transitions in explicit solvent. RaMD-db thus opens new avenues for understanding biomolecular self-assembly and functional dynamics occurring on long time and length scales.

Non-Adiabatic Molecular Dynamics Methods for Materials Discovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furche, Filipp; Parker, Shane M.; Muuronen, Mikko J.

2017-04-04

The flow of radiative energy in light-driven materials such as photosensitizer dyes or photocatalysts is governed by non-adiabatic transitions between electronic states and cannot be described within the Born-Oppenheimer approximation commonly used in electronic structure theory. The non-adiabatic molecular dynamics (NAMD) methods based on Tully surface hopping and time-dependent density functional theory developed in this project have greatly extended the range of molecular materials that can be tackled by NAMD simulations. New algorithms to compute molecular excited state and response properties efficiently were developed. Fundamental limitations of common non-linear response methods were discovered and characterized. Methods for accurate computations ofmore » vibronic spectra of materials such as black absorbers were developed and applied. It was shown that open-shell TDDFT methods capture bond breaking in NAMD simulations, a longstanding challenge for single-reference molecular dynamics simulations. The methods developed in this project were applied to study the photodissociation of acetaldehyde and revealed that non-adiabatic effects are experimentally observable in fragment kinetic energy distributions. Finally, the project enabled the first detailed NAMD simulations of photocatalytic water oxidation by titania nanoclusters, uncovering the mechanism of this fundamentally important reaction for fuel generation and storage.« less

Molecular dynamics simulation of a piston driven shock wave in a hard sphere gas. Final Contractor ReportPh.D. Thesis

NASA Technical Reports Server (NTRS)

Woo, Myeung-Jouh; Greber, Isaac

1995-01-01

Molecular dynamics simulation is used to study the piston driven shock wave at Mach 1.5, 3, and 10. A shock tube, whose shape is a circular cylinder, is filled with hard sphere molecules having a Maxwellian thermal velocity distribution and zero mean velocity. The piston moves and a shock wave is generated. All collisions are specular, including those between the molecules and the computational boundaries, so that the shock development is entirely causal, with no imposed statistics. The structure of the generated shock is examined in detail, and the wave speed; profiles of density, velocity, and temperature; and shock thickness are determined. The results are compared with published results of other methods, especially the direct simulation Monte-Carlo method. Property profiles are similar to those generated by direct simulation Monte-Carlo method. The shock wave thicknesses are smaller than the direct simulation Monte-Carlo results, but larger than those of the other methods. Simulation of a shock wave, which is one-dimensional, is a severe test of the molecular dynamics method, which is always three-dimensional. A major challenge of the thesis is to examine the capability of the molecular dynamics methods by choosing a difficult task.

The Importance of Three-Body Interactions in Molecular Dynamics Simulations of Water with the Fragment Molecular Orbital Method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pruitt, Spencer R.; Nakata, Hiroya; Nagata, Takeshi

2016-04-12

The analytic first derivative with respect to nuclear coordinates is formulated and implemented in the framework of the three-body fragment molecular orbital (FMO) method. The gradient has been derived and implemented for restricted Hartree-Fock, second-order Møller-Plesset perturbation, and density functional theories. The importance of the three-body fully analytic gradient is illustrated through the failure of the two-body FMO method during molecular dynamics simulations of a small water cluster. The parallel implementation of the fragment molecular orbital method, its parallel efficiency, and its scalability on the Blue Gene/Q architecture up to 262,144 CPU cores, are also discussed.

Spotting the difference in molecular dynamics simulations of biomolecules

NASA Astrophysics Data System (ADS)

Sakuraba, Shun; Kono, Hidetoshi

2016-08-01

Comparing two trajectories from molecular simulations conducted under different conditions is not a trivial task. In this study, we apply a method called Linear Discriminant Analysis with ITERative procedure (LDA-ITER) to compare two molecular simulation results by finding the appropriate projection vectors. Because LDA-ITER attempts to determine a projection such that the projections of the two trajectories do not overlap, the comparison does not suffer from a strong anisotropy, which is an issue in protein dynamics. LDA-ITER is applied to two test cases: the T4 lysozyme protein simulation with or without a point mutation and the allosteric protein PDZ2 domain of hPTP1E with or without a ligand. The projection determined by the method agrees with the experimental data and previous simulations. The proposed procedure, which complements existing methods, is a versatile analytical method that is specialized to find the "difference" between two trajectories.

Molecular-Level Simulations of the Turbulent Taylor-Green Flow

NASA Astrophysics Data System (ADS)

Gallis, M. A.; Bitter, N. P.; Koehler, T. P.; Plimpton, S. J.; Torczynski, J. R.; Papadakis, G.

2017-11-01

The Direct Simulation Monte Carlo (DSMC) method, a statistical, molecular-level technique that provides accurate solutions to the Boltzmann equation, is applied to the turbulent Taylor-Green vortex flow. The goal of this work is to investigate whether DSMC can accurately simulate energy decay in a turbulent flow. If so, then simulating turbulent flows at the molecular level can provide new insights because the energy decay can be examined in detail from molecular to macroscopic length scales, thereby directly linking molecular relaxation processes to macroscopic transport processes. The DSMC simulations are performed on half a million cores of Sequoia, the 17 Pflop platform at Lawrence Livermore National Laboratory, and the kinetic-energy dissipation rate and the energy spectrum are computed directly from the molecular velocities. The DSMC simulations are found to reproduce the Kolmogorov -5/3 law and to agree with corresponding Navier-Stokes simulations obtained using a spectral method. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA0003525.

Linear Response Path Following: A Molecular Dynamics Method To Simulate Global Conformational Changes of Protein upon Ligand Binding.

PubMed

Tamura, Koichi; Hayashi, Shigehiko

2015-07-14

Molecular functions of proteins are often fulfilled by global conformational changes that couple with local events such as the binding of ligand molecules. High molecular complexity of proteins has, however, been an obstacle to obtain an atomistic view of the global conformational transitions, imposing a limitation on the mechanistic understanding of the functional processes. In this study, we developed a new method of molecular dynamics (MD) simulation called the linear response path following (LRPF) to simulate a protein's global conformational changes upon ligand binding. The method introduces a biasing force based on a linear response theory, which determines a local reaction coordinate in the configuration space that represents linear coupling between local events of ligand binding and global conformational changes and thus provides one with fully atomistic models undergoing large conformational changes without knowledge of a target structure. The overall transition process involving nonlinear conformational changes is simulated through iterative cycles consisting of a biased MD simulation with an updated linear response force and a following unbiased MD simulation for relaxation. We applied the method to the simulation of global conformational changes of the yeast calmodulin N-terminal domain and successfully searched out the end conformation. The atomistically detailed trajectories revealed a sequence of molecular events that properly lead to the global conformational changes and identified key steps of local-global coupling that induce the conformational transitions. The LRPF method provides one with a powerful means to model conformational changes of proteins such as motors and transporters where local-global coupling plays a pivotal role in their functional processes.

Relaxation estimation of RMSD in molecular dynamics immunosimulations.

PubMed

Schreiner, Wolfgang; Karch, Rudolf; Knapp, Bernhard; Ilieva, Nevena

2012-01-01

Molecular dynamics simulations have to be sufficiently long to draw reliable conclusions. However, no method exists to prove that a simulation has converged. We suggest the method of "lagged RMSD-analysis" as a tool to judge if an MD simulation has not yet run long enough. The analysis is based on RMSD values between pairs of configurations separated by variable time intervals Δt. Unless RMSD(Δt) has reached a stationary shape, the simulation has not yet converged.

Free energy surface of an intrinsically disordered protein: comparison between temperature replica exchange molecular dynamics and bias-exchange metadynamics.

PubMed

Zerze, Gül H; Miller, Cayla M; Granata, Daniele; Mittal, Jeetain

2015-06-09

Intrinsically disordered proteins (IDPs), which are expected to be largely unstructured under physiological conditions, make up a large fraction of eukaryotic proteins. Molecular dynamics simulations have been utilized to probe structural characteristics of these proteins, which are not always easily accessible to experiments. However, exploration of the conformational space by brute force molecular dynamics simulations is often limited by short time scales. Present literature provides a number of enhanced sampling methods to explore protein conformational space in molecular simulations more efficiently. In this work, we present a comparison of two enhanced sampling methods: temperature replica exchange molecular dynamics and bias exchange metadynamics. By investigating both the free energy landscape as a function of pertinent order parameters and the per-residue secondary structures of an IDP, namely, human islet amyloid polypeptide, we found that the two methods yield similar results as expected. We also highlight the practical difference between the two methods by describing the path that we followed to obtain both sets of data.

Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods To Reproduce the Behavior of Fluorescent Labels on Proteins.

PubMed

Walczewska-Szewc, Katarzyna; Deplazes, Evelyne; Corry, Ben

2015-07-14

Adequately sampling the large number of conformations accessible to proteins and other macromolecules is one of the central challenges in molecular dynamics (MD) simulations; this activity can be difficult, even for relatively simple systems. An example where this problem arises is in the simulation of dye-labeled proteins, which are now being widely used in the design and interpretation of Förster resonance energy transfer (FRET) experiments. In this study, MD simulations are used to characterize the motion of two commonly used FRET dyes attached to an immobilized chain of polyproline. Even in this simple system, the dyes exhibit complex behavior that is a mixture of fast and slow motions. Consequently, very long MD simulations are required to sufficiently sample the entire range of dye motion. Here, we compare the ability of enhanced sampling methods to reproduce the behavior of fluorescent labels on proteins. In particular, we compared Accelerated Molecular Dynamics (AMD), metadynamics, Replica Exchange Molecular Dynamics (REMD), and High Temperature Molecular Dynamics (HTMD) to equilibrium MD simulations. We find that, in our system, all of these methods improve the sampling of the dye motion, but the most significant improvement is achieved using REMD.

An integrate-over-temperature approach for enhanced sampling.

PubMed

Gao, Yi Qin

2008-02-14

A simple method is introduced to achieve efficient random walking in the energy space in molecular dynamics simulations which thus enhances the sampling over a large energy range. The approach is closely related to multicanonical and replica exchange simulation methods in that it allows configurations of the system to be sampled in a wide energy range by making use of Boltzmann distribution functions at multiple temperatures. A biased potential is quickly generated using this method and is then used in accelerated molecular dynamics simulations.

Modeling charge transport in organic photovoltaic materials.

PubMed

Nelson, Jenny; Kwiatkowski, Joe J; Kirkpatrick, James; Frost, Jarvist M

2009-11-17

The performance of an organic photovoltaic cell depends critically on the mobility of charge carriers within the constituent molecular semiconductor materials. However, a complex combination of phenomena that span a range of length and time scales control charge transport in disordered organic semiconductors. As a result, it is difficult to rationalize charge transport properties in terms of material parameters. Until now, efforts to improve charge mobilities in molecular semiconductors have proceeded largely by trial and error rather than through systematic design. However, recent developments have enabled the first predictive simulation studies of charge transport in disordered organic semiconductors. This Account describes a set of computational methods, specifically molecular modeling methods, to simulate molecular packing, quantum chemical calculations of charge transfer rates, and Monte Carlo simulations of charge transport. Using case studies, we show how this combination of methods can reproduce experimental mobilities with few or no fitting parameters. Although currently applied to material systems of high symmetry or well-defined structure, further developments of this approach could address more complex systems such anisotropic or multicomponent solids and conjugated polymers. Even with an approximate treatment of packing disorder, these computational methods simulate experimental mobilities within an order of magnitude at high electric fields. We can both reproduce the relative values of electron and hole mobility in a conjugated small molecule and rationalize those values based on the symmetry of frontier orbitals. Using fully atomistic molecular dynamics simulations of molecular packing, we can quantitatively replicate vertical charge transport along stacks of discotic liquid crystals which vary only in the structure of their side chains. We can reproduce the trends in mobility with molecular weight for self-organizing polymers using a cheap, coarse-grained structural simulation method. Finally, we quantitatively reproduce the field-effect mobility in disordered C60 films. On the basis of these results, we conclude that all of the necessary building blocks are in place for the predictive simulation of charge transport in macromolecular electronic materials and that such methods can be used as a tool toward the future rational design of functional organic electronic materials.

Quantum Fragment Based ab Initio Molecular Dynamics for Proteins.

PubMed

Liu, Jinfeng; Zhu, Tong; Wang, Xianwei; He, Xiao; Zhang, John Z H

2015-12-08

Developing ab initio molecular dynamics (AIMD) methods for practical application in protein dynamics is of significant interest. Due to the large size of biomolecules, applying standard quantum chemical methods to compute energies for dynamic simulation is computationally prohibitive. In this work, a fragment based ab initio molecular dynamics approach is presented for practical application in protein dynamics study. In this approach, the energy and forces of the protein are calculated by a recently developed electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method. For simulation in explicit solvent, mechanical embedding is introduced to treat protein interaction with explicit water molecules. This AIMD approach has been applied to MD simulations of a small benchmark protein Trpcage (with 20 residues and 304 atoms) in both the gas phase and in solution. Comparison to the simulation result using the AMBER force field shows that the AIMD gives a more stable protein structure in the simulation, indicating that quantum chemical energy is more reliable. Importantly, the present fragment-based AIMD simulation captures quantum effects including electrostatic polarization and charge transfer that are missing in standard classical MD simulations. The current approach is linear-scaling, trivially parallel, and applicable to performing the AIMD simulation of proteins with a large size.

A new battery-charging method suggested by molecular dynamics simulations.

PubMed

Abou Hamad, Ibrahim; Novotny, M A; Wipf, D O; Rikvold, P A

2010-03-20

Based on large-scale molecular dynamics simulations, we propose a new charging method that should be capable of charging a lithium-ion battery in a fraction of the time needed when using traditional methods. This charging method uses an additional applied oscillatory electric field. Our simulation results show that this charging method offers a great reduction in the average intercalation time for Li(+) ions, which dominates the charging time. The oscillating field not only increases the diffusion rate of Li(+) ions in the electrolyte but, more importantly, also enhances intercalation by lowering the corresponding overall energy barrier.

Relaxation Estimation of RMSD in Molecular Dynamics Immunosimulations

PubMed Central

Schreiner, Wolfgang; Karch, Rudolf; Knapp, Bernhard; Ilieva, Nevena

2012-01-01

Molecular dynamics simulations have to be sufficiently long to draw reliable conclusions. However, no method exists to prove that a simulation has converged. We suggest the method of “lagged RMSD-analysis” as a tool to judge if an MD simulation has not yet run long enough. The analysis is based on RMSD values between pairs of configurations separated by variable time intervals Δt. Unless RMSD(Δt) has reached a stationary shape, the simulation has not yet converged. PMID:23019425

Full Quantum Dynamics Simulation of a Realistic Molecular System Using the Adaptive Time-Dependent Density Matrix Renormalization Group Method.

PubMed

Yao, Yao; Sun, Ke-Wei; Luo, Zhen; Ma, Haibo

2018-01-18

The accurate theoretical interpretation of ultrafast time-resolved spectroscopy experiments relies on full quantum dynamics simulations for the investigated system, which is nevertheless computationally prohibitive for realistic molecular systems with a large number of electronic and/or vibrational degrees of freedom. In this work, we propose a unitary transformation approach for realistic vibronic Hamiltonians, which can be coped with using the adaptive time-dependent density matrix renormalization group (t-DMRG) method to efficiently evolve the nonadiabatic dynamics of a large molecular system. We demonstrate the accuracy and efficiency of this approach with an example of simulating the exciton dissociation process within an oligothiophene/fullerene heterojunction, indicating that t-DMRG can be a promising method for full quantum dynamics simulation in large chemical systems. Moreover, it is also shown that the proper vibronic features in the ultrafast electronic process can be obtained by simulating the two-dimensional (2D) electronic spectrum by virtue of the high computational efficiency of the t-DMRG method.

Partial molar enthalpies and reaction enthalpies from equilibrium molecular dynamics simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schnell, Sondre K.; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, California 94720; Department of Chemistry, Faculty of Natural Science and Technology, Norwegian University of Science and Technology, 4791 Trondheim

2014-10-14

We present a new molecular simulation technique for determining partial molar enthalpies in mixtures of gases and liquids from single simulations, without relying on particle insertions, deletions, or identity changes. The method can also be applied to systems with chemical reactions. We demonstrate our method for binary mixtures of Weeks-Chandler-Anderson particles by comparing with conventional simulation techniques, as well as for a simple model that mimics a chemical reaction. The method considers small subsystems inside a large reservoir (i.e., the simulation box), and uses the construction of Hill to compute properties in the thermodynamic limit from small-scale fluctuations. Results obtainedmore » with the new method are in excellent agreement with those from previous methods. Especially for modeling chemical reactions, our method can be a valuable tool for determining reaction enthalpies directly from a single MD simulation.« less

Molecular Simulation of the Phase Diagram of Methane Hydrate: Free Energy Calculations, Direct Coexistence Method, and Hyperparallel Tempering.

PubMed

Jin, Dongliang; Coasne, Benoit

2017-10-24

Different molecular simulation strategies are used to assess the stability of methane hydrate under various temperature and pressure conditions. First, using two water molecular models, free energy calculations consisting of the Einstein molecule approach in combination with semigrand Monte Carlo simulations are used to determine the pressure-temperature phase diagram of methane hydrate. With these calculations, we also estimate the chemical potentials of water and methane and methane occupancy at coexistence. Second, we also consider two other advanced molecular simulation techniques that allow probing the phase diagram of methane hydrate: the direct coexistence method in the Grand Canonical ensemble and the hyperparallel tempering Monte Carlo method. These two direct techniques are found to provide stability conditions that are consistent with the pressure-temperature phase diagram obtained using rigorous free energy calculations. The phase diagram obtained in this work, which is found to be consistent with previous simulation studies, is close to its experimental counterpart provided the TIP4P/Ice model is used to describe the water molecule.

On simulation of local fluxes in molecular junctions

NASA Astrophysics Data System (ADS)

Cabra, Gabriel; Jensen, Anders; Galperin, Michael

2018-05-01

We present a pedagogical review of the current density simulation in molecular junction models indicating its advantages and deficiencies in analysis of local junction transport characteristics. In particular, we argue that current density is a universal tool which provides more information than traditionally simulated bond currents, especially when discussing inelastic processes. However, current density simulations are sensitive to the choice of basis and electronic structure method. We note that while discussing the local current conservation in junctions, one has to account for the source term caused by the open character of the system and intra-molecular interactions. Our considerations are illustrated with numerical simulations of a benzenedithiol molecular junction.

Visualizing functional motions of membrane transporters with molecular dynamics simulations.

PubMed

Shaikh, Saher A; Li, Jing; Enkavi, Giray; Wen, Po-Chao; Huang, Zhijian; Tajkhorshid, Emad

2013-01-29

Computational modeling and molecular simulation techniques have become an integral part of modern molecular research. Various areas of molecular sciences continue to benefit from, indeed rely on, the unparalleled spatial and temporal resolutions offered by these technologies, to provide a more complete picture of the molecular problems at hand. Because of the continuous development of more efficient algorithms harvesting ever-expanding computational resources, and the emergence of more advanced and novel theories and methodologies, the scope of computational studies has expanded significantly over the past decade, now including much larger molecular systems and far more complex molecular phenomena. Among the various computer modeling techniques, the application of molecular dynamics (MD) simulation and related techniques has particularly drawn attention in biomolecular research, because of the ability of the method to describe the dynamical nature of the molecular systems and thereby to provide a more realistic representation, which is often needed for understanding fundamental molecular properties. The method has proven to be remarkably successful in capturing molecular events and structural transitions highly relevant to the function and/or physicochemical properties of biomolecular systems. Herein, after a brief introduction to the method of MD, we use a number of membrane transport proteins studied in our laboratory as examples to showcase the scope and applicability of the method and its power in characterizing molecular motions of various magnitudes and time scales that are involved in the function of this important class of membrane proteins.

Visualizing Functional Motions of Membrane Transporters with Molecular Dynamics Simulations

PubMed Central

2013-01-01

Computational modeling and molecular simulation techniques have become an integral part of modern molecular research. Various areas of molecular sciences continue to benefit from, indeed rely on, the unparalleled spatial and temporal resolutions offered by these technologies, to provide a more complete picture of the molecular problems at hand. Because of the continuous development of more efficient algorithms harvesting ever-expanding computational resources, and the emergence of more advanced and novel theories and methodologies, the scope of computational studies has expanded significantly over the past decade, now including much larger molecular systems and far more complex molecular phenomena. Among the various computer modeling techniques, the application of molecular dynamics (MD) simulation and related techniques has particularly drawn attention in biomolecular research, because of the ability of the method to describe the dynamical nature of the molecular systems and thereby to provide a more realistic representation, which is often needed for understanding fundamental molecular properties. The method has proven to be remarkably successful in capturing molecular events and structural transitions highly relevant to the function and/or physicochemical properties of biomolecular systems. Herein, after a brief introduction to the method of MD, we use a number of membrane transport proteins studied in our laboratory as examples to showcase the scope and applicability of the method and its power in characterizing molecular motions of various magnitudes and time scales that are involved in the function of this important class of membrane proteins. PMID:23298176

MD Simulations of P-Type ATPases in a Lipid Bilayer System.

PubMed

Autzen, Henriette Elisabeth; Musgaard, Maria

2016-01-01

Molecular dynamics (MD) simulation is a computational method which provides insight on protein dynamics with high resolution in both space and time, in contrast to many experimental techniques. MD simulations can be used as a stand-alone method to study P-type ATPases as well as a complementary method aiding experimental studies. In particular, MD simulations have proved valuable in generating and confirming hypotheses relating to the structure and function of P-type ATPases. In the following, we describe a detailed practical procedure on how to set up and run a MD simulation of a P-type ATPase embedded in a lipid bilayer using software free of use for academics. We emphasize general considerations and problems typically encountered when setting up simulations. While full coverage of all possible procedures is beyond the scope of this chapter, we have chosen to illustrate the MD procedure with the Nanoscale Molecular Dynamics (NAMD) and the Visual Molecular Dynamics (VMD) software suites.

Subtle Monte Carlo Updates in Dense Molecular Systems.

PubMed

Bottaro, Sandro; Boomsma, Wouter; E Johansson, Kristoffer; Andreetta, Christian; Hamelryck, Thomas; Ferkinghoff-Borg, Jesper

2012-02-14

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

Scalable and fast heterogeneous molecular simulation with predictive parallelization schemes

NASA Astrophysics Data System (ADS)

Guzman, Horacio V.; Junghans, Christoph; Kremer, Kurt; Stuehn, Torsten

2017-11-01

Multiscale and inhomogeneous molecular systems are challenging topics in the field of molecular simulation. In particular, modeling biological systems in the context of multiscale simulations and exploring material properties are driving a permanent development of new simulation methods and optimization algorithms. In computational terms, those methods require parallelization schemes that make a productive use of computational resources for each simulation and from its genesis. Here, we introduce the heterogeneous domain decomposition approach, which is a combination of an heterogeneity-sensitive spatial domain decomposition with an a priori rearrangement of subdomain walls. Within this approach, the theoretical modeling and scaling laws for the force computation time are proposed and studied as a function of the number of particles and the spatial resolution ratio. We also show the new approach capabilities, by comparing it to both static domain decomposition algorithms and dynamic load-balancing schemes. Specifically, two representative molecular systems have been simulated and compared to the heterogeneous domain decomposition proposed in this work. These two systems comprise an adaptive resolution simulation of a biomolecule solvated in water and a phase-separated binary Lennard-Jones fluid.

Constraint methods that accelerate free-energy simulations of biomolecules.

PubMed

Perez, Alberto; MacCallum, Justin L; Coutsias, Evangelos A; Dill, Ken A

2015-12-28

Atomistic molecular dynamics simulations of biomolecules are critical for generating narratives about biological mechanisms. The power of atomistic simulations is that these are physics-based methods that satisfy Boltzmann's law, so they can be used to compute populations, dynamics, and mechanisms. But physical simulations are computationally intensive and do not scale well to the sizes of many important biomolecules. One way to speed up physical simulations is by coarse-graining the potential function. Another way is to harness structural knowledge, often by imposing spring-like restraints. But harnessing external knowledge in physical simulations is problematic because knowledge, data, or hunches have errors, noise, and combinatoric uncertainties. Here, we review recent principled methods for imposing restraints to speed up physics-based molecular simulations that promise to scale to larger biomolecules and motions.

A novel energy conversion based method for velocity correction in molecular dynamics simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Hanhui; Collaborative Innovation Center of Advanced Aero-Engine, Hangzhou 310027; Liu, Ningning

2017-05-01

Molecular dynamics (MD) simulation has become an important tool for studying micro- or nano-scale dynamics and the statistical properties of fluids and solids. In MD simulations, there are mainly two approaches: equilibrium and non-equilibrium molecular dynamics (EMD and NEMD). In this paper, a new energy conversion based correction (ECBC) method for MD is developed. Unlike the traditional systematic correction based on macroscopic parameters, the ECBC method is developed strictly based on the physical interaction processes between the pair of molecules or atoms. The developed ECBC method can apply to EMD and NEMD directly. While using MD with this method, themore » difference between the EMD and NEMD is eliminated, and no macroscopic parameters such as external imposed potentials or coefficients are needed. With this method, many limits of using MD are lifted. The application scope of MD is greatly extended.« less

Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation.

PubMed

Paluch, Andrew S; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L

2015-01-28

We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes.

Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation

NASA Astrophysics Data System (ADS)

Paluch, Andrew S.; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L.

2015-01-01

We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes.

Accelerated molecular dynamics: A promising and efficient simulation method for biomolecules

NASA Astrophysics Data System (ADS)

Hamelberg, Donald; Mongan, John; McCammon, J. Andrew

2004-06-01

Many interesting dynamic properties of biological molecules cannot be simulated directly using molecular dynamics because of nanosecond time scale limitations. These systems are trapped in potential energy minima with high free energy barriers for large numbers of computational steps. The dynamic evolution of many molecular systems occurs through a series of rare events as the system moves from one potential energy basin to another. Therefore, we have proposed a robust bias potential function that can be used in an efficient accelerated molecular dynamics approach to simulate the transition of high energy barriers without any advance knowledge of the location of either the potential energy wells or saddle points. In this method, the potential energy landscape is altered by adding a bias potential to the true potential such that the escape rates from potential wells are enhanced, which accelerates and extends the time scale in molecular dynamics simulations. Our definition of the bias potential echoes the underlying shape of the potential energy landscape on the modified surface, thus allowing for the potential energy minima to be well defined, and hence properly sampled during the simulation. We have shown that our approach, which can be extended to biomolecules, samples the conformational space more efficiently than normal molecular dynamics simulations, and converges to the correct canonical distribution.

Nonadiabatic Ab Initio Molecular Dynamics with the Floating Occupation Molecular Orbital-Complete Active Space Configuration Interaction Method [Non-Adiabatic Ab Initio Molecular Dynamics with Floating Occupation Molecular Orbitals CASCI Method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hollas, Daniel; Sistik, Lukas; Hohenstein, Edward G.

Here, we show that the floating occupation molecular orbital complete active space configuration interaction (FOMO-CASCI) method is a promising alternative to the widely used complete active space self-consistent field (CASSCF) method in direct nonadiabatic dynamics simulations. We have simulated photodynamics of three archetypal molecules in photodynamics: ethylene, methaniminium cation, and malonaldehyde. We compared the time evolution of electronic populations and reaction mechanisms as revealed by the FOMO-CASCI and CASSCF approaches. Generally, the two approaches provide similar results. Some dynamical differences are observed, but these can be traced back to energetically minor differences in the potential energy surfaces. We suggest thatmore » the FOMO-CASCI method represents, due to its efficiency and stability, a promising approach for direct ab initio dynamics in the excited state.« less

Nonholonomic Hamiltonian Method for Molecular Dynamics Simulations of Reacting Shocks

NASA Astrophysics Data System (ADS)

Fahrenthold, Eric; Bass, Joseph

2015-06-01

Conventional molecular dynamics simulations of reacting shocks employ a holonomic Hamiltonian formulation: the breaking and forming of covalent bonds is described by potential functions. In general these potential functions: (a) are algebraically complex, (b) must satisfy strict smoothness requirements, and (c) contain many fitted parameters. In recent research the authors have developed a new noholonomic formulation of reacting molecular dynamics. In this formulation bond orders are determined by rate equations and the bonding-debonding process need not be described by differentiable functions. This simplifies the representation of complex chemistry and reduces the number of fitted model parameters. Example applications of the method show molecular level shock to detonation simulations in nitromethane and RDX. Research supported by the Defense Threat Reduction Agency.

Grand canonical ensemble Monte Carlo simulation of the dCpG/proflavine crystal hydrate.

PubMed

Resat, H; Mezei, M

1996-09-01

The grand canonical ensemble Monte Carlo molecular simulation method is used to investigate hydration patterns in the crystal hydrate structure of the dCpG/proflavine intercalated complex. The objective of this study is to show by example that the recently advocated grand canonical ensemble simulation is a computationally efficient method for determining the positions of the hydrating water molecules in protein and nucleic acid structures. A detailed molecular simulation convergence analysis and an analogous comparison of the theoretical results with experiments clearly show that the grand ensemble simulations can be far more advantageous than the comparable canonical ensemble simulations.

Free energy calculation of single molecular interaction using Jarzynski's identity method: the case of HIV-1 protease inhibitor system

NASA Astrophysics Data System (ADS)

Li, De-Chang; Ji, Bao-Hua

2012-06-01

Jarzynski' identity (JI) method was suggested a promising tool for reconstructing free energy landscape of biomolecular interactions in numerical simulations and experiments. However, JI method has not yet been well tested in complex systems such as ligand-receptor molecular pairs. In this paper, we applied a huge number of steered molecular dynamics (SMD) simulations to dissociate the protease of human immunodeficiency type I virus (HIV-1 protease) and its inhibitors. We showed that because of intrinsic complexity of the ligand-receptor system, the energy barrier predicted by JI method at high pulling rates is much higher than experimental results. However, with a slower pulling rate and fewer switch times of simulations, the predictions of JI method can approach to the experiments. These results suggested that the JI method is more appropriate for reconstructing free energy landscape using the data taken from experiments, since the pulling rates used in experiments are often much slower than those in SMD simulations. Furthermore, we showed that a higher loading stiffness can produce higher precision of calculation of energy landscape because it yields a lower mean value and narrower bandwidth of work distribution in SMD simulations.

Faster protein folding using enhanced conformational sampling of molecular dynamics simulation.

PubMed

Kamberaj, Hiqmet

2018-05-01

In this study, we applied swarm particle-like molecular dynamics (SPMD) approach to enhance conformational sampling of replica exchange simulations. In particular, the approach showed significant improvement in sampling efficiency of conformational phase space when combined with replica exchange method (REM) in computer simulation of peptide/protein folding. First we introduce the augmented dynamical system of equations, and demonstrate the stability of the algorithm. Then, we illustrate the approach by using different fully atomistic and coarse-grained model systems, comparing them with the standard replica exchange method. In addition, we applied SPMD simulation to calculate the time correlation functions of the transitions in a two dimensional surface to demonstrate the enhancement of transition path sampling. Our results showed that folded structure can be obtained in a shorter simulation time using the new method when compared with non-augmented dynamical system. Typically, in less than 0.5 ns using replica exchange runs assuming that native folded structure is known and within simulation time scale of 40 ns in the case of blind structure prediction. Furthermore, the root mean square deviations from the reference structures were less than 2Å. To demonstrate the performance of new method, we also implemented three simulation protocols using CHARMM software. Comparisons are also performed with standard targeted molecular dynamics simulation method. Copyright © 2018 Elsevier Inc. All rights reserved.

Development of the Next Generation of Biogeochemistry Simulations Using EMSL's NWChem Molecular Modeling Software

NASA Astrophysics Data System (ADS)

Bylaska, E. J.; Kowalski, K.; Apra, E.; Govind, N.; Valiev, M.

2017-12-01

Methods of directly simulating the behavior of complex strongly interacting atomic systems (molecular dynamics, Monte Carlo) have provided important insight into the behavior of nanoparticles, biogeochemical systems, mineral/fluid systems, nanoparticles, actinide systems and geofluids. The limitation of these methods to even wider applications is the difficulty of developing accurate potential interactions in these systems at the molecular level that capture their complex chemistry. The well-developed tools of quantum chemistry and physics have been shown to approach the accuracy required. However, despite the continuous effort being put into improving their accuracy and efficiency, these tools will be of little value to condensed matter problems without continued improvements in techniques to traverse and sample the high-dimensional phase space needed to span the ˜10^12 time scale differences between molecular simulation and chemical events. In recent years, we have made considerable progress in developing electronic structure and AIMD methods tailored to treat biochemical and geochemical problems, including very efficient implementations of many-body methods, fast exact exchange methods, electron-transfer methods, excited state methods, QM/MM, and new parallel algorithms that scale to +100,000 cores. The poster will focus on the fundamentals of these methods and the realities in terms of system size, computational requirements and simulation times that are required for their application to complex biogeochemical systems.

A Lattice Boltzmann Method for Turbomachinery Simulations

NASA Technical Reports Server (NTRS)

Hsu, A. T.; Lopez, I.

2003-01-01

Lattice Boltzmann (LB) Method is a relatively new method for flow simulations. The start point of LB method is statistic mechanics and Boltzmann equation. The LB method tries to set up its model at molecular scale and simulate the flow at macroscopic scale. LBM has been applied to mostly incompressible flows and simple geometry.

Hybrid particle-field molecular dynamics simulation for polyelectrolyte systems.

PubMed

Zhu, You-Liang; Lu, Zhong-Yuan; Milano, Giuseppe; Shi, An-Chang; Sun, Zhao-Yan

2016-04-14

To achieve simulations on large spatial and temporal scales with high molecular chemical specificity, a hybrid particle-field method was proposed recently. This method is developed by combining molecular dynamics and self-consistent field theory (MD-SCF). The MD-SCF method has been validated by successfully predicting the experimentally observable properties of several systems. Here we propose an efficient scheme for the inclusion of electrostatic interactions in the MD-SCF framework. In this scheme, charged molecules are interacting with the external fields that are self-consistently determined from the charge densities. This method is validated by comparing the structural properties of polyelectrolytes in solution obtained from the MD-SCF and particle-based simulations. Moreover, taking PMMA-b-PEO and LiCF3SO3 as examples, the enhancement of immiscibility between the ion-dissolving block and the inert block by doping lithium salts into the copolymer is examined by using the MD-SCF method. By employing GPU-acceleration, the high performance of the MD-SCF method with explicit treatment of electrostatics facilitates the simulation study of many problems involving polyelectrolytes.

Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation

PubMed Central

Paluch, Andrew S.; Parameswaran, Sreeja; Liu, Shuai; Kolavennu, Anasuya; Mobley, David L.

2015-01-01

We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes. PMID:25637996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Jincheng; Rimsza, Jessica

Computational simulations at the atomistic level play an increasing important role in understanding the structures, behaviors, and the structure-property relationships of glass and amorphous materials. In this paper, we reviewed atomistic simulation methods ranging from first principles calculations and ab initio molecular dynamics (AIMD), to classical molecular dynamics (MD) and meso-scale kinetic Monte Carlo (KMC) simulations and their applications to glass-water interactions and glass dissolutions. Particularly, the use of these simulation methods in understanding the reaction mechanisms of water with oxide glasses, water-glass interfaces, hydrated porous silica gels formation, the structure and properties of multicomponent glasses, and microstructure evolution aremore » reviewed. Here, the advantages and disadvantageous of these methods are discussed and the current challenges and future direction of atomistic simulations in glass dissolution are presented.« less

Constant-pH molecular dynamics using stochastic titration

NASA Astrophysics Data System (ADS)

Baptista, António M.; Teixeira, Vitor H.; Soares, Cláudio M.

2002-09-01

A new method is proposed for performing constant-pH molecular dynamics (MD) simulations, that is, MD simulations where pH is one of the external thermodynamic parameters, like the temperature or the pressure. The protonation state of each titrable site in the solute is allowed to change during a molecular mechanics (MM) MD simulation, the new states being obtained from a combination of continuum electrostatics (CE) calculations and Monte Carlo (MC) simulation of protonation equilibrium. The coupling between the MM/MD and CE/MC algorithms is done in a way that ensures a proper Markov chain, sampling from the intended semigrand canonical distribution. This stochastic titration method is applied to succinic acid, aimed at illustrating the method and examining the choice of its adjustable parameters. The complete titration of succinic acid, using constant-pH MD simulations at different pH values, gives a clear picture of the coupling between the trans/gauche isomerization and the protonation process, making it possible to reconcile some apparently contradictory results of previous studies. The present constant-pH MD method is shown to require a moderate increase of computational cost when compared to the usual MD method.

Study of homogeneous bubble nucleation in liquid carbon dioxide by a hybrid approach combining molecular dynamics simulation and density gradient theory

NASA Astrophysics Data System (ADS)

Langenbach, K.; Heilig, M.; Horsch, M.; Hasse, H.

2018-03-01

A new method for predicting homogeneous bubble nucleation rates of pure compounds from vapor-liquid equilibrium (VLE) data is presented. It combines molecular dynamics simulation on the one side with density gradient theory using an equation of state (EOS) on the other. The new method is applied here to predict bubble nucleation rates in metastable liquid carbon dioxide (CO2). The molecular model of CO2 is taken from previous work of our group. PC-SAFT is used as an EOS. The consistency between the molecular model and the EOS is achieved by adjusting the PC-SAFT parameters to VLE data obtained from the molecular model. The influence parameter of density gradient theory is fitted to the surface tension of the molecular model. Massively parallel molecular dynamics simulations are performed close to the spinodal to compute bubble nucleation rates. From these simulations, the kinetic prefactor of the hybrid nucleation theory is estimated, whereas the nucleation barrier is calculated from density gradient theory. This enables the extrapolation of molecular simulation data to the whole metastable range including technically relevant densities. The results are tested against available experimental data and found to be in good agreement. The new method does not suffer from typical deficiencies of classical nucleation theory concerning the thermodynamic barrier at the spinodal and the bubble size dependence of surface tension, which is typically neglected in classical nucleation theory. In addition, the density in the center of critical bubbles and their surface tension is determined as a function of their radius. The usual linear Tolman correction to the capillarity approximation is found to be invalid.

Study of homogeneous bubble nucleation in liquid carbon dioxide by a hybrid approach combining molecular dynamics simulation and density gradient theory.

PubMed

Langenbach, K; Heilig, M; Horsch, M; Hasse, H

2018-03-28

A new method for predicting homogeneous bubble nucleation rates of pure compounds from vapor-liquid equilibrium (VLE) data is presented. It combines molecular dynamics simulation on the one side with density gradient theory using an equation of state (EOS) on the other. The new method is applied here to predict bubble nucleation rates in metastable liquid carbon dioxide (CO 2 ). The molecular model of CO 2 is taken from previous work of our group. PC-SAFT is used as an EOS. The consistency between the molecular model and the EOS is achieved by adjusting the PC-SAFT parameters to VLE data obtained from the molecular model. The influence parameter of density gradient theory is fitted to the surface tension of the molecular model. Massively parallel molecular dynamics simulations are performed close to the spinodal to compute bubble nucleation rates. From these simulations, the kinetic prefactor of the hybrid nucleation theory is estimated, whereas the nucleation barrier is calculated from density gradient theory. This enables the extrapolation of molecular simulation data to the whole metastable range including technically relevant densities. The results are tested against available experimental data and found to be in good agreement. The new method does not suffer from typical deficiencies of classical nucleation theory concerning the thermodynamic barrier at the spinodal and the bubble size dependence of surface tension, which is typically neglected in classical nucleation theory. In addition, the density in the center of critical bubbles and their surface tension is determined as a function of their radius. The usual linear Tolman correction to the capillarity approximation is found to be invalid.

Ensemble-Biased Metadynamics: A Molecular Simulation Method to Sample Experimental Distributions

PubMed Central

Marinelli, Fabrizio; Faraldo-Gómez, José D.

2015-01-01

We introduce an enhanced-sampling method for molecular dynamics (MD) simulations referred to as ensemble-biased metadynamics (EBMetaD). The method biases a conventional MD simulation to sample a molecular ensemble that is consistent with one or more probability distributions known a priori, e.g., experimental intramolecular distance distributions obtained by double electron-electron resonance or other spectroscopic techniques. To this end, EBMetaD adds an adaptive biasing potential throughout the simulation that discourages sampling of configurations inconsistent with the target probability distributions. The bias introduced is the minimum necessary to fulfill the target distributions, i.e., EBMetaD satisfies the maximum-entropy principle. Unlike other methods, EBMetaD does not require multiple simulation replicas or the introduction of Lagrange multipliers, and is therefore computationally efficient and straightforward in practice. We demonstrate the performance and accuracy of the method for a model system as well as for spin-labeled T4 lysozyme in explicit water, and show how EBMetaD reproduces three double electron-electron resonance distance distributions concurrently within a few tens of nanoseconds of simulation time. EBMetaD is integrated in the open-source PLUMED plug-in (www.plumed-code.org), and can be therefore readily used with multiple MD engines. PMID:26083917

Grand canonical ensemble Monte Carlo simulation of the dCpG/proflavine crystal hydrate.

PubMed Central

Resat, H; Mezei, M

1996-01-01

The grand canonical ensemble Monte Carlo molecular simulation method is used to investigate hydration patterns in the crystal hydrate structure of the dCpG/proflavine intercalated complex. The objective of this study is to show by example that the recently advocated grand canonical ensemble simulation is a computationally efficient method for determining the positions of the hydrating water molecules in protein and nucleic acid structures. A detailed molecular simulation convergence analysis and an analogous comparison of the theoretical results with experiments clearly show that the grand ensemble simulations can be far more advantageous than the comparable canonical ensemble simulations. Images FIGURE 5 FIGURE 7 PMID:8873992

LAMMPS integrated materials engine (LIME) for efficient automation of particle-based simulations: application to equation of state generation

NASA Astrophysics Data System (ADS)

Barnes, Brian C.; Leiter, Kenneth W.; Becker, Richard; Knap, Jaroslaw; Brennan, John K.

2017-07-01

We describe the development, accuracy, and efficiency of an automation package for molecular simulation, the large-scale atomic/molecular massively parallel simulator (LAMMPS) integrated materials engine (LIME). Heuristics and algorithms employed for equation of state (EOS) calculation using a particle-based model of a molecular crystal, hexahydro-1,3,5-trinitro-s-triazine (RDX), are described in detail. The simulation method for the particle-based model is energy-conserving dissipative particle dynamics, but the techniques used in LIME are generally applicable to molecular dynamics simulations with a variety of particle-based models. The newly created tool set is tested through use of its EOS data in plate impact and Taylor anvil impact continuum simulations of solid RDX. The coarse-grain model results from LIME provide an approach to bridge the scales from atomistic simulations to continuum simulations.

Scalable and fast heterogeneous molecular simulation with predictive parallelization schemes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guzman, Horacio V.; Junghans, Christoph; Kremer, Kurt

Multiscale and inhomogeneous molecular systems are challenging topics in the field of molecular simulation. In particular, modeling biological systems in the context of multiscale simulations and exploring material properties are driving a permanent development of new simulation methods and optimization algorithms. In computational terms, those methods require parallelization schemes that make a productive use of computational resources for each simulation and from its genesis. Here, we introduce the heterogeneous domain decomposition approach, which is a combination of an heterogeneity-sensitive spatial domain decomposition with an a priori rearrangement of subdomain walls. Within this approach and paper, the theoretical modeling and scalingmore » laws for the force computation time are proposed and studied as a function of the number of particles and the spatial resolution ratio. We also show the new approach capabilities, by comparing it to both static domain decomposition algorithms and dynamic load-balancing schemes. Specifically, two representative molecular systems have been simulated and compared to the heterogeneous domain decomposition proposed in this work. Finally, these two systems comprise an adaptive resolution simulation of a biomolecule solvated in water and a phase-separated binary Lennard-Jones fluid.« less

Scalable and fast heterogeneous molecular simulation with predictive parallelization schemes

DOE PAGES

Guzman, Horacio V.; Junghans, Christoph; Kremer, Kurt; ...

2017-11-27

Multiscale and inhomogeneous molecular systems are challenging topics in the field of molecular simulation. In particular, modeling biological systems in the context of multiscale simulations and exploring material properties are driving a permanent development of new simulation methods and optimization algorithms. In computational terms, those methods require parallelization schemes that make a productive use of computational resources for each simulation and from its genesis. Here, we introduce the heterogeneous domain decomposition approach, which is a combination of an heterogeneity-sensitive spatial domain decomposition with an a priori rearrangement of subdomain walls. Within this approach and paper, the theoretical modeling and scalingmore » laws for the force computation time are proposed and studied as a function of the number of particles and the spatial resolution ratio. We also show the new approach capabilities, by comparing it to both static domain decomposition algorithms and dynamic load-balancing schemes. Specifically, two representative molecular systems have been simulated and compared to the heterogeneous domain decomposition proposed in this work. Finally, these two systems comprise an adaptive resolution simulation of a biomolecule solvated in water and a phase-separated binary Lennard-Jones fluid.« less

Equilibrium simulations of proteins using molecular fragment replacement and NMR chemical shifts.

PubMed

Boomsma, Wouter; Tian, Pengfei; Frellsen, Jes; Ferkinghoff-Borg, Jesper; Hamelryck, Thomas; Lindorff-Larsen, Kresten; Vendruscolo, Michele

2014-09-23

Methods of protein structure determination based on NMR chemical shifts are becoming increasingly common. The most widely used approaches adopt the molecular fragment replacement strategy, in which structural fragments are repeatedly reassembled into different complete conformations in molecular simulations. Although these approaches are effective in generating individual structures consistent with the chemical shift data, they do not enable the sampling of the conformational space of proteins with correct statistical weights. Here, we present a method of molecular fragment replacement that makes it possible to perform equilibrium simulations of proteins, and hence to determine their free energy landscapes. This strategy is based on the encoding of the chemical shift information in a probabilistic model in Markov chain Monte Carlo simulations. First, we demonstrate that with this approach it is possible to fold proteins to their native states starting from extended structures. Second, we show that the method satisfies the detailed balance condition and hence it can be used to carry out an equilibrium sampling from the Boltzmann distribution corresponding to the force field used in the simulations. Third, by comparing the results of simulations carried out with and without chemical shift restraints we describe quantitatively the effects that these restraints have on the free energy landscapes of proteins. Taken together, these results demonstrate that the molecular fragment replacement strategy can be used in combination with chemical shift information to characterize not only the native structures of proteins but also their conformational fluctuations.

Uncertainty Quantification in Alchemical Free Energy Methods.

PubMed

Bhati, Agastya P; Wan, Shunzhou; Hu, Yuan; Sherborne, Brad; Coveney, Peter V

2018-06-12

Alchemical free energy methods have gained much importance recently from several reports of improved ligand-protein binding affinity predictions based on their implementation using molecular dynamics simulations. A large number of variants of such methods implementing different accelerated sampling techniques and free energy estimators are available, each claimed to be better than the others in its own way. However, the key features of reproducibility and quantification of associated uncertainties in such methods have barely been discussed. Here, we apply a systematic protocol for uncertainty quantification to a number of popular alchemical free energy methods, covering both absolute and relative free energy predictions. We show that a reliable measure of error estimation is provided by ensemble simulation-an ensemble of independent MD simulations-which applies irrespective of the free energy method. The need to use ensemble methods is fundamental and holds regardless of the duration of time of the molecular dynamics simulations performed.

Polymorphic phase transitions: Macroscopic theory and molecular simulation.

PubMed

Anwar, Jamshed; Zahn, Dirk

2017-08-01

Transformations in the solid state are of considerable interest, both for fundamental reasons and because they underpin important technological applications. The interest spans a wide spectrum of disciplines and application domains. For pharmaceuticals, a common issue is unexpected polymorphic transformation of the drug or excipient during processing or on storage, which can result in product failure. A more ambitious goal is that of exploiting the advantages of metastable polymorphs (e.g. higher solubility and dissolution rate) while ensuring their stability with respect to solid state transformation. To address these issues and to advance technology, there is an urgent need for significant insights that can only come from a detailed molecular level understanding of the involved processes. Whilst experimental approaches at best yield time- and space-averaged structural information, molecular simulation offers unprecedented, time-resolved molecular-level resolution of the processes taking place. This review aims to provide a comprehensive and critical account of state-of-the-art methods for modelling polymorph stability and transitions between solid phases. This is flanked by revisiting the associated macroscopic theoretical framework for phase transitions, including their classification, proposed molecular mechanisms, and kinetics. The simulation methods are presented in tutorial form, focusing on their application to phase transition phenomena. We describe molecular simulation studies for crystal structure prediction and polymorph screening, phase coexistence and phase diagrams, simulations of crystal-crystal transitions of various types (displacive/martensitic, reconstructive and diffusive), effects of defects, and phase stability and transitions at the nanoscale. Our selection of literature is intended to illustrate significant insights, concepts and understanding, as well as the current scope of using molecular simulations for understanding polymorphic transitions in an accessible way, rather than claiming completeness. With exciting prospects in both simulation methods development and enhancements in computer hardware, we are on the verge of accessing an unprecedented capability for designing and developing dosage forms and drug delivery systems in silico, including tackling challenges in polymorph control on a rational basis. Copyright © 2017 Elsevier B.V. All rights reserved.

Atomistic Computer Simulations of Water Interactions and Dissolution of Inorganic Glasses

DOE PAGES

Du, Jincheng; Rimsza, Jessica

2017-09-01

Computational simulations at the atomistic level play an increasing important role in understanding the structures, behaviors, and the structure-property relationships of glass and amorphous materials. In this paper, we reviewed atomistic simulation methods ranging from first principles calculations and ab initio molecular dynamics (AIMD), to classical molecular dynamics (MD) and meso-scale kinetic Monte Carlo (KMC) simulations and their applications to glass-water interactions and glass dissolutions. Particularly, the use of these simulation methods in understanding the reaction mechanisms of water with oxide glasses, water-glass interfaces, hydrated porous silica gels formation, the structure and properties of multicomponent glasses, and microstructure evolution aremore » reviewed. Here, the advantages and disadvantageous of these methods are discussed and the current challenges and future direction of atomistic simulations in glass dissolution are presented.« less

Local-feature analysis for automated coarse-graining of bulk-polymer molecular dynamics simulations.

PubMed

Xue, Y; Ludovice, P J; Grover, M A

2012-12-01

A method for automated coarse-graining of bulk polymers is presented, using the data-mining tool of local feature analysis. Most existing methods for polymer coarse-graining define superatoms based on their covalent bonding topology along the polymer backbone, but here superatoms are defined based only on their correlated motions, as observed in molecular dynamics simulations. Correlated atomic motions are identified in the simulation data using local feature analysis, between atoms in the same or in different polymer chains. Groups of highly correlated atoms constitute the superatoms in the coarse-graining scheme, and the positions of their seed coordinates are then projected forward in time. Based on only the seed positions, local feature analysis enables the full reconstruction of all atomic positions. This reconstruction suggests an iterative scheme to reduce the computation of the simulations to initialize another short molecular dynamic simulation, identify new superatoms, and again project forward in time.

Coulomb interactions in charged fluids.

PubMed

Vernizzi, Graziano; Guerrero-García, Guillermo Iván; de la Cruz, Monica Olvera

2011-07-01

The use of Ewald summation schemes for calculating long-range Coulomb interactions, originally applied to ionic crystalline solids, is a very common practice in molecular simulations of charged fluids at present. Such a choice imposes an artificial periodicity which is generally absent in the liquid state. In this paper we propose a simple analytical O(N(2)) method which is based on Gauss's law for computing exactly the Coulomb interaction between charged particles in a simulation box, when it is averaged over all possible orientations of a surrounding infinite lattice. This method mitigates the periodicity typical of crystalline systems and it is suitable for numerical studies of ionic liquids, charged molecular fluids, and colloidal systems with Monte Carlo and molecular dynamics simulations.

Multiscale Quantum Mechanics/Molecular Mechanics Simulations with Neural Networks.

PubMed

Shen, Lin; Wu, Jingheng; Yang, Weitao

2016-10-11

Molecular dynamics simulation with multiscale quantum mechanics/molecular mechanics (QM/MM) methods is a very powerful tool for understanding the mechanism of chemical and biological processes in solution or enzymes. However, its computational cost can be too high for many biochemical systems because of the large number of ab initio QM calculations. Semiempirical QM/MM simulations have much higher efficiency. Its accuracy can be improved with a correction to reach the ab initio QM/MM level. The computational cost on the ab initio calculation for the correction determines the efficiency. In this paper we developed a neural network method for QM/MM calculation as an extension of the neural-network representation reported by Behler and Parrinello. With this approach, the potential energy of any configuration along the reaction path for a given QM/MM system can be predicted at the ab initio QM/MM level based on the semiempirical QM/MM simulations. We further applied this method to three reactions in water to calculate the free energy changes. The free-energy profile obtained from the semiempirical QM/MM simulation is corrected to the ab initio QM/MM level with the potential energies predicted with the constructed neural network. The results are in excellent accordance with the reference data that are obtained from the ab initio QM/MM molecular dynamics simulation or corrected with direct ab initio QM/MM potential energies. Compared with the correction using direct ab initio QM/MM potential energies, our method shows a speed-up of 1 or 2 orders of magnitude. It demonstrates that the neural network method combined with the semiempirical QM/MM calculation can be an efficient and reliable strategy for chemical reaction simulations.

Multilevel summation with B-spline interpolation for pairwise interactions in molecular dynamics simulations.

PubMed

Hardy, David J; Wolff, Matthew A; Xia, Jianlin; Schulten, Klaus; Skeel, Robert D

2016-03-21

The multilevel summation method for calculating electrostatic interactions in molecular dynamics simulations constructs an approximation to a pairwise interaction kernel and its gradient, which can be evaluated at a cost that scales linearly with the number of atoms. The method smoothly splits the kernel into a sum of partial kernels of increasing range and decreasing variability with the longer-range parts interpolated from grids of increasing coarseness. Multilevel summation is especially appropriate in the context of dynamics and minimization, because it can produce continuous gradients. This article explores the use of B-splines to increase the accuracy of the multilevel summation method (for nonperiodic boundaries) without incurring additional computation other than a preprocessing step (whose cost also scales linearly). To obtain accurate results efficiently involves technical difficulties, which are overcome by a novel preprocessing algorithm. Numerical experiments demonstrate that the resulting method offers substantial improvements in accuracy and that its performance is competitive with an implementation of the fast multipole method in general and markedly better for Hamiltonian formulations of molecular dynamics. The improvement is great enough to establish multilevel summation as a serious contender for calculating pairwise interactions in molecular dynamics simulations. In particular, the method appears to be uniquely capable for molecular dynamics in two situations, nonperiodic boundary conditions and massively parallel computation, where the fast Fourier transform employed in the particle-mesh Ewald method falls short.

Multilevel summation with B-spline interpolation for pairwise interactions in molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Hardy, David J.; Wolff, Matthew A.; Xia, Jianlin; Schulten, Klaus; Skeel, Robert D.

2016-03-01

The multilevel summation method for calculating electrostatic interactions in molecular dynamics simulations constructs an approximation to a pairwise interaction kernel and its gradient, which can be evaluated at a cost that scales linearly with the number of atoms. The method smoothly splits the kernel into a sum of partial kernels of increasing range and decreasing variability with the longer-range parts interpolated from grids of increasing coarseness. Multilevel summation is especially appropriate in the context of dynamics and minimization, because it can produce continuous gradients. This article explores the use of B-splines to increase the accuracy of the multilevel summation method (for nonperiodic boundaries) without incurring additional computation other than a preprocessing step (whose cost also scales linearly). To obtain accurate results efficiently involves technical difficulties, which are overcome by a novel preprocessing algorithm. Numerical experiments demonstrate that the resulting method offers substantial improvements in accuracy and that its performance is competitive with an implementation of the fast multipole method in general and markedly better for Hamiltonian formulations of molecular dynamics. The improvement is great enough to establish multilevel summation as a serious contender for calculating pairwise interactions in molecular dynamics simulations. In particular, the method appears to be uniquely capable for molecular dynamics in two situations, nonperiodic boundary conditions and massively parallel computation, where the fast Fourier transform employed in the particle-mesh Ewald method falls short.

Internal Coordinate Molecular Dynamics: A Foundation for Multiscale Dynamics

PubMed Central

2015-01-01

Internal coordinates such as bond lengths, bond angles, and torsion angles (BAT) are natural coordinates for describing a bonded molecular system. However, the molecular dynamics (MD) simulation methods that are widely used for proteins, DNA, and polymers are based on Cartesian coordinates owing to the mathematical simplicity of the equations of motion. However, constraints are often needed with Cartesian MD simulations to enhance the conformational sampling. This makes the equations of motion in the Cartesian coordinates differential-algebraic, which adversely impacts the complexity and the robustness of the simulations. On the other hand, constraints can be easily placed in BAT coordinates by removing the degrees of freedom that need to be constrained. Thus, the internal coordinate MD (ICMD) offers an attractive alternative to Cartesian coordinate MD for developing multiscale MD method. The torsional MD method is a special adaptation of the ICMD method, where all the bond lengths and bond angles are kept rigid. The advantages of ICMD simulation methods are the longer time step size afforded by freezing high frequency degrees of freedom and performing a conformational search in the more important low frequency torsional degrees of freedom. However, the advancements in the ICMD simulations have been slow and stifled by long-standing mathematical bottlenecks. In this review, we summarize the recent mathematical advancements we have made based on spatial operator algebra, in developing a robust long time scale ICMD simulation toolkit useful for various applications. We also present the applications of ICMD simulations to study conformational changes in proteins and protein structure refinement. We review the advantages of the ICMD simulations over the Cartesian simulations when used with enhanced sampling methods and project the future use of ICMD simulations in protein dynamics. PMID:25517406

Molecular dynamics coupled with a virtual system for effective conformational sampling.

PubMed

Hayami, Tomonori; Kasahara, Kota; Nakamura, Haruki; Higo, Junichi

2018-07-15

An enhanced conformational sampling method is proposed: virtual-system coupled canonical molecular dynamics (VcMD). Although VcMD enhances sampling along a reaction coordinate, this method is free from estimation of a canonical distribution function along the reaction coordinate. This method introduces a virtual system that does not necessarily obey a physical law. To enhance sampling the virtual system couples with a molecular system to be studied. Resultant snapshots produce a canonical ensemble. This method was applied to a system consisting of two short peptides in an explicit solvent. Conventional molecular dynamics simulation, which is ten times longer than VcMD, was performed along with adaptive umbrella sampling. Free-energy landscapes computed from the three simulations mutually converged well. The VcMD provided quicker association/dissociation motions of peptides than the conventional molecular dynamics did. The VcMD method is applicable to various complicated systems because of its methodological simplicity. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Molecular-level Simulations of Shock Generation and Propagation in Polyurea

DTIC Science & Technology

2011-01-26

homepage: www.e lsev ier .com/ locate /msea Molecular-level simulations of shock generation and propagation in polyurea M. Grujicica,∗, B. Pandurangana... Polyurea Shock-wave generation and propagation Molecular-level calculations a b s t r a c t A non-equilibrium molecular dynamics method is employed in order...to study various phenomena accompanying the generation and propagation of shock waves in polyurea (a micro-phase segregated elastomer). Several

Evaluation of Kirkwood-Buff integrals via finite size scaling: a large scale molecular dynamics study

NASA Astrophysics Data System (ADS)

Dednam, W.; Botha, A. E.

2015-01-01

Solvation of bio-molecules in water is severely affected by the presence of co-solvent within the hydration shell of the solute structure. Furthermore, since solute molecules can range from small molecules, such as methane, to very large protein structures, it is imperative to understand the detailed structure-function relationship on the microscopic level. For example, it is useful know the conformational transitions that occur in protein structures. Although such an understanding can be obtained through large-scale molecular dynamic simulations, it is often the case that such simulations would require excessively large simulation times. In this context, Kirkwood-Buff theory, which connects the microscopic pair-wise molecular distributions to global thermodynamic properties, together with the recently developed technique, called finite size scaling, may provide a better method to reduce system sizes, and hence also the computational times. In this paper, we present molecular dynamics trial simulations of biologically relevant low-concentration solvents, solvated by aqueous co-solvent solutions. In particular we compare two different methods of calculating the relevant Kirkwood-Buff integrals. The first (traditional) method computes running integrals over the radial distribution functions, which must be obtained from large system-size NVT or NpT simulations. The second, newer method, employs finite size scaling to obtain the Kirkwood-Buff integrals directly by counting the particle number fluctuations in small, open sub-volumes embedded within a larger reservoir that can be well approximated by a much smaller simulation cell. In agreement with previous studies, which made a similar comparison for aqueous co-solvent solutions, without the additional solvent, we conclude that the finite size scaling method is also applicable to the present case, since it can produce computationally more efficient results which are equivalent to the more costly radial distribution function method.

III-Nitride, SiC and Diamond Materials for Electronic Devices. Symposium Held April 8-12 1996, San Francisco, California, U.S.A. Volume 423.

DTIC Science & Technology

1996-12-01

gallium, nitrogen and gallium nitride structures. Thus it can be shown to be transferable and efficient for predictive molecular -dynamic simulations on...potentials and forces for the molecular dynamics simulations are derived by means of a density-functional based nonorthogonal tight-binding (DF-TB) scheme...LDA). Molecular -dynamics simulations for determining the different reconstructions of the SiC surface use the slab method (two-dimensional periodic

Quantum ring-polymer contraction method: Including nuclear quantum effects at no additional computational cost in comparison to ab initio molecular dynamics

NASA Astrophysics Data System (ADS)

John, Christopher; Spura, Thomas; Habershon, Scott; Kühne, Thomas D.

2016-04-01

We present a simple and accurate computational method which facilitates ab initio path-integral molecular dynamics simulations, where the quantum-mechanical nature of the nuclei is explicitly taken into account, at essentially no additional computational cost in comparison to the corresponding calculation using classical nuclei. The predictive power of the proposed quantum ring-polymer contraction method is demonstrated by computing various static and dynamic properties of liquid water at ambient conditions using density functional theory. This development will enable routine inclusion of nuclear quantum effects in ab initio molecular dynamics simulations of condensed-phase systems.

Implementing a modeling software for animated protein-complex interactions using a physics simulation library.

PubMed

Ueno, Yutaka; Ito, Shuntaro; Konagaya, Akihiko

2014-12-01

To better understand the behaviors and structural dynamics of proteins within a cell, novel software tools are being developed that can create molecular animations based on the findings of structural biology. This study proposes our method developed based on our prototypes to detect collisions and examine the soft-body dynamics of molecular models. The code was implemented with a software development toolkit for rigid-body dynamics simulation and a three-dimensional graphics library. The essential functions of the target software system included the basic molecular modeling environment, collision detection in the molecular models, and physical simulations of the movement of the model. Taking advantage of recent software technologies such as physics simulation modules and interpreted scripting language, the functions required for accurate and meaningful molecular animation were implemented efficiently.

Assessment of Molecular Modeling & Simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 materialsmore » 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.« less

Extending rule-based methods to model molecular geometry and 3D model resolution.

PubMed

Hoard, Brittany; Jacobson, Bruna; Manavi, Kasra; Tapia, Lydia

2016-08-01

Computational modeling is an important tool for the study of complex biochemical processes associated with cell signaling networks. However, it is challenging to simulate processes that involve hundreds of large molecules due to the high computational cost of such simulations. Rule-based modeling is a method that can be used to simulate these processes with reasonably low computational cost, but traditional rule-based modeling approaches do not include details of molecular geometry. The incorporation of geometry into biochemical models can more accurately capture details of these processes, and may lead to insights into how geometry affects the products that form. Furthermore, geometric rule-based modeling can be used to complement other computational methods that explicitly represent molecular geometry in order to quantify binding site accessibility and steric effects. We propose a novel implementation of rule-based modeling that encodes details of molecular geometry into the rules and binding rates. We demonstrate how rules are constructed according to the molecular curvature. We then perform a study of antigen-antibody aggregation using our proposed method. We simulate the binding of antibody complexes to binding regions of the shrimp allergen Pen a 1 using a previously developed 3D rigid-body Monte Carlo simulation, and we analyze the aggregate sizes. Then, using our novel approach, we optimize a rule-based model according to the geometry of the Pen a 1 molecule and the data from the Monte Carlo simulation. We use the distances between the binding regions of Pen a 1 to optimize the rules and binding rates. We perform this procedure for multiple conformations of Pen a 1 and analyze the impact of conformation and resolution on the optimal rule-based model. We find that the optimized rule-based models provide information about the average steric hindrance between binding regions and the probability that antibodies will bind to these regions. These optimized models quantify the variation in aggregate size that results from differences in molecular geometry and from model resolution.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sotomayor, Marcos

Hair cell mechanotransduction happens in tens of microseconds, involves forces of a few picoNewtons, and is mediated by nanometer-scale molecular conformational changes. As proteins involved in this process become identified and their high resolution structures become available, multiple tools are being used to explore their “single-molecule responses” to force. Optical tweezers and atomic force microscopy offer exquisite force and extension resolution, but cannot reach the high loading rates expected for high frequency auditory stimuli. Molecular dynamics (MD) simulations can reach these fast time scales, and also provide a unique view of the molecular events underlying protein mechanics, but its predictionsmore » must be experimentally verified. Thus a combination of simulations and experiments might be appropriate to study the molecular mechanics of hearing. Here I review the basics of MD simulations and the different methods used to apply force and study protein mechanics in silico. Simulations of tip link proteins are used to illustrate the advantages and limitations of this method.« less

Next Generation Extended Lagrangian Quantum-based Molecular Dynamics

NASA Astrophysics Data System (ADS)

Negre, Christian

2017-06-01

A new framework for extended Lagrangian first-principles molecular dynamics simulations is presented, which overcomes shortcomings of regular, direct Born-Oppenheimer molecular dynamics, while maintaining important advantages of the unified extended Lagrangian formulation of density functional theory pioneered by Car and Parrinello three decades ago. The new framework allows, for the first time, energy conserving, linear-scaling Born-Oppenheimer molecular dynamics simulations, which is necessary to study larger and more realistic systems over longer simulation times than previously possible. Expensive, self-consinstent-field optimizations are avoided and normal integration time steps of regular, direct Born-Oppenheimer molecular dynamics can be used. Linear scaling electronic structure theory is presented using a graph-based approach that is ideal for parallel calculations on hybrid computer platforms. For the first time, quantum based Born-Oppenheimer molecular dynamics simulation is becoming a practically feasible approach in simulations of +100,000 atoms-representing a competitive alternative to classical polarizable force field methods. In collaboration with: Anders Niklasson, Los Alamos National Laboratory.

Multilevel summation with B-spline interpolation for pairwise interactions in molecular dynamics simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hardy, David J., E-mail: dhardy@illinois.edu; Schulten, Klaus; Wolff, Matthew A.

2016-03-21

The multilevel summation method for calculating electrostatic interactions in molecular dynamics simulations constructs an approximation to a pairwise interaction kernel and its gradient, which can be evaluated at a cost that scales linearly with the number of atoms. The method smoothly splits the kernel into a sum of partial kernels of increasing range and decreasing variability with the longer-range parts interpolated from grids of increasing coarseness. Multilevel summation is especially appropriate in the context of dynamics and minimization, because it can produce continuous gradients. This article explores the use of B-splines to increase the accuracy of the multilevel summation methodmore » (for nonperiodic boundaries) without incurring additional computation other than a preprocessing step (whose cost also scales linearly). To obtain accurate results efficiently involves technical difficulties, which are overcome by a novel preprocessing algorithm. Numerical experiments demonstrate that the resulting method offers substantial improvements in accuracy and that its performance is competitive with an implementation of the fast multipole method in general and markedly better for Hamiltonian formulations of molecular dynamics. The improvement is great enough to establish multilevel summation as a serious contender for calculating pairwise interactions in molecular dynamics simulations. In particular, the method appears to be uniquely capable for molecular dynamics in two situations, nonperiodic boundary conditions and massively parallel computation, where the fast Fourier transform employed in the particle–mesh Ewald method falls short.« less

Parallel Fast Multipole Method For Molecular Dynamics

DTIC Science & Technology

2007-06-01

Parallel Fast Multipole Method For Molecular Dynamics THESIS Reid G. Ormseth, Captain, USAF AFIT/GAP/ENP/07-J02 DEPARTMENT OF THE AIR FORCE AIR...the United States Government. AFIT/GAP/ENP/07-J02 Parallel Fast Multipole Method For Molecular Dynamics THESIS Presented to the Faculty Department of...has also been provided by ‘The Art of Molecular Dynamics Simulation ’ by Dennis Rapaport. This work is the clearest treatment of the Fast Multipole

Thermophysical Properties of Undercooled Alloys: An Overview of the Molecular Simulation Approaches

PubMed Central

Lv, Yong J.; Chen, Min

2011-01-01

We review the studies on the thermophysical properties of undercooled metals and alloys by molecular simulations in recent years. The simulation methods of melting temperature, enthalpy, specific heat, surface tension, diffusion coefficient and viscosity are introduced and the simulated results are summarized. By comparing the experimental results and various theoretical models, the temperature and the composition dependences of the thermophysical properties in undercooled regime are discussed. PMID:21339987

Thermodynamic properties for applications in chemical industry via classical force fields.

PubMed

Guevara-Carrion, Gabriela; Hasse, Hans; Vrabec, Jadran

2012-01-01

Thermodynamic properties of fluids are of key importance for the chemical industry. Presently, the fluid property models used in process design and optimization are mostly equations of state or G (E) models, which are parameterized using experimental data. Molecular modeling and simulation based on classical force fields is a promising alternative route, which in many cases reasonably complements the well established methods. This chapter gives an introduction to the state-of-the-art in this field regarding molecular models, simulation methods, and tools. Attention is given to the way modeling and simulation on the scale of molecular force fields interact with other scales, which is mainly by parameter inheritance. Parameters for molecular force fields are determined both bottom-up from quantum chemistry and top-down from experimental data. Commonly used functional forms for describing the intra- and intermolecular interactions are presented. Several approaches for ab initio to empirical force field parameterization are discussed. Some transferable force field families, which are frequently used in chemical engineering applications, are described. Furthermore, some examples of force fields that were parameterized for specific molecules are given. Molecular dynamics and Monte Carlo methods for the calculation of transport properties and vapor-liquid equilibria are introduced. Two case studies are presented. First, using liquid ammonia as an example, the capabilities of semi-empirical force fields, parameterized on the basis of quantum chemical information and experimental data, are discussed with respect to thermodynamic properties that are relevant for the chemical industry. Second, the ability of molecular simulation methods to describe accurately vapor-liquid equilibrium properties of binary mixtures containing CO(2) is shown.

Modeling and enhanced sampling of molecular systems with smooth and nonlinear data-driven collective variables

NASA Astrophysics Data System (ADS)

Hashemian, Behrooz; Millán, Daniel; Arroyo, Marino

2013-12-01

Collective variables (CVs) are low-dimensional representations of the state of a complex system, which help us rationalize molecular conformations and sample free energy landscapes with molecular dynamics simulations. Given their importance, there is need for systematic methods that effectively identify CVs for complex systems. In recent years, nonlinear manifold learning has shown its ability to automatically characterize molecular collective behavior. Unfortunately, these methods fail to provide a differentiable function mapping high-dimensional configurations to their low-dimensional representation, as required in enhanced sampling methods. We introduce a methodology that, starting from an ensemble representative of molecular flexibility, builds smooth and nonlinear data-driven collective variables (SandCV) from the output of nonlinear manifold learning algorithms. We demonstrate the method with a standard benchmark molecule, alanine dipeptide, and show how it can be non-intrusively combined with off-the-shelf enhanced sampling methods, here the adaptive biasing force method. We illustrate how enhanced sampling simulations with SandCV can explore regions that were poorly sampled in the original molecular ensemble. We further explore the transferability of SandCV from a simpler system, alanine dipeptide in vacuum, to a more complex system, alanine dipeptide in explicit water.

Modeling and enhanced sampling of molecular systems with smooth and nonlinear data-driven collective variables.

PubMed

Hashemian, Behrooz; Millán, Daniel; Arroyo, Marino

2013-12-07

Collective variables (CVs) are low-dimensional representations of the state of a complex system, which help us rationalize molecular conformations and sample free energy landscapes with molecular dynamics simulations. Given their importance, there is need for systematic methods that effectively identify CVs for complex systems. In recent years, nonlinear manifold learning has shown its ability to automatically characterize molecular collective behavior. Unfortunately, these methods fail to provide a differentiable function mapping high-dimensional configurations to their low-dimensional representation, as required in enhanced sampling methods. We introduce a methodology that, starting from an ensemble representative of molecular flexibility, builds smooth and nonlinear data-driven collective variables (SandCV) from the output of nonlinear manifold learning algorithms. We demonstrate the method with a standard benchmark molecule, alanine dipeptide, and show how it can be non-intrusively combined with off-the-shelf enhanced sampling methods, here the adaptive biasing force method. We illustrate how enhanced sampling simulations with SandCV can explore regions that were poorly sampled in the original molecular ensemble. We further explore the transferability of SandCV from a simpler system, alanine dipeptide in vacuum, to a more complex system, alanine dipeptide in explicit water.

Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design.

PubMed

Cole, Daniel J; Tirado-Rives, Julian; Jorgensen, William L

2015-05-01

Non-nucleoside inhibitors of HIV reverse transcriptase are an important component of treatment against HIV infection. Novel inhibitors are sought that increase potency against variants that contain the Tyr181Cys mutation. Molecular dynamics based free energy perturbation simulations have been run to study factors that contribute to protein-ligand binding, and the results are compared with those from previous Monte Carlo based simulations and activity data. Predictions of protein-ligand binding modes are very consistent for the two simulation methods; the accord is attributed to the use of an enhanced sampling protocol. The Tyr181Cys binding pocket supports large, hydrophobic substituents, which is in good agreement with experiment. Although some discrepancies exist between the results of the two simulation methods and experiment, free energy perturbation simulations can be used to rapidly test small molecules for gains in binding affinity. Free energy perturbation methods show promise in providing fast, reliable and accurate data that can be used to complement experiment in lead optimization projects. This article is part of a Special Issue entitled "Recent developments of molecular dynamics". Copyright © 2014 Elsevier B.V. All rights reserved.

VAMPnets for deep learning of molecular kinetics.

PubMed

Mardt, Andreas; Pasquali, Luca; Wu, Hao; Noé, Frank

2018-01-02

There is an increasing demand for computing the relevant structures, equilibria, and long-timescale kinetics of biomolecular processes, such as protein-drug binding, from high-throughput molecular dynamics simulations. Current methods employ transformation of simulated coordinates into structural features, dimension reduction, clustering the dimension-reduced data, and estimation of a Markov state model or related model of the interconversion rates between molecular structures. This handcrafted approach demands a substantial amount of modeling expertise, as poor decisions at any step will lead to large modeling errors. Here we employ the variational approach for Markov processes (VAMP) to develop a deep learning framework for molecular kinetics using neural networks, dubbed VAMPnets. A VAMPnet encodes the entire mapping from molecular coordinates to Markov states, thus combining the whole data processing pipeline in a single end-to-end framework. Our method performs equally or better than state-of-the-art Markov modeling methods and provides easily interpretable few-state kinetic models.

Uncovering molecular processes in crystal nucleation and growth by using molecular simulation.

PubMed

Anwar, Jamshed; Zahn, Dirk

2011-02-25

Exploring nucleation processes by molecular simulation provides a mechanistic understanding at the atomic level and also enables kinetic and thermodynamic quantities to be estimated. However, whilst the potential for modeling crystal nucleation and growth processes is immense, there are specific technical challenges to modeling. In general, rare events, such as nucleation cannot be simulated using a direct "brute force" molecular dynamics approach. The limited time and length scales that are accessible by conventional molecular dynamics simulations have inspired a number of advances to tackle problems that were considered outside the scope of molecular simulation. While general insights and features could be explored from efficient generic models, new methods paved the way to realistic crystal nucleation scenarios. The association of single ions in solvent environments, the mechanisms of motif formation, ripening reactions, and the self-organization of nanocrystals can now be investigated at the molecular level. The analysis of interactions with growth-controlling additives gives a new understanding of functionalized nanocrystals and the precipitation of composite materials. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced Molecular Dynamics Methods Applied to Drug Design Projects.

PubMed

Ziada, Sonia; Braka, Abdennour; Diharce, Julien; Aci-Sèche, Samia; Bonnet, Pascal

2018-01-01

Nobel Laureate Richard P. Feynman stated: "[…] everything that living things do can be understood in terms of jiggling and wiggling of atoms […]." The importance of computer simulations of macromolecules, which use classical mechanics principles to describe atom behavior, is widely acknowledged and nowadays, they are applied in many fields such as material sciences and drug discovery. With the increase of computing power, molecular dynamics simulations can be applied to understand biological mechanisms at realistic timescales. In this chapter, we share our computational experience providing a global view of two of the widely used enhanced molecular dynamics methods to study protein structure and dynamics through the description of their characteristics, limits and we provide some examples of their applications in drug design. We also discuss the appropriate choice of software and hardware. In a detailed practical procedure, we describe how to set up, run, and analyze two main molecular dynamics methods, the umbrella sampling (US) and the accelerated molecular dynamics (aMD) methods.

Internal force corrections with machine learning for quantum mechanics/molecular mechanics simulations.

PubMed

Wu, Jingheng; Shen, Lin; Yang, Weitao

2017-10-28

Ab initio quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulation is a useful tool to calculate thermodynamic properties such as potential of mean force for chemical reactions but intensely time consuming. In this paper, we developed a new method using the internal force correction for low-level semiempirical QM/MM molecular dynamics samplings with a predefined reaction coordinate. As a correction term, the internal force was predicted with a machine learning scheme, which provides a sophisticated force field, and added to the atomic forces on the reaction coordinate related atoms at each integration step. We applied this method to two reactions in aqueous solution and reproduced potentials of mean force at the ab initio QM/MM level. The saving in computational cost is about 2 orders of magnitude. The present work reveals great potentials for machine learning in QM/MM simulations to study complex chemical processes.

Simulation of weak polyelectrolytes: a comparison between the constant pH and the reaction ensemble method

NASA Astrophysics Data System (ADS)

Landsgesell, Jonas; Holm, Christian; Smiatek, Jens

2017-03-01

The reaction ensemble and the constant pH method are well-known chemical equilibrium approaches to simulate protonation and deprotonation reactions in classical molecular dynamics and Monte Carlo simulations. In this article, we demonstrate the similarity between both methods under certain conditions. We perform molecular dynamics simulations of a weak polyelectrolyte in order to compare the titration curves obtained by both approaches. Our findings reveal a good agreement between the methods when the reaction ensemble is used to sweep the reaction constant. Pronounced differences between the reaction ensemble and the constant pH method can be observed for stronger acids and bases in terms of adaptive pH values. These deviations are due to the presence of explicit protons in the reaction ensemble method which induce a screening of electrostatic interactions between the charged titrable groups of the polyelectrolyte. The outcomes of our simulation hint to a better applicability of the reaction ensemble method for systems in confined geometries and titrable groups in polyelectrolytes with different pKa values.

Discrimination between native and intentionally misfolded conformations of proteins: ES/IS, a new method for calculating conformational free energy that uses both dynamics simulations with an explicit solvent and an implicit solvent continuum model.

PubMed

Vorobjev, Y N; Almagro, J C; Hermans, J

1998-09-01

A new method for calculating the total conformational free energy of proteins in water solvent is presented. The method consists of a relatively brief simulation by molecular dynamics with explicit solvent (ES) molecules to produce a set of microstates of the macroscopic conformation. Conformational energy and entropy are obtained from the simulation, the latter in the quasi-harmonic approximation by analysis of the covariance matrix. The implicit solvent (IS) dielectric continuum model is used to calculate the average solvation free energy as the sum of the free energies of creating the solute-size hydrophobic cavity, of the van der Waals solute-solvent interactions, and of the polarization of water solvent by the solute's charges. The reliability of the solvation free energy depends on a number of factors: the details of arrangement of the protein's charges, especially those near the surface; the definition of the molecular surface; and the method chosen for solving the Poisson equation. Molecular dynamics simulation in explicit solvent relaxes the protein's conformation and allows polar surface groups to assume conformations compatible with interaction with solvent, while averaging of internal energy and solvation free energy tend to enhance the precision. Two recently developed methods--SIMS, for calculation of a smooth invariant molecular surface, and FAMBE, for solution of the Poisson equation via a fast adaptive multigrid boundary element--have been employed. The SIMS and FAMBE programs scale linearly with the number of atoms. SIMS is superior to Connolly's MS (molecular surface) program: it is faster, more accurate, and more stable, and it smooths singularities of the molecular surface. Solvation free energies calculated with these two programs do not depend on molecular position or orientation and are stable along a molecular dynamics trajectory. We have applied this method to calculate the conformational free energy of native and intentionally misfolded globular conformations of proteins (the EMBL set of deliberately misfolded proteins) and have obtained good discrimination in favor of the native conformations in all instances.

Molecular Optical Simulation Environment (MOSE): A Platform for the Simulation of Light Propagation in Turbid Media

PubMed Central

Ren, Shenghan; Chen, Xueli; Wang, Hailong; Qu, Xiaochao; Wang, Ge; Liang, Jimin; Tian, Jie

2013-01-01

The study of light propagation in turbid media has attracted extensive attention in the field of biomedical optical molecular imaging. In this paper, we present a software platform for the simulation of light propagation in turbid media named the “Molecular Optical Simulation Environment (MOSE)”. Based on the gold standard of the Monte Carlo method, MOSE simulates light propagation both in tissues with complicated structures and through free-space. In particular, MOSE synthesizes realistic data for bioluminescence tomography (BLT), fluorescence molecular tomography (FMT), and diffuse optical tomography (DOT). The user-friendly interface and powerful visualization tools facilitate data analysis and system evaluation. As a major measure for resource sharing and reproducible research, MOSE aims to provide freeware for research and educational institutions, which can be downloaded at http://www.mosetm.net. PMID:23577215

A molecular fragment cheminformatics roadmap for mesoscopic simulation.

PubMed

Truszkowski, Andreas; Daniel, Mirco; Kuhn, Hubert; Neumann, Stefan; Steinbeck, Christoph; Zielesny, Achim; Epple, Matthias

2014-12-01

Mesoscopic simulation studies the structure, dynamics and properties of large molecular ensembles with millions of atoms: Its basic interacting units (beads) are no longer the nuclei and electrons of quantum chemical ab-initio calculations or the atom types of molecular mechanics but molecular fragments, molecules or even larger molecular entities. For its simulation setup and output a mesoscopic simulation kernel software uses abstract matrix (array) representations for bead topology and connectivity. Therefore a pure kernel-based mesoscopic simulation task is a tedious, time-consuming and error-prone venture that limits its practical use and application. A consequent cheminformatics approach tackles these problems and provides solutions for a considerably enhanced accessibility. This study aims at outlining a complete cheminformatics roadmap that frames a mesoscopic Molecular Fragment Dynamics (MFD) simulation kernel to allow its efficient use and practical application. The molecular fragment cheminformatics roadmap consists of four consecutive building blocks: An adequate fragment structure representation (1), defined operations on these fragment structures (2), the description of compartments with defined compositions and structural alignments (3), and the graphical setup and analysis of a whole simulation box (4). The basis of the cheminformatics approach (i.e. building block 1) is a SMILES-like line notation (denoted f SMILES) with connected molecular fragments to represent a molecular structure. The f SMILES notation and the following concepts and methods for building blocks 2-4 are outlined with examples and practical usage scenarios. It is shown that the requirements of the roadmap may be partly covered by already existing open-source cheminformatics software. Mesoscopic simulation techniques like MFD may be considerably alleviated and broadened for practical use with a consequent cheminformatics layer that successfully tackles its setup subtleties and conceptual usage hurdles. Molecular Fragment Cheminformatics may be regarded as a crucial accelerator to propagate MFD and similar mesoscopic simulation techniques in the molecular sciences. Graphical abstractA molecular fragment cheminformatics roadmap for mesoscopic simulation.

Electric potential calculation in molecular simulation of electric double layer capacitors

NASA Astrophysics Data System (ADS)

Wang, Zhenxing; Olmsted, David L.; Asta, Mark; Laird, Brian B.

2016-11-01

For the molecular simulation of electric double layer capacitors (EDLCs), a number of methods have been proposed and implemented to determine the one-dimensional electric potential profile between the two electrodes at a fixed potential difference. In this work, we compare several of these methods for a model LiClO4-acetonitrile/graphite EDLC simulated using both the traditional fixed-charged method (FCM), in which a fixed charge is assigned a priori to the electrode atoms, or the recently developed constant potential method (CPM) (2007 J. Chem. Phys. 126 084704), where the electrode charges are allowed to fluctuate to keep the potential fixed. Based on an analysis of the full three-dimensional electric potential field, we suggest a method for determining the averaged one-dimensional electric potential profile that can be applied to both the FCM and CPM simulations. Compared to traditional methods based on numerically solving the one-dimensional Poisson’s equation, this method yields better accuracy and no supplemental assumptions.

Molecular dynamics simulations and applications in computational toxicology and nanotoxicology.

PubMed

Selvaraj, Chandrabose; Sakkiah, Sugunadevi; Tong, Weida; Hong, Huixiao

2018-02-01

Nanotoxicology studies toxicity of nanomaterials and has been widely applied in biomedical researches to explore toxicity of various biological systems. Investigating biological systems through in vivo and in vitro methods is expensive and time taking. Therefore, computational toxicology, a multi-discipline field that utilizes computational power and algorithms to examine toxicology of biological systems, has gained attractions to scientists. Molecular dynamics (MD) simulations of biomolecules such as proteins and DNA are popular for understanding of interactions between biological systems and chemicals in computational toxicology. In this paper, we review MD simulation methods, protocol for running MD simulations and their applications in studies of toxicity and nanotechnology. We also briefly summarize some popular software tools for execution of MD simulations. Published by Elsevier Ltd.

Melt-growth dynamics in CdTe crystals

DOE PAGES

Zhou, X. W.; Ward, D. K.; Wong, B. M.; ...

2012-06-01

We use a new, quantum-mechanics-based bond-order potential (BOP) to reveal melt growth dynamics and fine scale defect formation mechanisms in CdTe crystals. Previous molecular dynamics simulations of semiconductors have shown qualitatively incorrect behavior due to the lack of an interatomic potential capable of predicting both crystalline growth and property trends of many transitional structures encountered during the melt → crystal transformation. Here, we demonstrate successful molecular dynamics simulations of melt growth in CdTe using a BOP that significantly improves over other potentials on property trends of different phases. Our simulations result in a detailed understanding of defect formation during themore » melt growth process. Equally important, we show that the new BOP enables defect formation mechanisms to be studied at a scale level comparable to empirical molecular dynamics simulation methods with a fidelity level approaching quantum-mechanical methods.« less

First-principles simulations of heat transport

NASA Astrophysics Data System (ADS)

Puligheddu, Marcello; Gygi, Francois; Galli, Giulia

2017-11-01

Advances in understanding heat transport in solids were recently reported by both experiment and theory. However an efficient and predictive quantum simulation framework to investigate thermal properties of solids, with the same complexity as classical simulations, has not yet been developed. Here we present a method to compute the thermal conductivity of solids by performing ab initio molecular dynamics at close to equilibrium conditions, which only requires calculations of first-principles trajectories and atomic forces, thus avoiding direct computation of heat currents and energy densities. In addition the method requires much shorter sequential simulation times than ordinary molecular dynamics techniques, making it applicable within density functional theory. We discuss results for a representative oxide, MgO, at different temperatures and for ordered and nanostructured morphologies, showing the performance of the method in different conditions.

Towards the simulation of molecular collisions with a superconducting quantum computer

NASA Astrophysics Data System (ADS)

Geller, Michael

2013-05-01

I will discuss the prospects for the use of large-scale, error-corrected quantum computers to simulate complex quantum dynamics such as molecular collisions. This will likely require millions qubits. I will also discuss an alternative approach [M. R. Geller et al., arXiv:1210.5260] that is ideally suited for today's superconducting circuits, which uses the single-excitation subspace (SES) of a system of n tunably coupled qubits. The SES method allows many operations in the unitary group SU(n) to be implemented in a single step, bypassing the need for elementary gates, thereby making large computations possible without error correction. The method enables universal quantum simulation, including simulation of the time-dependent Schrodinger equation, and we argue that a 1000-qubit SES processor should be capable of achieving quantum speedup relative to a petaflop supercomputer. We speculate on the utility and practicality of such a simulator for atomic and molecular collision physics. Work supported by the US National Science Foundation CDI program.

Path integral molecular dynamic simulation of flexible molecular systems in their ground state: Application to the water dimer

NASA Astrophysics Data System (ADS)

Schmidt, Matthew; Roy, Pierre-Nicholas

2018-03-01

We extend the Langevin equation Path Integral Ground State (LePIGS), a ground state quantum molecular dynamics method, to simulate flexible molecular systems and calculate both energetic and structural properties. We test the approach with the H2O and D2O monomers and dimers. We systematically optimize all simulation parameters and use a unity trial wavefunction. We report ground state energies, dissociation energies, and structural properties using three different water models, two of which are empirically based, q-TIP4P/F and q-SPC/Fw, and one which is ab initio, MB-pol. We demonstrate that our energies calculated from LePIGS can be merged seamlessly with low temperature path integral molecular dynamics calculations and note the similarities between the two methods. We also benchmark our energies against previous diffusion Monte Carlo calculations using the same potentials and compare to experimental results. We further demonstrate that accurate vibrational energies of the H2O and D2O monomer can be calculated from imaginary time correlation functions generated from the LePIGS simulations using solely the unity trial wavefunction.

GneimoSim: A Modular Internal Coordinates Molecular Dynamics Simulation Package

PubMed Central

Larsen, Adrien B.; Wagner, Jeffrey R.; Kandel, Saugat; Salomon-Ferrer, Romelia; Vaidehi, Nagarajan; Jain, Abhinandan

2014-01-01

The Generalized Newton Euler Inverse Mass Operator (GNEIMO) method is an advanced method for internal coordinates molecular dynamics (ICMD). GNEIMO includes several theoretical and algorithmic advancements that address longstanding challenges with ICMD simulations. In this paper we describe the GneimoSim ICMD software package that implements the GNEIMO method. We believe that GneimoSim is the first software package to include advanced features such as the equipartition principle derived for internal coordinates, and a method for including the Fixman potential to eliminate systematic statistical biases introduced by the use of hard constraints. Moreover, by design, GneimoSim is extensible and can be easily interfaced with third party force field packages for ICMD simulations. Currently, GneimoSim includes interfaces to LAMMPS, OpenMM, Rosetta force field calculation packages. The availability of a comprehensive Python interface to the underlying C++ classes and their methods provides a powerful and versatile mechanism for users to develop simulation scripts to configure the simulation and control the simulation flow. GneimoSim has been used extensively for studying the dynamics of protein structures, refinement of protein homology models, and for simulating large scale protein conformational changes with enhanced sampling methods. GneimoSim is not limited to proteins and can also be used for the simulation of polymeric materials. PMID:25263538

GneimoSim: a modular internal coordinates molecular dynamics simulation package.

PubMed

Larsen, Adrien B; Wagner, Jeffrey R; Kandel, Saugat; Salomon-Ferrer, Romelia; Vaidehi, Nagarajan; Jain, Abhinandan

2014-12-05

The generalized Newton-Euler inverse mass operator (GNEIMO) method is an advanced method for internal coordinates molecular dynamics (ICMD). GNEIMO includes several theoretical and algorithmic advancements that address longstanding challenges with ICMD simulations. In this article, we describe the GneimoSim ICMD software package that implements the GNEIMO method. We believe that GneimoSim is the first software package to include advanced features such as the equipartition principle derived for internal coordinates, and a method for including the Fixman potential to eliminate systematic statistical biases introduced by the use of hard constraints. Moreover, by design, GneimoSim is extensible and can be easily interfaced with third party force field packages for ICMD simulations. Currently, GneimoSim includes interfaces to LAMMPS, OpenMM, and Rosetta force field calculation packages. The availability of a comprehensive Python interface to the underlying C++ classes and their methods provides a powerful and versatile mechanism for users to develop simulation scripts to configure the simulation and control the simulation flow. GneimoSim has been used extensively for studying the dynamics of protein structures, refinement of protein homology models, and for simulating large scale protein conformational changes with enhanced sampling methods. GneimoSim is not limited to proteins and can also be used for the simulation of polymeric materials. © 2014 Wiley Periodicals, Inc.

Development and application of ab initio QM/MM methods for mechanistic simulation of reactions in solution and in enzymes

PubMed Central

Hu, Hao; Yang, Weitao

2013-01-01

Determining the free energies and mechanisms of chemical reactions in solution and enzymes is a major challenge. For such complex reaction processes, combined quantum mechanics/molecular mechanics (QM/MM) method is the most effective simulation method to provide an accurate and efficient theoretical description of the molecular system. The computational costs of ab initio QM methods, however, have limited the application of ab initio QM/MM methods. Recent advances in ab initio QM/MM methods allowed the accurate simulation of the free energies for reactions in solution and in enzymes and thus paved the way for broader application of the ab initio QM/MM methods. We review here the theoretical developments and applications of the ab initio QM/MM methods, focusing on the determination of reaction path and the free energies of the reaction processes in solution and enzymes. PMID:24146439

Molecular dynamics simulation of highly charged proteins: Comparison of the particle-particle particle-mesh and reaction field methods for the calculation of electrostatic interactions

PubMed Central

Gargallo, Raimundo; Hünenberger, Philippe H.; Avilés, Francesc X.; Oliva, Baldomero

2003-01-01

Molecular dynamics (MD) simulations of the activation domain of porcine procarboxypeptidase B (ADBp) were performed to examine the effect of using the particle-particle particle-mesh (P3M) or the reaction field (RF) method for calculating electrostatic interactions in simulations of highly charged proteins. Several structural, thermodynamic, and dynamic observables were derived from the MD trajectories, including estimated entropies and solvation free energies and essential dynamics (ED). The P3M method leads to slightly higher atomic positional fluctuations and deviations from the crystallographic structure, along with somewhat lower values of the total energy and solvation free energy. However, the ED analysis of the system leads to nearly identical results for both simulations. Because of the strong similarity between the results, both methods appear well suited for the simulation of highly charged globular proteins in explicit solvent. However, the lower computational demand of the RF method in the present implementation represents a clear advantage over the P3M method. PMID:14500874

Comparison of mode estimation methods and application in molecular clock analysis

NASA Technical Reports Server (NTRS)

Hedges, S. Blair; Shah, Prachi

2003-01-01

BACKGROUND: Distributions of time estimates in molecular clock studies are sometimes skewed or contain outliers. In those cases, the mode is a better estimator of the overall time of divergence than the mean or median. However, different methods are available for estimating the mode. We compared these methods in simulations to determine their strengths and weaknesses and further assessed their performance when applied to real data sets from a molecular clock study. RESULTS: We found that the half-range mode and robust parametric mode methods have a lower bias than other mode methods under a diversity of conditions. However, the half-range mode suffers from a relatively high variance and the robust parametric mode is more susceptible to bias by outliers. We determined that bootstrapping reduces the variance of both mode estimators. Application of the different methods to real data sets yielded results that were concordant with the simulations. CONCLUSION: Because the half-range mode is a simple and fast method, and produced less bias overall in our simulations, we recommend the bootstrapped version of it as a general-purpose mode estimator and suggest a bootstrap method for obtaining the standard error and 95% confidence interval of the mode.

Importance of Vibronic Effects in the UV-Vis Spectrum of the 7,7,8,8-Tetracyanoquinodimethane Anion.

PubMed

Tapavicza, Enrico; Furche, Filipp; Sundholm, Dage

2016-10-11

We present a computational method for simulating vibronic absorption spectra in the ultraviolet-visible (UV-vis) range and apply it to the 7,7,8,8-tetracyanoquinodimethane anion (TCNQ - ), which has been used as a ligand in black absorbers. Gaussian broadening of vertical electronic excitation energies of TCNQ - from linear-response time-dependent density functional theory produces only one band, which is qualitatively incorrect. Thus, the harmonic vibrational modes of the two lowest doublet states were computed, and the vibronic UV-vis spectrum was simulated using the displaced harmonic oscillator approximation, the frequency-shifted harmonic oscillator approximation, and the full Duschinsky formalism. An efficient real-time generating function method was implemented to avoid the exponential complexity of conventional Franck-Condon approaches to vibronic spectra. The obtained UV-vis spectra for TCNQ - agree well with experiment; the Duschinsky rotation is found to have only a minor effect on the spectrum. Born-Oppenheimer molecular dynamics simulations combined with calculations of the electronic excitation energies for a large number of molecular structures were also used for simulating the UV-vis spectrum. The Born-Oppenheimer molecular dynamics simulations yield a broadening of the energetically lowest peak in the absorption spectrum, but additional vibrational bands present in the experimental and simulated quantum harmonic oscillator spectra are not observed in the molecular dynamics simulations. Our results underline the importance of vibronic effects for the UV-vis spectrum of TCNQ - , and they establish an efficient method for obtaining vibronic spectra using a combination of linear-response time-dependent density functional theory and a real-time generating function approach.

A hybrid algorithm for parallel molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Mangiardi, Chris M.; Meyer, R.

2017-10-01

This article describes algorithms for the hybrid parallelization and SIMD vectorization of molecular dynamics simulations with short-range forces. The parallelization method combines domain decomposition with a thread-based parallelization approach. The goal of the work is to enable efficient simulations of very large (tens of millions of atoms) and inhomogeneous systems on many-core processors with hundreds or thousands of cores and SIMD units with large vector sizes. In order to test the efficiency of the method, simulations of a variety of configurations with up to 74 million atoms have been performed. Results are shown that were obtained on multi-core systems with Sandy Bridge and Haswell processors as well as systems with Xeon Phi many-core processors.

Coupling discrete and continuum concentration particle models for multiscale and hybrid molecular-continuum simulations

NASA Astrophysics Data System (ADS)

Petsev, Nikolai D.; Leal, L. Gary; Shell, M. Scott

2017-12-01

Hybrid molecular-continuum simulation techniques afford a number of advantages for problems in the rapidly burgeoning area of nanoscale engineering and technology, though they are typically quite complex to implement and limited to single-component fluid systems. We describe an approach for modeling multicomponent hydrodynamic problems spanning multiple length scales when using particle-based descriptions for both the finely resolved (e.g., molecular dynamics) and coarse-grained (e.g., continuum) subregions within an overall simulation domain. This technique is based on the multiscale methodology previously developed for mesoscale binary fluids [N. D. Petsev, L. G. Leal, and M. S. Shell, J. Chem. Phys. 144, 084115 (2016)], simulated using a particle-based continuum method known as smoothed dissipative particle dynamics. An important application of this approach is the ability to perform coupled molecular dynamics (MD) and continuum modeling of molecularly miscible binary mixtures. In order to validate this technique, we investigate multicomponent hybrid MD-continuum simulations at equilibrium, as well as non-equilibrium cases featuring concentration gradients.

Is an intuitive convergence definition of molecular dynamics simulations solely based on the root mean square deviation possible?

PubMed

Knapp, B; Frantal, S; Cibena, M; Schreiner, W; Bauer, P

2011-08-01

Molecular dynamics is a commonly used technique in computational biology. One key issue of each molecular dynamics simulation is: When does this simulation reach equilibrium state? A widely used way to determine this is the visual and intuitive inspection of root mean square deviation (RMSD) plots of the simulation. Although this technique has been criticized several times, it is still often used. Therefore, we present a study proving that this method is not reliable at all. We conducted a survey with participants from the field in which we illustrated different RMSD plots to scientists in the field of molecular dynamics. These plots were randomized and repeated, using a statistical model and different variants of the plots. We show that there is no mutual consent about the point of equilibrium. The decisions are severely biased by different parameters. Therefore, we conclude that scientists should not discuss the equilibration of a molecular dynamics simulation on the basis of a RMSD plot.

Communication: A method to compute the transport coefficient of pure fluids diffusing through planar interfaces from equilibrium molecular dynamics simulations.

PubMed

Vermorel, Romain; Oulebsir, Fouad; Galliero, Guillaume

2017-09-14

The computation of diffusion coefficients in molecular systems ranks among the most useful applications of equilibrium molecular dynamics simulations. However, when dealing with the problem of fluid diffusion through vanishingly thin interfaces, classical techniques are not applicable. This is because the volume of space in which molecules diffuse is ill-defined. In such conditions, non-equilibrium techniques allow for the computation of transport coefficients per unit interface width, but their weak point lies in their inability to isolate the contribution of the different physical mechanisms prone to impact the flux of permeating molecules. In this work, we propose a simple and accurate method to compute the diffusional transport coefficient of a pure fluid through a planar interface from equilibrium molecular dynamics simulations, in the form of a diffusion coefficient per unit interface width. In order to demonstrate its validity and accuracy, we apply our method to the case study of a dilute gas diffusing through a smoothly repulsive single-layer porous solid. We believe this complementary technique can benefit to the interpretation of the results obtained on single-layer membranes by means of complex non-equilibrium methods.

Aspects of numerical and representational methods related to the finite-difference simulation of advective and dispersive transport of freshwater in a thin brackish aquifer

USGS Publications Warehouse

Merritt, M.L.

1993-01-01

The simulation of the transport of injected freshwater in a thin brackish aquifer, overlain and underlain by confining layers containing more saline water, is shown to be influenced by the choice of the finite-difference approximation method, the algorithm for representing vertical advective and dispersive fluxes, and the values assigned to parametric coefficients that specify the degree of vertical dispersion and molecular diffusion that occurs. Computed potable water recovery efficiencies will differ depending upon the choice of algorithm and approximation method, as will dispersion coefficients estimated based on the calibration of simulations to match measured data. A comparison of centered and backward finite-difference approximation methods shows that substantially different transition zones between injected and native waters are depicted by the different methods, and computed recovery efficiencies vary greatly. Standard and experimental algorithms and a variety of values for molecular diffusivity, transverse dispersivity, and vertical scaling factor were compared in simulations of freshwater storage in a thin brackish aquifer. Computed recovery efficiencies vary considerably, and appreciable differences are observed in the distribution of injected freshwater in the various cases tested. The results demonstrate both a qualitatively different description of transport using the experimental algorithms and the interrelated influences of molecular diffusion and transverse dispersion on simulated recovery efficiency. When simulating natural aquifer flow in cross-section, flushing of the aquifer occurred for all tested coefficient choices using both standard and experimental algorithms. ?? 1993.

myPresto/omegagene: a GPU-accelerated molecular dynamics simulator tailored for enhanced conformational sampling methods with a non-Ewald electrostatic scheme.

PubMed

Kasahara, Kota; Ma, Benson; Goto, Kota; Dasgupta, Bhaskar; Higo, Junichi; Fukuda, Ikuo; Mashimo, Tadaaki; Akiyama, Yutaka; Nakamura, Haruki

2016-01-01

Molecular dynamics (MD) is a promising computational approach to investigate dynamical behavior of molecular systems at the atomic level. Here, we present a new MD simulation engine named "myPresto/omegagene" that is tailored for enhanced conformational sampling methods with a non-Ewald electrostatic potential scheme. Our enhanced conformational sampling methods, e.g. , the virtual-system-coupled multi-canonical MD (V-McMD) method, replace a multi-process parallelized run with multiple independent runs to avoid inter-node communication overhead. In addition, adopting the non-Ewald-based zero-multipole summation method (ZMM) makes it possible to eliminate the Fourier space calculations altogether. The combination of these state-of-the-art techniques realizes efficient and accurate calculations of the conformational ensemble at an equilibrium state. By taking these advantages, myPresto/omegagene is specialized for the single process execution with Graphics Processing Unit (GPU). We performed benchmark simulations for the 20-mer peptide, Trp-cage, with explicit solvent. One of the most thermodynamically stable conformations generated by the V-McMD simulation is very similar to an experimentally solved native conformation. Furthermore, the computation speed is four-times faster than that of our previous simulation engine, myPresto/psygene-G. The new simulator, myPresto/omegagene, is freely available at the following URLs: http://www.protein.osaka-u.ac.jp/rcsfp/pi/omegagene/ and http://presto.protein.osaka-u.ac.jp/myPresto4/.

ls1 mardyn: The Massively Parallel Molecular Dynamics Code for Large Systems.

PubMed

Niethammer, Christoph; Becker, Stefan; Bernreuther, Martin; Buchholz, Martin; Eckhardt, Wolfgang; Heinecke, Alexander; Werth, Stephan; Bungartz, Hans-Joachim; Glass, Colin W; Hasse, Hans; Vrabec, Jadran; Horsch, Martin

2014-10-14

The molecular dynamics simulation code ls1 mardyn is presented. It is a highly scalable code, optimized for massively parallel execution on supercomputing architectures and currently holds the world record for the largest molecular simulation with over four trillion particles. It enables the application of pair potentials to length and time scales that were previously out of scope for molecular dynamics simulation. With an efficient dynamic load balancing scheme, it delivers high scalability even for challenging heterogeneous configurations. Presently, multicenter rigid potential models based on Lennard-Jones sites, point charges, and higher-order polarities are supported. Due to its modular design, ls1 mardyn can be extended to new physical models, methods, and algorithms, allowing future users to tailor it to suit their respective needs. Possible applications include scenarios with complex geometries, such as fluids at interfaces, as well as nonequilibrium molecular dynamics simulation of heat and mass transfer.

Incremental update of electrostatic interactions in adaptively restrained particle simulations.

PubMed

Edorh, Semeho Prince A; Redon, Stéphane

2018-04-06

The computation of long-range potentials is one of the demanding tasks in Molecular Dynamics. During the last decades, an inventive panoply of methods was developed to reduce the CPU time of this task. In this work, we propose a fast method dedicated to the computation of the electrostatic potential in adaptively restrained systems. We exploit the fact that, in such systems, only some particles are allowed to move at each timestep. We developed an incremental algorithm derived from a multigrid-based alternative to traditional Fourier-based methods. Our algorithm was implemented inside LAMMPS, a popular molecular dynamics simulation package. We evaluated the method on different systems. We showed that the new algorithm's computational complexity scales with the number of active particles in the simulated system, and is able to outperform the well-established Particle Particle Particle Mesh (P3M) for adaptively restrained simulations. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Multiscale methods for computational RNA enzymology

PubMed Central

Panteva, Maria T.; Dissanayake, Thakshila; Chen, Haoyuan; Radak, Brian K.; Kuechler, Erich R.; Giambaşu, George M.; Lee, Tai-Sung; York, Darrin M.

2016-01-01

RNA catalysis is of fundamental importance to biology and yet remains ill-understood due to its complex nature. The multi-dimensional “problem space” of RNA catalysis includes both local and global conformational rearrangements, changes in the ion atmosphere around nucleic acids and metal ion binding, dependence on potentially correlated protonation states of key residues and bond breaking/forming in the chemical steps of the reaction. The goal of this article is to summarize and apply multiscale modeling methods in an effort to target the different parts of the RNA catalysis problem space while also addressing the limitations and pitfalls of these methods. Classical molecular dynamics (MD) simulations, reference interaction site model (RISM) calculations, constant pH molecular dynamics (CpHMD) simulations, Hamiltonian replica exchange molecular dynamics (HREMD) and quantum mechanical/molecular mechanical (QM/MM) simulations will be discussed in the context of the study of RNA backbone cleavage transesterification. This reaction is catalyzed by both RNA and protein enzymes, and here we examine the different mechanistic strategies taken by the hepatitis delta virus ribozyme (HDVr) and RNase A. PMID:25726472

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

PubMed Central

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

2015-01-01

Protein and peptide structure predictions are of paramount importance for understanding their functions, as well as the interactions with other molecules. However, the use of molecular simulation techniques to directly predict the peptide structure from the primary amino acid sequence is always hindered by the rough topology of the conformational space and the limited simulation time scale. We developed here a new strategy, named Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) to identify the native states of a peptide and miniprotein. A cluster of near native structures could be obtained by using the MSA-MD method, which turned out to be significantly more efficient in reaching the native structure compared to continuous MD and conventional SA-MD simulation. PMID:26492886

Temperature specification in atomistic molecular dynamics and its impact on simulation efficacy

NASA Astrophysics Data System (ADS)

Ocaya, R. O.; Terblans, J. J.

2017-10-01

Temperature is a vital thermodynamical function for physical systems. Knowledge of system temperature permits assessment of system ergodicity, entropy, system state and stability. Rapid theoretical and computational developments in the fields of condensed matter physics, chemistry, material science, molecular biology, nanotechnology and others necessitate clarity in the temperature specification. Temperature-based materials simulations, both standalone and distributed computing, are projected to grow in prominence over diverse research fields. In this article we discuss the apparent variability of temperature modeling formalisms used currently in atomistic molecular dynamics simulations, with respect to system energetics,dynamics and structural evolution. Commercial simulation programs, which by nature are heuristic, do not openly discuss this fundamental question. We address temperature specification in the context of atomistic molecular dynamics. We define a thermostat at 400K relative to a heat bath at 300K firstly using a modified ab-initio Newtonian method, and secondly using a Monte-Carlo method. The thermostatic vacancy formation and cohesion energies, equilibrium lattice constant for FCC copper is then calculated. Finally we compare and contrast the results.

Development of simulation approach for two-dimensional chiral molecular self-assembly driven by hydrogen bond at the liquid/solid interface

NASA Astrophysics Data System (ADS)

Qin, Yuan; Yao, Man; Hao, Ce; Wan, Lijun; Wang, Yunhe; Chen, Ting; Wang, Dong; Wang, Xudong; Chen, Yonggang

2017-09-01

Two-dimensional (2D) chiral self-assembly system of 5-(benzyloxy)-isophthalic acid derivative/(S)-(+)-2-octanol/highly oriented pyrolytic graphite was studied. A combined density functional theory/molecular mechanics/molecular dynamics (DFT/MM/MD) approach for system of 2D chiral molecular self-assembly driven by hydrogen bond at the liquid/solid interface was thus proposed. Structural models of the chiral assembly were built on the basis of scanning tunneling microscopy (STM) images and simplified for DFT geometry optimization. Merck Molecular Force Field (MMFF) was singled out as the suitable force field by comparing the optimized configurations of MM and DFT. MM and MD simulations for hexagonal unit model which better represented the 2D assemble network were then preformed with MMFF. The adhesion energy, evolution of self-assembly process and characteristic parameters of hydrogen bond were obtained and analyzed. According to the above simulation, the stabilities of the clockwise and counterclockwise enantiomorphous networks were evaluated. The calculational results were supported by STM observations and the feasibility of the simulation method was confirmed by two other systems in the presence of chiral co-absorbers (R)-(-)-2-octanol and achiral co-absorbers 1-octanol. This theoretical simulation method assesses the stability trend of 2D enantiomorphous assemblies with atomic scale and can be applied to the similar hydrogen bond driven 2D chirality of molecular self-assembly system.

Predicting absorption and dispersion in acoustics by direct simulation Monte Carlo: Quantum and classical models for molecular relaxation.

PubMed

Hanford, Amanda D; O'Connor, Patrick D; Anderson, James B; Long, Lyle N

2008-06-01

In the current study, real gas effects in the propagation of sound waves are simulated using the direct simulation Monte Carlo method for a wide range of frequencies. This particle method allows for treatment of acoustic phenomena at high Knudsen numbers, corresponding to low densities and a high ratio of the molecular mean free path to wavelength. Different methods to model the internal degrees of freedom of diatomic molecules and the exchange of translational, rotational and vibrational energies in collisions are employed in the current simulations of a diatomic gas. One of these methods is the fully classical rigid-rotor/harmonic-oscillator model for rotation and vibration. A second method takes into account the discrete quantum energy levels for vibration with the closely spaced rotational levels classically treated. This method gives a more realistic representation of the internal structure of diatomic and polyatomic molecules. Applications of these methods are investigated in diatomic nitrogen gas in order to study the propagation of sound and its attenuation and dispersion along with their dependence on temperature. With the direct simulation method, significant deviations from continuum predictions are also observed for high Knudsen number flows.

Molecular Simulation of the Free Energy for the Accurate Determination of Phase Transition Properties of Molecular Solids

NASA Astrophysics Data System (ADS)

Sellers, Michael; Lisal, Martin; Brennan, John

2015-06-01

Investigating the ability of a molecular model to accurately represent a real material is crucial to model development and use. When the model simulates materials in extreme conditions, one such property worth evaluating is the phase transition point. However, phase transitions are often overlooked or approximated because of difficulty or inaccuracy when simulating them. Techniques such as super-heating or super-squeezing a material to induce a phase change suffer from inherent timescale limitations leading to ``over-driving,'' and dual-phase simulations require many long-time runs to seek out what frequently results in an inexact location of phase-coexistence. We present a compilation of methods for the determination of solid-solid and solid-liquid phase transition points through the accurate calculation of the chemical potential. The methods are applied to the Smith-Bharadwaj atomistic potential's representation of cyclotrimethylene trinitramine (RDX) to accurately determine its melting point (Tm) and the alpha to gamma solid phase transition pressure. We also determine Tm for a coarse-grain model of RDX, and compare its value to experiment and atomistic counterpart. All methods are employed via the LAMMPS simulator, resulting in 60-70 simulations that total 30-50 ns. Approved for public release. Distribution is unlimited.

Application of Multiplexed Replica Exchange Molecular Dynamics to the UNRES Force Field: Tests with alpha and alpha+beta Proteins.

PubMed

Czaplewski, Cezary; Kalinowski, Sebastian; Liwo, Adam; Scheraga, Harold A

2009-03-10

The replica exchange (RE) method is increasingly used to improve sampling in molecular dynamics (MD) simulations of biomolecular systems. Recently, we implemented the united-residue UNRES force field for mesoscopic MD. Initial results from UNRES MD simulations show that we are able to simulate folding events that take place in a microsecond or even a millisecond time scale. To speed up the search further, we applied the multiplexing replica exchange molecular dynamics (MREMD) method. The multiplexed variant (MREMD) of the RE method, developed by Rhee and Pande, differs from the original RE method in that several trajectories are run at a given temperature. Each set of trajectories run at a different temperature constitutes a layer. Exchanges are attempted not only within a single layer but also between layers. The code has been parallelized and scales up to 4000 processors. We present a comparison of canonical MD, REMD, and MREMD simulations of protein folding with the UNRES force-field. We demonstrate that the multiplexed procedure increases the power of replica exchange MD considerably and convergence of the thermodynamic quantities is achieved much faster.

Application of Multiplexed Replica Exchange Molecular Dynamics to the UNRES Force Field: Tests with α and α+β Proteins

PubMed Central

Czaplewski, Cezary; Kalinowski, Sebastian; Liwo, Adam; Scheraga, Harold A.

2009-01-01

The replica exchange (RE) method is increasingly used to improve sampling in molecular dynamics (MD) simulations of biomolecular systems. Recently, we implemented the united-residue UNRES force field for mesoscopic MD. Initial results from UNRES MD simulations show that we are able to simulate folding events that take place in a microsecond or even a millisecond time scale. To speed up the search further, we applied the multiplexing replica exchange molecular dynamics (MREMD) method. The multiplexed variant (MREMD) of the RE method, developed by Rhee and Pande, differs from the original RE method in that several trajectories are run at a given temperature. Each set of trajectories run at a different temperature constitutes a layer. Exchanges are attempted not only within a single layer but also between layers. The code has been parallelized and scales up to 4000 processors. We present a comparison of canonical MD, REMD, and MREMD simulations of protein folding with the UNRES force-field. We demonstrate that the multiplexed procedure increases the power of replica exchange MD considerably and convergence of the thermodynamic quantities is achieved much faster. PMID:20161452

Sampling enhancement for the quantum mechanical potential based molecular dynamics simulations: a general algorithm and its extension for free energy calculation on rugged energy surface.

PubMed

Li, Hongzhi; Yang, Wei

2007-03-21

An approach is developed in the replica exchange framework to enhance conformational sampling for the quantum mechanical (QM) potential based molecular dynamics simulations. Importantly, with our enhanced sampling treatment, a decent convergence for electronic structure self-consistent-field calculation is robustly guaranteed, which is made possible in our replica exchange design by avoiding direct structure exchanges between the QM-related replicas and the activated (scaled by low scaling parameters or treated with high "effective temperatures") molecular mechanical (MM) replicas. Although the present approach represents one of the early efforts in the enhanced sampling developments specifically for quantum mechanical potentials, the QM-based simulations treated with the present technique can possess the similar sampling efficiency to the MM based simulations treated with the Hamiltonian replica exchange method (HREM). In the present paper, by combining this sampling method with one of our recent developments (the dual-topology alchemical HREM approach), we also introduce a method for the sampling enhanced QM-based free energy calculations.

Multiscale investigation of chemical interference in proteins

NASA Astrophysics Data System (ADS)

Samiotakis, Antonios; Homouz, Dirar; Cheung, Margaret S.

2010-05-01

We developed a multiscale approach (MultiSCAAL) that integrates the potential of mean force obtained from all-atomistic molecular dynamics simulations with a knowledge-based energy function for coarse-grained molecular simulations in better exploring the energy landscape of a small protein under chemical interference such as chemical denaturation. An excessive amount of water molecules in all-atomistic molecular dynamics simulations often negatively impacts the sampling efficiency of some advanced sampling techniques such as the replica exchange method and it makes the investigation of chemical interferences on protein dynamics difficult. Thus, there is a need to develop an effective strategy that focuses on sampling structural changes in protein conformations rather than solvent molecule fluctuations. In this work, we address this issue by devising a multiscale simulation scheme (MultiSCAAL) that bridges the gap between all-atomistic molecular dynamics simulation and coarse-grained molecular simulation. The two key features of this scheme are the Boltzmann inversion and a protein atomistic reconstruction method we previously developed (SCAAL). Using MultiSCAAL, we were able to enhance the sampling efficiency of proteins solvated by explicit water molecules. Our method has been tested on the folding energy landscape of a small protein Trp-cage with explicit solvent under 8M urea using both the all-atomistic replica exchange molecular dynamics and MultiSCAAL. We compared computational analyses on ensemble conformations of Trp-cage with its available experimental NOE distances. The analysis demonstrated that conformations explored by MultiSCAAL better agree with the ones probed in the experiments because it can effectively capture the changes in side-chain orientations that can flip out of the hydrophobic pocket in the presence of urea and water molecules. In this regard, MultiSCAAL is a promising and effective sampling scheme for investigating chemical interference which presents a great challenge when modeling protein interactions in vivo.

Molecular dynamics simulations of hydrogen diffusion in aluminum

DOE PAGES

Zhou, X. W.; El Gabaly, F.; Stavila, V.; ...

2016-03-23

In this study, hydrogen diffusion impacts the performance of solid-state hydrogen storage materials and contributes to the embrittlement of structural materials under hydrogen-containing environments. In atomistic simulations, the diffusion energy barriers are usually calculated using molecular statics simulations where a nudged elastic band method is used to constrain a path connecting the two end points of an atomic jump. This approach requires prior knowledge of the “end points”. For alloy and defective systems, the number of possible atomic jumps with respect to local atomic configurations is tremendous. Even when these jumps can be exhaustively studied, it is still unclear howmore » they can be combined to give an overall diffusion behavior seen in experiments. Here we describe the use of molecular dynamics simulations to determine the overall diffusion energy barrier from the Arrhenius equation. This method does not require information about atomic jumps, and it has additional advantages, such as the ability to incorporate finite temperature effects and to determine the pre-exponential factor. As a test case for a generic method, we focus on hydrogen diffusion in bulk aluminum. We find that the challenge of this method is the statistical variation of the results. However, highly converged energy barriers can be achieved by an appropriate set of temperatures, output time intervals (for tracking hydrogen positions), and a long total simulation time. Our results help elucidate the inconsistencies of the experimental diffusion data published in the literature. The robust approach developed here may also open up future molecular dynamics simulations to rapidly study diffusion properties of complex material systems in multidimensional spaces involving composition and defects.« less

Combined Monte Carlo/torsion-angle molecular dynamics for ensemble modeling of proteins, nucleic acids and carbohydrates.

PubMed

Zhang, Weihong; Howell, Steven C; Wright, David W; Heindel, Andrew; Qiu, Xiangyun; Chen, Jianhan; Curtis, Joseph E

2017-05-01

We describe a general method to use Monte Carlo simulation followed by torsion-angle molecular dynamics simulations to create ensembles of structures to model a wide variety of soft-matter biological systems. Our particular emphasis is focused on modeling low-resolution small-angle scattering and reflectivity structural data. We provide examples of this method applied to HIV-1 Gag protein and derived fragment proteins, TraI protein, linear B-DNA, a nucleosome core particle, and a glycosylated monoclonal antibody. This procedure will enable a large community of researchers to model low-resolution experimental data with greater accuracy by using robust physics based simulation and sampling methods which are a significant improvement over traditional methods used to interpret such data. Published by Elsevier Inc.

An atomistic simulation scheme for modeling crystal formation from solution.

PubMed

Kawska, Agnieszka; Brickmann, Jürgen; Kniep, Rüdiger; Hochrein, Oliver; Zahn, Dirk

2006-01-14

We present an atomistic simulation scheme for investigating crystal growth from solution. Molecular-dynamics simulation studies of such processes typically suffer from considerable limitations concerning both system size and simulation times. In our method this time-length scale problem is circumvented by an iterative scheme which combines a Monte Carlo-type approach for the identification of ion adsorption sites and, after each growth step, structural optimization of the ion cluster and the solvent by means of molecular-dynamics simulation runs. An important approximation of our method is based on assuming full structural relaxation of the aggregates between each of the growth steps. This concept only holds for compounds of low solubility. To illustrate our method we studied CaF2 aggregate growth from aqueous solution, which may be taken as prototypes for compounds of very low solubility. The limitations of our simulation scheme are illustrated by the example of NaCl aggregation from aqueous solution, which corresponds to a solute/solvent combination of very high salt solubility.

Overcoming the Time Limitation in Molecular Dynamics Simulation of Crystal Nucleation: A Persistent-Embryo Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Yang; Song, Huajing; Zhang, Feng

The crystal nucleation from liquid in most cases is too rare to be accessed within the limited time scales of the conventional molecular dynamics (MD) simulation. Here, we developed a “persistent embryo” method to facilitate crystal nucleation in MD simulations by preventing small crystal embryos from melting using external spring forces. We applied this method to the pure Ni case for a moderate undercooling where no nucleation can be observed in the conventional MD simulation, and obtained nucleation rate in good agreement with the experimental data. Moreover, the method is applied to simulate an even more sluggish event: the nucleationmore » of the B2 phase in a strong glass-forming Cu-Zr alloy. The nucleation rate was found to be 8 orders of magnitude smaller than Ni at the same undercooling, which well explains the good glass formability of the alloy. In conclusion, our work opens a new avenue to study solidification under realistic experimental conditions via atomistic computer simulation.« less

Overcoming the Time Limitation in Molecular Dynamics Simulation of Crystal Nucleation: A Persistent-Embryo Approach

DOE PAGES

Sun, Yang; Song, Huajing; Zhang, Feng; ...

2018-02-23

The crystal nucleation from liquid in most cases is too rare to be accessed within the limited time scales of the conventional molecular dynamics (MD) simulation. Here, we developed a “persistent embryo” method to facilitate crystal nucleation in MD simulations by preventing small crystal embryos from melting using external spring forces. We applied this method to the pure Ni case for a moderate undercooling where no nucleation can be observed in the conventional MD simulation, and obtained nucleation rate in good agreement with the experimental data. Moreover, the method is applied to simulate an even more sluggish event: the nucleationmore » of the B2 phase in a strong glass-forming Cu-Zr alloy. The nucleation rate was found to be 8 orders of magnitude smaller than Ni at the same undercooling, which well explains the good glass formability of the alloy. In conclusion, our work opens a new avenue to study solidification under realistic experimental conditions via atomistic computer simulation.« less

Overcoming the Time Limitation in Molecular Dynamics Simulation of Crystal Nucleation: A Persistent-Embryo Approach

NASA Astrophysics Data System (ADS)

Sun, Yang; Song, Huajing; Zhang, Feng; Yang, Lin; Ye, Zhuo; Mendelev, Mikhail I.; Wang, Cai-Zhuang; Ho, Kai-Ming

2018-02-01

The crystal nucleation from liquid in most cases is too rare to be accessed within the limited time scales of the conventional molecular dynamics (MD) simulation. Here, we developed a "persistent embryo" method to facilitate crystal nucleation in MD simulations by preventing small crystal embryos from melting using external spring forces. We applied this method to the pure Ni case for a moderate undercooling where no nucleation can be observed in the conventional MD simulation, and obtained nucleation rate in good agreement with the experimental data. Moreover, the method is applied to simulate an even more sluggish event: the nucleation of the B 2 phase in a strong glass-forming Cu-Zr alloy. The nucleation rate was found to be 8 orders of magnitude smaller than Ni at the same undercooling, which well explains the good glass formability of the alloy. Thus, our work opens a new avenue to study solidification under realistic experimental conditions via atomistic computer simulation.

Overcoming the Time Limitation in Molecular Dynamics Simulation of Crystal Nucleation: A Persistent-Embryo Approach.

PubMed

Sun, Yang; Song, Huajing; Zhang, Feng; Yang, Lin; Ye, Zhuo; Mendelev, Mikhail I; Wang, Cai-Zhuang; Ho, Kai-Ming

2018-02-23

The crystal nucleation from liquid in most cases is too rare to be accessed within the limited time scales of the conventional molecular dynamics (MD) simulation. Here, we developed a "persistent embryo" method to facilitate crystal nucleation in MD simulations by preventing small crystal embryos from melting using external spring forces. We applied this method to the pure Ni case for a moderate undercooling where no nucleation can be observed in the conventional MD simulation, and obtained nucleation rate in good agreement with the experimental data. Moreover, the method is applied to simulate an even more sluggish event: the nucleation of the B2 phase in a strong glass-forming Cu-Zr alloy. The nucleation rate was found to be 8 orders of magnitude smaller than Ni at the same undercooling, which well explains the good glass formability of the alloy. Thus, our work opens a new avenue to study solidification under realistic experimental conditions via atomistic computer simulation.

Hydration of Li+ -ion in atom-bond electronegativity equalization method-7P water: a molecular dynamics simulation study.

PubMed

Li, Xin; Yang, Zhong-Zhi

2005-02-22

We have carried out molecular dynamics simulations of a Li(+) ion in water over a wide range of temperature (from 248 to 368 K). The simulations make use of the atom-bond electronegativity equalization method-7P water model, a seven-site flexible model with fluctuating charges, which has accurately reproduced many bulk water properties. The recently constructed Li(+)-water interaction potential through fitting to the experimental and ab initio gas-phase binding energies and to the measured structures for Li(+)-water clusters is adopted in the simulations. ABEEM was proposed and developed in terms of partitioning the electron density into atom and bond regions and using the electronegativity equalization method (EEM) and the density functional theory (DFT). Based on a combination of the atom-bond electronegativity equalization method and molecular mechanics (ABEEM/MM), a new set of water-water and Li(+)-water potentials, successfully applied to ionic clusters Li(+)(H(2)O)(n)(n=1-6,8), are further investigated in an aqueous solution of Li(+) in the present paper. Two points must be emphasized in the simulations: first, the model allows for the charges on the interacting sites fluctuating as a function of time; second, the ABEEM-7P model has applied the parameter k(lp,H)(R(lp,H)) to explicitly describe the short-range interaction of hydrogen bond in the hydrogen bond interaction region, and has a new description for the hydrogen bond. The static, dynamic, and thermodynamic properties have been studied in detail. In addition, at different temperatures, the structural properties such as radial distribution functions, and the dynamical properties such as diffusion coefficients and residence times of the water molecules in the first hydration shell of Li(+), are also simulated well. These simulation results show that the ABEEM/MM-based water-water and Li(+)-water potentials appear to be robust giving the overall characteristic hydration properties in excellent agreement with experiments and other molecular dynamics simulations on similar system.

The structure of aqueous sodium hydroxide solutions: a combined solution x-ray diffraction and simulation study.

PubMed

Megyes, Tünde; Bálint, Szabolcs; Grósz, Tamás; Radnai, Tamás; Bakó, Imre; Sipos, Pál

2008-01-28

To determine the structure of aqueous sodium hydroxide solutions, results obtained from x-ray diffraction and computer simulation (molecular dynamics and Car-Parrinello) have been compared. The capabilities and limitations of the methods in describing the solution structure are discussed. For the solutions studied, diffraction methods were found to perform very well in describing the hydration spheres of the sodium ion and yield structural information on the anion's hydration structure. Classical molecular dynamics simulations were not able to correctly describe the bulk structure of these solutions. However, Car-Parrinello simulation proved to be a suitable tool in the detailed interpretation of the hydration sphere of ions and bulk structure of solutions. The results of Car-Parrinello simulations were compared with the findings of diffraction experiments.

High performance computing in biology: multimillion atom simulations of nanoscale systems

PubMed Central

Sanbonmatsu, K. Y.; Tung, C.-S.

2007-01-01

Computational methods have been used in biology for sequence analysis (bioinformatics), all-atom simulation (molecular dynamics and quantum calculations), and more recently for modeling biological networks (systems biology). Of these three techniques, all-atom simulation is currently the most computationally demanding, in terms of compute load, communication speed, and memory load. Breakthroughs in electrostatic force calculation and dynamic load balancing have enabled molecular dynamics simulations of large biomolecular complexes. Here, we report simulation results for the ribosome, using approximately 2.64 million atoms, the largest all-atom biomolecular simulation published to date. Several other nanoscale systems with different numbers of atoms were studied to measure the performance of the NAMD molecular dynamics simulation program on the Los Alamos National Laboratory Q Machine. We demonstrate that multimillion atom systems represent a 'sweet spot' for the NAMD code on large supercomputers. NAMD displays an unprecedented 85% parallel scaling efficiency for the ribosome system on 1024 CPUs. We also review recent targeted molecular dynamics simulations of the ribosome that prove useful for studying conformational changes of this large biomolecular complex in atomic detail. PMID:17187988

Fast Particle Methods for Multiscale Phenomena Simulations

NASA Technical Reports Server (NTRS)

Koumoutsakos, P.; Wray, A.; Shariff, K.; Pohorille, Andrew

2000-01-01

We are developing particle methods oriented at improving computational modeling capabilities of multiscale physical phenomena in : (i) high Reynolds number unsteady vortical flows, (ii) particle laden and interfacial flows, (iii)molecular dynamics studies of nanoscale droplets and studies of the structure, functions, and evolution of the earliest living cell. The unifying computational approach involves particle methods implemented in parallel computer architectures. The inherent adaptivity, robustness and efficiency of particle methods makes them a multidisciplinary computational tool capable of bridging the gap of micro-scale and continuum flow simulations. Using efficient tree data structures, multipole expansion algorithms, and improved particle-grid interpolation, particle methods allow for simulations using millions of computational elements, making possible the resolution of a wide range of length and time scales of these important physical phenomena.The current challenges in these simulations are in : [i] the proper formulation of particle methods in the molecular and continuous level for the discretization of the governing equations [ii] the resolution of the wide range of time and length scales governing the phenomena under investigation. [iii] the minimization of numerical artifacts that may interfere with the physics of the systems under consideration. [iv] the parallelization of processes such as tree traversal and grid-particle interpolations We are conducting simulations using vortex methods, molecular dynamics and smooth particle hydrodynamics, exploiting their unifying concepts such as : the solution of the N-body problem in parallel computers, highly accurate particle-particle and grid-particle interpolations, parallel FFT's and the formulation of processes such as diffusion in the context of particle methods. This approach enables us to transcend among seemingly unrelated areas of research.

General framework for constraints in molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Kneller, Gerald R.

2017-06-01

The article presents a theoretical framework for molecular dynamics simulations of complex systems subject to any combination of holonomic and non-holonomic constraints. Using the concept of constrained inverse matrices both the particle accelerations and the associated constraint forces can be determined from given external forces and kinematical conditions. The formalism enables in particular the construction of explicit kinematical conditions which lead to the well-known Nosé-Hoover type equations of motion for the simulation of non-standard molecular dynamics ensembles. Illustrations are given for a few examples and an outline is presented for a numerical implementation of the method.

A fast recursive algorithm for molecular dynamics simulation

NASA Technical Reports Server (NTRS)

Jain, A.; Vaidehi, N.; Rodriguez, G.

1993-01-01

The present recursive algorithm for solving molecular systems' dynamical equations of motion employs internal variable models that reduce such simulations' computation time by an order of magnitude, relative to Cartesian models. Extensive use is made of spatial operator methods recently developed for analysis and simulation of the dynamics of multibody systems. A factor-of-450 speedup over the conventional O(N-cubed) algorithm is demonstrated for the case of a polypeptide molecule with 400 residues.

Computer Simulation of the Elastic Properties of Titanium Alloys for Medical Applications

NASA Astrophysics Data System (ADS)

Estevez, Elsa Paz; Burganova, R. M.; Lysogorskii, Yu. V.

2016-09-01

Results of a computer simulation of the elastic properties of α+β- and β-titanium alloys, used for medical purposes, within the framework of the molecular-dynamics method are presented. It is shown that β-titanium alloys are best suited for the use as bone implants because of their small moduli of elasticity. The advisability of the use of the molecular-dynamics method for the study of the elastic properties of titanium alloys, serving as bone implants, is demonstrated.

2D Quantum Simulation of MOSFET Using the Non Equilibrium Green's Function Method

NASA Technical Reports Server (NTRS)

Svizhenko, Alexel; Anantram, M. P.; Govindan, T. R.; Yan, Jerry (Technical Monitor)

2000-01-01

The objectives this viewgraph presentation summarizes include: (1) the development of a quantum mechanical simulator for ultra short channel MOSFET simulation, including theory, physical approximations, and computer code; (2) explore physics that is not accessible by semiclassical methods; (3) benchmarking of semiclassical and classical methods; and (4) study other two-dimensional devices and molecular structure, from discretized Hamiltonian to tight-binding Hamiltonian.

A Simple and Accurate Method To Calculate Free Energy Profiles and Reaction Rates from Restrained Molecular Simulations of Diffusive Processes.

PubMed

Ovchinnikov, Victor; Nam, Kwangho; Karplus, Martin

2016-08-25

A method is developed to obtain simultaneously free energy profiles and diffusion constants from restrained molecular simulations in diffusive systems. The method is based on low-order expansions of the free energy and diffusivity as functions of the reaction coordinate. These expansions lead to simple analytical relationships between simulation statistics and model parameters. The method is tested on 1D and 2D model systems; its accuracy is found to be comparable to or better than that of the existing alternatives, which are briefly discussed. An important aspect of the method is that the free energy is constructed by integrating its derivatives, which can be computed without need for overlapping sampling windows. The implementation of the method in any molecular simulation program that supports external umbrella potentials (e.g., CHARMM) requires modification of only a few lines of code. As a demonstration of its applicability to realistic biomolecular systems, the method is applied to model the α-helix ↔ β-sheet transition in a 16-residue peptide in implicit solvent, with the reaction coordinate provided by the string method. Possible modifications of the method are briefly discussed; they include generalization to multidimensional reaction coordinates [in the spirit of the model of Ermak and McCammon (Ermak, D. L.; McCammon, J. A. J. Chem. Phys. 1978, 69, 1352-1360)], a higher-order expansion of the free energy surface, applicability in nonequilibrium systems, and a simple test for Markovianity. In view of the small overhead of the method relative to standard umbrella sampling, we suggest its routine application in the cases where umbrella potential simulations are appropriate.

Exploring a multi-scale method for molecular simulation in continuum solvent model: Explicit simulation of continuum solvent as an incompressible fluid.

PubMed

Xiao, Li; Luo, Ray

2017-12-07

We explored a multi-scale algorithm for the Poisson-Boltzmann continuum solvent model for more robust simulations of biomolecules. In this method, the continuum solvent/solute interface is explicitly simulated with a numerical fluid dynamics procedure, which is tightly coupled to the solute molecular dynamics simulation. There are multiple benefits to adopt such a strategy as presented below. At this stage of the development, only nonelectrostatic interactions, i.e., van der Waals and hydrophobic interactions, are included in the algorithm to assess the quality of the solvent-solute interface generated by the new method. Nevertheless, numerical challenges exist in accurately interpolating the highly nonlinear van der Waals term when solving the finite-difference fluid dynamics equations. We were able to bypass the challenge rigorously by merging the van der Waals potential and pressure together when solving the fluid dynamics equations and by considering its contribution in the free-boundary condition analytically. The multi-scale simulation method was first validated by reproducing the solute-solvent interface of a single atom with analytical solution. Next, we performed the relaxation simulation of a restrained symmetrical monomer and observed a symmetrical solvent interface at equilibrium with detailed surface features resembling those found on the solvent excluded surface. Four typical small molecular complexes were then tested, both volume and force balancing analyses showing that these simple complexes can reach equilibrium within the simulation time window. Finally, we studied the quality of the multi-scale solute-solvent interfaces for the four tested dimer complexes and found that they agree well with the boundaries as sampled in the explicit water simulations.

Symplectic molecular dynamics simulations on specially designed parallel computers.

PubMed

Borstnik, Urban; Janezic, Dusanka

2005-01-01

We have developed a computer program for molecular dynamics (MD) simulation that implements the Split Integration Symplectic Method (SISM) and is designed to run on specialized parallel computers. The MD integration is performed by the SISM, which analytically treats high-frequency vibrational motion and thus enables the use of longer simulation time steps. The low-frequency motion is treated numerically on specially designed parallel computers, which decreases the computational time of each simulation time step. The combination of these approaches means that less time is required and fewer steps are needed and so enables fast MD simulations. We study the computational performance of MD simulation of molecular systems on specialized computers and provide a comparison to standard personal computers. The combination of the SISM with two specialized parallel computers is an effective way to increase the speed of MD simulations up to 16-fold over a single PC processor.

Simulating the flow of entangled polymers.

PubMed

Masubuchi, Yuichi

2014-01-01

To optimize automation for polymer processing, attempts have been made to simulate the flow of entangled polymers. In industry, fluid dynamics simulations with phenomenological constitutive equations have been practically established. However, to account for molecular characteristics, a method to obtain the constitutive relationship from the molecular structure is required. Molecular dynamics simulations with atomic description are not practical for this purpose; accordingly, coarse-grained models with reduced degrees of freedom have been developed. Although the modeling of entanglement is still a challenge, mesoscopic models with a priori settings to reproduce entangled polymer dynamics, such as tube models, have achieved remarkable success. To use the mesoscopic models as staging posts between atomistic and fluid dynamics simulations, studies have been undertaken to establish links from the coarse-grained model to the atomistic and macroscopic simulations. Consequently, integrated simulations from materials chemistry to predict the macroscopic flow in polymer processing are forthcoming.

An adaptive quantum mechanics/molecular mechanics method for the infrared spectrum of water: incorporation of the quantum effect between solute and solvent.

PubMed

Watanabe, Hiroshi C; Banno, Misa; Sakurai, Minoru

2016-03-14

Quantum effects in solute-solvent interactions, such as the many-body effect and the dipole-induced dipole, are known to be critical factors influencing the infrared spectra of species in the liquid phase. For accurate spectrum evaluation, the surrounding solvent molecules, in addition to the solute of interest, should be treated using a quantum mechanical method. However, conventional quantum mechanics/molecular mechanics (QM/MM) methods cannot handle free QM solvent molecules during molecular dynamics (MD) simulation because of the diffusion problem. To deal with this problem, we have previously proposed an adaptive QM/MM "size-consistent multipartitioning (SCMP) method". In the present study, as the first application of the SCMP method, we demonstrate the reproduction of the infrared spectrum of liquid-phase water, and evaluate the quantum effect in comparison with conventional QM/MM simulations.

Molecular simulation studies on chemical reactivity of methylcyclopentadiene.

PubMed

Wang, Qingsheng; Zhang, Yingchun; Rogers, William J; Mannan, M Sam

2009-06-15

Molecular simulations are important to predict thermodynamic values for reactive chemicals especially when sufficient experimental data are not available. Methylcyclopentadiene (MCP) is an example of a highly reactive and hazardous compound in the chemical process industry. In this work, chemical reactivity of 2-methylcyclopentadiene, including isomerization, dimerization, and oxidation reactions, is investigated in detail by theoretical computational chemistry methods and empirical thermodynamic-energy correlation. On the basis of molecular simulations, an average value of -15.2 kcal/mol for overall heat of dimerization and -45.6 kcal/mol for overall heat of oxidation were obtained in gaseous phase at 298 K and 1 atm. These molecular simulation studies can provide guidance for the design of safer chemical processes, safer handling of MCP, and also provide useful information for an investigation of the T2 Laboratories explosion on December 19, 2007, in Florida.

Investigation for Molecular Attraction Impact Between Contacting Surfaces in Micro-Gears

NASA Astrophysics Data System (ADS)

Yang, Ping; Li, Xialong; Zhao, Yanfang; Yang, Haiying; Wang, Shuting; Yang, Jianming

2013-10-01

The aim of this research work is to provide a systematic method to perform molecular attraction impact between contacting surfaces in micro-gear train. This method is established by integrating involute profile analysis and molecular dynamics simulation. A mathematical computation of micro-gear involute is presented based on geometrical properties, Taylor expression and Hamaker assumption. In the meantime, Morse potential function and the cut-off radius are introduced with a molecular dynamics simulation. So a hybrid computational method for the Van Der Waals force between the contacting faces in micro-gear train is developed. An example is illustrated to show the performance of this method. The results show that the change of Van Der Waals force in micro-gear train has a nonlinear characteristic with parameters change such as the modulus of the gear and the tooth number of gear etc. The procedure implies a potential feasibility that we can control the Van Der Waals force by adjusting the manufacturing parameters for gear train design.

Conformational analysis of oligosaccharides and polysaccharides using molecular dynamics simulations.

PubMed

Frank, Martin

2015-01-01

Complex carbohydrates usually have a large number of rotatable bonds and consequently a large number of theoretically possible conformations can be generated (combinatorial explosion). The application of systematic search methods for conformational analysis of carbohydrates is therefore limited to disaccharides and trisaccharides in a routine analysis. An alternative approach is to use Monte-Carlo methods or (high-temperature) molecular dynamics (MD) simulations to explore the conformational space of complex carbohydrates. This chapter describes how to use MD simulation data to perform a conformational analysis (conformational maps, hydrogen bonds) of oligosaccharides and how to build realistic 3D structures of large polysaccharides using Conformational Analysis Tools (CAT).

Implementation of the force decomposition machine for molecular dynamics simulations.

PubMed

Borštnik, Urban; Miller, Benjamin T; Brooks, Bernard R; Janežič, Dušanka

2012-09-01

We present the design and implementation of the force decomposition machine (FDM), a cluster of personal computers (PCs) that is tailored to running molecular dynamics (MD) simulations using the distributed diagonal force decomposition (DDFD) parallelization method. The cluster interconnect architecture is optimized for the communication pattern of the DDFD method. Our implementation of the FDM relies on standard commodity components even for networking. Although the cluster is meant for DDFD MD simulations, it remains general enough for other parallel computations. An analysis of several MD simulation runs on both the FDM and a standard PC cluster demonstrates that the FDM's interconnect architecture provides a greater performance compared to a more general cluster interconnect. Copyright © 2012 Elsevier Inc. All rights reserved.

A Simple Method for Automated Equilibration Detection in Molecular Simulations.

PubMed

Chodera, John D

2016-04-12

Molecular simulations intended to compute equilibrium properties are often initiated from configurations that are highly atypical of equilibrium samples, a practice which can generate a distinct initial transient in mechanical observables computed from the simulation trajectory. Traditional practice in simulation data analysis recommends this initial portion be discarded to equilibration, but no simple, general, and automated procedure for this process exists. Here, we suggest a conceptually simple automated procedure that does not make strict assumptions about the distribution of the observable of interest in which the equilibration time is chosen to maximize the number of effectively uncorrelated samples in the production timespan used to compute equilibrium averages. We present a simple Python reference implementation of this procedure and demonstrate its utility on typical molecular simulation data.

A simple method for automated equilibration detection in molecular simulations

PubMed Central

Chodera, John D.

2016-01-01

Molecular simulations intended to compute equilibrium properties are often initiated from configurations that are highly atypical of equilibrium samples, a practice which can generate a distinct initial transient in mechanical observables computed from the simulation trajectory. Traditional practice in simulation data analysis recommends this initial portion be discarded to equilibration, but no simple, general, and automated procedure for this process exists. Here, we suggest a conceptually simple automated procedure that does not make strict assumptions about the distribution of the observable of interest, in which the equilibration time is chosen to maximize the number of effectively uncorrelated samples in the production timespan used to compute equilibrium averages. We present a simple Python reference implementation of this procedure, and demonstrate its utility on typical molecular simulation data. PMID:26771390

Molecular effective coverage surface area of optical clearing agents for predicting optical clearing potential

NASA Astrophysics Data System (ADS)

Feng, Wei; Ma, Ning; Zhu, Dan

2015-03-01

The improvement of methods for optical clearing agent prediction exerts an important impact on tissue optical clearing technique. The molecular dynamic simulation is one of the most convincing and simplest approaches to predict the optical clearing potential of agents by analyzing the hydrogen bonds, hydrogen bridges and hydrogen bridges type forming between agents and collagen. However, the above analysis methods still suffer from some problem such as analysis of cyclic molecule by reason of molecular conformation. In this study, a molecular effective coverage surface area based on the molecular dynamic simulation was proposed to predict the potential of optical clearing agents. Several typical cyclic molecules, fructose, glucose and chain molecules, sorbitol, xylitol were analyzed by calculating their molecular effective coverage surface area, hydrogen bonds, hydrogen bridges and hydrogen bridges type, respectively. In order to verify this analysis methods, in vitro skin samples optical clearing efficacy were measured after 25 min immersing in the solutions, fructose, glucose, sorbitol and xylitol at concentration of 3.5 M using 1951 USAF resolution test target. The experimental results show accordance with prediction of molecular effective coverage surface area. Further to compare molecular effective coverage surface area with other parameters, it can show that molecular effective coverage surface area has a better performance in predicting OCP of agents.

Direct simulation of high-vorticity gas flows

NASA Technical Reports Server (NTRS)

Bird, G. A.

1987-01-01

The computational limitations associated with the molecular dynamics (MD) method and the direct simulation Monte Carlo (DSMC) method are reviewed in the context of the computation of dilute gas flows with high vorticity. It is concluded that the MD method is generally limited to the dense gas case in which the molecular diameter is one-tenth or more of the mean free path. It is shown that the cell size in DSMC calculations should be small in comparison with the mean free path, and that this may be facilitated by a new subcell procedure for the selection of collision partners.

Diffusion Coefficients from Molecular Dynamics Simulations in Binary and Ternary Mixtures

NASA Astrophysics Data System (ADS)

Liu, Xin; Schnell, Sondre K.; Simon, Jean-Marc; Krüger, Peter; Bedeaux, Dick; Kjelstrup, Signe; Bardow, André; Vlugt, Thijs J. H.

2013-07-01

Multicomponent diffusion in liquids is ubiquitous in (bio)chemical processes. It has gained considerable and increasing interest as it is often the rate limiting step in a process. In this paper, we review methods for calculating diffusion coefficients from molecular simulation and predictive engineering models. The main achievements of our research during the past years can be summarized as follows: (1) we introduced a consistent method for computing Fick diffusion coefficients using equilibrium molecular dynamics simulations; (2) we developed a multicomponent Darken equation for the description of the concentration dependence of Maxwell-Stefan diffusivities. In the case of infinite dilution, the multicomponent Darken equation provides an expression for [InlineEquation not available: see fulltext.] which can be used to parametrize the generalized Vignes equation; and (3) a predictive model for self-diffusivities was proposed for the parametrization of the multicomponent Darken equation. This equation accurately describes the concentration dependence of self-diffusivities in weakly associating systems. With these methods, a sound framework for the prediction of mutual diffusion in liquids is achieved.

Scaling of Multimillion-Atom Biological Molecular Dynamics Simulation on a Petascale Supercomputer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulz, Roland; Lindner, Benjamin; Petridis, Loukas

2009-01-01

A strategy is described for a fast all-atom molecular dynamics simulation of multimillion-atom biological systems on massively parallel supercomputers. The strategy is developed using benchmark systems of particular interest to bioenergy research, comprising models of cellulose and lignocellulosic biomass in an aqueous solution. The approach involves using the reaction field (RF) method for the computation of long-range electrostatic interactions, which permits efficient scaling on many thousands of cores. Although the range of applicability of the RF method for biomolecular systems remains to be demonstrated, for the benchmark systems the use of the RF produces molecular dipole moments, Kirkwood G factors,more » other structural properties, and mean-square fluctuations in excellent agreement with those obtained with the commonly used Particle Mesh Ewald method. With RF, three million- and five million atom biological systems scale well up to 30k cores, producing 30 ns/day. Atomistic simulations of very large systems for time scales approaching the microsecond would, therefore, appear now to be within reach.« less

Scaling of Multimillion-Atom Biological Molecular Dynamics Simulation on a Petascale Supercomputer.

PubMed

Schulz, Roland; Lindner, Benjamin; Petridis, Loukas; Smith, Jeremy C

2009-10-13

A strategy is described for a fast all-atom molecular dynamics simulation of multimillion-atom biological systems on massively parallel supercomputers. The strategy is developed using benchmark systems of particular interest to bioenergy research, comprising models of cellulose and lignocellulosic biomass in an aqueous solution. The approach involves using the reaction field (RF) method for the computation of long-range electrostatic interactions, which permits efficient scaling on many thousands of cores. Although the range of applicability of the RF method for biomolecular systems remains to be demonstrated, for the benchmark systems the use of the RF produces molecular dipole moments, Kirkwood G factors, other structural properties, and mean-square fluctuations in excellent agreement with those obtained with the commonly used Particle Mesh Ewald method. With RF, three million- and five million-atom biological systems scale well up to ∼30k cores, producing ∼30 ns/day. Atomistic simulations of very large systems for time scales approaching the microsecond would, therefore, appear now to be within reach.

A study on the plasticity of soda-lime silica glass via molecular dynamics simulations.

PubMed

Urata, Shingo; Sato, Yosuke

2017-11-07

Molecular dynamics (MD) simulations were applied to construct a plasticity model, which enables one to simulate deformations of soda-lime silica glass (SLSG) by using continuum methods. To model the plasticity, stress induced by uniaxial and a variety of biaxial deformations was measured by MD simulations. We found that the surfaces of yield and maximum stresses, which are evaluated from the equivalent stress-strain curves, are reasonably represented by the Mohr-Coulomb ellipsoid. Comparing a finite element model using the constructed plasticity model to a large scale atomistic model on a nanoindentation simulation of SLSG reveals that the empirical method is accurate enough to evaluate the SLSG mechanical responses. Furthermore, the effect of ion-exchange on the SLSG plasticity was examined by using MD simulations. As a result, it was demonstrated that the effects of the initial compressive stress on the yield and maximum stresses are anisotropic contrary to our expectations.

A study on the plasticity of soda-lime silica glass via molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Urata, Shingo; Sato, Yosuke

2017-11-01

Molecular dynamics (MD) simulations were applied to construct a plasticity model, which enables one to simulate deformations of soda-lime silica glass (SLSG) by using continuum methods. To model the plasticity, stress induced by uniaxial and a variety of biaxial deformations was measured by MD simulations. We found that the surfaces of yield and maximum stresses, which are evaluated from the equivalent stress-strain curves, are reasonably represented by the Mohr-Coulomb ellipsoid. Comparing a finite element model using the constructed plasticity model to a large scale atomistic model on a nanoindentation simulation of SLSG reveals that the empirical method is accurate enough to evaluate the SLSG mechanical responses. Furthermore, the effect of ion-exchange on the SLSG plasticity was examined by using MD simulations. As a result, it was demonstrated that the effects of the initial compressive stress on the yield and maximum stresses are anisotropic contrary to our expectations.

From classical to quantum and back: Hamiltonian adaptive resolution path integral, ring polymer, and centroid molecular dynamics

NASA Astrophysics Data System (ADS)

Kreis, Karsten; Kremer, Kurt; Potestio, Raffaello; Tuckerman, Mark E.

2017-12-01

Path integral-based methodologies play a crucial role for the investigation of nuclear quantum effects by means of computer simulations. However, these techniques are significantly more demanding than corresponding classical simulations. To reduce this numerical effort, we recently proposed a method, based on a rigorous Hamiltonian formulation, which restricts the quantum modeling to a small but relevant spatial region within a larger reservoir where particles are treated classically. In this work, we extend this idea and show how it can be implemented along with state-of-the-art path integral simulation techniques, including path-integral molecular dynamics, which allows for the calculation of quantum statistical properties, and ring-polymer and centroid molecular dynamics, which allow the calculation of approximate quantum dynamical properties. To this end, we derive a new integration algorithm that also makes use of multiple time-stepping. The scheme is validated via adaptive classical-path-integral simulations of liquid water. Potential applications of the proposed multiresolution method are diverse and include efficient quantum simulations of interfaces as well as complex biomolecular systems such as membranes and proteins.

Computer simulation of surface and film processes

NASA Technical Reports Server (NTRS)

Tiller, W. A.; Halicioglu, M. T.

1984-01-01

All the investigations which were performed employed in one way or another a computer simulation technique based on atomistic level considerations. In general, three types of simulation methods were used for modeling systems with discrete particles that interact via well defined potential functions: molecular dynamics (a general method for solving the classical equations of motion of a model system); Monte Carlo (the use of Markov chain ensemble averaging technique to model equilibrium properties of a system); and molecular statics (provides properties of a system at T = 0 K). The effects of three-body forces on the vibrational frequencies of triatomic cluster were investigated. The multilayer relaxation phenomena for low index planes of an fcc crystal was analyzed also as a function of the three-body interactions. Various surface properties for Si and SiC system were calculated. Results obtained from static simulation calculations for slip formation were presented. The more elaborate molecular dynamics calculations on the propagation of cracks in two-dimensional systems were outlined.

Overcoming time scale and finite size limitations to compute nucleation rates from small scale well tempered metadynamics simulations.

PubMed

Salvalaglio, Matteo; Tiwary, Pratyush; Maggioni, Giovanni Maria; Mazzotti, Marco; Parrinello, Michele

2016-12-07

Condensation of a liquid droplet from a supersaturated vapour phase is initiated by a prototypical nucleation event. As such it is challenging to compute its rate from atomistic molecular dynamics simulations. In fact at realistic supersaturation conditions condensation occurs on time scales that far exceed what can be reached with conventional molecular dynamics methods. Another known problem in this context is the distortion of the free energy profile associated to nucleation due to the small, finite size of typical simulation boxes. In this work the problem of time scale is addressed with a recently developed enhanced sampling method while contextually correcting for finite size effects. We demonstrate our approach by studying the condensation of argon, and showing that characteristic nucleation times of the order of magnitude of hours can be reliably calculated. Nucleation rates spanning a range of 10 orders of magnitude are computed at moderate supersaturation levels, thus bridging the gap between what standard molecular dynamics simulations can do and real physical systems.

Overcoming time scale and finite size limitations to compute nucleation rates from small scale well tempered metadynamics simulations

NASA Astrophysics Data System (ADS)

Salvalaglio, Matteo; Tiwary, Pratyush; Maggioni, Giovanni Maria; Mazzotti, Marco; Parrinello, Michele

2016-12-01

Condensation of a liquid droplet from a supersaturated vapour phase is initiated by a prototypical nucleation event. As such it is challenging to compute its rate from atomistic molecular dynamics simulations. In fact at realistic supersaturation conditions condensation occurs on time scales that far exceed what can be reached with conventional molecular dynamics methods. Another known problem in this context is the distortion of the free energy profile associated to nucleation due to the small, finite size of typical simulation boxes. In this work the problem of time scale is addressed with a recently developed enhanced sampling method while contextually correcting for finite size effects. We demonstrate our approach by studying the condensation of argon, and showing that characteristic nucleation times of the order of magnitude of hours can be reliably calculated. Nucleation rates spanning a range of 10 orders of magnitude are computed at moderate supersaturation levels, thus bridging the gap between what standard molecular dynamics simulations can do and real physical systems.

Molecular dynamics simulations using temperature-enhanced essential dynamics replica exchange.

PubMed

Kubitzki, Marcus B; de Groot, Bert L

2007-06-15

Today's standard molecular dynamics simulations of moderately sized biomolecular systems at full atomic resolution are typically limited to the nanosecond timescale and therefore suffer from limited conformational sampling. Efficient ensemble-preserving algorithms like replica exchange (REX) may alleviate this problem somewhat but are still computationally prohibitive due to the large number of degrees of freedom involved. Aiming at increased sampling efficiency, we present a novel simulation method combining the ideas of essential dynamics and REX. Unlike standard REX, in each replica only a selection of essential collective modes of a subsystem of interest (essential subspace) is coupled to a higher temperature, with the remainder of the system staying at a reference temperature, T(0). This selective excitation along with the replica framework permits efficient approximate ensemble-preserving conformational sampling and allows much larger temperature differences between replicas, thereby considerably enhancing sampling efficiency. Ensemble properties and sampling performance of the method are discussed using dialanine and guanylin test systems, with multi-microsecond molecular dynamics simulations of these test systems serving as references.

Transient Nonequilibrium Molecular Dynamic Simulations of Thermal Conductivity: 1. Simple Fluids

NASA Astrophysics Data System (ADS)

Hulse, R. J.; Rowley, R. L.; Wilding, W. V.

2005-01-01

Thermal conductivity has been previously obtained from molecular dynamics (MD) simulations using either equilibrium (EMD) simulations (from Green--Kubo equations) or from steady-state nonequilibrium (NEMD) simulations. In the case of NEMD, either boundary-driven steady states are simulated or constrained equations of motion are used to obtain steady-state heat transfer rates. Like their experimental counterparts, these nonequilibrium steady-state methods are time consuming and may have convection problems. Here we report a new transient method developed to provide accurate thermal conductivity predictions from MD simulations. In the proposed MD method, molecules that lie within a specified volume are instantaneously heated. The temperature decay of the system of molecules inside the heated volume is compared to the solution of the transient energy equation, and the thermal diffusivity is regressed. Since the density of the fluid is set in the simulation, only the isochoric heat capacity is needed in order to obtain the thermal conductivity. In this study the isochoric heat capacity is determined from energy fluctuations within the simulated fluid. The method is valid in the liquid, vapor, and critical regions. Simulated values for the thermal conductivity of a Lennard-Jones (LJ) fluid were obtained using this new method over a temperature range of 90 to 900 K and a density range of 1-35 kmol · m-3. These values compare favorably with experimental values for argon. The new method has a precision of ±10%. Compared to other methods, the algorithm is quick, easy to code, and applicable to small systems, making the simulations very efficient.

A Prediction Method of Binding Free Energy of Protein and Ligand

NASA Astrophysics Data System (ADS)

Yang, Kun; Wang, Xicheng

2010-05-01

Predicting the binding free energy is an important problem in bimolecular simulation. Such prediction would be great benefit in understanding protein functions, and may be useful for computational prediction of ligand binding strengths, e.g., in discovering pharmaceutical drugs. Free energy perturbation (FEP)/thermodynamics integration (TI) is a classical method to explicitly predict free energy. However, this method need plenty of time to collect datum, and that attempts to deal with some simple systems and small changes of molecular structures. Another one for estimating ligand binding affinities is linear interaction energy (LIE) method. This method employs averages of interaction potential energy terms from molecular dynamics simulations or other thermal conformational sampling techniques. Incorporation of systematic deviations from electrostatic linear response, derived from free energy perturbation studies, into the absolute binding free energy expression significantly enhances the accuracy of the approach. However, it also is time-consuming work. In this paper, a new prediction method based on steered molecular dynamics (SMD) with direction optimization is developed to compute binding free energy. Jarzynski's equality is used to derive the PMF or free-energy. The results for two numerical examples are presented, showing that the method has good accuracy and efficiency. The novel method can also simulate whole binding proceeding and give some important structural information about development of new drugs.

Optimization of the molecular dynamics method for simulations of DNA and ion transport through biological nanopores.

PubMed

Wells, David B; Bhattacharya, Swati; Carr, Rogan; Maffeo, Christopher; Ho, Anthony; Comer, Jeffrey; Aksimentiev, Aleksei

2012-01-01

Molecular dynamics (MD) simulations have become a standard method for the rational design and interpretation of experimental studies of DNA translocation through nanopores. The MD method, however, offers a multitude of algorithms, parameters, and other protocol choices that can affect the accuracy of the resulting data as well as computational efficiency. In this chapter, we examine the most popular choices offered by the MD method, seeking an optimal set of parameters that enable the most computationally efficient and accurate simulations of DNA and ion transport through biological nanopores. In particular, we examine the influence of short-range cutoff, integration timestep and force field parameters on the temperature and concentration dependence of bulk ion conductivity, ion pairing, ion solvation energy, DNA structure, DNA-ion interactions, and the ionic current through a nanopore.

Simulation of electric double-layer capacitors: evaluation of constant potential method

NASA Astrophysics Data System (ADS)

Wang, Zhenxing; Laird, Brian; Yang, Yang; Olmsted, David; Asta, Mark

2014-03-01

Atomistic simulations can play an important role in understanding electric double-layer capacitors (EDLCs) at a molecular level. In such simulations, typically the electrode surface is modeled using fixed surface charges, which ignores the charge fluctuation induced by local fluctuations in the electrolyte solution. In this work we evaluate an explicit treatment of charges, namely constant potential method (CPM)[1], in which the electrode charges are dynamically updated to maintain constant electrode potential. We employ a model system with a graphite electrode and a LiClO4/acetonitrile electrolyte, examined as a function of electrode potential differences. Using various molecular and macroscopic properties as metrics, we compare CPM simulations on this system to results using fixed surface charges. Specifically, results for predicted capacity, electric potential gradient and solvent density profile are identical between the two methods; However, ion density profiles and solvation structure yield significantly different results.

Mimicking coarse-grained simulations without coarse-graining: enhanced sampling by damping short-range interactions.

PubMed

Wei, Dongshan; Wang, Feng

2010-08-28

The damped-short-range-interaction (DSRI) method is proposed to mimic coarse-grained simulations by propagating an atomistic scale system on a smoothed potential energy surface. The DSRI method has the benefit of enhanced sampling provided by a typical coarse-grained simulation without the need to perform coarse-graining. Our method was used to simulate liquid water, alanine dipeptide folding, and the self-assembly of dimyristoylphosphatidylcholine lipid. In each case, our method appreciably accelerated the dynamics without significantly changing the free energy surface. Additional insights from DSRI simulations and the promise of coupling our DSRI method with Hamiltonian replica-exchange molecular dynamics are discussed.

Mimicking coarse-grained simulations without coarse-graining: Enhanced sampling by damping short-range interactions

NASA Astrophysics Data System (ADS)

Wei, Dongshan; Wang, Feng

2010-08-01

The damped-short-range-interaction (DSRI) method is proposed to mimic coarse-grained simulations by propagating an atomistic scale system on a smoothed potential energy surface. The DSRI method has the benefit of enhanced sampling provided by a typical coarse-grained simulation without the need to perform coarse-graining. Our method was used to simulate liquid water, alanine dipeptide folding, and the self-assembly of dimyristoylphosphatidylcholine lipid. In each case, our method appreciably accelerated the dynamics without significantly changing the free energy surface. Additional insights from DSRI simulations and the promise of coupling our DSRI method with Hamiltonian replica-exchange molecular dynamics are discussed.

Mapping Conformational Dynamics of Proteins Using Torsional Dynamics Simulations

PubMed Central

Gangupomu, Vamshi K.; Wagner, Jeffrey R.; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

2013-01-01

All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein’s experimentally established conformational substates. Conformational transition of calmodulin from the Ca2+-bound to the Ca2+-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in proteins. PMID:23663843

Mapping conformational dynamics of proteins using torsional dynamics simulations.

PubMed

Gangupomu, Vamshi K; Wagner, Jeffrey R; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

2013-05-07

All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein's experimentally established conformational substates. Conformational transition of calmodulin from the Ca(2+)-bound to the Ca(2+)-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in proteins. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Computing pKa Values with a Mixing Hamiltonian Quantum Mechanical/Molecular Mechanical Approach.

PubMed

Liu, Yang; Fan, Xiaoli; Jin, Yingdi; Hu, Xiangqian; Hu, Hao

2013-09-10

Accurate computation of the pKa value of a compound in solution is important but challenging. Here, a new mixing quantum mechanical/molecular mechanical (QM/MM) Hamiltonian method is developed to simulate the free-energy change associated with the protonation/deprotonation processes in solution. The mixing Hamiltonian method is designed for efficient quantum mechanical free-energy simulations by alchemically varying the nuclear potential, i.e., the nuclear charge of the transforming nucleus. In pKa calculation, the charge on the proton is varied in fraction between 0 and 1, corresponding to the fully deprotonated and protonated states, respectively. Inspired by the mixing potential QM/MM free energy simulation method developed previously [H. Hu and W. T. Yang, J. Chem. Phys. 2005, 123, 041102], this method succeeds many advantages of a large class of λ-coupled free-energy simulation methods and the linear combination of atomic potential approach. Theory and technique details of this method, along with the calculation results of the pKa of methanol and methanethiol molecules in aqueous solution, are reported. The results show satisfactory agreement with the experimental data.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLaughlin, E.; Gupta, S.

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 themore » 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.« less

Recent applications of boxed molecular dynamics: a simple multiscale technique for atomistic simulations.

PubMed

Booth, Jonathan; Vazquez, Saulo; Martinez-Nunez, Emilio; Marks, Alison; Rodgers, Jeff; Glowacki, David R; Shalashilin, Dmitrii V

2014-08-06

In this paper, we briefly review the boxed molecular dynamics (BXD) method which allows analysis of thermodynamics and kinetics in complicated molecular systems. BXD is a multiscale technique, in which thermodynamics and long-time dynamics are recovered from a set of short-time simulations. In this paper, we review previous applications of BXD to peptide cyclization, solution phase organic reaction dynamics and desorption of ions from self-assembled monolayers (SAMs). We also report preliminary results of simulations of diamond etching mechanisms and protein unfolding in atomic force microscopy experiments. The latter demonstrate a correlation between the protein's structural motifs and its potential of mean force. Simulations of these processes by standard molecular dynamics (MD) is typically not possible, because the experimental time scales are very long. However, BXD yields well-converged and physically meaningful results. Compared with other methods of accelerated MD, our BXD approach is very simple; it is easy to implement, and it provides an integrated approach for simultaneously obtaining both thermodynamics and kinetics. It also provides a strategy for obtaining statistically meaningful dynamical results in regions of configuration space that standard MD approaches would visit only very rarely.

Gibbs Ensemble Simulations of the Solvent Swelling of Polymer Films

NASA Astrophysics Data System (ADS)

Gartner, Thomas; Epps, Thomas, III; Jayaraman, Arthi

Solvent vapor annealing (SVA) is a useful technique to tune the morphology of block polymer, polymer blend, and polymer nanocomposite films. Despite SVA's utility, standardized SVA protocols have not been established, partly due to a lack of fundamental knowledge regarding the interplay between the polymer(s), solvent, substrate, and free-surface during solvent annealing and evaporation. An understanding of how to tune polymer film properties in a controllable manner through SVA processes is needed. Herein, the thermodynamic implications of the presence of solvent in the swollen polymer film is explored through two alternative Gibbs ensemble simulation methods that we have developed and extended: Gibbs ensemble molecular dynamics (GEMD) and hybrid Monte Carlo (MC)/molecular dynamics (MD). In this poster, we will describe these simulation methods and demonstrate their application to polystyrene films swollen by toluene and n-hexane. Polymer film swelling experiments, Gibbs ensemble molecular simulations, and polymer reference interaction site model (PRISM) theory are combined to calculate an effective Flory-Huggins χ (χeff) for polymer-solvent mixtures. The effects of solvent chemistry, solvent content, polymer molecular weight, and polymer architecture on χeff are examined, providing a platform to control and understand the thermodynamics of polymer film swelling.

Multiresolution molecular mechanics: Implementation and efficiency

NASA Astrophysics Data System (ADS)

Biyikli, Emre; To, Albert C.

2017-01-01

Atomistic/continuum coupling methods combine accurate atomistic methods and efficient continuum methods to simulate the behavior of highly ordered crystalline systems. Coupled methods utilize the advantages of both approaches to simulate systems at a lower computational cost, while retaining the accuracy associated with atomistic methods. Many concurrent atomistic/continuum coupling methods have been proposed in the past; however, their true computational efficiency has not been demonstrated. The present work presents an efficient implementation of a concurrent coupling method called the Multiresolution Molecular Mechanics (MMM) for serial, parallel, and adaptive analysis. First, we present the features of the software implemented along with the associated technologies. The scalability of the software implementation is demonstrated, and the competing effects of multiscale modeling and parallelization are discussed. Then, the algorithms contributing to the efficiency of the software are presented. These include algorithms for eliminating latent ghost atoms from calculations and measurement-based dynamic balancing of parallel workload. The efficiency improvements made by these algorithms are demonstrated by benchmark tests. The efficiency of the software is found to be on par with LAMMPS, a state-of-the-art Molecular Dynamics (MD) simulation code, when performing full atomistic simulations. Speed-up of the MMM method is shown to be directly proportional to the reduction of the number of the atoms visited in force computation. Finally, an adaptive MMM analysis on a nanoindentation problem, containing over a million atoms, is performed, yielding an improvement of 6.3-8.5 times in efficiency, over the full atomistic MD method. For the first time, the efficiency of a concurrent atomistic/continuum coupling method is comprehensively investigated and demonstrated.

Ab initio molecular simulations on specific interactions between amyloid beta and monosaccharides

NASA Astrophysics Data System (ADS)

Nomura, Kazuya; Okamoto, Akisumi; Yano, Atsushi; Higai, Shin'ichi; Kondo, Takashi; Kamba, Seiji; Kurita, Noriyuki

2012-09-01

Aggregation of amyloid β (Aβ) peptides, which is a key pathogenetic event in Alzheimer's disease, can be caused by cell-surface saccharides. We here investigated stable structures of the solvated complexes of Aβ with some types of monosaccharides using molecular simulations based on protein-ligand docking and classical molecular mechanics methods. Moreover, the specific interactions between Aβ and the monosaccharides were elucidated at an electronic level by ab initio fragment molecular orbital calculations. Based on the results, we proposed which type of monosaccharide prefers to have large binding affinity to Aβ and inhibit the Aβ aggregation.

Parallel Discrete Molecular Dynamics Simulation With Speculation and In-Order Commitment*†

PubMed Central

Khan, Md. Ashfaquzzaman; Herbordt, Martin C.

2011-01-01

Discrete molecular dynamics simulation (DMD) uses simplified and discretized models enabling simulations to advance by event rather than by timestep. DMD is an instance of discrete event simulation and so is difficult to scale: even in this multi-core era, all reported DMD codes are serial. In this paper we discuss the inherent difficulties of scaling DMD and present our method of parallelizing DMD through event-based decomposition. Our method is microarchitecture inspired: speculative processing of events exposes parallelism, while in-order commitment ensures correctness. We analyze the potential of this parallelization method for shared-memory multiprocessors. Achieving scalability required extensive experimentation with scheduling and synchronization methods to mitigate serialization. The speed-up achieved for a variety of system sizes and complexities is nearly 6× on an 8-core and over 9× on a 12-core processor. We present and verify analytical models that account for the achieved performance as a function of available concurrency and architectural limitations. PMID:21822327

Parallel Discrete Molecular Dynamics Simulation With Speculation and In-Order Commitment.

PubMed

Khan, Md Ashfaquzzaman; Herbordt, Martin C

2011-07-20

Discrete molecular dynamics simulation (DMD) uses simplified and discretized models enabling simulations to advance by event rather than by timestep. DMD is an instance of discrete event simulation and so is difficult to scale: even in this multi-core era, all reported DMD codes are serial. In this paper we discuss the inherent difficulties of scaling DMD and present our method of parallelizing DMD through event-based decomposition. Our method is microarchitecture inspired: speculative processing of events exposes parallelism, while in-order commitment ensures correctness. We analyze the potential of this parallelization method for shared-memory multiprocessors. Achieving scalability required extensive experimentation with scheduling and synchronization methods to mitigate serialization. The speed-up achieved for a variety of system sizes and complexities is nearly 6× on an 8-core and over 9× on a 12-core processor. We present and verify analytical models that account for the achieved performance as a function of available concurrency and architectural limitations.

Cosolvent-Based Molecular Dynamics for Ensemble Docking: Practical Method for Generating Druggable Protein Conformations.

PubMed

Uehara, Shota; Tanaka, Shigenori

2017-04-24

Protein flexibility is a major hurdle in current structure-based virtual screening (VS). In spite of the recent advances in high-performance computing, protein-ligand docking methods still demand tremendous computational cost to take into account the full degree of protein flexibility. In this context, ensemble docking has proven its utility and efficiency for VS studies, but it still needs a rational and efficient method to select and/or generate multiple protein conformations. Molecular dynamics (MD) simulations are useful to produce distinct protein conformations without abundant experimental structures. In this study, we present a novel strategy that makes use of cosolvent-based molecular dynamics (CMD) simulations for ensemble docking. By mixing small organic molecules into a solvent, CMD can stimulate dynamic protein motions and induce partial conformational changes of binding pocket residues appropriate for the binding of diverse ligands. The present method has been applied to six diverse target proteins and assessed by VS experiments using many actives and decoys of DEKOIS 2.0. The simulation results have revealed that the CMD is beneficial for ensemble docking. Utilizing cosolvent simulation allows the generation of druggable protein conformations, improving the VS performance compared with the use of a single experimental structure or ensemble docking by standard MD with pure water as the solvent.

Molecular dynamics simulations of substitutional diffusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Xiaowang; Jones, Reese E.; Gruber, Jacob

2016-12-18

In atomistic simulations, diffusion energy barriers are usually calculated for each atomic jump path using a nudged elastic band method. Practical materials often involve thousands of distinct atomic jump paths that are not known a priori. Hence, it is often preferred to determine an overall diffusion energy barrier and an overall pre-exponential factor from the Arrhenius equation constructed through molecular dynamics simulations of mean square displacement of the diffusion species at different temperatures. This approach has been well established for interstitial diffusion, but not for substitutional diffusion at the same confidence. Using In 0.1 Ga 0.9 N as an example,more » we have identified conditions where molecular dynamics simulations can be used to calculate highly converged Arrhenius plots for substitutional alloys. As a result, this may enable many complex diffusion problems to be easily and reliably studied in the future using molecular dynamics, provided that moderate computing resources are available.« less

Adaptively restrained molecular dynamics in LAMMPS

NASA Astrophysics Data System (ADS)

Kant Singh, Krishna; Redon, Stephane

2017-07-01

Adaptively restrained molecular dynamics (ARMD) is a recently introduced particles simulation method that switches positional degrees of freedom on and off during simulation in order to speed up calculations. In the NVE ensemble, ARMD allows users to trade between precision and speed while, in the NVT ensemble, it makes it possible to compute statistical averages faster. Despite the conceptual simplicity of the approach, however, integrating it in existing molecular dynamics packages is non-trivial, in particular since implemented potentials should a priori be rewritten to take advantage of frozen particles and achieve a speed-up. In this paper, we present novel algorithms for integrating ARMD in LAMMPS, a popular multi-purpose molecular simulation package. In particular, we demonstrate how to enable ARMD in LAMMPS without having to re-implement all available force fields. The proposed algorithms are assessed on four different benchmarks, and show how they allow us to speed up simulations up to one order of magnitude.

Soil Organic Matter (SOM): Molecular Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersen, Amity

Molecular simulation is a powerful tool used to gain an atomistic, molecular, and nanoscale level understanding of the structure, dynamics, and interactions from adsorption on minerals and assembly in aggregates of soil organic matter (SOM). Given the importance of SOM fate and persistence in soils and the current knowledge gaps, applications of atomistic scale simulations to study the complex compounds in SOM and their interactions in self-assembled aggregates composed of different organic matter compounds and with mineral surfaces of different types common in soils are few and far between. Here, we describe various molecular simulation methods that are currently inmore » use in various areas and applicable to SOM research, followed by a brief survey of specific applications to SOM research and an illustration with our own recent efforts in this area. We conclude with an outlook and the challenges for future research in this area.« less

Molecular dynamics simulations in hybrid particle-continuum schemes: Pitfalls and caveats

NASA Astrophysics Data System (ADS)

Stalter, S.; Yelash, L.; Emamy, N.; Statt, A.; Hanke, M.; Lukáčová-Medvid'ová, M.; Virnau, P.

2018-03-01

Heterogeneous multiscale methods (HMM) combine molecular accuracy of particle-based simulations with the computational efficiency of continuum descriptions to model flow in soft matter liquids. In these schemes, molecular simulations typically pose a computational bottleneck, which we investigate in detail in this study. We find that it is preferable to simulate many small systems as opposed to a few large systems, and that a choice of a simple isokinetic thermostat is typically sufficient while thermostats such as Lowe-Andersen allow for simulations at elevated viscosity. We discuss suitable choices for time steps and finite-size effects which arise in the limit of very small simulation boxes. We also argue that if colloidal systems are considered as opposed to atomistic systems, the gap between microscopic and macroscopic simulations regarding time and length scales is significantly smaller. We propose a novel reduced-order technique for the coupling to the macroscopic solver, which allows us to approximate a non-linear stress-strain relation efficiently and thus further reduce computational effort of microscopic simulations.

Protocols for Molecular Dynamics Simulations of RNA Nanostructures.

PubMed

Kim, Taejin; Kasprzak, Wojciech K; Shapiro, Bruce A

2017-01-01

Molecular dynamics (MD) simulations have been used as one of the main research tools to study a wide range of biological systems and bridge the gap between X-ray crystallography or NMR structures and biological mechanism. In the field of RNA nanostructures, MD simulations have been used to fix steric clashes in computationally designed RNA nanostructures, characterize the dynamics, and investigate the interaction between RNA and other biomolecules such as delivery agents and membranes.In this chapter we present examples of computational protocols for molecular dynamics simulations in explicit and implicit solvent using the Amber Molecular Dynamics Package. We also show examples of post-simulation analysis steps and briefly mention selected tools beyond the Amber package. Limitations of the methods, tools, and protocols are also discussed. Most of the examples are illustrated for a small RNA duplex (helix), but the protocols are applicable to any nucleic acid structure, subject only to the computational speed and memory limitations of the hardware available to the user.

Physics Computing '92: Proceedings of the 4th International Conference

NASA Astrophysics Data System (ADS)

de Groot, Robert A.; Nadrchal, Jaroslav

1993-04-01

The Table of Contents for the book is as follows: * Preface * INVITED PAPERS * Ab Initio Theoretical Approaches to the Structural, Electronic and Vibrational Properties of Small Clusters and Fullerenes: The State of the Art * Neural Multigrid Methods for Gauge Theories and Other Disordered Systems * Multicanonical Monte Carlo Simulations * On the Use of the Symbolic Language Maple in Physics and Chemistry: Several Examples * Nonequilibrium Phase Transitions in Catalysis and Population Models * Computer Algebra, Symmetry Analysis and Integrability of Nonlinear Evolution Equations * The Path-Integral Quantum Simulation of Hydrogen in Metals * Digital Optical Computing: A New Approach of Systolic Arrays Based on Coherence Modulation of Light and Integrated Optics Technology * Molecular Dynamics Simulations of Granular Materials * Numerical Implementation of a K.A.M. Algorithm * Quasi-Monte Carlo, Quasi-Random Numbers and Quasi-Error Estimates * What Can We Learn from QMC Simulations * Physics of Fluctuating Membranes * Plato, Apollonius, and Klein: Playing with Spheres * Steady States in Nonequilibrium Lattice Systems * CONVODE: A REDUCE Package for Differential Equations * Chaos in Coupled Rotators * Symplectic Numerical Methods for Hamiltonian Problems * Computer Simulations of Surfactant Self Assembly * High-dimensional and Very Large Cellular Automata for Immunological Shape Space * A Review of the Lattice Boltzmann Method * Electronic Structure of Solids in the Self-interaction Corrected Local-spin-density Approximation * Dedicated Computers for Lattice Gauge Theory Simulations * Physics Education: A Survey of Problems and Possible Solutions * Parallel Computing and Electronic-Structure Theory * High Precision Simulation Techniques for Lattice Field Theory * CONTRIBUTED PAPERS * Case Study of Microscale Hydrodynamics Using Molecular Dynamics and Lattice Gas Methods * Computer Modelling of the Structural and Electronic Properties of the Supported Metal Catalysis * Ordered Particle Simulations for Serial and MIMD Parallel Computers * "NOLP" -- Program Package for Laser Plasma Nonlinear Optics * Algorithms to Solve Nonlinear Least Square Problems * Distribution of Hydrogen Atoms in Pd-H Computed by Molecular Dynamics * A Ray Tracing of Optical System for Protein Crystallography Beamline at Storage Ring-SIBERIA-2 * Vibrational Properties of a Pseudobinary Linear Chain with Correlated Substitutional Disorder * Application of the Software Package Mathematica in Generalized Master Equation Method * Linelist: An Interactive Program for Analysing Beam-foil Spectra * GROMACS: A Parallel Computer for Molecular Dynamics Simulations * GROMACS Method of Virial Calculation Using a Single Sum * The Interactive Program for the Solution of the Laplace Equation with the Elimination of Singularities for Boundary Functions * Random-Number Generators: Testing Procedures and Comparison of RNG Algorithms * Micro-TOPIC: A Tokamak Plasma Impurities Code * Rotational Molecular Scattering Calculations * Orthonormal Polynomial Method for Calibrating of Cryogenic Temperature Sensors * Frame-based System Representing Basis of Physics * The Role of Massively Data-parallel Computers in Large Scale Molecular Dynamics Simulations * Short-range Molecular Dynamics on a Network of Processors and Workstations * An Algorithm for Higher-order Perturbation Theory in Radiative Transfer Computations * Hydrostochastics: The Master Equation Formulation of Fluid Dynamics * HPP Lattice Gas on Transputers and Networked Workstations * Study on the Hysteresis Cycle Simulation Using Modeling with Different Functions on Intervals * Refined Pruning Techniques for Feed-forward Neural Networks * Random Walk Simulation of the Motion of Transient Charges in Photoconductors * The Optical Hysteresis in Hydrogenated Amorphous Silicon * Diffusion Monte Carlo Analysis of Modern Interatomic Potentials for He * A Parallel Strategy for Molecular Dynamics Simulations of Polar Liquids on Transputer Arrays * Distribution of Ions Reflected on Rough Surfaces * The Study of Step Density Distribution During Molecular Beam Epitaxy Growth: Monte Carlo Computer Simulation * Towards a Formal Approach to the Construction of Large-scale Scientific Applications Software * Correlated Random Walk and Discrete Modelling of Propagation through Inhomogeneous Media * Teaching Plasma Physics Simulation * A Theoretical Determination of the Au-Ni Phase Diagram * Boson and Fermion Kinetics in One-dimensional Lattices * Computational Physics Course on the Technical University * Symbolic Computations in Simulation Code Development and Femtosecond-pulse Laser-plasma Interaction Studies * Computer Algebra and Integrated Computing Systems in Education of Physical Sciences * Coordinated System of Programs for Undergraduate Physics Instruction * Program Package MIRIAM and Atomic Physics of Extreme Systems * High Energy Physics Simulation on the T_Node * The Chapman-Kolmogorov Equation as Representation of Huygens' Principle and the Monolithic Self-consistent Numerical Modelling of Lasers * Authoring System for Simulation Developments * Molecular Dynamics Study of Ion Charge Effects in the Structure of Ionic Crystals * A Computational Physics Introductory Course * Computer Calculation of Substrate Temperature Field in MBE System * Multimagnetical Simulation of the Ising Model in Two and Three Dimensions * Failure of the CTRW Treatment of the Quasicoherent Excitation Transfer * Implementation of a Parallel Conjugate Gradient Method for Simulation of Elastic Light Scattering * Algorithms for Study of Thin Film Growth * Algorithms and Programs for Physics Teaching in Romanian Technical Universities * Multicanonical Simulation of 1st order Transitions: Interface Tension of the 2D 7-State Potts Model * Two Numerical Methods for the Calculation of Periodic Orbits in Hamiltonian Systems * Chaotic Behavior in a Probabilistic Cellular Automata? * Wave Optics Computing by a Networked-based Vector Wave Automaton * Tensor Manipulation Package in REDUCE * Propagation of Electromagnetic Pulses in Stratified Media * The Simple Molecular Dynamics Model for the Study of Thermalization of the Hot Nucleon Gas * Electron Spin Polarization in PdCo Alloys Calculated by KKR-CPA-LSD Method * Simulation Studies of Microscopic Droplet Spreading * A Vectorizable Algorithm for the Multicolor Successive Overrelaxation Method * Tetragonality of the CuAu I Lattice and Its Relation to Electronic Specific Heat and Spin Susceptibility * Computer Simulation of the Formation of Metallic Aggregates Produced by Chemical Reactions in Aqueous Solution * Scaling in Growth Models with Diffusion: A Monte Carlo Study * The Nucleus as the Mesoscopic System * Neural Network Computation as Dynamic System Simulation * First-principles Theory of Surface Segregation in Binary Alloys * Data Smooth Approximation Algorithm for Estimating the Temperature Dependence of the Ice Nucleation Rate * Genetic Algorithms in Optical Design * Application of 2D-FFT in the Study of Molecular Exchange Processes by NMR * Advanced Mobility Model for Electron Transport in P-Si Inversion Layers * Computer Simulation for Film Surfaces and its Fractal Dimension * Parallel Computation Techniques and the Structure of Catalyst Surfaces * Educational SW to Teach Digital Electronics and the Corresponding Text Book * Primitive Trinomials (Mod 2) Whose Degree is a Mersenne Exponent * Stochastic Modelisation and Parallel Computing * Remarks on the Hybrid Monte Carlo Algorithm for the ∫4 Model * An Experimental Computer Assisted Workbench for Physics Teaching * A Fully Implicit Code to Model Tokamak Plasma Edge Transport * EXPFIT: An Interactive Program for Automatic Beam-foil Decay Curve Analysis * Mapping Technique for Solving General, 1-D Hamiltonian Systems * Freeway Traffic, Cellular Automata, and Some (Self-Organizing) Criticality * Photonuclear Yield Analysis by Dynamic Programming * Incremental Representation of the Simply Connected Planar Curves * Self-convergence in Monte Carlo Methods * Adaptive Mesh Technique for Shock Wave Propagation * Simulation of Supersonic Coronal Streams and Their Interaction with the Solar Wind * The Nature of Chaos in Two Systems of Ordinary Nonlinear Differential Equations * Considerations of a Window-shopper * Interpretation of Data Obtained by RTP 4-Channel Pulsed Radar Reflectometer Using a Multi Layer Perceptron * Statistics of Lattice Bosons for Finite Systems * Fractal Based Image Compression with Affine Transformations * Algorithmic Studies on Simulation Codes for Heavy-ion Reactions * An Energy-Wise Computer Simulation of DNA-Ion-Water Interactions Explains the Abnormal Structure of Poly[d(A)]:Poly[d(T)] * Computer Simulation Study of Kosterlitz-Thouless-Like Transitions * Problem-oriented Software Package GUN-EBT for Computer Simulation of Beam Formation and Transport in Technological Electron-Optical Systems * Parallelization of a Boundary Value Solver and its Application in Nonlinear Dynamics * The Symbolic Classification of Real Four-dimensional Lie Algebras * Short, Singular Pulses Generation by a Dye Laser at Two Wavelengths Simultaneously * Quantum Monte Carlo Simulations of the Apex-Oxygen-Model * Approximation Procedures for the Axial Symmetric Static Einstein-Maxwell-Higgs Theory * Crystallization on a Sphere: Parallel Simulation on a Transputer Network * FAMULUS: A Software Product (also) for Physics Education * MathCAD vs. FAMULUS -- A Brief Comparison * First-principles Dynamics Used to Study Dissociative Chemisorption * A Computer Controlled System for Crystal Growth from Melt * A Time Resolved Spectroscopic Method for Short Pulsed Particle Emission * Green's Function Computation in Radiative Transfer Theory * Random Search Optimization Technique for One-criteria and Multi-criteria Problems * Hartley Transform Applications to Thermal Drift Elimination in Scanning Tunneling Microscopy * Algorithms of Measuring, Processing and Interpretation of Experimental Data Obtained with Scanning Tunneling Microscope * Time-dependent Atom-surface Interactions * Local and Global Minima on Molecular Potential Energy Surfaces: An Example of N3 Radical * Computation of Bifurcation Surfaces * Symbolic Computations in Quantum Mechanics: Energies in Next-to-solvable Systems * A Tool for RTP Reactor and Lamp Field Design * Modelling of Particle Spectra for the Analysis of Solid State Surface * List of Participants

Analysis of three-phase equilibrium conditions for methane hydrate by isometric-isothermal molecular dynamics simulations.

PubMed

Yuhara, Daisuke; Brumby, Paul E; Wu, David T; Sum, Amadeu K; Yasuoka, Kenji

2018-05-14

To develop prediction methods of three-phase equilibrium (coexistence) conditions of methane hydrate by molecular simulations, we examined the use of NVT (isometric-isothermal) molecular dynamics (MD) simulations. NVT MD simulations of coexisting solid hydrate, liquid water, and vapor methane phases were performed at four different temperatures, namely, 285, 290, 295, and 300 K. NVT simulations do not require complex pressure control schemes in multi-phase systems, and the growth or dissociation of the hydrate phase can lead to significant pressure changes in the approach toward equilibrium conditions. We found that the calculated equilibrium pressures tended to be higher than those reported by previous NPT (isobaric-isothermal) simulation studies using the same water model. The deviations of equilibrium conditions from previous simulation studies are mainly attributable to the employed calculation methods of pressure and Lennard-Jones interactions. We monitored the pressure in the methane phase, far from the interfaces with other phases, and confirmed that it was higher than the total pressure of the system calculated by previous studies. This fact clearly highlights the difficulties associated with the pressure calculation and control for multi-phase systems. The treatment of Lennard-Jones interactions without tail corrections in MD simulations also contributes to the overestimation of equilibrium pressure. Although improvements are still required to obtain accurate equilibrium conditions, NVT MD simulations exhibit potential for the prediction of equilibrium conditions of multi-phase systems.

Analysis of three-phase equilibrium conditions for methane hydrate by isometric-isothermal molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Yuhara, Daisuke; Brumby, Paul E.; Wu, David T.; Sum, Amadeu K.; Yasuoka, Kenji

2018-05-01

To develop prediction methods of three-phase equilibrium (coexistence) conditions of methane hydrate by molecular simulations, we examined the use of NVT (isometric-isothermal) molecular dynamics (MD) simulations. NVT MD simulations of coexisting solid hydrate, liquid water, and vapor methane phases were performed at four different temperatures, namely, 285, 290, 295, and 300 K. NVT simulations do not require complex pressure control schemes in multi-phase systems, and the growth or dissociation of the hydrate phase can lead to significant pressure changes in the approach toward equilibrium conditions. We found that the calculated equilibrium pressures tended to be higher than those reported by previous NPT (isobaric-isothermal) simulation studies using the same water model. The deviations of equilibrium conditions from previous simulation studies are mainly attributable to the employed calculation methods of pressure and Lennard-Jones interactions. We monitored the pressure in the methane phase, far from the interfaces with other phases, and confirmed that it was higher than the total pressure of the system calculated by previous studies. This fact clearly highlights the difficulties associated with the pressure calculation and control for multi-phase systems. The treatment of Lennard-Jones interactions without tail corrections in MD simulations also contributes to the overestimation of equilibrium pressure. Although improvements are still required to obtain accurate equilibrium conditions, NVT MD simulations exhibit potential for the prediction of equilibrium conditions of multi-phase systems.

Molecular dynamics simulations of thermally activated edge dislocation unpinning from voids in α -Fe

NASA Astrophysics Data System (ADS)

Byggmästar, J.; Granberg, F.; Nordlund, K.

2017-10-01

In this study, thermal unpinning of edge dislocations from voids in α -Fe is investigated by means of molecular dynamics simulations. The activation energy as a function of shear stress and temperature is systematically determined. Simulations with a constant applied stress are compared with dynamic simulations with a constant strain rate. We found that a constant applied stress results in a temperature-dependent activation energy. The temperature dependence is attributed to the elastic softening of iron. If the stress is normalized with the softening of the specific shear modulus, the activation energy is shown to be temperature-independent. From the dynamic simulations, the activation energy as a function of critical shear stress was determined using previously developed methods. The results from the dynamic simulations are in good agreement with the constant stress simulations, after the normalization. This indicates that the computationally more efficient dynamic method can be used to obtain the activation energy as a function of stress and temperature. The obtained relation between stress, temperature, and activation energy can be used to introduce a stochastic unpinning event in larger-scale simulation methods, such as discrete dislocation dynamics.

Examinations of tRNA Range of Motion Using Simulations of Cryo-EM Microscopy and X-Ray Data.

PubMed

Caulfield, Thomas R; Devkota, Batsal; Rollins, Geoffrey C

2011-01-01

We examined tRNA flexibility using a combination of steered and unbiased molecular dynamics simulations. Using Maxwell's demon algorithm, molecular dynamics was used to steer X-ray structure data toward that from an alternative state obtained from cryogenic-electron microscopy density maps. Thus, we were able to fit X-ray structures of tRNA onto cryogenic-electron microscopy density maps for hybrid states of tRNA. Additionally, we employed both Maxwell's demon molecular dynamics simulations and unbiased simulation methods to identify possible ribosome-tRNA contact areas where the ribosome may discriminate tRNAs during translation. Herein, we collected >500 ns of simulation data to assess the global range of motion for tRNAs. Biased simulations can be used to steer between known conformational stop points, while unbiased simulations allow for a general testing of conformational space previously unexplored. The unbiased molecular dynamics data describes the global conformational changes of tRNA on a sub-microsecond time scale for comparison with steered data. Additionally, the unbiased molecular dynamics data was used to identify putative contacts between tRNA and the ribosome during the accommodation step of translation. We found that the primary contact regions were H71 and H92 of the 50S subunit and ribosomal proteins L14 and L16.

Molecular simulation of the thermophysical properties and phase behaviour of impure CO2 relevant to CCS.

PubMed

Cresswell, Alexander J; Wheatley, Richard J; Wilkinson, Richard D; Graham, Richard S

2016-10-20

Impurities from the CCS chain can greatly influence the physical properties of CO 2 . This has important design, safety and cost implications for the compression, transport and storage of CO 2 . There is an urgent need to understand and predict the properties of impure CO 2 to assist with CCS implementation. However, CCS presents demanding modelling requirements. A suitable model must both accurately and robustly predict CO 2 phase behaviour over a wide range of temperatures and pressures, and maintain that predictive power for CO 2 mixtures with numerous, mutually interacting chemical species. A promising technique to address this task is molecular simulation. It offers a molecular approach, with foundations in firmly established physical principles, along with the potential to predict the wide range of physical properties required for CCS. The quality of predictions from molecular simulation depends on accurate force-fields to describe the interactions between CO 2 and other molecules. Unfortunately, there is currently no universally applicable method to obtain force-fields suitable for molecular simulation. In this paper we present two methods of obtaining force-fields: the first being semi-empirical and the second using ab initio quantum-chemical calculations. In the first approach we optimise the impurity force-field against measurements of the phase and pressure-volume behaviour of CO 2 binary mixtures with N 2 , O 2 , Ar and H 2 . A gradient-free optimiser allows us to use the simulation itself as the underlying model. This leads to accurate and robust predictions under conditions relevant to CCS. In the second approach we use quantum-chemical calculations to produce ab initio evaluations of the interactions between CO 2 and relevant impurities, taking N 2 as an exemplar. We use a modest number of these calculations to train a machine-learning algorithm, known as a Gaussian process, to describe these data. The resulting model is then able to accurately predict a much broader set of ab initio force-field calculations at comparatively low numerical cost. Although our method is not yet ready to be implemented in a molecular simulation, we outline the necessary steps here. Such simulations have the potential to deliver first-principles simulation of the thermodynamic properties of impure CO 2 , without fitting to experimental data.

Molecular dynamics simulations of classical sound absorption in a monatomic gas

NASA Astrophysics Data System (ADS)

Ayub, M.; Zander, A. C.; Huang, D. M.; Cazzolato, B. S.; Howard, C. Q.

2018-05-01

Sound wave propagation in argon gas is simulated using molecular dynamics (MD) in order to determine the attenuation of acoustic energy due to classical (viscous and thermal) losses at high frequencies. In addition, a method is described to estimate attenuation of acoustic energy using the thermodynamic concept of exergy. The results are compared against standing wave theory and the predictions of the theory of continuum mechanics. Acoustic energy losses are studied by evaluating various attenuation parameters and by comparing the changes in behavior at three different frequencies. This study demonstrates acoustic absorption effects in a gas simulated in a thermostatted molecular simulation and quantifies the classical losses in terms of the sound attenuation constant. The approach can be extended to further understanding of acoustic loss mechanisms in the presence of nanoscale porous materials in the simulation domain.

The Bravyi-Kitaev transformation for quantum computation of electronic structure

NASA Astrophysics Data System (ADS)

Seeley, Jacob T.; Richard, Martin J.; Love, Peter J.

2012-12-01

Quantum simulation is an important application of future quantum computers with applications in quantum chemistry, condensed matter, and beyond. Quantum simulation of fermionic systems presents a specific challenge. The Jordan-Wigner transformation allows for representation of a fermionic operator by O(n) qubit operations. Here, we develop an alternative method of simulating fermions with qubits, first proposed by Bravyi and Kitaev [Ann. Phys. 298, 210 (2002), 10.1006/aphy.2002.6254; e-print arXiv:quant-ph/0003137v2], that reduces the simulation cost to O(log n) qubit operations for one fermionic operation. We apply this new Bravyi-Kitaev transformation to the task of simulating quantum chemical Hamiltonians, and give a detailed example for the simplest possible case of molecular hydrogen in a minimal basis. We show that the quantum circuit for simulating a single Trotter time step of the Bravyi-Kitaev derived Hamiltonian for H2 requires fewer gate applications than the equivalent circuit derived from the Jordan-Wigner transformation. Since the scaling of the Bravyi-Kitaev method is asymptotically better than the Jordan-Wigner method, this result for molecular hydrogen in a minimal basis demonstrates the superior efficiency of the Bravyi-Kitaev method for all quantum computations of electronic structure.

Molecular dynamics simulations and novel drug discovery.

PubMed

Liu, Xuewei; Shi, Danfeng; Zhou, Shuangyan; Liu, Hongli; Liu, Huanxiang; Yao, Xiaojun

2018-01-01

Molecular dynamics (MD) simulations can provide not only plentiful dynamical structural information on biomacromolecules but also a wealth of energetic information about protein and ligand interactions. Such information is very important to understanding the structure-function relationship of the target and the essence of protein-ligand interactions and to guiding the drug discovery and design process. Thus, MD simulations have been applied widely and successfully in each step of modern drug discovery. Areas covered: In this review, the authors review the applications of MD simulations in novel drug discovery, including the pathogenic mechanisms of amyloidosis diseases, virtual screening and the interaction mechanisms between drugs and targets. Expert opinion: MD simulations have been used widely in investigating the pathogenic mechanisms of diseases caused by protein misfolding, in virtual screening, and in investigating drug resistance mechanisms caused by mutations of the target. These issues are very difficult to solve by experimental methods alone. Thus, in the future, MD simulations will have wider application with the further improvement of computational capacity and the development of better sampling methods and more accurate force fields together with more efficient analysis methods.

Molecular dynamics study of the melting curve of NiTi alloy under pressure

NASA Astrophysics Data System (ADS)

Zeng, Zhao-Yi; Hu, Cui-E.; Cai, Ling-Cang; Chen, Xiang-Rong; Jing, Fu-Qian

2011-02-01

The melting curve of NiTi alloy was predicted by using molecular dynamics simulations combining with the embedded atom model potential. The calculated thermal equation of state consists well with our previous results obtained from quasiharmonic Debye approximation. Fitting the well-known Simon form to our Tm data yields the melting curves for NiTi: 1850(1 + P/21.938)0.328 (for one-phase method) and 1575(1 + P/7.476)0.305 (for two-phase method). The two-phase simulations can effectively eliminate the superheating in one-phase simulations. At 1 bar, the melting temperature of NiTi is 1575 ± 25 K and the corresponding melting slope is 64 K/GPa.

Discrete Molecular Dynamics Approach to the Study of Disordered and Aggregating Proteins.

PubMed

Emperador, Agustí; Orozco, Modesto

2017-03-14

We present a refinement of the Coarse Grained PACSAB force field for Discrete Molecular Dynamics (DMD) simulations of proteins in aqueous conditions. As the original version, the refined method provides good representation of the structure and dynamics of folded proteins but provides much better representations of a variety of unfolded proteins, including some very large, impossible to analyze by atomistic simulation methods. The PACSAB/DMD method also reproduces accurately aggregation properties, providing good pictures of the structural ensembles of proteins showing a folded core and an intrinsically disordered region. The combination of accuracy and speed makes the method presented here a good alternative for the exploration of unstructured protein systems.

Molecular Dynamics Simulations with Quantum Mechanics/Molecular Mechanics and Adaptive Neural Networks.

PubMed

Shen, Lin; Yang, Weitao

2018-03-13

Direct molecular dynamics (MD) simulation with ab initio quantum mechanical and molecular mechanical (QM/MM) methods is very powerful for studying the mechanism of chemical reactions in a complex environment but also very time-consuming. The computational cost of QM/MM calculations during MD simulations can be reduced significantly using semiempirical QM/MM methods with lower accuracy. To achieve higher accuracy at the ab initio QM/MM level, a correction on the existing semiempirical QM/MM model is an attractive idea. Recently, we reported a neural network (NN) method as QM/MM-NN to predict the potential energy difference between semiempirical and ab initio QM/MM approaches. The high-level results can be obtained using neural network based on semiempirical QM/MM MD simulations, but the lack of direct MD samplings at the ab initio QM/MM level is still a deficiency that limits the applications of QM/MM-NN. In the present paper, we developed a dynamic scheme of QM/MM-NN for direct MD simulations on the NN-predicted potential energy surface to approximate ab initio QM/MM MD. Since some configurations excluded from the database for NN training were encountered during simulations, which may cause some difficulties on MD samplings, an adaptive procedure inspired by the selection scheme reported by Behler [ Behler Int. J. Quantum Chem. 2015 , 115 , 1032 ; Behler Angew. Chem., Int. Ed. 2017 , 56 , 12828 ] was employed with some adaptions to update NN and carry out MD iteratively. We further applied the adaptive QM/MM-NN MD method to the free energy calculation and transition path optimization on chemical reactions in water. The results at the ab initio QM/MM level can be well reproduced using this method after 2-4 iteration cycles. The saving in computational cost is about 2 orders of magnitude. It demonstrates that the QM/MM-NN with direct MD simulations has great potentials not only for the calculation of thermodynamic properties but also for the characterization of reaction dynamics, which provides a useful tool to study chemical or biochemical systems in solution or enzymes.

Why human milk is more nutritious than cow milk

NASA Astrophysics Data System (ADS)

Voorhoeve, Niels; Allan, Douglas C.; Moret, M. A.; Zebende, G. F.; Phillips, J. C.

2018-05-01

The evolution of milk, the key infant nutrient, is analyzed using a novel thermodynamic molecular method. The method is general, and it has many advantages compared to conventional molecular dynamics simulations. It is much simpler, and it connects amino acid sequences directly to function, often without knowing detailed "folded" globular structures. It emphasizes synchronized critical fluctuations due to long-range correlations in globular curvatures. The titled question has not been answered, or even discussed successfully, by other molecular methods.

Perspectives on the simulation of protein–surface interactions using empirical force field methods

PubMed Central

Latour, Robert A.

2014-01-01

Protein–surface interactions are of fundamental importance for a broad range of applications in the fields of biomaterials and biotechnology. Present experimental methods are limited in their ability to provide a comprehensive depiction of these interactions at the atomistic level. In contrast, empirical force field based simulation methods inherently provide the ability to predict and visualize protein–surface interactions with full atomistic detail. These methods, however, must be carefully developed, validated, and properly applied before confidence can be placed in results from the simulations. In this perspectives paper, I provide an overview of the critical aspects that I consider being of greatest importance for the development of these methods, with a focus on the research that my combined experimental and molecular simulation groups have conducted over the past decade to address these issues. These critical issues include the tuning of interfacial force field parameters to accurately represent the thermodynamics of interfacial behavior, adequate sampling of these types of complex molecular systems to generate results that can be comparable with experimental data, and the generation of experimental data that can be used for simulation results evaluation and validation. PMID:25028242

Coupling all-atom molecular dynamics simulations of ions in water with Brownian dynamics.

PubMed

Erban, Radek

2016-02-01

Molecular dynamics (MD) simulations of ions (K + , Na + , Ca 2+ and Cl - ) in aqueous solutions are investigated. Water is described using the SPC/E model. A stochastic coarse-grained description for ion behaviour is presented and parametrized using MD simulations. It is given as a system of coupled stochastic and ordinary differential equations, describing the ion position, velocity and acceleration. The stochastic coarse-grained model provides an intermediate description between all-atom MD simulations and Brownian dynamics (BD) models. It is used to develop a multiscale method which uses all-atom MD simulations in parts of the computational domain and (less detailed) BD simulations in the remainder of the domain.

Coarse-grained molecular dynamics simulations for giant protein-DNA complexes

NASA Astrophysics Data System (ADS)

Takada, Shoji

Biomolecules are highly hierarchic and intrinsically flexible. Thus, computational modeling calls for multi-scale methodologies. We have been developing a coarse-grained biomolecular model where on-average 10-20 atoms are grouped into one coarse-grained (CG) particle. Interactions among CG particles are tuned based on atomistic interactions and the fluctuation matching algorithm. CG molecular dynamics methods enable us to simulate much longer time scale motions of much larger molecular systems than fully atomistic models. After broad sampling of structures with CG models, we can easily reconstruct atomistic models, from which one can continue conventional molecular dynamics simulations if desired. Here, we describe our CG modeling methodology for protein-DNA complexes, together with various biological applications, such as the DNA duplication initiation complex, model chromatins, and transcription factor dynamics on chromatin-like environment.

Bond-valence methods for pKa prediction. II. Bond-valence, electrostatic, molecular geometry, and solvation effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bickmore, Barry R.; Rosso, Kevin M.; Tadanier, Christopher J.

2006-08-15

In a previous contribution, we outlined a method for predicting (hydr)oxy-acid and oxide surface acidity constants based on three main factors: bond valence, Me?O bond ionicity, and molecular shape. Here electrostatics calculations and ab initio molecular dynamics simulations are used to qualitatively show that Me?O bond ionicity controls the extent to which the electrostatic work of proton removal departs from ideality, bond valence controls the extent of solvation of individual functional groups, and bond valence and molecular shape controls local dielectric response. These results are consistent with our model of acidity, but completely at odds with other methods of predictingmore » acidity constants for use in multisite complexation models. In particular, our ab initio molecular dynamics simulations of solvated monomers clearly indicate that hydrogen bonding between (hydr)oxo-groups and water molecules adjusts to obey the valence sum rule, rather than maintaining a fixed valence based on the coordination of the oxygen atom as predicted by the standard MUSIC model.« less

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

PubMed

Curuksu, Jeremy; Zacharias, Martin

2009-03-14

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

Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

NASA Astrophysics Data System (ADS)

Matsushita, Y.; Murakawa, T.; Shimamura, K.; Oishi, M.; Ohyama, T.; Kurita, N.

2015-02-01

The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA.

Reproducing Quantum Probability Distributions at the Speed of Classical Dynamics: A New Approach for Developing Force-Field Functors.

PubMed

Sundar, Vikram; Gelbwaser-Klimovsky, David; Aspuru-Guzik, Alán

2018-04-05

Modeling nuclear quantum effects is required for accurate molecular dynamics (MD) simulations of molecules. The community has paid special attention to water and other biomolecules that show hydrogen bonding. Standard methods of modeling nuclear quantum effects like Ring Polymer Molecular Dynamics (RPMD) are computationally costlier than running classical trajectories. A force-field functor (FFF) is an alternative method that computes an effective force field that replicates quantum properties of the original force field. In this work, we propose an efficient method of computing FFF using the Wigner-Kirkwood expansion. As a test case, we calculate a range of thermodynamic properties of Neon, obtaining the same level of accuracy as RPMD, but with the shorter runtime of classical simulations. By modifying existing MD programs, the proposed method could be used in the future to increase the efficiency and accuracy of MD simulations involving water and proteins.

Automated sampling assessment for molecular simulations using the effective sample size

PubMed Central

Zhang, Xin; Bhatt, Divesh; Zuckerman, Daniel M.

2010-01-01

To quantify the progress in the development of algorithms and forcefields used in molecular simulations, a general method for the assessment of the sampling quality is needed. Statistical mechanics principles suggest the populations of physical states characterize equilibrium sampling in a fundamental way. We therefore develop an approach for analyzing the variances in state populations, which quantifies the degree of sampling in terms of the effective sample size (ESS). The ESS estimates the number of statistically independent configurations contained in a simulated ensemble. The method is applicable to both traditional dynamics simulations as well as more modern (e.g., multi–canonical) approaches. Our procedure is tested in a variety of systems from toy models to atomistic protein simulations. We also introduce a simple automated procedure to obtain approximate physical states from dynamic trajectories: this allows sample–size estimation in systems for which physical states are not known in advance. PMID:21221418

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

PubMed Central

Wabik, Jacek; Kmiecik, Sebastian; Gront, Dominik; Kouza, Maksim; Koliński, 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. PMID:23665897

Teaching Ionic Solvation Structure with a Monte Carlo Liquid Simulation Program

ERIC Educational Resources Information Center

Serrano, Agostinho; Santos, Flavia M. T.; Greca, Ileana M.

2004-01-01

The use of molecular dynamics and Monte Carlo methods has provided efficient means to stimulate the behavior of molecular liquids and solutions. A Monte Carlo simulation program is used to compute the structure of liquid water and of water as a solvent to Na(super +), Cl(super -), and Ar on a personal computer to show that it is easily feasible to…

Parallel Decomposition of the Fictitious Lagrangian Algorithm and its Accuracy for Molecular Dynamics Simulations of Semiconductors.

NASA Astrophysics Data System (ADS)

Yeh, Mei-Ling

We have performed a parallel decomposition of the fictitious Lagrangian method for molecular dynamics with tight-binding total energy expression into the hypercube computer. This is the first time in literature that the dynamical simulation of semiconducting systems containing more than 512 silicon atoms has become possible with the electrons treated as quantum particles. With the utilization of the Intel Paragon system, our timing analysis predicts that our code is expected to perform realistic simulations on very large systems consisting of thousands of atoms with time requirements of the order of tens of hours. Timing results and performance analysis of our parallel code are presented in terms of calculation time, communication time, and setup time. The accuracy of the fictitious Lagrangian method in molecular dynamics simulation is also investigated, especially the energy conservation of the total energy of ions. We find that the accuracy of the fictitious Lagrangian scheme in small silicon cluster and very large silicon system simulations is good for as long as the simulations proceed, even though we quench the electronic coordinates to the Born-Oppenheimer surface only in the beginning of the run. The kinetic energy of electrons does not increase as time goes on, and the energy conservation of the ionic subsystem remains very good. This means that, as far as the ionic subsystem is concerned, the electrons are on the average in the true quantum ground states. We also tie up some odds and ends regarding a few remaining questions about the fictitious Lagrangian method, such as the difference between the results obtained from the Gram-Schmidt and SHAKE method of orthonormalization, and differences between simulations where the electrons are quenched to the Born -Oppenheimer surface only once compared with periodic quenching.

PyRETIS: A well-done, medium-sized python library for rare events.

PubMed

Lervik, Anders; Riccardi, Enrico; van Erp, Titus S

2017-10-30

Transition path sampling techniques are becoming common approaches in the study of rare events at the molecular scale. More efficient methods, such as transition interface sampling (TIS) and replica exchange transition interface sampling (RETIS), allow the investigation of rare events, for example, chemical reactions and structural/morphological transitions, in a reasonable computational time. Here, we present PyRETIS, a Python library for performing TIS and RETIS simulations. PyRETIS directs molecular dynamics (MD) simulations in order to sample rare events with unbiased dynamics. PyRETIS is designed to be easily interfaced with any molecular simulation package and in the present release, it has been interfaced with GROMACS and CP2K, for classical and ab initio MD simulations, respectively. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Binomial tau-leap spatial stochastic simulation algorithm for applications in chemical kinetics.

PubMed

Marquez-Lago, Tatiana T; Burrage, Kevin

2007-09-14

In cell biology, cell signaling pathway problems are often tackled with deterministic temporal models, well mixed stochastic simulators, and/or hybrid methods. But, in fact, three dimensional stochastic spatial modeling of reactions happening inside the cell is needed in order to fully understand these cell signaling pathways. This is because noise effects, low molecular concentrations, and spatial heterogeneity can all affect the cellular dynamics. However, there are ways in which important effects can be accounted without going to the extent of using highly resolved spatial simulators (such as single-particle software), hence reducing the overall computation time significantly. We present a new coarse grained modified version of the next subvolume method that allows the user to consider both diffusion and reaction events in relatively long simulation time spans as compared with the original method and other commonly used fully stochastic computational methods. Benchmarking of the simulation algorithm was performed through comparison with the next subvolume method and well mixed models (MATLAB), as well as stochastic particle reaction and transport simulations (CHEMCELL, Sandia National Laboratories). Additionally, we construct a model based on a set of chemical reactions in the epidermal growth factor receptor pathway. For this particular application and a bistable chemical system example, we analyze and outline the advantages of our presented binomial tau-leap spatial stochastic simulation algorithm, in terms of efficiency and accuracy, in scenarios of both molecular homogeneity and heterogeneity.

Computer simulation and experimental study of the polysaccharide-polysaccharide interaction in the bacteria Azospirillum brasilense Sp245

NASA Astrophysics Data System (ADS)

Arefeva, Oksana A.; Kuznetsov, Pavel E.; Tolmachev, Sergey A.; Kupadze, Machammad S.; Khlebtsov, Boris N.; Rogacheva, Svetlana M.

2003-09-01

We have studied the conformational properties and molecular dynamics of polysaccharides by using molecular modeling methods. Theoretical and experimental results of polysaccharide-polysaccharide interactions are described.

Misclassification Errors in Unsupervised Classification Methods. Comparison Based on the Simulation of Targeted Proteomics Data

PubMed Central

Andreev, Victor P; Gillespie, Brenda W; Helfand, Brian T; Merion, Robert M

2016-01-01

Unsupervised classification methods are gaining acceptance in omics studies of complex common diseases, which are often vaguely defined and are likely the collections of disease subtypes. Unsupervised classification based on the molecular signatures identified in omics studies have the potential to reflect molecular mechanisms of the subtypes of the disease and to lead to more targeted and successful interventions for the identified subtypes. Multiple classification algorithms exist but none is ideal for all types of data. Importantly, there are no established methods to estimate sample size in unsupervised classification (unlike power analysis in hypothesis testing). Therefore, we developed a simulation approach allowing comparison of misclassification errors and estimating the required sample size for a given effect size, number, and correlation matrix of the differentially abundant proteins in targeted proteomics studies. All the experiments were performed in silico. The simulated data imitated the expected one from the study of the plasma of patients with lower urinary tract dysfunction with the aptamer proteomics assay Somascan (SomaLogic Inc, Boulder, CO), which targeted 1129 proteins, including 330 involved in inflammation, 180 in stress response, 80 in aging, etc. Three popular clustering methods (hierarchical, k-means, and k-medoids) were compared. K-means clustering performed much better for the simulated data than the other two methods and enabled classification with misclassification error below 5% in the simulated cohort of 100 patients based on the molecular signatures of 40 differentially abundant proteins (effect size 1.5) from among the 1129-protein panel. PMID:27524871

A Review of Computational Methods in Materials Science: Examples from Shock-Wave and Polymer Physics

PubMed Central

Steinhauser, Martin O.; Hiermaier, Stefan

2009-01-01

This review discusses several computational methods used on different length and time scales for the simulation of material behavior. First, the importance of physical modeling and its relation to computer simulation on multiscales is discussed. Then, computational methods used on different scales are shortly reviewed, before we focus on the molecular dynamics (MD) method. Here we survey in a tutorial-like fashion some key issues including several MD optimization techniques. Thereafter, computational examples for the capabilities of numerical simulations in materials research are discussed. We focus on recent results of shock wave simulations of a solid which are based on two different modeling approaches and we discuss their respective assets and drawbacks with a view to their application on multiscales. Then, the prospects of computer simulations on the molecular length scale using coarse-grained MD methods are covered by means of examples pertaining to complex topological polymer structures including star-polymers, biomacromolecules such as polyelectrolytes and polymers with intrinsic stiffness. This review ends by highlighting new emerging interdisciplinary applications of computational methods in the field of medical engineering where the application of concepts of polymer physics and of shock waves to biological systems holds a lot of promise for improving medical applications such as extracorporeal shock wave lithotripsy or tumor treatment. PMID:20054467

Hybrid molecular dynamics simulation for plasma induced damage analysis

NASA Astrophysics Data System (ADS)

Matsukuma, Masaaki

2016-09-01

In order to enable further device size reduction (also known as Moore's law) and improved power performance, the semiconductor industry is introducing new materials and device structures into the semiconductor fabrication process. Materials now include III-V compounds, germanium, cobalt, ruthenium, hafnium, and others. The device structure in both memory and logic has been evolving from planar to three dimensional (3D). One such device is the FinFET, where the transistor gate is a vertical fin made either of silicon, silicon-germanium or germanium. These changes have brought renewed interests in the structural damages caused by energetic ion bombardment of the fin sidewalls which are exposed to the ion flux from the plasma during the fin-strip off step. Better control of the physical damage of the 3D devices requires a better understanding of the damage formation mechanisms on such new materials and structures. In this study, the damage formation processes by ion bombardment have been simulated for Si and Ge substrate by Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid simulations and compared to the results from the classical molecular dynamics (MD) simulations. In our QM/MM simulations, the highly reactive region in which the structural damage is created is simulated with the Density Functional based Tight Binding (DFTB) method and the region remote from the primary region is simulated using classical MD with the Stillinger-Weber and Moliere potentials. The learn on the fly method is also used to reduce the computational load. Hence our QM/MM simulation is much faster than the full QC-MD simulations and the original QM/MM simulations. The amorphous layers profile simulated with QM/MM have obvious differences in their thickness for silicon and germanium substrate. The profile of damaged structure in the germanium substrate is characterized by a deeper tail then in silicon. These traits are also observed in the results from the mass selected ion beam experiments. This observed damage profile dependence on species and substrate cannot be reproduced using classical MD simulations. While the Moliere potential is convenient to describe the interactions between halogens and other atoms, more accurate interatomic modeling such as DFTB method which takes the molecular orbitals into account should be utilized to make the simulations more realistic. Based on the simulations results, the damage formation scenario will be discussed.

Estimation of Nanodiamond Surface Charge Density from Zeta Potential and Molecular Dynamics Simulations.

PubMed

Ge, Zhenpeng; Wang, Yi

2017-04-20

Molecular dynamics simulations of nanoparticles (NPs) are increasingly used to study their interactions with various biological macromolecules. Such simulations generally require detailed knowledge of the surface composition of the NP under investigation. Even for some well-characterized nanoparticles, however, this knowledge is not always available. An example is nanodiamond, a nanoscale diamond particle with surface dominated by oxygen-containing functional groups. In this work, we explore using the harmonic restraint method developed by Venable et al., to estimate the surface charge density (σ) of nanodiamonds. Based on the Gouy-Chapman theory, we convert the experimentally determined zeta potential of a nanodiamond to an effective charge density (σ eff ), and then use the latter to estimate σ via molecular dynamics simulations. Through scanning a series of nanodiamond models, we show that the above method provides a straightforward protocol to determine the surface charge density of relatively large (> ∼100 nm) NPs. Overall, our results suggest that despite certain limitation, the above protocol can be readily employed to guide the model construction for MD simulations, which is particularly useful when only limited experimental information on the NP surface composition is available to a modeler.

Motions and entropies in proteins as seen in NMR relaxation experiments and molecular dynamics simulations.

PubMed

Allnér, Olof; Foloppe, Nicolas; Nilsson, Lennart

2015-01-22

Molecular dynamics simulations of E. coli glutaredoxin1 in water have been performed to relate the dynamical parameters and entropy obtained in NMR relaxation experiments, with results extracted from simulated trajectory data. NMR relaxation is the most widely used experimental method to obtain data on dynamics of proteins, but it is limited to relatively short timescales and to motions of backbone amides or in some cases (13)C-H vectors. By relating the experimental data to the all-atom picture obtained in molecular dynamics simulations, valuable insights on the interpretation of the experiment can be gained. We have estimated the internal dynamics and their timescales by calculating the generalized order parameters (O) for different time windows. We then calculate the quasiharmonic entropy (S) and compare it to the entropy calculated from the NMR-derived generalized order parameter of the amide vectors. Special emphasis is put on characterizing dynamics that are not expressed through the motions of the amide group. The NMR and MD methods suffer from complementary limitations, with NMR being restricted to local vectors and dynamics on a timescale determined by the rotational diffusion of the solute, while in simulations, it may be difficult to obtain sufficient sampling to ensure convergence of the results. We also evaluate the amount of sampling obtained with molecular dynamics simulations and how it is affected by the length of individual simulations, by clustering of the sampled conformations. We find that two structural turns act as hinges, allowing the α helix between them to undergo large, long timescale motions that cannot be detected in the time window of the NMR dipolar relaxation experiments. We also show that the entropy obtained from the amide vector does not account for correlated motions of adjacent residues. Finally, we show that the sampling in a total of 100 ns molecular dynamics simulation can be increased by around 50%, by dividing the trajectory into 10 replicas with different starting velocities.

Diffusion-Based Model for Synaptic Molecular Communication Channel.

PubMed

Khan, Tooba; Bilgin, Bilgesu A; Akan, Ozgur B

2017-06-01

Computational methods have been extensively used to understand the underlying dynamics of molecular communication methods employed by nature. One very effective and popular approach is to utilize a Monte Carlo simulation. Although it is very reliable, this method can have a very high computational cost, which in some cases renders the simulation impractical. Therefore, in this paper, for the special case of an excitatory synaptic molecular communication channel, we present a novel mathematical model for the diffusion and binding of neurotransmitters that takes into account the effects of synaptic geometry in 3-D space and re-absorption of neurotransmitters by the transmitting neuron. Based on this model we develop a fast deterministic algorithm, which calculates expected value of the output of this channel, namely, the amplitude of excitatory postsynaptic potential (EPSP), for given synaptic parameters. We validate our algorithm by a Monte Carlo simulation, which shows total agreement between the results of the two methods. Finally, we utilize our model to quantify the effects of variation in synaptic parameters, such as position of release site, receptor density, size of postsynaptic density, diffusion coefficient, uptake probability, and number of neurotransmitters in a vesicle, on maximum number of bound receptors that directly affect the peak amplitude of EPSP.

Fully Anisotropic Rotational Diffusion Tensor from Molecular Dynamics Simulations.

PubMed

Linke, Max; Köfinger, Jürgen; Hummer, Gerhard

2018-05-31

We present a method to calculate the fully anisotropic rotational diffusion tensor from molecular dynamics simulations. Our approach is based on fitting the time-dependent covariance matrix of the quaternions that describe the rigid-body rotational dynamics. Explicit analytical expressions have been derived for the covariances by Favro, which are valid irrespective of the degree of anisotropy. We use these expressions to determine an optimal rotational diffusion tensor from trajectory data. The molecular structures are aligned against a reference by optimal rigid-body superposition. The quaternion covariances can then be obtained directly from the rotation matrices used in the alignment. The rotational diffusion tensor is determined by a fit to the time-dependent quaternion covariances, or directly by Laplace transformation and matrix diagonalization. To quantify uncertainties in the fit, we derive analytical expressions and compare them with the results of Brownian dynamics simulations of anisotropic rotational diffusion. We apply the method to microsecond long trajectories of the Dickerson-Drew B-DNA dodecamer and of horse heart myoglobin. The anisotropic rotational diffusion tensors calculated from simulations agree well with predictions from hydrodynamics.

Crystal Nucleation in Liquids: Open Questions and Future Challenges in Molecular Dynamics Simulations

PubMed Central

2016-01-01

The nucleation of crystals in liquids is one of nature’s most ubiquitous phenomena, playing an important role in areas such as climate change and the production of drugs. As the early stages of nucleation involve exceedingly small time and length scales, atomistic computer simulations can provide unique insights into the microscopic aspects of crystallization. In this review, we take stock of the numerous molecular dynamics simulations that, in the past few decades, have unraveled crucial aspects of crystal nucleation in liquids. We put into context the theoretical framework of classical nucleation theory and the state-of-the-art computational methods by reviewing simulations of such processes as ice nucleation and the crystallization of molecules in solutions. We shall see that molecular dynamics simulations have provided key insights into diverse nucleation scenarios, ranging from colloidal particles to natural gas hydrates, and that, as a result, the general applicability of classical nucleation theory has been repeatedly called into question. We have attempted to identify the most pressing open questions in the field. We believe that, by improving (i) existing interatomic potentials and (ii) currently available enhanced sampling methods, the community can move toward accurate investigations of realistic systems of practical interest, thus bringing simulations a step closer to experiments. PMID:27228560

Crystal Nucleation in Liquids: Open Questions and Future Challenges in Molecular Dynamics Simulations.

PubMed

Sosso, Gabriele C; Chen, Ji; Cox, Stephen J; Fitzner, Martin; Pedevilla, Philipp; Zen, Andrea; Michaelides, Angelos

2016-06-22

The nucleation of crystals in liquids is one of nature's most ubiquitous phenomena, playing an important role in areas such as climate change and the production of drugs. As the early stages of nucleation involve exceedingly small time and length scales, atomistic computer simulations can provide unique insights into the microscopic aspects of crystallization. In this review, we take stock of the numerous molecular dynamics simulations that, in the past few decades, have unraveled crucial aspects of crystal nucleation in liquids. We put into context the theoretical framework of classical nucleation theory and the state-of-the-art computational methods by reviewing simulations of such processes as ice nucleation and the crystallization of molecules in solutions. We shall see that molecular dynamics simulations have provided key insights into diverse nucleation scenarios, ranging from colloidal particles to natural gas hydrates, and that, as a result, the general applicability of classical nucleation theory has been repeatedly called into question. We have attempted to identify the most pressing open questions in the field. We believe that, by improving (i) existing interatomic potentials and (ii) currently available enhanced sampling methods, the community can move toward accurate investigations of realistic systems of practical interest, thus bringing simulations a step closer to experiments.

Demonstrating an Order-of-Magnitude Sampling Enhancement in Molecular Dynamics Simulations of Complex Protein Systems.

PubMed

Pan, Albert C; Weinreich, Thomas M; Piana, Stefano; Shaw, David E

2016-03-08

Molecular dynamics (MD) simulations can describe protein motions in atomic detail, but transitions between protein conformational states sometimes take place on time scales that are infeasible or very expensive to reach by direct simulation. Enhanced sampling methods, the aim of which is to increase the sampling efficiency of MD simulations, have thus been extensively employed. The effectiveness of such methods when applied to complex biological systems like proteins, however, has been difficult to establish because even enhanced sampling simulations of such systems do not typically reach time scales at which convergence is extensive enough to reliably quantify sampling efficiency. Here, we obtain sufficiently converged simulations of three proteins to evaluate the performance of simulated tempering, a member of a widely used class of enhanced sampling methods that use elevated temperature to accelerate sampling. Simulated tempering simulations with individual lengths of up to 100 μs were compared to (previously published) conventional MD simulations with individual lengths of up to 1 ms. With two proteins, BPTI and ubiquitin, we evaluated the efficiency of sampling of conformational states near the native state, and for the third, the villin headpiece, we examined the rate of folding and unfolding. Our comparisons demonstrate that simulated tempering can consistently achieve a substantial sampling speedup of an order of magnitude or more relative to conventional MD.

ms2: A molecular simulation tool for thermodynamic properties

NASA Astrophysics Data System (ADS)

Deublein, Stephan; Eckl, Bernhard; Stoll, Jürgen; Lishchuk, Sergey V.; Guevara-Carrion, Gabriela; Glass, Colin W.; Merker, Thorsten; Bernreuther, Martin; Hasse, Hans; Vrabec, Jadran

2011-11-01

This work presents the molecular simulation program ms2 that is designed for the calculation of thermodynamic properties of bulk fluids in equilibrium consisting of small electro-neutral molecules. ms2 features the two main molecular simulation techniques, molecular dynamics (MD) and Monte-Carlo. It supports the calculation of vapor-liquid equilibria of pure fluids and multi-component mixtures described by rigid molecular models on the basis of the grand equilibrium method. Furthermore, it is capable of sampling various classical ensembles and yields numerous thermodynamic properties. To evaluate the chemical potential, Widom's test molecule method and gradual insertion are implemented. Transport properties are determined by equilibrium MD simulations following the Green-Kubo formalism. ms2 is designed to meet the requirements of academia and industry, particularly achieving short response times and straightforward handling. It is written in Fortran90 and optimized for a fast execution on a broad range of computer architectures, spanning from single processor PCs over PC-clusters and vector computers to high-end parallel machines. The standard Message Passing Interface (MPI) is used for parallelization and ms2 is therefore easily portable to different computing platforms. Feature tools facilitate the interaction with the code and the interpretation of input and output files. The accuracy and reliability of ms2 has been shown for a large variety of fluids in preceding work. Program summaryProgram title:ms2 Catalogue identifier: AEJF_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEJF_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Special Licence supplied by the authors No. of lines in distributed program, including test data, etc.: 82 794 No. of bytes in distributed program, including test data, etc.: 793 705 Distribution format: tar.gz Programming language: Fortran90 Computer: The simulation tool ms2 is usable on a wide variety of platforms, from single processor machines over PC-clusters and vector computers to vector-parallel architectures. (Tested with Fortran compilers: gfortran, Intel, PathScale, Portland Group and Sun Studio.) Operating system: Unix/Linux, Windows Has the code been vectorized or parallelized?: Yes. Message Passing Interface (MPI) protocol Scalability. Excellent scalability up to 16 processors for molecular dynamics and >512 processors for Monte-Carlo simulations. RAM:ms2 runs on single processors with 512 MB RAM. The memory demand rises with increasing number of processors used per node and increasing number of molecules. Classification: 7.7, 7.9, 12 External routines: Message Passing Interface (MPI) Nature of problem: Calculation of application oriented thermodynamic properties for rigid electro-neutral molecules: vapor-liquid equilibria, thermal and caloric data as well as transport properties of pure fluids and multi-component mixtures. Solution method: Molecular dynamics, Monte-Carlo, various classical ensembles, grand equilibrium method, Green-Kubo formalism. Restrictions: No. The system size is user-defined. Typical problems addressed by ms2 can be solved by simulating systems containing typically 2000 molecules or less. Unusual features: Feature tools are available for creating input files, analyzing simulation results and visualizing molecular trajectories. Additional comments: Sample makefiles for multiple operation platforms are provided. Documentation is provided with the installation package and is available at http://www.ms-2.de. Running time: The running time of ms2 depends on the problem set, the system size and the number of processes used in the simulation. Running four processes on a "Nehalem" processor, simulations calculating VLE data take between two and twelve hours, calculating transport properties between six and 24 hours.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamberaj, Hiqmet, E-mail: hkamberaj@ibu.edu.mk

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

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

NASA Astrophysics Data System (ADS)

Kamberaj, Hiqmet

2015-09-01

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

Self-Assembly Behavior of Amphiphilic Janus Dendrimers in Water: A Combined Experimental and Coarse-Grained Molecular Dynamics Simulation Approach.

PubMed

Elizondo-García, Mariana E; Márquez-Miranda, Valeria; Araya-Durán, Ingrid; Valencia-Gallegos, Jesús A; González-Nilo, Fernando D

2018-04-21

Amphiphilic Janus dendrimers (JDs) are repetitively branched molecules with hydrophilic and hydrophobic components that self-assemble in water to form a variety of morphologies, including vesicles analogous to liposomes with potential pharmaceutical and medical application. To date, the self-assembly of JDs has not been fully investigated thus it is important to gain insight into its mechanism and dependence on JDs’ molecular structure. In this study, the aggregation behavior in water of a second-generation bis-MPA JD was evaluated using experimental and computational methods. Dispersions of JDs in water were carried out using the thin-film hydration and ethanol injection methods. Resulting assemblies were characterized by dynamic light scattering, confocal microscopy, and atomic force microscopy. Furthermore, a coarse-grained molecular dynamics (CG-MD) simulation was performed to study the mechanism of JDs aggregation. The obtaining of assemblies in water with no interdigitated bilayers was confirmed by the experimental characterization and CG-MD simulation. Assemblies with dendrimersome characteristics were obtained using the ethanol injection method. The results of this study establish a relationship between the molecular structure of the JD and the properties of its aggregates in water. Thus, our findings could be relevant for the design of novel JDs with tailored assemblies suitable for drug delivery systems.

Mathematical modeling of the crack growth in linear elastic isotropic materials by conventional fracture mechanics approaches and by molecular dynamics method: crack propagation direction angle under mixed mode loading

NASA Astrophysics Data System (ADS)

Stepanova, Larisa; Bronnikov, Sergej

2018-03-01

The crack growth directional angles in the isotropic linear elastic plane with the central crack under mixed-mode loading conditions for the full range of the mixity parameter are found. Two fracture criteria of traditional linear fracture mechanics (maximum tangential stress and minimum strain energy density criteria) are used. Atomistic simulations of the central crack growth process in an infinite plane medium under mixed-mode loading using Large-scale Molecular Massively Parallel Simulator (LAMMPS), a classical molecular dynamics code, are performed. The inter-atomic potential used in this investigation is Embedded Atom Method (EAM) potential. The plane specimens with initial central crack were subjected to Mixed-Mode loadings. The simulation cell contains 400000 atoms. The crack propagation direction angles under different values of the mixity parameter in a wide range of values from pure tensile loading to pure shear loading in a wide diapason of temperatures (from 0.1 К to 800 К) are obtained and analyzed. It is shown that the crack propagation direction angles obtained by molecular dynamics method coincide with the crack propagation direction angles given by the multi-parameter fracture criteria based on the strain energy density and the multi-parameter description of the crack-tip fields.

Distance-Based Configurational Entropy of Proteins from Molecular Dynamics Simulations

PubMed Central

Fogolari, Federico; Corazza, Alessandra; Fortuna, Sara; Soler, Miguel Angel; VanSchouwen, Bryan; Brancolini, Giorgia; Corni, Stefano; Melacini, Giuseppe; Esposito, Gennaro

2015-01-01

Estimation of configurational entropy from molecular dynamics trajectories is a difficult task which is often performed using quasi-harmonic or histogram analysis. An entirely different approach, proposed recently, estimates local density distribution around each conformational sample by measuring the distance from its nearest neighbors. In this work we show this theoretically well grounded the method can be easily applied to estimate the entropy from conformational sampling. We consider a set of systems that are representative of important biomolecular processes. In particular: reference entropies for amino acids in unfolded proteins are obtained from a database of residues not participating in secondary structure elements;the conformational entropy of folding of β2-microglobulin is computed from molecular dynamics simulations using reference entropies for the unfolded state;backbone conformational entropy is computed from molecular dynamics simulations of four different states of the EPAC protein and compared with order parameters (often used as a measure of entropy);the conformational and rototranslational entropy of binding is computed from simulations of 20 tripeptides bound to the peptide binding protein OppA and of β2-microglobulin bound to a citrate coated gold surface. This work shows the potential of the method in the most representative biological processes involving proteins, and provides a valuable alternative, principally in the shown cases, where other approaches are problematic. PMID:26177039

Distance-Based Configurational Entropy of Proteins from Molecular Dynamics Simulations.

PubMed

Fogolari, Federico; Corazza, Alessandra; Fortuna, Sara; Soler, Miguel Angel; VanSchouwen, Bryan; Brancolini, Giorgia; Corni, Stefano; Melacini, Giuseppe; Esposito, Gennaro

2015-01-01

Estimation of configurational entropy from molecular dynamics trajectories is a difficult task which is often performed using quasi-harmonic or histogram analysis. An entirely different approach, proposed recently, estimates local density distribution around each conformational sample by measuring the distance from its nearest neighbors. In this work we show this theoretically well grounded the method can be easily applied to estimate the entropy from conformational sampling. We consider a set of systems that are representative of important biomolecular processes. In particular: reference entropies for amino acids in unfolded proteins are obtained from a database of residues not participating in secondary structure elements;the conformational entropy of folding of β2-microglobulin is computed from molecular dynamics simulations using reference entropies for the unfolded state;backbone conformational entropy is computed from molecular dynamics simulations of four different states of the EPAC protein and compared with order parameters (often used as a measure of entropy);the conformational and rototranslational entropy of binding is computed from simulations of 20 tripeptides bound to the peptide binding protein OppA and of β2-microglobulin bound to a citrate coated gold surface. This work shows the potential of the method in the most representative biological processes involving proteins, and provides a valuable alternative, principally in the shown cases, where other approaches are problematic.

Constant pressure and temperature discrete-time Langevin molecular dynamics

NASA Astrophysics Data System (ADS)

Grønbech-Jensen, Niels; Farago, Oded

2014-11-01

We present a new and improved method for simultaneous control of temperature and pressure in molecular dynamics simulations with periodic boundary conditions. The thermostat-barostat equations are built on our previously developed stochastic thermostat, which has been shown to provide correct statistical configurational sampling for any time step that yields stable trajectories. Here, we extend the method and develop a set of discrete-time equations of motion for both particle dynamics and system volume in order to seek pressure control that is insensitive to the choice of the numerical time step. The resulting method is simple, practical, and efficient. The method is demonstrated through direct numerical simulations of two characteristic model systems—a one-dimensional particle chain for which exact statistical results can be obtained and used as benchmarks, and a three-dimensional system of Lennard-Jones interacting particles simulated in both solid and liquid phases. The results, which are compared against the method of Kolb and Dünweg [J. Chem. Phys. 111, 4453 (1999)], show that the new method behaves according to the objective, namely that acquired statistical averages and fluctuations of configurational measures are accurate and robust against the chosen time step applied to the simulation.

Analytic second derivative of the energy for density-functional tight-binding combined with the fragment molecular orbital method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakata, Hiroya, E-mail: hiroya.nakata.gt@kyocera.jp; Nishimoto, Yoshio; Fedorov, Dmitri G.

2016-07-28

The analytic second derivative of the energy is developed for the fragment molecular orbital (FMO) method combined with density-functional tight-binding (DFTB), enabling simulations of infrared and Raman spectra of large molecular systems. The accuracy of the method is established in comparison to full DFTB without fragmentation for a set of representative systems. The performance of the FMO-DFTB Hessian is discussed for molecular systems containing up to 10 041 atoms. The method is applied to the study of the binding of α-cyclodextrin to polyethylene glycol, and the calculated IR spectrum of an epoxy amine oligomer reproduces experiment reasonably well.

Examinations of tRNA Range of Motion Using Simulations of Cryo-EM Microscopy and X-Ray Data

PubMed Central

Caulfield, Thomas R.; Devkota, Batsal; Rollins, Geoffrey C.

2011-01-01

We examined tRNA flexibility using a combination of steered and unbiased molecular dynamics simulations. Using Maxwell's demon algorithm, molecular dynamics was used to steer X-ray structure data toward that from an alternative state obtained from cryogenic-electron microscopy density maps. Thus, we were able to fit X-ray structures of tRNA onto cryogenic-electron microscopy density maps for hybrid states of tRNA. Additionally, we employed both Maxwell's demon molecular dynamics simulations and unbiased simulation methods to identify possible ribosome-tRNA contact areas where the ribosome may discriminate tRNAs during translation. Herein, we collected >500 ns of simulation data to assess the global range of motion for tRNAs. Biased simulations can be used to steer between known conformational stop points, while unbiased simulations allow for a general testing of conformational space previously unexplored. The unbiased molecular dynamics data describes the global conformational changes of tRNA on a sub-microsecond time scale for comparison with steered data. Additionally, the unbiased molecular dynamics data was used to identify putative contacts between tRNA and the ribosome during the accommodation step of translation. We found that the primary contact regions were H71 and H92 of the 50S subunit and ribosomal proteins L14 and L16. PMID:21716650

Coupling discrete and continuum concentration particle models for multiscale and hybrid molecular-continuum simulations

DOE PAGES

Petsev, Nikolai Dimitrov; Leal, L. Gary; Shell, M. Scott

2017-12-21

Hybrid molecular-continuum simulation techniques afford a number of advantages for problems in the rapidly burgeoning area of nanoscale engineering and technology, though they are typically quite complex to implement and limited to single-component fluid systems. We describe an approach for modeling multicomponent hydrodynamic problems spanning multiple length scales when using particle-based descriptions for both the finely-resolved (e.g. molecular dynamics) and coarse-grained (e.g. continuum) subregions within an overall simulation domain. This technique is based on the multiscale methodology previously developed for mesoscale binary fluids [N. D. Petsev, L. G. Leal, and M. S. Shell, J. Chem. Phys. 144, 84115 (2016)], simulatedmore » using a particle-based continuum method known as smoothed dissipative particle dynamics (SDPD). An important application of this approach is the ability to perform coupled molecular dynamics (MD) and continuum modeling of molecularly miscible binary mixtures. In order to validate this technique, we investigate multicomponent hybrid MD-continuum simulations at equilibrium, as well as non-equilibrium cases featuring concentration gradients.« less

Coupling discrete and continuum concentration particle models for multiscale and hybrid molecular-continuum simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petsev, Nikolai Dimitrov; Leal, L. Gary; Shell, M. Scott

Hybrid molecular-continuum simulation techniques afford a number of advantages for problems in the rapidly burgeoning area of nanoscale engineering and technology, though they are typically quite complex to implement and limited to single-component fluid systems. We describe an approach for modeling multicomponent hydrodynamic problems spanning multiple length scales when using particle-based descriptions for both the finely-resolved (e.g. molecular dynamics) and coarse-grained (e.g. continuum) subregions within an overall simulation domain. This technique is based on the multiscale methodology previously developed for mesoscale binary fluids [N. D. Petsev, L. G. Leal, and M. S. Shell, J. Chem. Phys. 144, 84115 (2016)], simulatedmore » using a particle-based continuum method known as smoothed dissipative particle dynamics (SDPD). An important application of this approach is the ability to perform coupled molecular dynamics (MD) and continuum modeling of molecularly miscible binary mixtures. In order to validate this technique, we investigate multicomponent hybrid MD-continuum simulations at equilibrium, as well as non-equilibrium cases featuring concentration gradients.« less

Diamond-like nanoparticles influence on flavonoids transport: molecular modelling

NASA Astrophysics Data System (ADS)

Plastun, Inna L.; Agandeeva, Ksenia E.; Bokarev, Andrey N.; Zenkin, Nikita S.

2017-03-01

Intermolecular interaction of diamond-like nanoparticles and flavonoids is investigated by numerical simulation. Using molecular modelling by the density functional theory method, we analyze hydrogen bonds formation and their influence on IR - spectra and structure of molecular complex which is formed due to interaction between flavonoids and nanodiamonds surrounded with carboxylic groups. Enriched adamantane (1,3,5,7 - adamantanetetracarboxylic acid) is used as an example of diamond-like nanoparticles. Intermolecular forces and structure of hydrogen bonds are investigated. IR - spectra and structure parameters of quercetin - adamantanetetracarboxylic acid molecular complex are obtained by numerical simulation using the Gaussian software complex. Received data coincide well with experimental results. Intermolecular interactions and hydrogen bonding structure in the obtained molecular complex are examined. Possibilities of flavonoids interaction with DNA at the molecular level are also considered.

OpenMM 7: Rapid development of high performance algorithms for molecular dynamics

PubMed Central

Swails, Jason; Zhao, Yutong; Beauchamp, Kyle A.; Wang, Lee-Ping; Stern, Chaya D.; Brooks, Bernard R.; Pande, Vijay S.

2017-01-01

OpenMM is a molecular dynamics simulation toolkit with a unique focus on extensibility. It allows users to easily add new features, including forces with novel functional forms, new integration algorithms, and new simulation protocols. Those features automatically work on all supported hardware types (including both CPUs and GPUs) and perform well on all of them. In many cases they require minimal coding, just a mathematical description of the desired function. They also require no modification to OpenMM itself and can be distributed independently of OpenMM. This makes it an ideal tool for researchers developing new simulation methods, and also allows those new methods to be immediately available to the larger community. PMID:28746339

GPU accelerated Discrete Element Method (DEM) molecular dynamics for conservative, faceted particle simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spellings, Matthew; Biointerfaces Institute, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109; Marson, Ryan L.

Faceted shapes, such as polyhedra, are commonly found in systems of nanoscale, colloidal, and granular particles. Many interesting physical phenomena, like crystal 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 provide an implementation of this method intended for simulation of hard, faceted nanoparticles, with a conservative Weeks–Chandler–Andersen (WCA) interparticle potential, coupled to a thermodynamic ensemble. This method ismore » a natural extension of classical molecular dynamics and enables rigorous thermodynamic calculations for faceted particles.« less

Nucleation Rate Analysis of Methane Hydrate from Molecular Dynamics Simulations

DOE PAGES

Yuhara, Daisuke; Barnes, Brian C.; Suh, Donguk; ...

2015-01-06

Clathrate hydrates are solid crystalline structures most commonly formed from solutions that have nucleated to form a mixed solid composed of water and gas. Understanding the mechanism of clathrate hydrate nucleation is essential to grasp the fundamental chemistry of these complex structures and their applications. Molecular dynamics (MD) simulation is an ideal method to study nucleation at the molecular level because the size of the critical nucleus and formation rate occur on the nano scale. Moreover, various analysis methods for nucleation have been developed through MD to analyze nucleation. In particular, the mean first-passage time (MFPT) and survival probability (SP)more » methods have proven to be effective in procuring the nucleation rate and critical nucleus size for monatomic systems. This study assesses the MFPT and SP methods, previously used for monatomic systems, when applied to analyzing clathrate hydrate nucleation. Because clathrate hydrate nucleation is relatively difficult to observe in MD simulations (due to its high free energy barrier), these methods have yet to be applied to clathrate hydrate systems. In this study, we have analyzed the nucleation rate and critical nucleus size of methane hydrate using MFPT and SP methods from data generated by MD simulations at 255 K and 50 MPa. MFPT was modified for clathrate hydrate from the original version by adding the maximum likelihood estimate and growth effect term. The nucleation rates were calculated by MFPT and SP methods and are within 5%; the critical nucleus size estimated by the MFPT method was 50% higher, than values obtained through other more rigorous but computationally expensive estimates. These methods can also be extended to the analysis of other clathrate hydrates.« less

Nucleation Rate Analysis of Methane Hydrate from Molecular Dynamics Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuhara, Daisuke; Barnes, Brian C.; Suh, Donguk

Clathrate hydrates are solid crystalline structures most commonly formed from solutions that have nucleated to form a mixed solid composed of water and gas. Understanding the mechanism of clathrate hydrate nucleation is essential to grasp the fundamental chemistry of these complex structures and their applications. Molecular dynamics (MD) simulation is an ideal method to study nucleation at the molecular level because the size of the critical nucleus and formation rate occur on the nano scale. Moreover, various analysis methods for nucleation have been developed through MD to analyze nucleation. In particular, the mean first-passage time (MFPT) and survival probability (SP)more » methods have proven to be effective in procuring the nucleation rate and critical nucleus size for monatomic systems. This study assesses the MFPT and SP methods, previously used for monatomic systems, when applied to analyzing clathrate hydrate nucleation. Because clathrate hydrate nucleation is relatively difficult to observe in MD simulations (due to its high free energy barrier), these methods have yet to be applied to clathrate hydrate systems. In this study, we have analyzed the nucleation rate and critical nucleus size of methane hydrate using MFPT and SP methods from data generated by MD simulations at 255 K and 50 MPa. MFPT was modified for clathrate hydrate from the original version by adding the maximum likelihood estimate and growth effect term. The nucleation rates were calculated by MFPT and SP methods and are within 5%; the critical nucleus size estimated by the MFPT method was 50% higher, than values obtained through other more rigorous but computationally expensive estimates. These methods can also be extended to the analysis of other clathrate hydrates.« less

Simulation assisted characterization of kaolinite-methanol intercalation complexes synthesized using cost-efficient homogenization method

NASA Astrophysics Data System (ADS)

Makó, Éva; Kovács, András; Ható, Zoltán; Kristóf, Tamás

2015-12-01

Recent experimental and simulation findings with kaolinite-methanol intercalation complexes raised the question of the existence of more stable structures in wet and dry state, which has not been fully cleared up yet. Experimental and molecular simulation analyses were used to investigate different types of kaolinite-methanol complexes, revealing their real structures. Cost-efficient homogenization methods were applied to synthesize the kaolinite-dimethyl sulfoxide and kaolinite-urea pre-intercalation complexes of the kaolinite-methanol ones. The tested homogenization method required an order of magnitude lower amount of reagents than the generally applied solution method. The influence of the type of pre-intercalated molecules and of the wetting or drying (at room temperature and at 150 °C) procedure on the intercalation was characterized experimentally by X-ray diffraction and thermal analysis. Consistent with the suggestion from the present simulations, 1.12-nm and 0.83-nm stable kaolinite-methanol complexes were identified. For these complexes, our molecular simulations predict either single-layered structures of mobile methanol/water molecules or non-intercalated structures of methoxy-functionalized kaolinite. We found that the methoxy-modified kaolinite can easily be intercalated by liquid methanol.

Simulating botulinum neurotoxin with constant pH molecular dynamics in Generalized Born implicit solvent

NASA Astrophysics Data System (ADS)

Chen, Yongzhi; Chen, Xin; Deng, Yuefan

2007-07-01

A new method was proposed by Mongan et al. for constant pH molecular dynamics simulation and was implemented in AMBER 8 package. Protonation states are modeled with different charge sets, and titrating residues are sampled from a Boltzmann distribution of protonation states. The simulation periodically adopts Monte Carlo sampling based on Generalized Born (GB) derived energies. However, when this approach was applied to a bio-toxin, Botulinum Neurotoxin Type A (BoNT/A) at pH 4.4, 4.7, 5.0, 6.8 and 7.2, the pK predictions yielded by the method were inconsistent with the experimental values. The systems being simulated were divergent. Furthermore, the system behaviors in a very weak acidic solution (pH 6.8) and in a very weak basic solution (pH 7.2) were significantly different from the neutral case (pH 7.0). Hence, we speculate this method may require further study for modeling large biomolecule.

Empirical evaluation of data normalization methods for molecular classification.

PubMed

Huang, Huei-Chung; Qin, Li-Xuan

2018-01-01

Data artifacts due to variations in experimental handling are ubiquitous in microarray studies, and they can lead to biased and irreproducible findings. A popular approach to correct for such artifacts is through post hoc data adjustment such as data normalization. Statistical methods for data normalization have been developed and evaluated primarily for the discovery of individual molecular biomarkers. Their performance has rarely been studied for the development of multi-marker molecular classifiers-an increasingly important application of microarrays in the era of personalized medicine. In this study, we set out to evaluate the performance of three commonly used methods for data normalization in the context of molecular classification, using extensive simulations based on re-sampling from a unique pair of microRNA microarray datasets for the same set of samples. The data and code for our simulations are freely available as R packages at GitHub. In the presence of confounding handling effects, all three normalization methods tended to improve the accuracy of the classifier when evaluated in an independent test data. The level of improvement and the relative performance among the normalization methods depended on the relative level of molecular signal, the distributional pattern of handling effects (e.g., location shift vs scale change), and the statistical method used for building the classifier. In addition, cross-validation was associated with biased estimation of classification accuracy in the over-optimistic direction for all three normalization methods. Normalization may improve the accuracy of molecular classification for data with confounding handling effects; however, it cannot circumvent the over-optimistic findings associated with cross-validation for assessing classification accuracy.

Accelerated Molecular Dynamics Simulations with the AMOEBA Polarizable Force Field on Graphics Processing Units

PubMed Central

2013-01-01

The accelerated molecular dynamics (aMD) method has recently been shown to enhance the sampling of biomolecules in molecular dynamics (MD) simulations, often by several orders of magnitude. Here, we describe an implementation of the aMD method for the OpenMM application layer that takes full advantage of graphics processing units (GPUs) computing. The aMD method is shown to work in combination with the AMOEBA polarizable force field (AMOEBA-aMD), allowing the simulation of long time-scale events with a polarizable force field. Benchmarks are provided to show that the AMOEBA-aMD method is efficiently implemented and produces accurate results in its standard parametrization. For the BPTI protein, we demonstrate that the protein structure described with AMOEBA remains stable even on the extended time scales accessed at high levels of accelerations. For the DNA repair metalloenzyme endonuclease IV, we show that the use of the AMOEBA force field is a significant improvement over fixed charged models for describing the enzyme active-site. The new AMOEBA-aMD method is publicly available (http://wiki.simtk.org/openmm/VirtualRepository) and promises to be interesting for studying complex systems that can benefit from both the use of a polarizable force field and enhanced sampling. PMID:24634618

Simulated tempering based on global balance or detailed balance conditions: Suwa-Todo, heat bath, and Metropolis algorithms.

PubMed

Mori, Yoshiharu; Okumura, Hisashi

2015-12-05

Simulated tempering (ST) is a useful method to enhance sampling of molecular simulations. When ST is used, the Metropolis algorithm, which satisfies the detailed balance condition, is usually applied to calculate the transition probability. Recently, an alternative method that satisfies the global balance condition instead of the detailed balance condition has been proposed by Suwa and Todo. In this study, ST method with the Suwa-Todo algorithm is proposed. Molecular dynamics simulations with ST are performed with three algorithms (the Metropolis, heat bath, and Suwa-Todo algorithms) to calculate the transition probability. Among the three algorithms, the Suwa-Todo algorithm yields the highest acceptance ratio and the shortest autocorrelation time. These suggest that sampling by a ST simulation with the Suwa-Todo algorithm is most efficient. In addition, because the acceptance ratio of the Suwa-Todo algorithm is higher than that of the Metropolis algorithm, the number of temperature states can be reduced by 25% for the Suwa-Todo algorithm when compared with the Metropolis algorithm. © 2015 Wiley Periodicals, Inc.

Molecular simulations of carbohydrates and protein-carbohydrate interactions: motivation, issues and prospects.

PubMed

Fadda, Elisa; Woods, Robert J

2010-08-01

The characterization of the 3D structure of oligosaccharides, their conjugates and analogs is particularly challenging for traditional experimental methods. Molecular simulation methods provide a basis for interpreting sparse experimental data and for independently predicting conformational and dynamic properties of glycans. Here, we summarize and analyze the issues associated with modeling carbohydrates, with a detailed discussion of four of the most recently developed carbohydrate force fields, reviewed in terms of applicability to natural glycans, carbohydrate-protein complexes and the emerging area of glycomimetic drugs. In addition, we discuss prospectives and new applications of carbohydrate modeling in drug discovery.

Enhanced Sampling of Molecular Dynamics Simulations of a Polyalanine Octapeptide: Effects of the Periodic Boundary Conditions on Peptide Conformation.

PubMed

Kasahara, Kota; Sakuraba, Shun; Fukuda, Ikuo

2018-03-08

We investigate the problem of artifacts caused by the periodic boundary conditions (PBC) used in molecular simulation studies. Despite the long history of simulations with PBCs, the existence of measurable artifacts originating from PBCs applied to inherently nonperiodic physical systems remains controversial. Specifically, these artifacts appear as differences between simulations of the same system but with different simulation-cell sizes. Earlier studies have implied that, even in the simple case of a small model peptide in water, sampling inefficiency is a major obstacle to understanding these artifacts. In this study, we have resolved the sampling issue using the replica exchange molecular dynamics (REMD) enhanced-sampling method to explore PBC artifacts. Explicitly solvated zwitterionic polyalanine octapeptides with three different cubic-cells, having dimensions of L = 30, 40, and 50 Å, were investigated to elucidate the differences with 64 replica × 500 ns REMD simulations using the AMBER parm99SB force field. The differences among them were not large overall, and the results for the L = 30 and 40 Å simulations in the conformational free energy landscape were found to be very similar at room temperature. However, a small but statistically significant difference was seen for L = 50 Å. We observed that extended conformations were slightly overstabilized in the smaller systems. The origin of these artifacts is discussed by comparison to an electrostatic calculation method without PBCs.

Revealing Atomic-Level Mechanisms of Protein Allostery with Molecular Dynamics Simulations.

PubMed

Hertig, Samuel; Latorraca, Naomi R; Dror, Ron O

2016-06-01

Molecular dynamics (MD) simulations have become a powerful and popular method for the study of protein allostery, the widespread phenomenon in which a stimulus at one site on a protein influences the properties of another site on the protein. By capturing the motions of a protein's constituent atoms, simulations can enable the discovery of allosteric binding sites and the determination of the mechanistic basis for allostery. These results can provide a foundation for applications including rational drug design and protein engineering. Here, we provide an introduction to the investigation of protein allostery using molecular dynamics simulation. We emphasize the importance of designing simulations that include appropriate perturbations to the molecular system, such as the addition or removal of ligands or the application of mechanical force. We also demonstrate how the bidirectional nature of allostery-the fact that the two sites involved influence one another in a symmetrical manner-can facilitate such investigations. Through a series of case studies, we illustrate how these concepts have been used to reveal the structural basis for allostery in several proteins and protein complexes of biological and pharmaceutical interest.

MaMiCo: Software design for parallel molecular-continuum flow simulations

NASA Astrophysics Data System (ADS)

Neumann, Philipp; Flohr, Hanno; Arora, Rahul; Jarmatz, Piet; Tchipev, Nikola; Bungartz, Hans-Joachim

2016-03-01

The macro-micro-coupling tool (MaMiCo) was developed to ease the development of and modularize molecular-continuum simulations, retaining sequential and parallel performance. We demonstrate the functionality and performance of MaMiCo by coupling the spatially adaptive Lattice Boltzmann framework waLBerla with four molecular dynamics (MD) codes: the light-weight Lennard-Jones-based implementation SimpleMD, the node-level optimized software ls1 mardyn, and the community codes ESPResSo and LAMMPS. We detail interface implementations to connect each solver with MaMiCo. The coupling for each waLBerla-MD setup is validated in three-dimensional channel flow simulations which are solved by means of a state-based coupling method. We provide sequential and strong scaling measurements for the four molecular-continuum simulations. The overhead of MaMiCo is found to come at 10%-20% of the total (MD) runtime. The measurements further show that scalability of the hybrid simulations is reached on up to 500 Intel SandyBridge, and more than 1000 AMD Bulldozer compute cores.

Beyond Standard Molecular Dynamics: Investigating the Molecular Mechanisms of G Protein-Coupled Receptors with Enhanced Molecular Dynamics Methods

PubMed Central

Johnston, Jennifer M.

2014-01-01

The majority of biological processes mediated by G Protein-Coupled Receptors (GPCRs) take place on timescales that are not conveniently accessible to standard molecular dynamics (MD) approaches, notwithstanding the current availability of specialized parallel computer architectures, and efficient simulation algorithms. Enhanced MD-based methods have started to assume an important role in the study of the rugged energy landscape of GPCRs by providing mechanistic details of complex receptor processes such as ligand recognition, activation, and oligomerization. We provide here an overview of these methods in their most recent application to the field. PMID:24158803

Quantum Monte Carlo Methods for First Principles Simulation of Liquid Water

ERIC Educational Resources Information Center

Gergely, John Robert

2009-01-01

Obtaining an accurate microscopic description of water structure and dynamics is of great interest to molecular biology researchers and in the physics and quantum chemistry simulation communities. This dissertation describes efforts to apply quantum Monte Carlo methods to this problem with the goal of making progress toward a fully "ab initio"…

Accelerating atomistic simulations through self-learning bond-boost hyperdynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez, Danny; Voter, Arthur F

2008-01-01

By altering the potential energy landscape on which molecular dynamics are carried out, the hyperdynamics method of Voter enables one to significantly accelerate the simulation state-to-state dynamics of physical systems. While very powerful, successful application of the method entails solving the subtle problem of the parametrization of the so-called bias potential. In this study, we first clarify the constraints that must be obeyed by the bias potential and demonstrate that fast sampling of the biased landscape is key to the obtention of proper kinetics. We then propose an approach by which the bond boost potential of Miron and Fichthorn canmore » be safely parametrized based on data acquired in the course of a molecular dynamics simulation. Finally, we introduce a procedure, the Self-Learning Bond Boost method, in which the parametrization is step efficiently carried out on-the-fly for each new state that is visited during the simulation by safely ramping up the strength of the bias potential up to its optimal value. The stability and accuracy of the method are demonstrated.« less

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

ERIC Educational Resources Information Center

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,…

Conformational ensembles of RNA oligonucleotides from integrating NMR and molecular simulations.

PubMed

Bottaro, Sandro; Bussi, Giovanni; Kennedy, Scott D; Turner, Douglas H; Lindorff-Larsen, Kresten

2018-05-01

RNA molecules are key players in numerous cellular processes and are characterized by a complex relationship between structure, dynamics, and function. Despite their apparent simplicity, RNA oligonucleotides are very flexible molecules, and understanding their internal dynamics is particularly challenging using experimental data alone. We show how to reconstruct the conformational ensemble of four RNA tetranucleotides by combining atomistic molecular dynamics simulations with nuclear magnetic resonance spectroscopy data. The goal is achieved by reweighting simulations using a maximum entropy/Bayesian approach. In this way, we overcome problems of current simulation methods, as well as in interpreting ensemble- and time-averaged experimental data. We determine the populations of different conformational states by considering several nuclear magnetic resonance parameters and point toward properties that are not captured by state-of-the-art molecular force fields. Although our approach is applied on a set of model systems, it is fully general and may be used to study the conformational dynamics of flexible biomolecules and to detect inaccuracies in molecular dynamics force fields.

Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology

PubMed Central

Amemiya, Takahiro; Honma, Masashi; Kariya, Yoshiaki; Ghosh, Samik; Kitano, Hiroaki; Kurachi, Yoshihisa; Fujita, Ken-ichi; Sasaki, Yasutsuna; Homma, Yukio; Abernethy, Darrel R; Kume, Haruki; Suzuki, Hiroshi

2015-01-01

Background/Objectives: Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. Methods: First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. Results: In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. Conclusions: A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions. PMID:28725458

Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations.

PubMed

Hou, Tingjun; Wang, Junmei; Li, Youyong; Wang, Wei

2011-01-24

The Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) and the Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) methods calculate binding free energies for macromolecules by combining molecular mechanics calculations and continuum solvation models. To systematically evaluate the performance of these methods, we report here an extensive study of 59 ligands interacting with six different proteins. First, we explored the effects of the length of the molecular dynamics (MD) simulation, ranging from 400 to 4800 ps, and the solute dielectric constant (1, 2, or 4) on the binding free energies predicted by MM/PBSA. The following three important conclusions could be observed: (1) MD simulation length has an obvious impact on the predictions, and longer MD simulation is not always necessary to achieve better predictions. (2) The predictions are quite sensitive to the solute dielectric constant, and this parameter should be carefully determined according to the characteristics of the protein/ligand binding interface. (3) Conformational entropy often show large fluctuations in MD trajectories, and a large number of snapshots are necessary to achieve stable predictions. Next, we evaluated the accuracy of the binding free energies calculated by three Generalized Born (GB) models. We found that the GB model developed by Onufriev and Case was the most successful model in ranking the binding affinities of the studied inhibitors. Finally, we evaluated the performance of MM/GBSA and MM/PBSA in predicting binding free energies. Our results showed that MM/PBSA performed better in calculating absolute, but not necessarily relative, binding free energies than MM/GBSA. Considering its computational efficiency, MM/GBSA can serve as a powerful tool in drug design, where correct ranking of inhibitors is often emphasized.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagaoka, Masataka; Core Research for Evolutional Science and Technology; ESICB, Kyoto University, Kyodai Katsura, Nishikyo-ku, Kyoto 615-8520

A new efficient hybrid Monte Carlo (MC)/molecular dynamics (MD) reaction method with a rare event-driving mechanism is introduced as a practical ‘atomistic’ molecular simulation of large-scale chemically reactive systems. Starting its demonstrative application to the racemization reaction of (R)-2-chlorobutane in N,N-dimethylformamide solution, several other applications are shown from the practical viewpoint of molecular controlling of complex chemical reactions, stereochemistry and aggregate structures. Finally, I would like to mention the future applications of the hybrid MC/MD reaction method.

Hybrid classical/quantum simulation for infrared spectroscopy of water

NASA Astrophysics Data System (ADS)

Maekawa, Yuki; Sasaoka, Kenji; Ube, Takuji; Ishiguro, Takashi; Yamamoto, Takahiro

2018-05-01

We have developed a hybrid classical/quantum simulation method to calculate the infrared (IR) spectrum of water. The proposed method achieves much higher accuracy than conventional classical molecular dynamics (MD) simulations at a much lower computational cost than ab initio MD simulations. The IR spectrum of water is obtained as an ensemble average of the eigenvalues of the dynamical matrix constructed by ab initio calculations, using the positions of oxygen atoms that constitute water molecules obtained from the classical MD simulation. The calculated IR spectrum is in excellent agreement with the experimental IR spectrum.

Ensemble Sampling vs. Time Sampling in Molecular Dynamics Simulations of Thermal Conductivity

DOE PAGES

Gordiz, Kiarash; Singh, David J.; Henry, Asegun

2015-01-29

In this report we compare time sampling and ensemble averaging as two different methods available for phase space sampling. For the comparison, we calculate thermal conductivities of solid argon and silicon structures, using equilibrium molecular dynamics. We introduce two different schemes for the ensemble averaging approach, and show that both can reduce the total simulation time as compared to time averaging. It is also found that velocity rescaling is an efficient mechanism for phase space exploration. Although our methodology is tested using classical molecular dynamics, the ensemble generation approaches may find their greatest utility in computationally expensive simulations such asmore » first principles molecular dynamics. For such simulations, where each time step is costly, time sampling can require long simulation times because each time step must be evaluated sequentially and therefore phase space averaging is achieved through sequential operations. On the other hand, with ensemble averaging, phase space sampling can be achieved through parallel operations, since each ensemble is independent. For this reason, particularly when using massively parallel architectures, ensemble sampling can result in much shorter simulation times and exhibits similar overall computational effort.« less

Development of Simulation Methods in the Gibbs Ensemble to Predict Polymer-Solvent Phase Equilibria

NASA Astrophysics Data System (ADS)

Gartner, Thomas; Epps, Thomas; Jayaraman, Arthi

Solvent vapor annealing (SVA) of polymer thin films is a promising method for post-deposition polymer film morphology control. The large number of important parameters relevant to SVA (polymer, solvent, and substrate chemistries, incoming film condition, annealing and solvent evaporation conditions) makes systematic experimental study of SVA a time-consuming endeavor, motivating the application of simulation and theory to the SVA system to provide both mechanistic insight and scans of this wide parameter space. However, to rigorously treat the phase equilibrium between polymer film and solvent vapor while still probing the dynamics of SVA, new simulation methods must be developed. In this presentation, we compare two methods to study polymer-solvent phase equilibrium-Gibbs Ensemble Molecular Dynamics (GEMD) and Hybrid Monte Carlo/Molecular Dynamics (Hybrid MC/MD). Liquid-vapor equilibrium results are presented for the Lennard Jones fluid and for coarse-grained polymer-solvent systems relevant to SVA. We found that the Hybrid MC/MD method is more stable and consistent than GEMD, but GEMD has significant advantages in computational efficiency. We propose that Hybrid MC/MD simulations be used for unfamiliar systems in certain choice conditions, followed by much faster GEMD simulations to map out the remainder of the phase window.

Principal Component Relaxation Mode Analysis of an All-Atom Molecular Dynamics Simulation of Human Lysozyme

NASA Astrophysics Data System (ADS)

Nagai, Toshiki; Mitsutake, Ayori; Takano, Hiroshi

2013-02-01

A new relaxation mode analysis method, which is referred to as the principal component relaxation mode analysis method, has been proposed to handle a large number of degrees of freedom of protein systems. In this method, principal component analysis is carried out first and then relaxation mode analysis is applied to a small number of principal components with large fluctuations. To reduce the contribution of fast relaxation modes in these principal components efficiently, we have also proposed a relaxation mode analysis method using multiple evolution times. The principal component relaxation mode analysis method using two evolution times has been applied to an all-atom molecular dynamics simulation of human lysozyme in aqueous solution. Slow relaxation modes and corresponding relaxation times have been appropriately estimated, demonstrating that the method is applicable to protein systems.

Adaptively biased molecular dynamics: An umbrella sampling method with a time-dependent potential

NASA Astrophysics Data System (ADS)

Babin, Volodymyr; Karpusenka, Vadzim; Moradi, Mahmoud; Roland, Christopher; Sagui, Celeste

We discuss an adaptively biased molecular dynamics (ABMD) method for the computation of a free energy surface for a set of reaction coordinates. The ABMD method belongs to the general category of umbrella sampling methods with an evolving biasing potential. It is characterized by a small number of control parameters and an O(t) numerical cost with simulation time t. The method naturally allows for extensions based on multiple walkers and replica exchange mechanism. The workings of the method are illustrated with a number of examples, including sugar puckering, and free energy landscapes for polymethionine and polyproline peptides, and for a short β-turn peptide. ABMD has been implemented into the latest version (Case et al., AMBER 10; University of California: San Francisco, 2008) of the AMBER software package and is freely available to the simulation community.

Prediction of glass transition temperature of freeze-dried formulations by molecular dynamics simulation.

PubMed

Yoshioka, Sumie; Aso, Yukio; Kojima, Shigeo

2003-06-01

To examine whether the glass transition temperature (Tg) of freeze-dried formulations containing polymer excipients can be accurately predicted by molecular dynamics simulation using software currently available on the market. Molecular dynamics simulations were carried out for isomaltodecaose, a fragment of dextran, and alpha-glucose, the repeated unit of dextran. in the presence or absence of water molecules. Estimated values of Tg were compared with experimental values obtained by differential scanning calorimetry (DSC). Isothermal-isobaric molecular dynamics simulations (NPTMD) and isothermal molecular dynamics simulations at a constant volume (NVTMD) were carried out using the software package DISCOVER (Material Studio) with the Polymer Consortium Force Field. Mean-squared displacement and radial distribution function were calculated. NVTMD using the values of density obtained by NPTMD provided the diffusivity of glucose-ring oxygen and water oxygen in amorphous alpha-glucose and isomaltodecaose, which exhibited a discontinuity in temperature dependence due to glass transition. Tg was estimated to be approximately 400K and 500K for pure amorphous a-glucose and isomaltodecaose, respectively, and in the presence of one water molecule per glucose unit, Tg was 340K and 360K, respectively. Estimated Tg values were higher than experimentally determined values because of the very fast cooling rates in the simulations. However, decreases in Tg on hydration and increases in Tg associated with larger fragment size could be demonstrated. The results indicate that molecular dynamics simulation is a useful method for investigating the effects of hydration and molecular weight on the Tg of lyophilized formulations containing polymer excipients. although the relationship between cooling rates and Tg must first be elucidated to predict Tg vales observed by DSC measurement. January 16.

SSAGES: Software Suite for Advanced General Ensemble Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sidky, Hythem; Colón, Yamil J.; Helfferich, Julian

Molecular simulation has emerged as an essential tool for modern-day research, but obtaining proper results and making reliable conclusions from simulations requires adequate sampling of the system under consideration. To this end, a variety of methods exist in the literature that can enhance sampling considerably, and increasingly sophisticated, effective algorithms continue to be developed at a rapid pace. Implementation of these techniques, however, can be challenging for experts and non-experts alike. There is a clear need for software that provides rapid, reliable, and easy access to a wide range of advanced sampling methods, and that facilitates implementation of new techniquesmore » as they emerge. Here we present SSAGES, a publicly available Software Suite for Advanced General Ensemble Simulations designed to interface with multiple widely used molecular dynamics simulations packages. SSAGES allows facile application of a variety of enhanced sampling techniques—including adaptive biasing force, string methods, and forward flux sampling—that extract meaningful free energy and transition path data from all-atom and coarse grained simulations. A noteworthy feature of SSAGES is a user-friendly framework that facilitates further development and implementation of new methods and collective variables. In this work, the use of SSAGES is illustrated in the context of simple representative applications involving distinct methods and different collective variables that are available in the current release of the suite.« less

SSAGES: Software Suite for Advanced General Ensemble Simulations.

PubMed

Sidky, Hythem; Colón, Yamil J; Helfferich, Julian; Sikora, Benjamin J; Bezik, Cody; Chu, Weiwei; Giberti, Federico; Guo, Ashley Z; Jiang, Xikai; Lequieu, Joshua; Li, Jiyuan; Moller, Joshua; Quevillon, Michael J; Rahimi, Mohammad; Ramezani-Dakhel, Hadi; Rathee, Vikramjit S; Reid, Daniel R; Sevgen, Emre; Thapar, Vikram; Webb, Michael A; Whitmer, Jonathan K; de Pablo, Juan J

2018-01-28

Molecular simulation has emerged as an essential tool for modern-day research, but obtaining proper results and making reliable conclusions from simulations requires adequate sampling of the system under consideration. To this end, a variety of methods exist in the literature that can enhance sampling considerably, and increasingly sophisticated, effective algorithms continue to be developed at a rapid pace. Implementation of these techniques, however, can be challenging for experts and non-experts alike. There is a clear need for software that provides rapid, reliable, and easy access to a wide range of advanced sampling methods and that facilitates implementation of new techniques as they emerge. Here we present SSAGES, a publicly available Software Suite for Advanced General Ensemble Simulations designed to interface with multiple widely used molecular dynamics simulations packages. SSAGES allows facile application of a variety of enhanced sampling techniques-including adaptive biasing force, string methods, and forward flux sampling-that extract meaningful free energy and transition path data from all-atom and coarse-grained simulations. A noteworthy feature of SSAGES is a user-friendly framework that facilitates further development and implementation of new methods and collective variables. In this work, the use of SSAGES is illustrated in the context of simple representative applications involving distinct methods and different collective variables that are available in the current release of the suite. The code may be found at: https://github.com/MICCoM/SSAGES-public.

SSAGES: Software Suite for Advanced General Ensemble Simulations

NASA Astrophysics Data System (ADS)

Sidky, Hythem; Colón, Yamil J.; Helfferich, Julian; Sikora, Benjamin J.; Bezik, Cody; Chu, Weiwei; Giberti, Federico; Guo, Ashley Z.; Jiang, Xikai; Lequieu, Joshua; Li, Jiyuan; Moller, Joshua; Quevillon, Michael J.; Rahimi, Mohammad; Ramezani-Dakhel, Hadi; Rathee, Vikramjit S.; Reid, Daniel R.; Sevgen, Emre; Thapar, Vikram; Webb, Michael A.; Whitmer, Jonathan K.; de Pablo, Juan J.

2018-01-01

Molecular simulation has emerged as an essential tool for modern-day research, but obtaining proper results and making reliable conclusions from simulations requires adequate sampling of the system under consideration. To this end, a variety of methods exist in the literature that can enhance sampling considerably, and increasingly sophisticated, effective algorithms continue to be developed at a rapid pace. Implementation of these techniques, however, can be challenging for experts and non-experts alike. There is a clear need for software that provides rapid, reliable, and easy access to a wide range of advanced sampling methods and that facilitates implementation of new techniques as they emerge. Here we present SSAGES, a publicly available Software Suite for Advanced General Ensemble Simulations designed to interface with multiple widely used molecular dynamics simulations packages. SSAGES allows facile application of a variety of enhanced sampling techniques—including adaptive biasing force, string methods, and forward flux sampling—that extract meaningful free energy and transition path data from all-atom and coarse-grained simulations. A noteworthy feature of SSAGES is a user-friendly framework that facilitates further development and implementation of new methods and collective variables. In this work, the use of SSAGES is illustrated in the context of simple representative applications involving distinct methods and different collective variables that are available in the current release of the suite. The code may be found at: https://github.com/MICCoM/SSAGES-public.

Prediction of binding poses to FXR using multi-targeted docking combined with molecular dynamics and enhanced sampling

NASA Astrophysics Data System (ADS)

Bhakat, Soumendranath; Åberg, Emil; Söderhjelm, Pär

2018-01-01

Advanced molecular docking methods often aim at capturing the flexibility of the protein upon binding to the ligand. In this study, we investigate whether instead a simple rigid docking method can be applied, if combined with multiple target structures to model the backbone flexibility and molecular dynamics simulations to model the sidechain and ligand flexibility. The methods are tested for the binding of 35 ligands to FXR as part of the first stage of the Drug Design Data Resource (D3R) Grand Challenge 2 blind challenge. The results show that the multiple-target docking protocol performs surprisingly well, with correct poses found for 21 of the ligands. MD simulations started on the docked structures are remarkably stable, but show almost no tendency of refining the structure closer to the experimentally found binding pose. Reconnaissance metadynamics enhances the exploration of new binding poses, but additional collective variables involving the protein are needed to exploit the full potential of the method.

Prediction of binding poses to FXR using multi-targeted docking combined with molecular dynamics and enhanced sampling.

PubMed

Bhakat, Soumendranath; Åberg, Emil; Söderhjelm, Pär

2018-01-01

Advanced molecular docking methods often aim at capturing the flexibility of the protein upon binding to the ligand. In this study, we investigate whether instead a simple rigid docking method can be applied, if combined with multiple target structures to model the backbone flexibility and molecular dynamics simulations to model the sidechain and ligand flexibility. The methods are tested for the binding of 35 ligands to FXR as part of the first stage of the Drug Design Data Resource (D3R) Grand Challenge 2 blind challenge. The results show that the multiple-target docking protocol performs surprisingly well, with correct poses found for 21 of the ligands. MD simulations started on the docked structures are remarkably stable, but show almost no tendency of refining the structure closer to the experimentally found binding pose. Reconnaissance metadynamics enhances the exploration of new binding poses, but additional collective variables involving the protein are needed to exploit the full potential of the method.

Cluster analysis of molecular simulation trajectories for systems where both conformation and orientation of the sampled states are important.

PubMed

Abramyan, Tigran M; Snyder, James A; Thyparambil, Aby A; Stuart, Steven J; Latour, Robert A

2016-08-05

Clustering methods have been widely used to group together similar conformational states from molecular simulations of biomolecules in solution. For applications such as the interaction of a protein with a surface, the orientation of the protein relative to the surface is also an important clustering parameter because of its potential effect on adsorbed-state bioactivity. This study presents cluster analysis methods that are specifically designed for systems where both molecular orientation and conformation are important, and the methods are demonstrated using test cases of adsorbed proteins for validation. Additionally, because cluster analysis can be a very subjective process, an objective procedure for identifying both the optimal number of clusters and the best clustering algorithm to be applied to analyze a given dataset is presented. The method is demonstrated for several agglomerative hierarchical clustering algorithms used in conjunction with three cluster validation techniques. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Molecular Dynamics Simulations of Adhesion at Epoxy Interfaces

NASA Technical Reports Server (NTRS)

Frankland, Sarah-Jane V.; Clancy, Thomas C.; Hinkley, J. A.; Gates. T. S.

2008-01-01

The effect of moisture on adhesives used in aerospace applications can be modeled with chemically specific techniques such as molecular dynamics simulation. In the present study, the surface energy and work of adhesion are calculated for epoxy surfaces and interfaces, respectively, by using molecular dynamics simulation. Modifications are made to current theory to calculate the work of adhesion at the epoxy-epoxy interface with and without water. Quantitative agreement with experimental values is obtained for the surface energy and work of adhesion at the interface without water. The work of adhesion agrees qualitatively with the experimental values for the interface with water: the magnitude is reduced 15% with respect to the value for the interface without water. A variation of 26% in the magnitude is observed depending on the water configuration at a concentration of 1.6 wt%. The methods and modifications to the method that are employed to obtain these values are expected to be applicable for other epoxy adhesives to determine the effects of moisture uptake on their work of adhesion.

vmdICE: a plug-in for rapid evaluation of molecular dynamics simulations using VMD.

PubMed

Knapp, Bernhard; Lederer, Nadja; Omasits, Ulrich; Schreiner, Wolfgang

2010-12-01

Molecular dynamics (MD) is a powerful in silico method to investigate the interactions between biomolecules. It solves Newton's equations of motion for atoms over a specified period of time and yields a trajectory file, containing the different spatial arrangements of atoms during the simulation. The movements and energies of each single atom are recorded. For evaluating of these simulation trajectories with regard to biomedical implications, several methods are available. Three well-known ones are the root mean square deviation (RMSD), the root mean square fluctuation (RMSF) and solvent accessible surface area (SASA). Herein, we present a novel plug-in for the software "visual molecular dynamics" (VMD) that allows an interactive 3D representation of RMSD, RMSF, and SASA, directly on the molecule. On the one hand, our plug-in is easy to handle for inexperienced users, and on the other hand, it provides a fast and flexible graphical impression of the spatial dynamics of a system for experts in the field. © 2010 Wiley Periodicals, Inc.

Extended Phase-Space Methods for Enhanced Sampling in Molecular Simulations: A Review.

PubMed

Fujisaki, Hiroshi; Moritsugu, Kei; Matsunaga, Yasuhiro; Morishita, Tetsuya; Maragliano, Luca

2015-01-01

Molecular Dynamics simulations are a powerful approach to study biomolecular conformational changes or protein-ligand, protein-protein, and protein-DNA/RNA interactions. Straightforward applications, however, are often hampered by incomplete sampling, since in a typical simulated trajectory the system will spend most of its time trapped by high energy barriers in restricted regions of the configuration space. Over the years, several techniques have been designed to overcome this problem and enhance space sampling. Here, we review a class of methods that rely on the idea of extending the set of dynamical variables of the system by adding extra ones associated to functions describing the process under study. In particular, we illustrate the Temperature Accelerated Molecular Dynamics (TAMD), Logarithmic Mean Force Dynamics (LogMFD), and Multiscale Enhanced Sampling (MSES) algorithms. We also discuss combinations with techniques for searching reaction paths. We show the advantages presented by this approach and how it allows to quickly sample important regions of the free-energy landscape via automatic exploration.

A molecular simulation protocol to avoid sampling redundancy and discover new states.

PubMed

Bacci, Marco; Vitalis, Andreas; Caflisch, Amedeo

2015-05-01

For biomacromolecules or their assemblies, experimental knowledge is often restricted to specific states. Ambiguity pervades simulations of these complex systems because there is no prior knowledge of relevant phase space domains, and sampling recurrence is difficult to achieve. In molecular dynamics methods, ruggedness of the free energy surface exacerbates this problem by slowing down the unbiased exploration of phase space. Sampling is inefficient if dwell times in metastable states are large. We suggest a heuristic algorithm to terminate and reseed trajectories run in multiple copies in parallel. It uses a recent method to order snapshots, which provides notions of "interesting" and "unique" for individual simulations. We define criteria to guide the reseeding of runs from more "interesting" points if they sample overlapping regions of phase space. Using a pedagogical example and an α-helical peptide, the approach is demonstrated to amplify the rate of exploration of phase space and to discover metastable states not found by conventional sampling schemes. Evidence is provided that accurate kinetics and pathways can be extracted from the simulations. The method, termed PIGS for Progress Index Guided Sampling, proceeds in unsupervised fashion, is scalable, and benefits synergistically from larger numbers of replicas. Results confirm that the underlying ideas are appropriate and sufficient to enhance sampling. In molecular simulations, errors caused by not exploring relevant domains in phase space are always unquantifiable and can be arbitrarily large. Our protocol adds to the toolkit available to researchers in reducing these types of errors. This article is part of a Special Issue entitled "Recent developments of molecular dynamics". Copyright © 2014 Elsevier B.V. All rights reserved.

The Application of Ligand-Mapping Molecular Dynamics Simulations to the Rational Design of Peptidic Modulators of Protein-Protein Interactions.

PubMed

Tan, Yaw Sing; Spring, David R; Abell, Chris; Verma, Chandra S

2015-07-14

A computational ligand-mapping approach to detect protein surface pockets that interact with hydrophobic moieties is presented. In this method, we incorporated benzene molecules into explicit solvent molecular dynamics simulations of various protein targets. The benzene molecules successfully identified the binding locations of hydrophobic hot-spot residues and all-hydrocarbon cross-links from known peptidic ligands. They also unveiled cryptic binding sites that are occluded by side chains and the protein backbone. Our results demonstrate that ligand-mapping molecular dynamics simulations hold immense promise to guide the rational design of peptidic modulators of protein-protein interactions, including that of stapled peptides, which show promise as an exciting new class of cell-penetrating therapeutic molecules.

An analytical derivation of MC-SCF vibrational wave functions for the quantum dynamical simulation of multiple proton transfer reactions: Initial application to protonated water chains

NASA Astrophysics Data System (ADS)

Drukker, Karen; Hammes-Schiffer, Sharon

1997-07-01

This paper presents an analytical derivation of a multiconfigurational self-consistent-field (MC-SCF) solution of the time-independent Schrödinger equation for nuclear motion (i.e. vibrational modes). This variational MC-SCF method is designed for the mixed quantum/classical molecular dynamics simulation of multiple proton transfer reactions, where the transferring protons are treated quantum mechanically while the remaining degrees of freedom are treated classically. This paper presents a proof that the Hellmann-Feynman forces on the classical degrees of freedom are identical to the exact forces (i.e. the Pulay corrections vanish) when this MC-SCF method is used with an appropriate choice of basis functions. This new MC-SCF method is applied to multiple proton transfer in a protonated chain of three hydrogen-bonded water molecules. The ground state and the first three excited state energies and the ground state forces agree well with full configuration interaction calculations. Sample trajectories are obtained using adiabatic molecular dynamics methods, and nonadiabatic effects are found to be insignificant for these sample trajectories. The accuracy of the excited states will enable this MC-SCF method to be used in conjunction with nonadiabatic molecular dynamics methods. This application differs from previous work in that it is a real-time quantum dynamical nonequilibrium simulation of multiple proton transfer in a chain of water molecules.

Oxygen transport properties estimation by DSMC-CT simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruno, Domenico; Frezzotti, Aldo; Ghiroldi, Gian Pietro

Coupling DSMC simulations with classical trajectories calculations is emerging as a powerful tool to improve predictive capabilities of computational rarefied gas dynamics. The considerable increase of computational effort outlined in the early application of the method (Koura,1997) can be compensated by running simulations on massively parallel computers. In particular, GPU acceleration has been found quite effective in reducing computing time (Ferrigni,2012; Norman et al.,2013) of DSMC-CT simulations. The aim of the present work is to study rarefied Oxygen flows by modeling binary collisions through an accurate potential energy surface, obtained by molecular beams scattering (Aquilanti, et al.,1999). The accuracy ofmore » the method is assessed by calculating molecular Oxygen shear viscosity and heat conductivity following three different DSMC-CT simulation methods. In the first one, transport properties are obtained from DSMC-CT simulations of spontaneous fluctuation of an equilibrium state (Bruno et al, Phys. Fluids, 23, 093104, 2011). In the second method, the collision trajectory calculation is incorporated in a Monte Carlo integration procedure to evaluate the Taxman’s expressions for the transport properties of polyatomic gases (Taxman,1959). In the third, non-equilibrium zero and one-dimensional rarefied gas dynamic simulations are adopted and the transport properties are computed from the non-equilibrium fluxes of momentum and energy. The three methods provide close values of the transport properties, their estimated statistical error not exceeding 3%. The experimental values are slightly underestimated, the percentage deviation being, again, few percent.« less

Empirical evaluation of data normalization methods for molecular classification

PubMed Central

Huang, Huei-Chung

2018-01-01

Background Data artifacts due to variations in experimental handling are ubiquitous in microarray studies, and they can lead to biased and irreproducible findings. A popular approach to correct for such artifacts is through post hoc data adjustment such as data normalization. Statistical methods for data normalization have been developed and evaluated primarily for the discovery of individual molecular biomarkers. Their performance has rarely been studied for the development of multi-marker molecular classifiers—an increasingly important application of microarrays in the era of personalized medicine. Methods In this study, we set out to evaluate the performance of three commonly used methods for data normalization in the context of molecular classification, using extensive simulations based on re-sampling from a unique pair of microRNA microarray datasets for the same set of samples. The data and code for our simulations are freely available as R packages at GitHub. Results In the presence of confounding handling effects, all three normalization methods tended to improve the accuracy of the classifier when evaluated in an independent test data. The level of improvement and the relative performance among the normalization methods depended on the relative level of molecular signal, the distributional pattern of handling effects (e.g., location shift vs scale change), and the statistical method used for building the classifier. In addition, cross-validation was associated with biased estimation of classification accuracy in the over-optimistic direction for all three normalization methods. Conclusion Normalization may improve the accuracy of molecular classification for data with confounding handling effects; however, it cannot circumvent the over-optimistic findings associated with cross-validation for assessing classification accuracy. PMID:29666754

Biochemical simulations: stochastic, approximate stochastic and hybrid approaches.

PubMed

Pahle, Jürgen

2009-01-01

Computer simulations have become an invaluable tool to study the sometimes counterintuitive temporal dynamics of (bio-)chemical systems. In particular, stochastic simulation methods have attracted increasing interest recently. In contrast to the well-known deterministic approach based on ordinary differential equations, they can capture effects that occur due to the underlying discreteness of the systems and random fluctuations in molecular numbers. Numerous stochastic, approximate stochastic and hybrid simulation methods have been proposed in the literature. In this article, they are systematically reviewed in order to guide the researcher and help her find the appropriate method for a specific problem.

Biochemical simulations: stochastic, approximate stochastic and hybrid approaches

PubMed Central

2009-01-01

Computer simulations have become an invaluable tool to study the sometimes counterintuitive temporal dynamics of (bio-)chemical systems. In particular, stochastic simulation methods have attracted increasing interest recently. In contrast to the well-known deterministic approach based on ordinary differential equations, they can capture effects that occur due to the underlying discreteness of the systems and random fluctuations in molecular numbers. Numerous stochastic, approximate stochastic and hybrid simulation methods have been proposed in the literature. In this article, they are systematically reviewed in order to guide the researcher and help her find the appropriate method for a specific problem. PMID:19151097

A Probabilistic Framework for Constructing Temporal Relations in Replica Exchange Molecular Trajectories.

PubMed

Chattopadhyay, Aditya; Zheng, Min; Waller, Mark Paul; Priyakumar, U Deva

2018-05-23

Knowledge of the structure and dynamics of biomolecules is essential for elucidating the underlying mechanisms of biological processes. Given the stochastic nature of many biological processes, like protein unfolding, it's almost impossible that two independent simulations will generate the exact same sequence of events, which makes direct analysis of simulations difficult. Statistical models like Markov Chains, transition networks etc. help in shedding some light on the mechanistic nature of such processes by predicting long-time dynamics of these systems from short simulations. However, such methods fall short in analyzing trajectories with partial or no temporal information, for example, replica exchange molecular dynamics or Monte Carlo simulations. In this work we propose a probabilistic algorithm, borrowing concepts from graph theory and machine learning, to extract reactive pathways from molecular trajectories in the absence of temporal data. A suitable vector representation was chosen to represent each frame in the macromolecular trajectory (as a series of interaction and conformational energies) and dimensionality reduction was performed using principal component analysis (PCA). The trajectory was then clustered using a density-based clustering algorithm, where each cluster represents a metastable state on the potential energy surface (PES) of the biomolecule under study. A graph was created with these clusters as nodes with the edges learnt using an iterative expectation maximization algorithm. The most reactive path is conceived as the widest path along this graph. We have tested our method on RNA hairpin unfolding trajectory in aqueous urea solution. Our method makes the understanding of the mechanism of unfolding in RNA hairpin molecule more tractable. As this method doesn't rely on temporal data it can be used to analyze trajectories from Monte Carlo sampling techniques and replica exchange molecular dynamics (REMD).

A network of molecular switches controls the activation of the two-component response regulator NtrC

NASA Astrophysics Data System (ADS)

Vanatta, Dan K.; Shukla, Diwakar; Lawrenz, Morgan; Pande, Vijay S.

2015-06-01

Recent successes in simulating protein structure and folding dynamics have demonstrated the power of molecular dynamics to predict the long timescale behaviour of proteins. Here, we extend and improve these methods to predict molecular switches that characterize conformational change pathways between the active and inactive state of nitrogen regulatory protein C (NtrC). By employing unbiased Markov state model-based molecular dynamics simulations, we construct a dynamic picture of the activation pathways of this key bacterial signalling protein that is consistent with experimental observations and predicts new mutants that could be used for validation of the mechanism. Moreover, these results suggest a novel mechanistic paradigm for conformational switching.

Simulating Energy Relaxation in Pump-Probe Vibrational Spectroscopy of Hydrogen-Bonded Liquids.

PubMed

Dettori, Riccardo; Ceriotti, Michele; Hunger, Johannes; Melis, Claudio; Colombo, Luciano; Donadio, Davide

2017-03-14

We introduce a nonequilibrium molecular dynamics simulation approach, based on the generalized Langevin equation, to study vibrational energy relaxation in pump-probe spectroscopy. A colored noise thermostat is used to selectively excite a set of vibrational modes, leaving the other modes nearly unperturbed, to mimic the effect of a monochromatic laser pump. Energy relaxation is probed by analyzing the evolution of the system after excitation in the microcanonical ensemble, thus providing direct information about the energy redistribution paths at the molecular level and their time scale. The method is applied to hydrogen-bonded molecular liquids, specifically deuterated methanol and water, providing a robust picture of energy relaxation at the molecular scale.

Understanding the kinetics of ligand binding to globins with molecular dynamics simulations: the necessity of multiple state models.

PubMed

Estarellas Martin, Carolina; Seira Castan, Constantí; Luque Garriga, F Javier; Bidon-Chanal Badia, Axel

2015-10-01

Residue conformational changes and internal cavity migration processes play a key role in regulating the kinetics of ligand migration and binding events in globins. Molecular dynamics simulations have demonstrated their value in the study of these processes in different haemoglobins, but derivation of kinetic data demands the use of more complex techniques like enhanced sampling molecular dynamics methods. This review discusses the different methodologies that are currently applied to study the ligand migration process in globins and highlight those specially developed to derive kinetic data. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multinuclear NMR of CaSiO(3) glass: simulation from first-principles.

PubMed

Pedone, Alfonso; Charpentier, Thibault; Menziani, Maria Cristina

2010-06-21

An integrated computational method which couples classical molecular dynamics simulations with density functional theory calculations is used to simulate the solid-state NMR spectra of amorphous CaSiO(3). Two CaSiO(3) glass models are obtained by shell-model molecular dynamics simulations, successively relaxed at the GGA-PBE level of theory. The calculation of the NMR parameters (chemical shielding and quadrupolar parameters), which are then used to simulate solid-state 1D and 2D-NMR spectra of silicon-29, oxygen-17 and calcium-43, is achieved by the gauge including projector augmented-wave (GIPAW) and the projector augmented-wave (PAW) methods. It is shown that the limitations due to the finite size of the MD models can be overcome using a Kernel Estimation Density (KDE) approach to simulate the spectra since it better accounts for the disorder effects on the NMR parameter distribution. KDE allows reconstructing a smoothed NMR parameter distribution from the MD/GIPAW data. Simulated NMR spectra calculated with the present approach are found to be in excellent agreement with the experimental data. This further validates the CaSiO(3) structural model obtained by MD simulations allowing the inference of relationships between structural data and NMR response. The methods used to simulate 1D and 2D-NMR spectra from MD GIPAW data have been integrated in a package (called fpNMR) freely available on request.

Multi-Conformation Monte Carlo: A Method for Introducing Flexibility in Efficient Simulations of Many-Protein Systems.

PubMed

Prytkova, Vera; Heyden, Matthias; Khago, Domarin; Freites, J Alfredo; Butts, Carter T; Martin, Rachel W; Tobias, Douglas J

2016-08-25

We present a novel multi-conformation Monte Carlo simulation method that enables the modeling of protein-protein interactions and aggregation in crowded protein solutions. This approach is relevant to a molecular-scale description of realistic biological environments, including the cytoplasm and the extracellular matrix, which are characterized by high concentrations of biomolecular solutes (e.g., 300-400 mg/mL for proteins and nucleic acids in the cytoplasm of Escherichia coli). Simulation of such environments necessitates the inclusion of a large number of protein molecules. Therefore, computationally inexpensive methods, such as rigid-body Brownian dynamics (BD) or Monte Carlo simulations, can be particularly useful. However, as we demonstrate herein, the rigid-body representation typically employed in simulations of many-protein systems gives rise to certain artifacts in protein-protein interactions. Our approach allows us to incorporate molecular flexibility in Monte Carlo simulations at low computational cost, thereby eliminating ambiguities arising from structure selection in rigid-body simulations. We benchmark and validate the methodology using simulations of hen egg white lysozyme in solution, a well-studied system for which extensive experimental data, including osmotic second virial coefficients, small-angle scattering structure factors, and multiple structures determined by X-ray and neutron crystallography and solution NMR, as well as rigid-body BD simulation results, are available for comparison.

A Fast Algorithm for Massively Parallel, Long-Term, Simulation of Complex Molecular Dynamics Systems

NASA Technical Reports Server (NTRS)

Jaramillo-Botero, Andres; Goddard, William A, III; Fijany, Amir

1997-01-01

The advances in theory and computing technology over the last decade have led to enormous progress in applying atomistic molecular dynamics (MD) methods to the characterization, prediction, and design of chemical, biological, and material systems,.

Accelerated weight histogram method for exploring free energy landscapes

NASA Astrophysics Data System (ADS)

Lindahl, V.; Lidmar, J.; Hess, B.

2014-07-01

Calculating free energies is an important and notoriously difficult task for molecular simulations. The rapid increase in computational power has made it possible to probe increasingly complex systems, yet extracting accurate free energies from these simulations remains a major challenge. Fully exploring the free energy landscape of, say, a biological macromolecule typically requires sampling large conformational changes and slow transitions. Often, the only feasible way to study such a system is to simulate it using an enhanced sampling method. The accelerated weight histogram (AWH) method is a new, efficient extended ensemble sampling technique which adaptively biases the simulation to promote exploration of the free energy landscape. The AWH method uses a probability weight histogram which allows for efficient free energy updates and results in an easy discretization procedure. A major advantage of the method is its general formulation, making it a powerful platform for developing further extensions and analyzing its relation to already existing methods. Here, we demonstrate its efficiency and general applicability by calculating the potential of mean force along a reaction coordinate for both a single dimension and multiple dimensions. We make use of a non-uniform, free energy dependent target distribution in reaction coordinate space so that computational efforts are not wasted on physically irrelevant regions. We present numerical results for molecular dynamics simulations of lithium acetate in solution and chignolin, a 10-residue long peptide that folds into a β-hairpin. We further present practical guidelines for setting up and running an AWH simulation.

A New Maximum Likelihood Approach for Free Energy Profile Construction from Molecular Simulations

PubMed Central

Lee, Tai-Sung; Radak, Brian K.; Pabis, Anna; York, Darrin M.

2013-01-01

A novel variational method for construction of free energy profiles from molecular simulation data is presented. The variational free energy profile (VFEP) method uses the maximum likelihood principle applied to the global free energy profile based on the entire set of simulation data (e.g from multiple biased simulations) that spans the free energy surface. The new method addresses common obstacles in two major problems usually observed in traditional methods for estimating free energy surfaces: the need for overlap in the re-weighting procedure and the problem of data representation. Test cases demonstrate that VFEP outperforms other methods in terms of the amount and sparsity of the data needed to construct the overall free energy profiles. For typical chemical reactions, only ~5 windows and ~20-35 independent data points per window are sufficient to obtain an overall qualitatively correct free energy profile with sampling errors an order of magnitude smaller than the free energy barrier. The proposed approach thus provides a feasible mechanism to quickly construct the global free energy profile and identify free energy barriers and basins in free energy simulations via a robust, variational procedure that determines an analytic representation of the free energy profile without the requirement of numerically unstable histograms or binning procedures. It can serve as a new framework for biased simulations and is suitable to be used together with other methods to tackle with the free energy estimation problem. PMID:23457427

Accelerated weight histogram method for exploring free energy landscapes.

PubMed

Lindahl, V; Lidmar, J; Hess, B

2014-07-28

Calculating free energies is an important and notoriously difficult task for molecular simulations. The rapid increase in computational power has made it possible to probe increasingly complex systems, yet extracting accurate free energies from these simulations remains a major challenge. Fully exploring the free energy landscape of, say, a biological macromolecule typically requires sampling large conformational changes and slow transitions. Often, the only feasible way to study such a system is to simulate it using an enhanced sampling method. The accelerated weight histogram (AWH) method is a new, efficient extended ensemble sampling technique which adaptively biases the simulation to promote exploration of the free energy landscape. The AWH method uses a probability weight histogram which allows for efficient free energy updates and results in an easy discretization procedure. A major advantage of the method is its general formulation, making it a powerful platform for developing further extensions and analyzing its relation to already existing methods. Here, we demonstrate its efficiency and general applicability by calculating the potential of mean force along a reaction coordinate for both a single dimension and multiple dimensions. We make use of a non-uniform, free energy dependent target distribution in reaction coordinate space so that computational efforts are not wasted on physically irrelevant regions. We present numerical results for molecular dynamics simulations of lithium acetate in solution and chignolin, a 10-residue long peptide that folds into a β-hairpin. We further present practical guidelines for setting up and running an AWH simulation.

Combining configurational energies and forces for molecular force field optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vlcek, Lukas; Sun, Weiwei; Kent, Paul R. C.

While quantum chemical simulations have been increasingly used as an invaluable source of information for atomistic model development, the high computational expenses typically associated with these techniques often limit thorough sampling of the systems of interest. It is therefore of great practical importance to use all available information as efficiently as possible, and in a way that allows for consistent addition of constraints that may be provided by macroscopic experiments. We propose a simple approach that combines information from configurational energies and forces generated in a molecular dynamics simulation to increase the effective number of samples. Subsequently, this information ismore » used to optimize a molecular force field by minimizing the statistical distance similarity metric. We also illustrate the methodology on an example of a trajectory of configurations generated in equilibrium molecular dynamics simulations of argon and water and compare the results with those based on the force matching method.« less

Combining configurational energies and forces for molecular force field optimization

DOE PAGES

Vlcek, Lukas; Sun, Weiwei; Kent, Paul R. C.

2017-07-21

While quantum chemical simulations have been increasingly used as an invaluable source of information for atomistic model development, the high computational expenses typically associated with these techniques often limit thorough sampling of the systems of interest. It is therefore of great practical importance to use all available information as efficiently as possible, and in a way that allows for consistent addition of constraints that may be provided by macroscopic experiments. We propose a simple approach that combines information from configurational energies and forces generated in a molecular dynamics simulation to increase the effective number of samples. Subsequently, this information ismore » used to optimize a molecular force field by minimizing the statistical distance similarity metric. We also illustrate the methodology on an example of a trajectory of configurations generated in equilibrium molecular dynamics simulations of argon and water and compare the results with those based on the force matching method.« less

Faunus: An object oriented framework for molecular simulation

PubMed Central

Lund, Mikael; Trulsson, Martin; Persson, Björn

2008-01-01

Background We present a C++ class library for Monte Carlo simulation of molecular systems, including proteins in solution. The design is generic and highly modular, enabling multiple developers to easily implement additional features. The statistical mechanical methods are documented by extensive use of code comments that – subsequently – are collected to automatically build a web-based manual. Results We show how an object oriented design can be used to create an intuitively appealing coding framework for molecular simulation. This is exemplified in a minimalistic C++ program that can calculate protein protonation states. We further discuss performance issues related to high level coding abstraction. Conclusion C++ and the Standard Template Library (STL) provide a high-performance platform for generic molecular modeling. Automatic generation of code documentation from inline comments has proven particularly useful in that no separate manual needs to be maintained. PMID:18241331

Discrete Optimization of Electronic Hyperpolarizabilities in a Chemical Subspace

DTIC Science & Technology

2009-05-01

molecular design. Methods for optimization in discrete spaces have been studied extensively and recently reviewed ( 5). Optimization methods include...integer programming, as in branch-and-bound techniques (including dead-end elimination [ 6]), simulated annealing ( 7), and genetic algorithms ( 8...These algorithms have found renewed interest and application in molecular and materials design (9- 12) . Recently, new approaches have been

Variational Identification of Markovian Transition States

NASA Astrophysics Data System (ADS)

Martini, Linda; Kells, Adam; Covino, Roberto; Hummer, Gerhard; Buchete, Nicolae-Viorel; Rosta, Edina

2017-07-01

We present a method that enables the identification and analysis of conformational Markovian transition states from atomistic or coarse-grained molecular dynamics (MD) trajectories. Our algorithm is presented by using both analytical models and examples from MD simulations of the benchmark system helix-forming peptide Ala5 , and of larger, biomedically important systems: the 15-lipoxygenase-2 enzyme (15-LOX-2), the epidermal growth factor receptor (EGFR) protein, and the Mga2 fungal transcription factor. The analysis of 15-LOX-2 uses data generated exclusively from biased umbrella sampling simulations carried out at the hybrid ab initio density functional theory (DFT) quantum mechanics/molecular mechanics (QM/MM) level of theory. In all cases, our method automatically identifies the corresponding transition states and metastable conformations in a variationally optimal way, with the input of a set of relevant coordinates, by accurately reproducing the intrinsic slowest relaxation rate of each system. Our approach offers a general yet easy-to-implement analysis method that provides unique insight into the molecular mechanism and the rare but crucial (i.e., rate-limiting) transition states occurring along conformational transition paths in complex dynamical systems such as molecular trajectories.

Girsanov reweighting for path ensembles and Markov state models

NASA Astrophysics Data System (ADS)

Donati, L.; Hartmann, C.; Keller, B. G.

2017-06-01

The sensitivity of molecular dynamics on changes in the potential energy function plays an important role in understanding the dynamics and function of complex molecules. We present a method to obtain path ensemble averages of a perturbed dynamics from a set of paths generated by a reference dynamics. It is based on the concept of path probability measure and the Girsanov theorem, a result from stochastic analysis to estimate a change of measure of a path ensemble. Since Markov state models (MSMs) of the molecular dynamics can be formulated as a combined phase-space and path ensemble average, the method can be extended to reweight MSMs by combining it with a reweighting of the Boltzmann distribution. We demonstrate how to efficiently implement the Girsanov reweighting in a molecular dynamics simulation program by calculating parts of the reweighting factor "on the fly" during the simulation, and we benchmark the method on test systems ranging from a two-dimensional diffusion process and an artificial many-body system to alanine dipeptide and valine dipeptide in implicit and explicit water. The method can be used to study the sensitivity of molecular dynamics on external perturbations as well as to reweight trajectories generated by enhanced sampling schemes to the original dynamics.

Computational Evaluation of Mg–Salen Compounds as Subsurface Fluid Tracers: Molecular Dynamics Simulations in Toluene–Water Mixtures and Clay Mineral Nanopores

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greathouse, Jeffery A.; Boyle, Timothy J.; Kemp, Richard A.

Molecular tracers that can be selectively placed underground and uniquely identified at the surface using simple on-site spectroscopic methods would significantly enhance subsurface fluid monitoring capabilities. To ensure their widespread utility, the solubility of these tracers must be easily tuned to oil- or water-wet conditions as well as reducing or eliminating their propensity to adsorb onto subsurface rock and/or mineral phases. In this work, molecular dynamics simulations were used to investigate the relative solubilities and mineral surface adsorption properties of three candidate tracer compounds comprising Mg–salen derivatives of varying degrees of hydrophilic character. Simulations in water–toluene liquid mixtures indicate thatmore » the partitioning of each Mg–salen compound relative to the interface is strongly influenced by the degree of hydrophobicity of the compound. Simulations of these complexes in fluid-filled mineral nanopores containing neutral (kaolinite) and negatively charged (montmorillonite) mineral surfaces reveal that adsorption tendencies depend upon a variety of parameters, including tracer chemical properties, mineral surface type, and solvent type (water or toluene). Simulation snapshots and averaged density profiles reveal insight into the solvation and adsorption mechanisms that control the partitioning of these complexes in mixed liquid phases and nanopore environments. As a result, this work demonstrates the utility of molecular simulation in the design and screening of molecular tracers for use in subsurface applications.« less

Computational Evaluation of Mg–Salen Compounds as Subsurface Fluid Tracers: Molecular Dynamics Simulations in Toluene–Water Mixtures and Clay Mineral Nanopores

DOE PAGES

Greathouse, Jeffery A.; Boyle, Timothy J.; Kemp, Richard A.

2018-04-11

Molecular tracers that can be selectively placed underground and uniquely identified at the surface using simple on-site spectroscopic methods would significantly enhance subsurface fluid monitoring capabilities. To ensure their widespread utility, the solubility of these tracers must be easily tuned to oil- or water-wet conditions as well as reducing or eliminating their propensity to adsorb onto subsurface rock and/or mineral phases. In this work, molecular dynamics simulations were used to investigate the relative solubilities and mineral surface adsorption properties of three candidate tracer compounds comprising Mg–salen derivatives of varying degrees of hydrophilic character. Simulations in water–toluene liquid mixtures indicate thatmore » the partitioning of each Mg–salen compound relative to the interface is strongly influenced by the degree of hydrophobicity of the compound. Simulations of these complexes in fluid-filled mineral nanopores containing neutral (kaolinite) and negatively charged (montmorillonite) mineral surfaces reveal that adsorption tendencies depend upon a variety of parameters, including tracer chemical properties, mineral surface type, and solvent type (water or toluene). Simulation snapshots and averaged density profiles reveal insight into the solvation and adsorption mechanisms that control the partitioning of these complexes in mixed liquid phases and nanopore environments. As a result, this work demonstrates the utility of molecular simulation in the design and screening of molecular tracers for use in subsurface applications.« less

Molecular dynamics simulations and free energy calculations on the enzyme 4-hydroxyphenylpyruvate dioxygenase.

PubMed

De Beer, Stephanie B A; Glättli, Alice; Hutzler, Johannes; Vermeulen, Nico P E; Oostenbrink, Chris

2011-07-30

4-Hydroxyphenylpyruvate dioxygenase is a relevant target in both pharmaceutical and agricultural research. We report on molecular dynamics simulations and free energy calculations on this enzyme, in complex with 12 inhibitors for which experimental affinities were determined. We applied the thermodynamic integration approach and the more efficient one-step perturbation. Even though simulations seem well converged and both methods show excellent agreement between them, the correlation with the experimental values remains poor. We investigate the effect of slight modifications on the charge distribution of these highly conjugated systems and find that accurate models can be obtained when using improved force field parameters. This study gives insight into the applicability of free energy methods and current limitations in force field parameterization. Copyright © 2011 Wiley Periodicals, Inc.

Modeling of crack growth under mixed-mode loading by a molecular dynamics method and a linear fracture mechanics approach

NASA Astrophysics Data System (ADS)

Stepanova, L. V.

2017-12-01

Atomistic simulations of the central crack growth process in an infinite plane medium under mixed-mode loading using Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS), a classical molecular dynamics code, are performed. The inter-atomic potential used in this investigation is the Embedded Atom Method (EAM) potential. Plane specimens with an initial central crack are subjected to mixed-mode loadings. The simulation cell contains 400,000 atoms. The crack propagation direction angles under different values of the mixity parameter in a wide range of values from pure tensile loading to pure shear loading in a wide range of temperatures (from 0.1 K to 800 K) are obtained and analyzed. It is shown that the crack propagation direction angles obtained by molecular dynamics coincide with the crack propagation direction angles given by the multi-parameter fracture criteria based on the strain energy density and the multi-parameter description of the crack-tip fields. The multi-parameter fracture criteria are based on the multi-parameter stress field description taking into account the higher order terms of the Williams series expansion of the crack tip fields.

Cyclocurcumin, a curcumin derivative, exhibits immune-modulating ability and is a potential compound for the treatment of rheumatoid arthritis as predicted by the MM-PBSA method.

PubMed

Fu, Min; Chen, Lihui; Zhang, Limin; Yu, Xiao; Yang, Qingrui

2017-05-01

The control and treatment of rheumatoid arthritis is a challenge in today's world. Therefore, the pursuit of natural disease-modifying antirheumatic drugs (DMRDs) remains a top priority in rheumatology. The present study focused on curcumin and its derivatives in the search for new DMRDs. We focused on prominent p38 mitogen-activated protein (MAP) kinase p38α which is a prime regulator of tumor necrosis factor-α (TNF-α), a key mediator of rheumatoid arthritis. In the present study, we used the X-ray crystallographic structure of p38α for molecular docking simulations and molecular dynamic simulations to study the binding modes of curcumin and its derivatives with the active site of p38α. The ATP-binding domain was used for evaluating curcumin and its derivatives. Molecular docking simulation results were used to select 4 out of 8 compounds. These 4 compounds were simulated using GROMACS molecular simulation platform; the results generated were subjected to molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) calculations. The results showed cyclocurcumin as a potential natural compound for development of a potent DMRD. These data were further supported by inhibition of TNF-α release from lipopolysaccharide (LPS)-stimulated human macrophages following cyclocurcumin treatment.

Statistical physics approaches to Alzheimer's disease

NASA Astrophysics Data System (ADS)

Peng, Shouyong

Alzheimer's disease (AD) is the most common cause of late life dementia. In the brain of an AD patient, neurons are lost and spatial neuronal organizations (microcolumns) are disrupted. An adequate quantitative analysis of microcolumns requires that we automate the neuron recognition stage in the analysis of microscopic images of human brain tissue. We propose a recognition method based on statistical physics. Specifically, Monte Carlo simulations of an inhomogeneous Potts model are applied for image segmentation. Unlike most traditional methods, this method improves the recognition of overlapped neurons, and thus improves the overall recognition percentage. Although the exact causes of AD are unknown, as experimental advances have revealed the molecular origin of AD, they have continued to support the amyloid cascade hypothesis, which states that early stages of aggregation of amyloid beta (Abeta) peptides lead to neurodegeneration and death. X-ray diffraction studies reveal the common cross-beta structural features of the final stable aggregates-amyloid fibrils. Solid-state NMR studies also reveal structural features for some well-ordered fibrils. But currently there is no feasible experimental technique that can reveal the exact structure or the precise dynamics of assembly and thus help us understand the aggregation mechanism. Computer simulation offers a way to understand the aggregation mechanism on the molecular level. Because traditional all-atom continuous molecular dynamics simulations are not fast enough to investigate the whole aggregation process, we apply coarse-grained models and discrete molecular dynamics methods to increase the simulation speed. First we use a coarse-grained two-bead (two beads per amino acid) model. Simulations show that peptides can aggregate into multilayer beta-sheet structures, which agree with X-ray diffraction experiments. To better represent the secondary structure transition happening during aggregation, we refine the model to four beads per amino acid. Typical essential interactions, such as backbone hydrogen bond, hydrophobic and electrostatic interactions, are incorporated into our model. We study the aggregation of Abeta16-22, a peptide that can aggregate into a well-ordered fibrillar structure in experiments. Our results show that randomly-oriented monomers can aggregate into fibrillar subunits, which agree not only with X-ray diffraction experiments but also with solid-state NMR studies. Our findings demonstrate that coarse-grained models and discrete molecular dynamics simulations can help researchers understand the aggregation mechanism of amyloid peptides.

Glucose oxidase from Penicillium amagasakiense: characterization of the transition state of its denaturation from molecular dynamics simulations.

PubMed

Todde, Guido; Hovmöller, Sven; Laaksonen, Aatto; Mocci, Francesca

2014-10-01

Glucose oxidase (GOx) is a flavoenzyme having applications in food and medical industries. However, GOx, as many other enzymes when extracted from the cells, has relatively short operational lifetimes. Several recent studies (both experimental and theoretical), carried out on small proteins (or small fractions of large proteins), show that a detailed knowledge of how the breakdown process starts and proceeds on molecular level could be of significant help to artificially improve the stability of fragile proteins. We have performed extended molecular dynamics (MD) simulations to study the denaturation of GOx (a protein dimer containing nearly 1200 amino acids) to identify weak points in its structure and in this way gather information to later make it more stable, for example, by mutations. A denaturation of a protein can be simulated by increasing the temperature far above physiological temperature. We have performed a series of MD simulations at different temperatures (300, 400, 500, and 600 K). The exit from the protein's native state has been successfully identified with the clustering method and supported by other methods used to analyze the simulation data. A common set of amino acids is regularly found to initiate the denaturation, suggesting a moiety where the enzyme could be strengthened by a suitable amino acid based modification. © 2014 Wiley Periodicals, Inc.

The calculation of viscosity of liquid n-decane and n-hexadecane by the Green-Kubo method

NASA Astrophysics Data System (ADS)

Cui, S. T.; Cummings, P. T.; Cochran, H. D.

This short commentary presents the result of long molecular dynamics simulation calculations of the shear viscosity of liquid n-decane and n-hexadecane using the Green-Kubo integration method. The relaxation time of the stress-stress correlation function is compared with those of rotation and diffusion. The rotational and diffusional relaxation times, which are easy to calculate, provide useful guides for the required simulation time in viscosity calculations. Also, the computational time required for viscosity calculations of these systems by the Green-Kubo method is compared with the time required for previous non-equilibrium molecular dynamics calculations of the same systems. The method of choice for a particular calculation is determined largely by the properties of interest, since the efficiencies of the two methods are comparable for calculation of the zero strain rate viscosity.

Convergence acceleration of molecular dynamics methods for shocked materials using velocity scaling

NASA Astrophysics Data System (ADS)

Taylor, DeCarlos E.

2017-03-01

In this work, a convergence acceleration method applicable to extended system molecular dynamics techniques for shock simulations of materials is presented. The method uses velocity scaling to reduce the instantaneous value of the Rankine-Hugoniot conservation of energy constraint used in extended system molecular dynamics methods to more rapidly drive the system towards a converged Hugoniot state. When used in conjunction with the constant stress Hugoniostat method, the velocity scaled trajectories show faster convergence to the final Hugoniot state with little difference observed in the converged Hugoniot energy, pressure, volume and temperature. A derivation of the scale factor is presented and the performance of the technique is demonstrated using the boron carbide armour ceramic as a test material. It is shown that simulation of boron carbide Hugoniot states, from 5 to 20 GPa, using both a classical Tersoff potential and an ab initio density functional, are more rapidly convergent when the velocity scaling algorithm is applied. The accelerated convergence afforded by the current algorithm enables more rapid determination of Hugoniot states thus reducing the computational demand of such studies when using expensive ab initio or classical potentials.

Predicting solute partitioning in lipid bilayers: Free energies and partition coefficients from molecular dynamics simulations and COSMOmic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jakobtorweihen, S., E-mail: jakobtorweihen@tuhh.de; Ingram, T.; Gerlach, T.

2014-07-28

Quantitative predictions of biomembrane/water partition coefficients are important, as they are a key property in pharmaceutical applications and toxicological studies. Molecular dynamics (MD) simulations are used to calculate free energy profiles for different solutes in lipid bilayers. How to calculate partition coefficients from these profiles is discussed in detail and different definitions of partition coefficients are compared. Importantly, it is shown that the calculated coefficients are in quantitative agreement with experimental results. Furthermore, we compare free energy profiles from MD simulations to profiles obtained by the recent method COSMOmic, which is an extension of the conductor-like screening model for realisticmore » solvation to micelles and biomembranes. The free energy profiles from these molecular methods are in good agreement. Additionally, solute orientations calculated with MD and COSMOmic are compared and again a good agreement is found. Four different solutes are investigated in detail: 4-ethylphenol, propanol, 5-phenylvaleric acid, and dibenz[a,h]anthracene, whereby the latter belongs to the class of polycyclic aromatic hydrocarbons. The convergence of the free energy profiles from biased MD simulations is discussed and the results are shown to be comparable to equilibrium MD simulations. For 5-phenylvaleric acid the influence of the carboxyl group dihedral angle on free energy profiles is analyzed with MD simulations.« less

Systematic Computation of Nonlinear Cellular and Molecular Dynamics with Low-Power CytoMimetic Circuits: A Simulation Study

PubMed Central

Papadimitriou, Konstantinos I.; Stan, Guy-Bart V.; Drakakis, Emmanuel M.

2013-01-01

This paper presents a novel method for the systematic implementation of low-power microelectronic circuits aimed at computing nonlinear cellular and molecular dynamics. The method proposed is based on the Nonlinear Bernoulli Cell Formalism (NBCF), an advanced mathematical framework stemming from the Bernoulli Cell Formalism (BCF) originally exploited for the modular synthesis and analysis of linear, time-invariant, high dynamic range, logarithmic filters. Our approach identifies and exploits the striking similarities existing between the NBCF and coupled nonlinear ordinary differential equations (ODEs) typically appearing in models of naturally encountered biochemical systems. The resulting continuous-time, continuous-value, low-power CytoMimetic electronic circuits succeed in simulating fast and with good accuracy cellular and molecular dynamics. The application of the method is illustrated by synthesising for the first time microelectronic CytoMimetic topologies which simulate successfully: 1) a nonlinear intracellular calcium oscillations model for several Hill coefficient values and 2) a gene-protein regulatory system model. The dynamic behaviours generated by the proposed CytoMimetic circuits are compared and found to be in very good agreement with their biological counterparts. The circuits exploit the exponential law codifying the low-power subthreshold operation regime and have been simulated with realistic parameters from a commercially available CMOS process. They occupy an area of a fraction of a square-millimetre, while consuming between 1 and 12 microwatts of power. Simulations of fabrication-related variability results are also presented. PMID:23393550

Stabilization of Model Membrane Systems by Disaccharides. Quasielastic Neutron Scattering Experiments and Atomistic Simulations

NASA Astrophysics Data System (ADS)

Doxastakis, Emmanouil; Garcia Sakai, Victoria; Ohtake, Satoshi; Maranas, Janna K.; de Pablo, Juan J.

2006-03-01

Trehalose, a disaccharide of glucose, is often used for the stabilization of cell membranes in the absence of water. This work studies the effects of trehalose on model membrane systems as they undergo a melting transition using a combination of experimental methods and atomistic molecular simulations. Quasielastic neutron scattering experiments on selectively deuterated samples provide the incoherent dynamic structure over a wide time range. Elastic scans probing the lipid tail dynamics display clear evidence of a main melting transition that is significantly lowered in the presence of trehalose. Lipid headgroup mobility is considerably restricted at high temperatures and directly associated with the dynamics of the sugar in the mixture. Molecular simulations provide a detailed overview of the dynamics and their spatial and time dependence. The combined simulation and experimental methodology offers a unique, molecular view of the physics of systems commonly employed in cryopreservation and lyophilization processes.

Using molecular simulation to explore the nanoscale dynamics of the plant kinome.

PubMed

Moffett, Alexander S; Shukla, Diwakar

2018-03-09

Eukaryotic protein kinases (PKs) are a large family of proteins critical for cellular response to external signals, acting as molecular switches. PKs propagate biochemical signals by catalyzing phosphorylation of other proteins, including other PKs, which can undergo conformational changes upon phosphorylation and catalyze further phosphorylations. Although PKs have been studied thoroughly across the domains of life, the structures of these proteins are sparsely understood in numerous groups of organisms, including plants. In addition to efforts towards determining crystal structures of PKs, research on human PKs has incorporated molecular dynamics (MD) simulations to study the conformational dynamics underlying the switching of PK function. This approach of experimental structural biology coupled with computational biophysics has led to improved understanding of how PKs become catalytically active and why mutations cause pathological PK behavior, at spatial and temporal resolutions inaccessible to current experimental methods alone. In this review, we argue for the value of applying MD simulation to plant PKs. We review the basics of MD simulation methodology, the successes achieved through MD simulation in animal PKs, and current work on plant PKs using MD simulation. We conclude with a discussion of the future of MD simulations and plant PKs, arguing for the importance of molecular simulation in the future of plant PK research. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

A Multi-Scale Method for Dynamics Simulation in Continuum Solvent Models I: Finite-Difference Algorithm for Navier-Stokes Equation.

PubMed

Xiao, Li; Cai, Qin; Li, Zhilin; Zhao, Hongkai; Luo, Ray

2014-11-25

A multi-scale framework is proposed for more realistic molecular dynamics simulations in continuum solvent models by coupling a molecular mechanics treatment of solute with a fluid mechanics treatment of solvent. This article reports our initial efforts to formulate the physical concepts necessary for coupling the two mechanics and develop a 3D numerical algorithm to simulate the solvent fluid via the Navier-Stokes equation. The numerical algorithm was validated with multiple test cases. The validation shows that the algorithm is effective and stable, with observed accuracy consistent with our design.

Keep It Flexible: Driving Macromolecular Rotary Motions in Atomistic Simulations with GROMACS

PubMed Central

2011-01-01

We describe a versatile method to enforce the rotation of subsets of atoms, e.g., a protein subunit, in molecular dynamics (MD) simulations. In particular, we introduce a “flexible axis” technique that allows realistic flexible adaptions of both the rotary subunit as well as the local rotation axis during the simulation. A variety of useful rotation potentials were implemented for the GROMACS 4.5 MD package. Application to the molecular motor F1-ATP synthase demonstrates the advantages of the flexible axis approach over the established fixed axis rotation technique. PMID:21566696

Studies on thermal decomposition behaviors of polypropylene using molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Huang, Jinbao; He, Chao; Tong, Hong; Pan, Guiying

2017-11-01

Polypropylene (PP) is one of the main components of waste plastics. In order to understand the mechanism of PP thermal decomposition, the pyrolysis behaviour of PP has been simulated from 300 to 1000 K in periodic boundary conditions by molecular dynamic method, based on AMBER force field. The simulation results show that the pyrolysis process of PP can mostly be divided into three stages: low temperature pyrolysis stage, intermediate temperature stage and high temperature pyrolysis stage. PP pyrolysis is typical of random main-chain scission, and the possible formation mechanism of major pyrolysis products was analyzed.

Using collective variables to drive molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Fiorin, Giacomo; Klein, Michael L.; Hénin, Jérôme

2013-12-01

A software framework is introduced that facilitates the application of biasing algorithms to collective variables of the type commonly employed to drive massively parallel molecular dynamics (MD) simulations. The modular framework that is presented enables one to combine existing collective variables into new ones, and combine any chosen collective variable with available biasing methods. The latter include the classic time-dependent biases referred to as steered MD and targeted MD, the temperature-accelerated MD algorithm, as well as the adaptive free-energy biases called metadynamics and adaptive biasing force. The present modular software is extensible, and portable between commonly used MD simulation engines.

Flexible docking of a ligand peptide to a receptor protein by multicanonical molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Nakajima, Nobuyuki; Higo, Junichi; Kidera, Akinori; Nakamura, Haruki

1997-10-01

A new method for flexible docking by multicanonical molecular dynamics simulation is presented. The method was applied to the binding of a short proline-rich peptide to a Src homology 3 (SH3) domain. The peptide and the side-chains at the ligand binding cleft of SH3 were completely flexible and the large number of possible conformations and dispositions of the peptide were sampled. The reweighted canonical resemble at 300 K resulted in only a few predominant binding modes, one of which was similar to the complex crystal structure. The inverted peptide orientation was also observed in the other binding modes.

Molecular simulations of carbohydrates and protein-carbohydrate interactions: motivation, issues and prospects

PubMed Central

Fadda, Elisa; Woods, Robert J.

2014-01-01

The characterization of the 3D structure of oligosaccharides, their conjugates and analogs is particularly challenging for traditional experimental methods. Molecular simulation methods provide a basis for interpreting sparse experimental data and for independently predicting conformational and dynamic properties of glycans. Here, we summarize and analyze the issues associated with modeling carbohydrates, with a detailed discussion of four of the most recently developed carbohydrate force fields, reviewed in terms of applicability to natural glycans, carbohydrate–protein complexes and the emerging area of glycomimetic drugs. In addition, we discuss prospectives and new applications of carbohydrate modeling in drug discovery. PMID:20594934

Recommender engine for continuous-time quantum Monte Carlo methods

NASA Astrophysics Data System (ADS)

Huang, Li; Yang, Yi-feng; Wang, Lei

2017-03-01

Recommender systems play an essential role in the modern business world. They recommend favorable items such as books, movies, and search queries to users based on their past preferences. Applying similar ideas and techniques to Monte Carlo simulations of physical systems boosts their efficiency without sacrificing accuracy. Exploiting the quantum to classical mapping inherent in the continuous-time quantum Monte Carlo methods, we construct a classical molecular gas model to reproduce the quantum distributions. We then utilize powerful molecular simulation techniques to propose efficient quantum Monte Carlo updates. The recommender engine approach provides a general way to speed up the quantum impurity solvers.

Transition Pathway and Its Free-Energy Profile: A Protocol for Protein Folding Simulations

PubMed Central

Lee, In-Ho; Kim, Seung-Yeon; Lee, Jooyoung

2013-01-01

We propose a protocol that provides a systematic definition of reaction coordinate and related free-energy profile as the function of temperature for the protein-folding simulation. First, using action-derived molecular dynamics (ADMD), we investigate the dynamic folding pathway model of a protein between a fixed extended conformation and a compact conformation. We choose the pathway model to be the reaction coordinate, and the folding and unfolding processes are characterized by the ADMD step index, in contrast to the common a priori reaction coordinate as used in conventional studies. Second, we calculate free-energy profile as the function of temperature, by employing the replica-exchange molecular dynamics (REMD) method. The current method provides efficient exploration of conformational space and proper characterization of protein folding/unfolding dynamics from/to an arbitrary extended conformation. We demonstrate that combination of the two simulation methods, ADMD and REMD, provides understanding on molecular conformational changes in proteins. The protocol is tested on a small protein, penta-peptide of met-enkephalin. For the neuropeptide met-enkephalin system, folded, extended, and intermediate sates are well-defined through the free-energy profile over the reaction coordinate. Results are consistent with those in the literature. PMID:23917881

Essential energy space random walk via energy space metadynamics method to accelerate molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Li, Hongzhi; Min, Donghong; Liu, Yusong; Yang, Wei

2007-09-01

To overcome the possible pseudoergodicity problem, molecular dynamic simulation can be accelerated via the realization of an energy space random walk. To achieve this, a biased free energy function (BFEF) needs to be priori obtained. Although the quality of BFEF is essential for sampling efficiency, its generation is usually tedious and nontrivial. In this work, we present an energy space metadynamics algorithm to efficiently and robustly obtain BFEFs. Moreover, in order to deal with the associated diffusion sampling problem caused by the random walk in the total energy space, the idea in the original umbrella sampling method is generalized to be the random walk in the essential energy space, which only includes the energy terms determining the conformation of a region of interest. This essential energy space generalization allows the realization of efficient localized enhanced sampling and also offers the possibility of further sampling efficiency improvement when high frequency energy terms irrelevant to the target events are free of activation. The energy space metadynamics method and its generalization in the essential energy space for the molecular dynamics acceleration are demonstrated in the simulation of a pentanelike system, the blocked alanine dipeptide model, and the leucine model.

An Integrated In Silico Method to Discover Novel Rock1 Inhibitors: Multi- Complex-Based Pharmacophore, Molecular Dynamics Simulation and Hybrid Protocol Virtual Screening.

PubMed

Chen, Haining; Li, Sijia; Hu, Yajiao; Chen, Guo; Jiang, Qinglin; Tong, Rongsheng; Zang, Zhihe; Cai, Lulu

2016-01-01

Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) is an important regulator of focal adhesion, actomyosin contraction and cell motility. In this manuscript, a combination of the multi-complex-based pharmacophore (MCBP), molecular dynamics simulation and a hybrid protocol of a virtual screening method, comprised of multipharmacophore- based virtual screening (PBVS) and ensemble docking-based virtual screening (DBVS) methods were used for retrieving novel ROCK1 inhibitors from the natural products database embedded in the ZINC database. Ten hit compounds were selected from the hit compounds, and five compounds were tested experimentally. Thus, these results may provide valuable information for further discovery of more novel ROCK1 inhibitors.

Constant-pH Hybrid Nonequilibrium Molecular Dynamics–Monte Carlo Simulation Method

PubMed Central

2016-01-01

A computational method is developed to carry out explicit solvent simulations of complex molecular systems under conditions of constant pH. In constant-pH simulations, preidentified ionizable sites are allowed to spontaneously protonate and deprotonate as a function of time in response to the environment and the imposed pH. The method, based on a hybrid scheme originally proposed by H. A. Stern (J. Chem. Phys.2007, 126, 164112), consists of carrying out short nonequilibrium molecular dynamics (neMD) switching trajectories to generate physically plausible configurations with changed protonation states that are subsequently accepted or rejected according to a Metropolis Monte Carlo (MC) criterion. To ensure microscopic detailed balance arising from such nonequilibrium switches, the atomic momenta are altered according to the symmetric two-ends momentum reversal prescription. To achieve higher efficiency, the original neMD–MC scheme is separated into two steps, reducing the need for generating a large number of unproductive and costly nonequilibrium trajectories. In the first step, the protonation state of a site is randomly attributed via a Metropolis MC process on the basis of an intrinsic pKa; an attempted nonequilibrium switch is generated only if this change in protonation state is accepted. This hybrid two-step inherent pKa neMD–MC simulation method is tested with single amino acids in solution (Asp, Glu, and His) and then applied to turkey ovomucoid third domain and hen egg-white lysozyme. Because of the simple linear increase in the computational cost relative to the number of titratable sites, the present method is naturally able to treat extremely large systems. PMID:26300709

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

PubMed

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.

Computer simulation of liquid metals

NASA Astrophysics Data System (ADS)

Belashchenko, D. K.

2013-12-01

Methods for and the results of the computer simulation of liquid metals are reviewed. Two basic methods, classical molecular dynamics with known interparticle potentials and the ab initio method, are considered. Most attention is given to the simulated results obtained using the embedded atom model (EAM). The thermodynamic, structural, and diffusion properties of liquid metal models under normal and extreme (shock) pressure conditions are considered. Liquid-metal simulated results for the Groups I - IV elements, a number of transition metals, and some binary systems (Fe - C, Fe - S) are examined. Possibilities for the simulation to account for the thermal contribution of delocalized electrons to energy and pressure are considered. Solidification features of supercooled metals are also discussed.

Energy transport pathway in proteins: Insights from non-equilibrium molecular dynamics with elastic network model.

PubMed

Wang, Wei Bu; Liang, Yu; Zhang, Jing; Wu, Yi Dong; Du, Jian Jun; Li, Qi Ming; Zhu, Jian Zhuo; Su, Ji Guo

2018-06-22

Intra-molecular energy transport between distant functional sites plays important roles in allosterically regulating the biochemical activity of proteins. How to identify the specific intra-molecular signaling pathway from protein tertiary structure remains a challenging problem. In the present work, a non-equilibrium dynamics method based on the elastic network model (ENM) was proposed to simulate the energy propagation process and identify the specific signaling pathways within proteins. In this method, a given residue was perturbed and the propagation of energy was simulated by non-equilibrium dynamics in the normal modes space of ENM. After that, the simulation results were transformed from the normal modes space to the Cartesian coordinate space to identify the intra-protein energy transduction pathways. The proposed method was applied to myosin and the third PDZ domain (PDZ3) of PSD-95 as case studies. For myosin, two signaling pathways were identified, which mediate the energy transductions form the nucleotide binding site to the 50 kDa cleft and the converter subdomain, respectively. For PDZ3, one specific signaling pathway was identified, through which the intra-protein energy was transduced from ligand binding site to the distant opposite side of the protein. It is also found that comparing with the commonly used cross-correlation analysis method, the proposed method can identify the anisotropic energy transduction pathways more effectively.

Free energy calculations along entropic pathways. I. Homogeneous vapor-liquid nucleation for atomic and molecular systems

NASA Astrophysics Data System (ADS)

Desgranges, Caroline; Delhommelle, Jerome

2016-11-01

Using the entropy S as a reaction coordinate, we determine the free energy barrier associated with the formation of a liquid droplet from a supersaturated vapor for atomic and molecular fluids. For this purpose, we develop the μ V T -S simulation method that combines the advantages of the grand-canonical ensemble, that allows for a direct evaluation of the entropy, and of the umbrella sampling method, that is well suited to the study of an activated process like nucleation. Applying this approach to an atomic system such as Ar allows us to test the method. The results show that the μ V T -S method gives the correct dependence on supersaturation of the height of the free energy barrier and of the size of the critical droplet, when compared to predictions from the classical nucleation theory and to previous simulation results. In addition, it provides insight into the relation between the entropy and droplet formation throughout this process. An additional advantage of the μ V T -S approach is its direct transferability to molecular systems, since it uses the entropy of the system as the reaction coordinate. Applications of the μ V T -S simulation method to N2 and CO2 are presented and discussed in this work, showing the versatility of the μ V T -S approach.

Plane-Wave DFT Methods for Chemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bylaska, Eric J.

A detailed description of modern plane-wave DFT methods and software (contained in the NWChem package) are described that allow for both geometry optimization and ab initio molecular dynamics simulations. Significant emphasis is placed on aspects of these methods that are of interest to computational chemists and useful for simulating chemistry, including techniques for calculating charged systems, exact exchange (i.e. hybrid DFT methods), and highly efficient AIMD/MM methods. Sample applications on the structure of the goethite+water interface and the hydrolysis of nitroaromatic molecules are described.

Hetero-diffusion of Au epitaxy on stepped Ag(110) surface: Study of the jump rate and diffusion coefficient

NASA Astrophysics Data System (ADS)

Benlattar, M.; El koraychy, E.; Kotri, A.; Mazroui, M.

2017-12-01

We have used molecular dynamics simulations combined with an interatomic potential derived from the embedded atom method, to investigate the hetero-diffusion of Au adatom near a stepped Ag(110) surface with the height of one monoatomic layer. The activation energies for different diffusion processes, which occur on the terrace and near the step edge, are calculated both by molecular statics and molecular dynamics simulations. Static energies are found by the drag method, whereas the dynamic barriers are computed at high temperature from the Arrhenius plots. Our numerical results reveal that the jump process requires very high activation energy compared to the exchange process either on the terrace or near the step edge. In this work, other processes, such as upward and downward diffusion at step edges, have also been discussed.

Phenomenological and molecular-level Petri net modeling and simulation of long-term potentiation.

PubMed

Hardy, S; Robillard, P N

2005-10-01

Petri net-based modeling methods have been used in many research projects to represent biological systems. Among these, the hybrid functional Petri net (HFPN) was developed especially for biological modeling in order to provide biologists with a more intuitive Petri net-based method. In the literature, HFPNs are used to represent kinetic models at the molecular level. We present two models of long-term potentiation previously represented by differential equations which we have transformed into HFPN models: a phenomenological synapse model and a molecular-level model of the CaMKII regulation pathway. Through simulation, we obtained results similar to those of previous studies using these models. Our results open the way to a new type of modeling for systems biology where HFPNs are used to combine different levels of abstraction within one model. This approach can be useful in fully modeling a system at the molecular level when kinetic data is missing or when a full study of a system at the molecular level it is not within the scope of the research.

Equivalence of the equilibrium and the nonequilibrium molecular dynamics methods for thermal conductivity calculations: From bulk to nanowire silicon

NASA Astrophysics Data System (ADS)

Dong, Haikuan; Fan, Zheyong; Shi, Libin; Harju, Ari; Ala-Nissila, Tapio

2018-03-01

Molecular dynamics (MD) simulations play an important role in studying heat transport in complex materials. The lattice thermal conductivity can be computed either using the Green-Kubo formula in equilibrium MD (EMD) simulations or using Fourier's law in nonequilibrium MD (NEMD) simulations. These two methods have not been systematically compared for materials with different dimensions and inconsistencies between them have been occasionally reported in the literature. Here we give an in-depth comparison of them in terms of heat transport in three allotropes of Si: three-dimensional bulk silicon, two-dimensional silicene, and quasi-one-dimensional silicon nanowire. By multiplying the correlation time in the Green-Kubo formula with an appropriate effective group velocity, we can express the running thermal conductivity in the EMD method as a function of an effective length and directly compare it to the length-dependent thermal conductivity in the NEMD method. We find that the two methods quantitatively agree with each other for all the systems studied, firmly establishing their equivalence in computing thermal conductivity.

Low-Density Nozzle Flow by the Direct Simulation Monte Carlo and Continuum Methods

NASA Technical Reports Server (NTRS)

Chung, Chang-Hong; Kim, Sku C.; Stubbs, Robert M.; Dewitt, Kenneth J.

1994-01-01

Two different approaches, the direct simulation Monte Carlo (DSMC) method based on molecular gasdynamics, and a finite-volume approximation of the Navier-Stokes equations, which are based on continuum gasdynamics, are employed in the analysis of a low-density gas flow in a small converging-diverging nozzle. The fluid experiences various kinds of flow regimes including continuum, slip, transition, and free-molecular. Results from the two numerical methods are compared with Rothe's experimental data, in which density and rotational temperature variations along the centerline and at various locations inside a low-density nozzle were measured by the electron-beam fluorescence technique. The continuum approach showed good agreement with the experimental data as far as density is concerned. The results from the DSMC method showed good agreement with the experimental data, both in the density and the rotational temperature. It is also shown that the simulation parameters, such as the gas/surface interaction model, the energy exchange model between rotational and translational modes, and the viscosity-temperature exponent, have substantial effects on the results of the DSMC method.

Synthesis and conformational analysis by 1H NMR and restrained molecular dynamics simulations of the cyclic decapeptide [Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly

NASA Astrophysics Data System (ADS)

Buono, Ronald A.; Kucharczyk, Nathalie; Neuenschwander, Magrit; Kemmink, Johan; Hwang, Lih-Yueh; Fauchère, Jean-Luc; Venanzi, Carol A.

1996-06-01

The design of enzyme mimics with therapeutic and industrial applications has interested both experimental and computational chemists for several decades. Recent advances in the computational methodology of restrained molecular dynamics, used in conjunction with data obtained from two-dimensional 1H NMR spectroscopy, make it a promising method to study peptide and protein structure and function. Several issues, however, need to be addressed in order to assess the validity of this method for its explanatory and predictive value. Among the issues addressed in this study are: the accuracy and generizability of the GROMOS peptide molecular mechanics force field; the effect of inclusion of solvent on the simulations; and the effect of different types of restraining algorithms on the computational results. The decapeptide Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly, which corresponds to the sequence of ACTH1-10, has been synthesized, cyclized, and studied by two-dimensional 1H NMR spectroscopy. Restrained molecular dynamics (RMD) and time-averaged restrained molecular dynamics (TARMD) simulations were carried out on four different distance-geometry starting structures in order to determine and contrast the behavior of cyclic ACTH1-10 in vacuum and in solution. For the RMD simulations, the structures did not fit the NOE data well, even at high values of the restraining potential. The TARMD simulation method, however, was able to give structures that fit the NOE data at high values of the restraining potential. In both cases, inclusion of explicit solvent molecules in the simulation had little effect on the quality of the fit, although it was found to dampen the motion of the cyclic peptide. For both simulation techniques, the number and size of the NOE violations increased as the restraining potential approached zero. This is due, presumably, to inadequacies in the force field. Additional TARMD vacuum-phase simulations, run with a larger memory length or with a larger sampling size (16 additional distance-geometry structures), yielded no significantly different results. The computed data were then analyzed to help explain the sparse NOE data and poor chymotryptic activity of the cyclic peptide. Cyclic ACTH1-10, which contains the functional moieties of the catalytic triad of chymotrypsin, was evaluated as a potential mimic of chymotrypsin by measurement of the rate of hydrolysis of esters of L-and d-phenylalanine. The poor rate of hydrolysis is attributed to the flexibility of the decapeptide, the motion of the side chains, which result in the absence of long-range NOEs, the small size of the macrocycle relative to that of the substrate, and the inappropriate orientation of the Gly, His, and Ser residues. The results demonstrate the utility of this method in computer-aided molecular design of cyclic peptides and suggest structural modifications for future work based on a larger and more rigid peptide framework.

The Computer Simulation of Liquids by Molecular Dynamics.

ERIC Educational Resources Information Center

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)

New approach in direct-simulation of gas mixtures

NASA Technical Reports Server (NTRS)

Chung, Chan-Hong; De Witt, Kenneth J.; Jeng, Duen-Ren

1991-01-01

Results are reported for an investigation of a new direct-simulation Monte Carlo method by which energy transfer and chemical reactions are calculated. The new method, which reduces to the variable cross-section hard sphere model as a special case, allows different viscosity-temperature exponents for each species in a gas mixture when combined with a modified Larsen-Borgnakke phenomenological model. This removes the most serious limitation of the usefulness of the model for engineering simulations. The necessary kinetic theory for the application of the new method to mixtures of monatomic or polyatomic gases is presented, including gas mixtures involving chemical reactions. Calculations are made for the relaxation of a diatomic gas mixture, a plane shock wave in a gas mixture, and a chemically reacting gas flow along the stagnation streamline in front of a hypersonic vehicle. Calculated results show that the introduction of different molecular interactions for each species in a gas mixture produces significant differences in comparison with a common molecular interaction for all species in the mixture. This effect should not be neglected for accurate DSMC simulations in an engineering context.

Development of a group contribution method for estimating free energy of peptides in a dodecane-water system via molecular dynamic simulations.

PubMed

Mora Osorio, Camilo Andrés; González Barrios, Andrés Fernando

2016-12-07

Calculation of the Gibbs free energy changes of biological molecules at the oil-water interface is commonly performed with Molecular Dynamics simulations (MD). It is a process that could be performed repeatedly in order to find some molecules of high stability in this medium. Here, an alternative method of calculation has been proposed: a group contribution method (GCM) for peptides based on MD of the twenty classic amino acids to obtain free energy change during the insertion of any peptide chain in water-dodecane interfaces. Multiple MD of the twenty classic amino acids located at the interface of rectangular simulation boxes with a dodecane-water medium were performed. A GCM to calculate the free energy of entire peptides is then proposed. The method uses the summation of the Gibbs free energy of each amino acid adjusted in function of its presence or absence in the chain as well as its hydrophobic characteristics. Validation of the equation was performed with twenty-one peptides all simulated using MD in dodecane-water rectangular boxes in previous work, obtaining an average relative error of 16%.

Fluctuation Flooding Method (FFM) for accelerating conformational transitions of proteins.

PubMed

Harada, Ryuhei; Takano, Yu; Shigeta, Yasuteru

2014-03-28

A powerful conformational sampling method for accelerating structural transitions of proteins, "Fluctuation Flooding Method (FFM)," is proposed. In FFM, cycles of the following steps enhance the transitions: (i) extractions of largely fluctuating snapshots along anisotropic modes obtained from trajectories of multiple independent molecular dynamics (MD) simulations and (ii) conformational re-sampling of the snapshots via re-generations of initial velocities when re-starting MD simulations. In an application to bacteriophage T4 lysozyme, FFM successfully accelerated the open-closed transition with the 6 ns simulation starting solely from the open state, although the 1-μs canonical MD simulation failed to sample such a rare event.

Fluctuation Flooding Method (FFM) for accelerating conformational transitions of proteins

NASA Astrophysics Data System (ADS)

Harada, Ryuhei; Takano, Yu; Shigeta, Yasuteru

2014-03-01

A powerful conformational sampling method for accelerating structural transitions of proteins, "Fluctuation Flooding Method (FFM)," is proposed. In FFM, cycles of the following steps enhance the transitions: (i) extractions of largely fluctuating snapshots along anisotropic modes obtained from trajectories of multiple independent molecular dynamics (MD) simulations and (ii) conformational re-sampling of the snapshots via re-generations of initial velocities when re-starting MD simulations. In an application to bacteriophage T4 lysozyme, FFM successfully accelerated the open-closed transition with the 6 ns simulation starting solely from the open state, although the 1-μs canonical MD simulation failed to sample such a rare event.

Coarse-grained versus atomistic simulations: realistic interaction free energies for real proteins.

PubMed

May, Ali; Pool, René; van Dijk, Erik; Bijlard, Jochem; Abeln, Sanne; Heringa, Jaap; Feenstra, K Anton

2014-02-01

To assess whether two proteins will interact under physiological conditions, information on the interaction free energy is needed. Statistical learning techniques and docking methods for predicting protein-protein interactions cannot quantitatively estimate binding free energies. Full atomistic molecular simulation methods do have this potential, but are completely unfeasible for large-scale applications in terms of computational cost required. Here we investigate whether applying coarse-grained (CG) molecular dynamics simulations is a viable alternative for complexes of known structure. We calculate the free energy barrier with respect to the bound state based on molecular dynamics simulations using both a full atomistic and a CG force field for the TCR-pMHC complex and the MP1-p14 scaffolding complex. We find that the free energy barriers from the CG simulations are of similar accuracy as those from the full atomistic ones, while achieving a speedup of >500-fold. We also observe that extensive sampling is extremely important to obtain accurate free energy barriers, which is only within reach for the CG models. Finally, we show that the CG model preserves biological relevance of the interactions: (i) we observe a strong correlation between evolutionary likelihood of mutations and the impact on the free energy barrier with respect to the bound state; and (ii) we confirm the dominant role of the interface core in these interactions. Therefore, our results suggest that CG molecular simulations can realistically be used for the accurate prediction of protein-protein interaction strength. The python analysis framework and data files are available for download at http://www.ibi.vu.nl/downloads/bioinformatics-2013-btt675.tgz.

Testing the accuracy of correlations for multicomponent mass transport of adsorbed gases in metal-organic frameworks: diffusion of H2/CH4 mixtures in CuBTC.

PubMed

Keskin, Seda; Liu, Jinchen; Johnson, J Karl; Sholl, David S

2008-08-05

Mass transport of chemical mixtures in nanoporous materials is important in applications such as membrane separations, but measuring diffusion of mixtures experimentally is challenging. Methods that can predict multicomponent diffusion coefficients from single-component data can be extremely useful if these methods are known to be accurate. We present the first test of a method of this kind for molecules adsorbed in a metal-organic framework (MOF). Specifically, we examine the method proposed by Skoulidas, Sholl, and Krishna (SSK) ( Langmuir, 2003, 19, 7977) by comparing predictions made with this method to molecular simulations of mixture transport of H 2/CH 4 mixtures in CuBTC. These calculations provide the first direct information on mixture transport of any species in a MOF. The predictions of the SSK approach are in good agreement with our direct simulations of binary diffusion, suggesting that this approach may be a powerful one for examining multicomponent diffusion in MOFs. We also use our molecular simulation data to test the ideal adsorbed solution theory method for predicting binary adsorption isotherms and a method for predicting mixture self-diffusion coefficients.

Molecular dynamics simulations of membrane proteins and their interactions: from nanoscale to mesoscale.

PubMed

Chavent, Matthieu; Duncan, Anna L; Sansom, Mark Sp

2016-10-01

Molecular dynamics simulations provide a computational tool to probe membrane proteins and systems at length scales ranging from nanometers to close to a micrometer, and on microsecond timescales. All atom and coarse-grained simulations may be used to explore in detail the interactions of membrane proteins and specific lipids, yielding predictions of lipid binding sites in good agreement with available structural data. Building on the success of protein-lipid interaction simulations, larger scale simulations reveal crowding and clustering of proteins, resulting in slow and anomalous diffusional dynamics, within realistic models of cell membranes. Current methods allow near atomic resolution simulations of small membrane organelles, and of enveloped viruses to be performed, revealing key aspects of their structure and functionally important dynamics. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

A Linked-Cell Domain Decomposition Method for Molecular Dynamics Simulation on a Scalable Multiprocessor

DOE PAGES

Yang, L. H.; Brooks III, E. D.; Belak, J.

1992-01-01

A molecular dynamics algorithm for performing large-scale simulations using the Parallel C Preprocessor (PCP) programming paradigm on the BBN TC2000, a massively parallel computer, is discussed. The algorithm uses a linked-cell data structure to obtain the near neighbors of each atom as time evoles. Each processor is assigned to a geometric domain containing many subcells and the storage for that domain is private to the processor. Within this scheme, the interdomain (i.e., interprocessor) communication is minimized.

Combined 3D-QSAR, molecular docking, molecular dynamics simulation, and binding free energy calculation studies on the 5-hydroxy-2H-pyridazin-3-one derivatives as HCV NS5B polymerase inhibitors.

PubMed

Yu, Haijing; Fang, Yu; Lu, Xia; Liu, Yongjuan; Zhang, Huabei

2014-01-01

The NS5B RNA-dependent RNA polymerase (RdRP) is a promising therapeutic target for developing novel anti-hepatitis C virus (HCV) drugs. In this work, a combined molecular modeling study was performed on a series of 193 5-hydroxy-2H-pyridazin-3-one derivatives as inhibitors of HCV NS5B Polymerase. The best 3D-QSAR models, including CoMFA and CoMSIA, are based on receptor (or docking). Furthermore, a 40-ns molecular dynamics (MD) simulation and binding free energy calculations using docked structures of NS5B with ten compounds, which have diverse structures and pIC50 values, were employed to determine the detailed binding process and to compare the binding modes of the inhibitors with different activities. On one side, the stability and rationality of molecular docking and 3D-QSAR results were validated by MD simulation. The binding free energies calculated by the MM-PBSA method gave a good correlation with the experimental biological activity. On the other side, by analyzing some differences between the molecular docking and the MD simulation results, we can find that the MD simulation could also remedy the defects of molecular docking. The analyses of the combined molecular modeling results have identified that Tyr448, Ser556, and Asp318 are the key amino acid residues in the NS5B binding pocket. The results from this study can provide some insights into the development of novel potent NS5B inhibitors. © 2013 John Wiley & Sons A/S.

New analytic results for speciation times in neutral models.

PubMed

Gernhard, Tanja

2008-05-01

In this paper, we investigate the standard Yule model, and a recently studied model of speciation and extinction, the "critical branching process." We develop an analytic way-as opposed to the common simulation approach-for calculating the speciation times in a reconstructed phylogenetic tree. Simple expressions for the density and the moments of the speciation times are obtained. Methods for dating a speciation event become valuable, if for the reconstructed phylogenetic trees, no time scale is available. A missing time scale could be due to supertree methods, morphological data, or molecular data which violates the molecular clock. Our analytic approach is, in particular, useful for the model with extinction, since simulations of birth-death processes which are conditioned on obtaining n extant species today are quite delicate. Further, simulations are very time consuming for big n under both models.

ProtoMD: A prototyping toolkit for multiscale molecular dynamics

NASA Astrophysics Data System (ADS)

Somogyi, Endre; Mansour, Andrew Abi; Ortoleva, Peter J.

2016-05-01

ProtoMD is a toolkit that facilitates the development of algorithms for multiscale molecular dynamics (MD) simulations. It is designed for multiscale methods which capture the dynamic transfer of information across multiple spatial scales, such as the atomic to the mesoscopic scale, via coevolving microscopic and coarse-grained (CG) variables. ProtoMD can be also be used to calibrate parameters needed in traditional CG-MD methods. The toolkit integrates 'GROMACS wrapper' to initiate MD simulations, and 'MDAnalysis' to analyze and manipulate trajectory files. It facilitates experimentation with a spectrum of coarse-grained variables, prototyping rare events (such as chemical reactions), or simulating nanocharacterization experiments such as terahertz spectroscopy, AFM, nanopore, and time-of-flight mass spectroscopy. ProtoMD is written in python and is freely available under the GNU General Public License from github.com/CTCNano/proto_md.

Time scale bridging in atomistic simulation of slow dynamics: viscous relaxation and defect activation

NASA Astrophysics Data System (ADS)

Kushima, A.; Eapen, J.; Li, Ju; Yip, S.; Zhu, T.

2011-08-01

Atomistic simulation methods are known for timescale limitations in resolving slow dynamical processes. Two well-known scenarios of slow dynamics are viscous relaxation in supercooled liquids and creep deformation in stressed solids. In both phenomena the challenge to theory and simulation is to sample the transition state pathways efficiently and follow the dynamical processes on long timescales. We present a perspective based on the biased molecular simulation methods such as metadynamics, autonomous basin climbing (ABC), strain-boost and adaptive boost simulations. Such algorithms can enable an atomic-level explanation of the temperature variation of the shear viscosity of glassy liquids, and the relaxation behavior in solids undergoing creep deformation. By discussing the dynamics of slow relaxation in two quite different areas of condensed matter science, we hope to draw attention to other complex problems where anthropological or geological-scale time behavior can be simulated at atomic resolution and understood in terms of micro-scale processes of molecular rearrangements and collective interactions. As examples of a class of phenomena that can be broadly classified as materials ageing, we point to stress corrosion cracking and cement setting as opportunities for atomistic modeling and simulations.

An implementation of the maximum-caliber principle by replica-averaged time-resolved restrained simulations

NASA Astrophysics Data System (ADS)

Capelli, Riccardo; Tiana, Guido; Camilloni, Carlo

2018-05-01

Inferential methods can be used to integrate experimental informations and molecular simulations. The maximum entropy principle provides a framework for using equilibrium experimental data, and it has been shown that replica-averaged simulations, restrained using a static potential, are a practical and powerful implementation of such a principle. Here we show that replica-averaged simulations restrained using a time-dependent potential are equivalent to the principle of maximum caliber, the dynamic version of the principle of maximum entropy, and thus may allow us to integrate time-resolved data in molecular dynamics simulations. We provide an analytical proof of the equivalence as well as a computational validation making use of simple models and synthetic data. Some limitations and possible solutions are also discussed.

CABS-flex: server for fast simulation of protein structure fluctuations

PubMed Central

Jamroz, Michal; Kolinski, Andrzej; Kmiecik, Sebastian

2013-01-01

The CABS-flex server (http://biocomp.chem.uw.edu.pl/CABSflex) implements CABS-model–based protocol for the fast simulations of near-native dynamics of globular proteins. In this application, the CABS model was shown to be a computationally efficient alternative to all-atom molecular dynamics—a classical simulation approach. The simulation method has been validated on a large set of molecular dynamics simulation data. Using a single input (user-provided file in PDB format), the CABS-flex server outputs an ensemble of protein models (in all-atom PDB format) reflecting the flexibility of the input structure, together with the accompanying analysis (residue mean-square-fluctuation profile and others). The ensemble of predicted models can be used in structure-based studies of protein functions and interactions. PMID:23658222

CABS-flex: Server for fast simulation of protein structure fluctuations.

PubMed

Jamroz, Michal; Kolinski, Andrzej; Kmiecik, Sebastian

2013-07-01

The CABS-flex server (http://biocomp.chem.uw.edu.pl/CABSflex) implements CABS-model-based protocol for the fast simulations of near-native dynamics of globular proteins. In this application, the CABS model was shown to be a computationally efficient alternative to all-atom molecular dynamics--a classical simulation approach. The simulation method has been validated on a large set of molecular dynamics simulation data. Using a single input (user-provided file in PDB format), the CABS-flex server outputs an ensemble of protein models (in all-atom PDB format) reflecting the flexibility of the input structure, together with the accompanying analysis (residue mean-square-fluctuation profile and others). The ensemble of predicted models can be used in structure-based studies of protein functions and interactions.

An implementation of the maximum-caliber principle by replica-averaged time-resolved restrained simulations.

PubMed

Capelli, Riccardo; Tiana, Guido; Camilloni, Carlo

2018-05-14

Inferential methods can be used to integrate experimental informations and molecular simulations. The maximum entropy principle provides a framework for using equilibrium experimental data, and it has been shown that replica-averaged simulations, restrained using a static potential, are a practical and powerful implementation of such a principle. Here we show that replica-averaged simulations restrained using a time-dependent potential are equivalent to the principle of maximum caliber, the dynamic version of the principle of maximum entropy, and thus may allow us to integrate time-resolved data in molecular dynamics simulations. We provide an analytical proof of the equivalence as well as a computational validation making use of simple models and synthetic data. Some limitations and possible solutions are also discussed.

Monte Carlo simulations on atropisomerism of thienotriazolodiazepines applicable to slow transition phenomena using potential energy surfaces by ab initio molecular orbital calculations.

PubMed

Morikami, Kenji; Itezono, Yoshiko; Nishimoto, Masahiro; Ohta, Masateru

2014-01-01

Compounds with a medium-sized flexible ring often show atropisomerism that is caused by the high-energy barriers between long-lived conformers that can be isolated and often have different biological properties to each other. In this study, the frequency of the transition between the two stable conformers, aS and aR, of thienotriazolodiazepine compounds with flexible 7-membered rings was estimated computationally by Monte Carlo (MC) simulations and validated experimentally by NMR experiments. To estimate the energy barriers for transitions as precisely as possible, the potential energy (PE) surfaces used in the MC simulations were calculated by molecular orbital (MO) methods. To accomplish the MC simulations with the MO-based PE surfaces in a practical central processing unit (CPU) time, the MO-based PE of each conformer was pre-calculated and stored before the MC simulations, and then only referred to during the MC simulations. The activation energies for transitions calculated by the MC simulations agreed well with the experimental ΔG determined by the NMR experiments. The analysis of the transition trajectories of the MC simulations revealed that the transition occurred not only through the transition states, but also through many different transition paths. Our computational methods gave us quantitative estimates of atropisomerism of the thienotriazolodiazepine compounds in a practical period of time, and the method could be applicable for other slow-dynamics phenomena that cannot be investigated by other atomistic simulations.

Educational aspects of molecular simulation

NASA Astrophysics Data System (ADS)

Allen, Michael P.

This article addresses some aspects of teaching simulation methods to undergraduates and graduate students. Simulation is increasingly a cross-disciplinary activity, which means that the students who need to learn about simulation methods may have widely differing backgrounds. Also, they may have a wide range of views on what constitutes an interesting application of simulation methods. Almost always, a successful simulation course includes an element of practical, hands-on activity: a balance always needs to be struck between treating the simulation software as a 'black box', and becoming bogged down in programming issues. With notebook computers becoming widely available, students often wish to take away the programs to run themselves, and access to raw computer power is not the limiting factor that it once was; on the other hand, the software should be portable and, if possible, free. Examples will be drawn from the author's experience in three different contexts. (1) An annual simulation summer school for graduate students, run by the UK CCP5 organization, in which practical sessions are combined with an intensive programme of lectures describing the methodology. (2) A molecular modelling module, given as part of a doctoral training centre in the Life Sciences at Warwick, for students who might not have a first degree in the physical sciences. (3) An undergraduate module in Physics at Warwick, also taken by students from other disciplines, teaching high performance computing, visualization, and scripting in the context of a physical application such as Monte Carlo simulation.

Molecular dynamics computer simulation of permeation in solids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pohl, P.I.; Heffelfinger, G.S.; Fisler, D.K.

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} = 3.8more » {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.« less

Improved Density Functional Tight Binding Potentials for Metalloid Aluminum Clusters

DTIC Science & Technology

2016-06-01

simulations of the oxidation of Al4Cp * 4 show reasonable comparison with a DFT-based Car -Parrinello method, including correct prediction of hydride transfers...comparison with a DFT-based Car -Parrinello method, including correct prediction of hydride transfers from Cp* to the metal centers during the...initio molecular dynamics of the oxidation of Al4Cp * 4 using a DFT-based Car -Parrinello method. This simulation, which 43 several months on the

Enhanced Sampling in Free Energy Calculations: Combining SGLD with the Bennett's Acceptance Ratio and Enveloping Distribution Sampling Methods.

PubMed

König, Gerhard; Miller, Benjamin T; Boresch, Stefan; Wu, Xiongwu; Brooks, Bernard R

2012-10-09

One of the key requirements for the accurate calculation of free energy differences is proper sampling of conformational space. Especially in biological applications, molecular dynamics simulations are often confronted with rugged energy surfaces and high energy barriers, leading to insufficient sampling and, in turn, poor convergence of the free energy results. In this work, we address this problem by employing enhanced sampling methods. We explore the possibility of using self-guided Langevin dynamics (SGLD) to speed up the exploration process in free energy simulations. To obtain improved free energy differences from such simulations, it is necessary to account for the effects of the bias due to the guiding forces. We demonstrate how this can be accomplished for the Bennett's acceptance ratio (BAR) and the enveloping distribution sampling (EDS) methods. While BAR is considered among the most efficient methods available for free energy calculations, the EDS method developed by Christ and van Gunsteren is a promising development that reduces the computational costs of free energy calculations by simulating a single reference state. To evaluate the accuracy of both approaches in connection with enhanced sampling, EDS was implemented in CHARMM. For testing, we employ benchmark systems with analytical reference results and the mutation of alanine to serine. We find that SGLD with reweighting can provide accurate results for BAR and EDS where conventional molecular dynamics simulations fail. In addition, we compare the performance of EDS with other free energy methods. We briefly discuss the implications of our results and provide practical guidelines for conducting free energy simulations with SGLD.

Shock-induced transformations in crystalline RDX: a uniaxial constant-stress Hugoniostat molecular dynamics simulation study.

PubMed

Bedrov, Dmitry; Hooper, Justin B; Smith, Grant D; Sewell, Thomas D

2009-07-21

Molecular dynamics (MD) simulations of uniaxial shock compression along the [100] and [001] directions in the alpha polymorph of hexahydro-1,3,5-trinitro-1,3,5-triazine (alpha-RDX) have been conducted over a wide range of shock pressures using the uniaxial constant stress Hugoniostat method [Ravelo et al., Phys. Rev. B 70, 014103 (2004)]. We demonstrate that the Hugoniostat method is suitable for studying shock compression in atomic-scale models of energetic materials without the necessity to consider the extremely large simulation cells required for an explicit shock wave simulation. Specifically, direct comparison of results obtained using the Hugoniostat approach to those reported by Thompson and co-workers [Phys. Rev. B 78, 014107 (2008)] based on large-scale MD simulations of shocks using the shock front absorbing boundary condition (SFABC) approach indicates that Hugoniostat simulations of systems containing several thousand molecules reproduced the salient features observed in the SFABC simulations involving roughly a quarter-million molecules, namely, nucleation and growth of nanoscale shear bands for shocks propagating along the [100] direction and the polymorphic alpha-gamma phase transition for shocks directed along the [001] direction. The Hugoniostat simulations yielded predictions of the Hugoniot elastic limit for the [100] shock direction consistent with SFABC simulation results.

Essential energy space random walks to accelerate molecular dynamics simulations: Convergence improvements via an adaptive-length self-healing strategy

NASA Astrophysics Data System (ADS)

Zheng, Lianqing; Yang, Wei

2008-07-01

Recently, accelerated molecular dynamics (AMD) technique was generalized to realize essential energy space random walks so that further sampling enhancement and effective localized enhanced sampling could be achieved. This method is especially meaningful when essential coordinates of the target events are not priori known; moreover, the energy space metadynamics method was also introduced so that biasing free energy functions can be robustly generated. Despite the promising features of this method, due to the nonequilibrium nature of the metadynamics recursion, it is challenging to rigorously use the data obtained at the recursion stage to perform equilibrium analysis, such as free energy surface mapping; therefore, a large amount of data ought to be wasted. To resolve such problem so as to further improve simulation convergence, as promised in our original paper, we are reporting an alternate approach: the adaptive-length self-healing (ALSH) strategy for AMD simulations; this development is based on a recent self-healing umbrella sampling method. Here, the unit simulation length for each self-healing recursion is increasingly updated based on the Wang-Landau flattening judgment. When the unit simulation length for each update is long enough, all the following unit simulations naturally run into the equilibrium regime. Thereafter, these unit simulations can serve for the dual purposes of recursion and equilibrium analysis. As demonstrated in our model studies, by applying ALSH, both fast recursion and short nonequilibrium data waste can be compromised. As a result, combining all the data obtained from all the unit simulations that are in the equilibrium regime via the weighted histogram analysis method, efficient convergence can be robustly ensured, especially for the purpose of free energy surface mapping.

Simulation of meso-damage of refractory based on cohesion model and molecular dynamics method

NASA Astrophysics Data System (ADS)

Zhao, Jiuling; Shang, Hehao; Zhu, Zhaojun; Zhang, Guoxing; Duan, Leiguang; Sun, Xinya

2018-06-01

In order to describe the meso-damage of the refractories more accurately, and to study of the relationship between the mesostructured of the refractories and the macro-mechanics, this paper takes the magnesia-carbon refractories as the research object and uses the molecular dynamics method to instead the traditional sequential algorithm to establish the meso-particles filling model including small and large particles. Finally, the finite element software-ABAQUS is used to conducts numerical simulation on the meso-damage evolution process of refractory materials. From the results, the process of initiation and propagation of microscopic interface cracks can be observed intuitively, and the macroscopic stress-strain curve of the refractory material is obtained. The results show that the combination of molecular dynamics modeling and the use of Python in the interface to insert the cohesive element numerical simulation, obtaining of more accurate interface parameters through parameter inversion, can be more accurate to observe the interface of the meso-damage evolution process and effective to consider the effect of the mesostructured of the refractory material on its macroscopic mechanical properties.

Treating electrostatics with Wolf summation in combined quantum mechanical and molecular mechanical simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ojeda-May, Pedro; Pu, Jingzhi, E-mail: jpu@iupui.edu

The Wolf summation approach [D. Wolf et al., J. Chem. Phys. 110, 8254 (1999)], in the damped shifted force (DSF) formalism [C. J. Fennell and J. D. Gezelter, J. Chem. Phys. 124, 234104 (2006)], is extended for treating electrostatics in combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations. In this development, we split the QM/MM electrostatic potential energy function into the conventional Coulomb r{sup −1} term and a term that contains the DSF contribution. The former is handled by the standard machinery of cutoff-based QM/MM simulations whereas the latter is incorporated into the QM/MM interaction Hamiltonian as amore » Fock matrix correction. We tested the resulting QM/MM-DSF method for two solution-phase reactions, i.e., the association of ammonium and chloride ions and a symmetric SN{sub 2} reaction in which a methyl group is exchanged between two chloride ions. The performance of the QM/MM-DSF method was assessed by comparing the potential of mean force (PMF) profiles with those from the QM/MM-Ewald and QM/MM-isotropic periodic sum (IPS) methods, both of which include long-range electrostatics explicitly. For ion association, the QM/MM-DSF method successfully eliminates the artificial free energy drift observed in the QM/MM-Cutoff simulations, in a remarkable agreement with the two long-range-containing methods. For the SN{sub 2} reaction, the free energy of activation obtained by the QM/MM-DSF method agrees well with both the QM/MM-Ewald and QM/MM-IPS results. The latter, however, requires a greater cutoff distance than QM/MM-DSF for a proper convergence of the PMF. Avoiding time-consuming lattice summation, the QM/MM-DSF method yields a 55% reduction in computational cost compared with the QM/MM-Ewald method. These results suggest that, in addition to QM/MM-IPS, the QM/MM-DSF method may serve as another efficient and accurate alternative to QM/MM-Ewald for treating electrostatics in condensed-phase simulations of chemical reactions.« less

Treating electrostatics with Wolf summation in combined quantum mechanical and molecular mechanical simulations.

PubMed

Ojeda-May, Pedro; Pu, Jingzhi

2015-11-07

The Wolf summation approach [D. Wolf et al., J. Chem. Phys. 110, 8254 (1999)], in the damped shifted force (DSF) formalism [C. J. Fennell and J. D. Gezelter, J. Chem. Phys. 124, 234104 (2006)], is extended for treating electrostatics in combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations. In this development, we split the QM/MM electrostatic potential energy function into the conventional Coulomb r(-1) term and a term that contains the DSF contribution. The former is handled by the standard machinery of cutoff-based QM/MM simulations whereas the latter is incorporated into the QM/MM interaction Hamiltonian as a Fock matrix correction. We tested the resulting QM/MM-DSF method for two solution-phase reactions, i.e., the association of ammonium and chloride ions and a symmetric SN2 reaction in which a methyl group is exchanged between two chloride ions. The performance of the QM/MM-DSF method was assessed by comparing the potential of mean force (PMF) profiles with those from the QM/MM-Ewald and QM/MM-isotropic periodic sum (IPS) methods, both of which include long-range electrostatics explicitly. For ion association, the QM/MM-DSF method successfully eliminates the artificial free energy drift observed in the QM/MM-Cutoff simulations, in a remarkable agreement with the two long-range-containing methods. For the SN2 reaction, the free energy of activation obtained by the QM/MM-DSF method agrees well with both the QM/MM-Ewald and QM/MM-IPS results. The latter, however, requires a greater cutoff distance than QM/MM-DSF for a proper convergence of the PMF. Avoiding time-consuming lattice summation, the QM/MM-DSF method yields a 55% reduction in computational cost compared with the QM/MM-Ewald method. These results suggest that, in addition to QM/MM-IPS, the QM/MM-DSF method may serve as another efficient and accurate alternative to QM/MM-Ewald for treating electrostatics in condensed-phase simulations of chemical reactions.

Treating electrostatics with Wolf summation in combined quantum mechanical and molecular mechanical simulations

NASA Astrophysics Data System (ADS)

Ojeda-May, Pedro; Pu, Jingzhi

2015-11-01

The Wolf summation approach [D. Wolf et al., J. Chem. Phys. 110, 8254 (1999)], in the damped shifted force (DSF) formalism [C. J. Fennell and J. D. Gezelter, J. Chem. Phys. 124, 234104 (2006)], is extended for treating electrostatics in combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations. In this development, we split the QM/MM electrostatic potential energy function into the conventional Coulomb r-1 term and a term that contains the DSF contribution. The former is handled by the standard machinery of cutoff-based QM/MM simulations whereas the latter is incorporated into the QM/MM interaction Hamiltonian as a Fock matrix correction. We tested the resulting QM/MM-DSF method for two solution-phase reactions, i.e., the association of ammonium and chloride ions and a symmetric SN2 reaction in which a methyl group is exchanged between two chloride ions. The performance of the QM/MM-DSF method was assessed by comparing the potential of mean force (PMF) profiles with those from the QM/MM-Ewald and QM/MM-isotropic periodic sum (IPS) methods, both of which include long-range electrostatics explicitly. For ion association, the QM/MM-DSF method successfully eliminates the artificial free energy drift observed in the QM/MM-Cutoff simulations, in a remarkable agreement with the two long-range-containing methods. For the SN2 reaction, the free energy of activation obtained by the QM/MM-DSF method agrees well with both the QM/MM-Ewald and QM/MM-IPS results. The latter, however, requires a greater cutoff distance than QM/MM-DSF for a proper convergence of the PMF. Avoiding time-consuming lattice summation, the QM/MM-DSF method yields a 55% reduction in computational cost compared with the QM/MM-Ewald method. These results suggest that, in addition to QM/MM-IPS, the QM/MM-DSF method may serve as another efficient and accurate alternative to QM/MM-Ewald for treating electrostatics in condensed-phase simulations of chemical reactions.

Computationally Efficient Multiconfigurational Reactive Molecular Dynamics

PubMed Central

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

2012-01-01

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. PMID:25100924

A Multi-Scale Method for Dynamics Simulation in Continuum Solvent Models I: Finite-Difference Algorithm for Navier-Stokes Equation

PubMed Central

Xiao, Li; Cai, Qin; Li, Zhilin; Zhao, Hongkai; Luo, Ray

2014-01-01

A multi-scale framework is proposed for more realistic molecular dynamics simulations in continuum solvent models by coupling a molecular mechanics treatment of solute with a fluid mechanics treatment of solvent. This article reports our initial efforts to formulate the physical concepts necessary for coupling the two mechanics and develop a 3D numerical algorithm to simulate the solvent fluid via the Navier-Stokes equation. The numerical algorithm was validated with multiple test cases. The validation shows that the algorithm is effective and stable, with observed accuracy consistent with our design. PMID:25404761

Using simulation to interpret experimental data in terms of protein conformational ensembles.

PubMed

Allison, Jane R

2017-04-01

In their biological environment, proteins are dynamic molecules, necessitating an ensemble structural description. Molecular dynamics simulations and solution-state experiments provide complimentary information in the form of atomically detailed coordinates and averaged or distributions of structural properties or related quantities. Recently, increases in the temporal and spatial scale of conformational sampling and comparison of the more diverse conformational ensembles thus generated have revealed the importance of sampling rare events. Excitingly, new methods based on maximum entropy and Bayesian inference are promising to provide a statistically sound mechanism for combining experimental data with molecular dynamics simulations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Directly calculated electrical conductivity of hot dense hydrogen from molecular dynamics simulation beyond Kubo-Greenwood formula

NASA Astrophysics Data System (ADS)

Ma, Qian; Kang, Dongdong; Zhao, Zengxiu; Dai, Jiayu

2018-01-01

Electrical conductivity of hot dense hydrogen is directly calculated by molecular dynamics simulation with a reduced electron force field method, in which the electrons are represented as Gaussian wave packets with fixed sizes. Here, the temperature is higher than electron Fermi temperature ( T > 300 eV , ρ = 40 g / cc ). The present method can avoid the Coulomb catastrophe and give the limit of electrical conductivity based on the Coulomb interaction. We investigate the effect of ion-electron coupled movements, which is lost in the static method such as density functional theory based Kubo-Greenwood framework. It is found that the ionic dynamics, which contributes to the dynamical electrical microfield and electron-ion collisions, will reduce the conductivity significantly compared with the fixed ion configuration calculations.

Recent developments in structural proteomics for protein structure determination.

PubMed

Liu, Hsuan-Liang; Hsu, Jyh-Ping

2005-05-01

The major challenges in structural proteomics include identifying all the proteins on the genome-wide scale, determining their structure-function relationships, and outlining the precise three-dimensional structures of the proteins. Protein structures are typically determined by experimental approaches such as X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy. However, the knowledge of three-dimensional space by these techniques is still limited. Thus, computational methods such as comparative and de novo approaches and molecular dynamic simulations are intensively used as alternative tools to predict the three-dimensional structures and dynamic behavior of proteins. This review summarizes recent developments in structural proteomics for protein structure determination; including instrumental methods such as X-ray crystallography and NMR spectroscopy, and computational methods such as comparative and de novo structure prediction and molecular dynamics simulations.

Local structure in anisotropic systems determined by molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Komolkin, Andrei V.; Maliniak, Arnold

In the present communication we describe the investigation of local structure using a new visualization technique. The approach is based on two-dimensional pair correlation functions derived from a molecular dynamics computer simulation. We have used this method to analyse a trajectory produced in a simulation of a nematic liquid crystal of 4-n-pentyl-4'-cyanobiphenyl (5CB) (Komolkin et al., 1994, J. chem. Phys., 101, 4103). The molecule is assumed to have cylindrical symmetry, and the liquid crystalline phase is treated as uniaxial. The pair correlation functions or cylindrical distribution functions (CDFs) are calculated in the molecular (m) and laboratory (l) frames, gm2(z1 2, d1 2) and g12(Z1 2, D1 2). Anisotropic molecular organization in the liquid crystal is reflected in laboratory frame CDFs. The molecular excluded volume is determined and the effect of the fast motion in the alkyl chain is observed. The intramolecular distributions are included in the CDFs and indicate the size of the motional amplitude in the chain. Absence of long range order was confirmed, a feature typical for a nematic liquid crystal.

MODELING FUNCTIONALLY GRADED INTERPHASE REGIONS IN CARBON NANOTUBE REINFORCED COMPOSITES

NASA Technical Reports Server (NTRS)

Seidel, G. D.; Lagoudas, D. C.; Frankland, S. J. V.; Gates, T. S.

2006-01-01

A combination of micromechanics methods and molecular dynamics simulations are used to obtain the effective properties of the carbon nanotube reinforced composites with functionally graded interphase regions. The multilayer composite cylinders method accounts for the effects of non-perfect load transfer in carbon nanotube reinforced polymer matrix composites using a piecewise functionally graded interphase. The functional form of the properties in the interphase region, as well as the interphase thickness, is derived from molecular dynamics simulations of carbon nanotubes in a polymer matrix. Results indicate that the functional form of the interphase can have a significant effect on all the effective elastic constants except for the effective axial modulus for which no noticeable effects are evident.

Molecular Modeling of Thermodynamic and Transport Properties for CO 2 and Aqueous Brines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Hao; Economou, Ioannis G.; Panagiotopoulos, Athanassios Z.

Molecular simulation techniques using classical force-fields occupy the space between ab initio quantum mechanical methods and phenomenological correlations. In particular, Monte Carlo and molecular dynamics algorithms can be used to provide quantitative predictions of thermodynamic and transport properties of fluids relevant for geologic carbon sequestration at conditions for which experimental data are uncertain or not available. These methods can cover time and length scales far exceeding those of quantum chemical methods, while maintaining transferability and predictive power lacking from phenomenological correlations. The accuracy of predictions depends sensitively on the quality of the molecular models used. Many existing fixed-point-charge models formore » water and aqueous mixtures fail to represent accurately these fluid properties, especially when descriptions covering broad ranges of thermodynamic conditions are needed. Recent work on development of accurate models for water, CO 2, and dissolved salts, as well as their mixtures, is summarized in this Account. Polarizable models that can respond to the different dielectric environments in aqueous versus nonaqueous phases are necessary for predictions of properties over extended ranges of temperatures and pressures. Phase compositions and densities, activity coefficients of the dissolved salts, interfacial tensions, viscosities and diffusivities can be obtained in near-quantitative agreement to available experimental data, using relatively modest computational resources. In some cases, for example, for the composition of the CO 2-rich phase in coexistence with an aqueous phase, recent results from molecular simulations have helped discriminate among conflicting experimental data sets. The sensitivity of properties on the quality of the intermolecular interaction model varies significantly. Properties such as the phase compositions or electrolyte activity coefficients are much more sensitive than phase densities, viscosities, or component diffusivities. Strong confinement effects on physical properties in nanoscale media can also be directly obtained from molecular simulations. Future work on molecular modeling for CO 2 and aqueous brines is likely to be focused on more systematic generation of interaction models by utilizing quantum chemical as well as direct experimental measurements. New ion models need to be developed for use with the current generation of polarizable water models, including ion–ion interactions that will allow for accurate description of dense, mixed brines. Methods will need to be devised that go beyond the use of effective potentials for incorporation of quantum effects known to be important for water, and reactive force fields developed that can handle bond creation and breaking in systems with carbonate and silicate minerals. Lastly, another area of potential future work is the integration of molecular simulation methods in multiscale models for the chemical reactions leading to mineral dissolution and flow within the porous media in underground formations.« less

Molecular Modeling of Thermodynamic and Transport Properties for CO2 and Aqueous Brines.

PubMed

Jiang, Hao; Economou, Ioannis G; Panagiotopoulos, Athanassios Z

2017-04-18

Molecular simulation techniques using classical force-fields occupy the space between ab initio quantum mechanical methods and phenomenological correlations. In particular, Monte Carlo and molecular dynamics algorithms can be used to provide quantitative predictions of thermodynamic and transport properties of fluids relevant for geologic carbon sequestration at conditions for which experimental data are uncertain or not available. These methods can cover time and length scales far exceeding those of quantum chemical methods, while maintaining transferability and predictive power lacking from phenomenological correlations. The accuracy of predictions depends sensitively on the quality of the molecular models used. Many existing fixed-point-charge models for water and aqueous mixtures fail to represent accurately these fluid properties, especially when descriptions covering broad ranges of thermodynamic conditions are needed. Recent work on development of accurate models for water, CO 2 , and dissolved salts, as well as their mixtures, is summarized in this Account. Polarizable models that can respond to the different dielectric environments in aqueous versus nonaqueous phases are necessary for predictions of properties over extended ranges of temperatures and pressures. Phase compositions and densities, activity coefficients of the dissolved salts, interfacial tensions, viscosities and diffusivities can be obtained in near-quantitative agreement to available experimental data, using relatively modest computational resources. In some cases, for example, for the composition of the CO 2 -rich phase in coexistence with an aqueous phase, recent results from molecular simulations have helped discriminate among conflicting experimental data sets. The sensitivity of properties on the quality of the intermolecular interaction model varies significantly. Properties such as the phase compositions or electrolyte activity coefficients are much more sensitive than phase densities, viscosities, or component diffusivities. Strong confinement effects on physical properties in nanoscale media can also be directly obtained from molecular simulations. Future work on molecular modeling for CO 2 and aqueous brines is likely to be focused on more systematic generation of interaction models by utilizing quantum chemical as well as direct experimental measurements. New ion models need to be developed for use with the current generation of polarizable water models, including ion-ion interactions that will allow for accurate description of dense, mixed brines. Methods will need to be devised that go beyond the use of effective potentials for incorporation of quantum effects known to be important for water, and reactive force fields developed that can handle bond creation and breaking in systems with carbonate and silicate minerals. Another area of potential future work is the integration of molecular simulation methods in multiscale models for the chemical reactions leading to mineral dissolution and flow within the porous media in underground formations.

Molecular Modeling of Thermodynamic and Transport Properties for CO 2 and Aqueous Brines

DOE PAGES

Jiang, Hao; Economou, Ioannis G.; Panagiotopoulos, Athanassios Z.

2017-02-24

Molecular simulation techniques using classical force-fields occupy the space between ab initio quantum mechanical methods and phenomenological correlations. In particular, Monte Carlo and molecular dynamics algorithms can be used to provide quantitative predictions of thermodynamic and transport properties of fluids relevant for geologic carbon sequestration at conditions for which experimental data are uncertain or not available. These methods can cover time and length scales far exceeding those of quantum chemical methods, while maintaining transferability and predictive power lacking from phenomenological correlations. The accuracy of predictions depends sensitively on the quality of the molecular models used. Many existing fixed-point-charge models formore » water and aqueous mixtures fail to represent accurately these fluid properties, especially when descriptions covering broad ranges of thermodynamic conditions are needed. Recent work on development of accurate models for water, CO 2, and dissolved salts, as well as their mixtures, is summarized in this Account. Polarizable models that can respond to the different dielectric environments in aqueous versus nonaqueous phases are necessary for predictions of properties over extended ranges of temperatures and pressures. Phase compositions and densities, activity coefficients of the dissolved salts, interfacial tensions, viscosities and diffusivities can be obtained in near-quantitative agreement to available experimental data, using relatively modest computational resources. In some cases, for example, for the composition of the CO 2-rich phase in coexistence with an aqueous phase, recent results from molecular simulations have helped discriminate among conflicting experimental data sets. The sensitivity of properties on the quality of the intermolecular interaction model varies significantly. Properties such as the phase compositions or electrolyte activity coefficients are much more sensitive than phase densities, viscosities, or component diffusivities. Strong confinement effects on physical properties in nanoscale media can also be directly obtained from molecular simulations. Future work on molecular modeling for CO 2 and aqueous brines is likely to be focused on more systematic generation of interaction models by utilizing quantum chemical as well as direct experimental measurements. New ion models need to be developed for use with the current generation of polarizable water models, including ion–ion interactions that will allow for accurate description of dense, mixed brines. Methods will need to be devised that go beyond the use of effective potentials for incorporation of quantum effects known to be important for water, and reactive force fields developed that can handle bond creation and breaking in systems with carbonate and silicate minerals. Lastly, another area of potential future work is the integration of molecular simulation methods in multiscale models for the chemical reactions leading to mineral dissolution and flow within the porous media in underground formations.« less

Analysis of nanoscale two-phase flow of argon using molecular dynamics

NASA Astrophysics Data System (ADS)

Verma, Abhishek Kumar; Kumar, Rakesh

2014-12-01

Two phase flows through micro and nanochannels have attracted a lot of attention because of their immense applicability to many advanced fields such as MEMS/NEMS, electronic cooling, bioengineering etc. In this work, a molecular dynamics simulation method is employed to study the condensation process of superheated argon vapor force driven flow through a nanochannel combining fluid flow and heat transfer. A simple and effective particle insertion method is proposed to model phase change of argon based on non-periodic boundary conditions in the simulation domain. Starting from a crystalline solid wall of channel, the condensation process evolves from a transient unsteady state where we study the influence of different wall temperatures and fluid wall interactions on interfacial and heat transport properties of two phase flows. Subsequently, we analyzed transient temperature, density and velocity fields across the channel and their dependency on varying wall temperature and fluid wall interaction, after a dynamic equilibrium is achieved in phase transition. Quasi-steady nonequilibrium temperature profile, heat flux and interfacial thermal resistance were analyzed. The results demonstrate that the molecular dynamics method, with the proposed particle insertion method, effectively solves unsteady nonequilibrium two phase flows at nanoscale resolutions whose interphase between liquid and vapor phase is typically of the order of a few molecular diameters.

Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

PubMed

Shen, Lin; Yang, Weitao

2016-04-12

We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer.

Peptide kinetics from picoseconds to microseconds using boxed molecular dynamics: Power law rate coefficients in cyclisation reactions

NASA Astrophysics Data System (ADS)

Shalashilin, Dmitrii V.; Beddard, Godfrey S.; Paci, Emanuele; Glowacki, David R.

2012-10-01

Molecular dynamics (MD) methods are increasingly widespread, but simulation of rare events in complex molecular systems remains a challenge. We recently introduced the boxed molecular dynamics (BXD) method, which accelerates rare events, and simultaneously provides both kinetic and thermodynamic information. We illustrate how the BXD method may be used to obtain high-resolution kinetic data from explicit MD simulations, spanning picoseconds to microseconds. The method is applied to investigate the loop formation dynamics and kinetics of cyclisation for a range of polypeptides, and recovers a power law dependence of the instantaneous rate coefficient over six orders of magnitude in time, in good agreement with experimental observations. Analysis of our BXD results shows that this power law behaviour arises when there is a broad and nearly uniform spectrum of reaction rate coefficients. For the systems investigated in this work, where the free energy surfaces have relatively small barriers, the kinetics is very sensitive to the initial conditions: strongly non-equilibrium conditions give rise to power law kinetics, while equilibrium initial conditions result in a rate coefficient with only a weak dependence on time. These results suggest that BXD may offer us a powerful and general algorithm for describing kinetics and thermodynamics in chemical and biochemical systems.

Detecting vapour bubbles in simulations of metastable water

DOE Office of Scientific and Technical Information (OSTI.GOV)

González, Miguel A.; Abascal, Jose L. F.; Valeriani, Chantal, E-mail: christoph.dellago@univie.ac.at, E-mail: cvaleriani@quim.ucm.es

2014-11-14

The investigation of cavitation in metastable liquids with molecular simulations requires an appropriate definition of the volume of the vapour bubble forming within the metastable liquid phase. Commonly used approaches for bubble detection exhibit two significant flaws: first, when applied to water they often identify the voids within the hydrogen bond network as bubbles thus masking the signature of emerging bubbles and, second, they lack thermodynamic consistency. Here, we present two grid-based methods, the M-method and the V-method, to detect bubbles in metastable water specifically designed to address these shortcomings. The M-method incorporates information about neighbouring grid cells to distinguishmore » between liquid- and vapour-like cells, which allows for a very sensitive detection of small bubbles and high spatial resolution of the detected bubbles. The V-method is calibrated such that its estimates for the bubble volume correspond to the average change in system volume and are thus thermodynamically consistent. Both methods are computationally inexpensive such that they can be used in molecular dynamics and Monte Carlo simulations of cavitation. We illustrate them by computing the free energy barrier and the size of the critical bubble for cavitation in water at negative pressure.« less

A multilevel-skin neighbor list algorithm for molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Zhang, Chenglong; Zhao, Mingcan; Hou, Chaofeng; Ge, Wei

2018-01-01

Searching of the interaction pairs and organization of the interaction processes are important steps in molecular dynamics (MD) algorithms and are critical to the overall efficiency of the simulation. Neighbor lists are widely used for these steps, where thicker skin can reduce the frequency of list updating but is discounted by more computation in distance check for the particle pairs. In this paper, we propose a new neighbor-list-based algorithm with a precisely designed multilevel skin which can reduce unnecessary computation on inter-particle distances. The performance advantages over traditional methods are then analyzed against the main simulation parameters on Intel CPUs and MICs (many integrated cores), and are clearly demonstrated. The algorithm can be generalized for various discrete simulations using neighbor lists.

Quantum molecular dynamics simulation of structural and thermodynamic properties of NiAl

NASA Astrophysics Data System (ADS)

Karchevskaya, E. S.; Minakov, D. V.; Levashov, P. R.

2018-01-01

In this work, structural and thermodynamic properties of a solid and liquid Ni-Al compound are studied using an ab initio method of quantum molecular dynamics (QMD). Simulations were carried out in 700-3000 K temperature range at atmospheric pressure. Radial distribution functions are analyzed to determine the presence of Ni-Al chemical bonds. Diffusion coefficients for individual components are also calculated. Another goal of this work is the investigation of the reaction propagation in thermally-initiated Ni-Al foils. For this purpose, we performed QMD simulations of Ni-Al layers in the microcanonical ensemble. An exothermic reaction between the solid Ni-Al layers is observed in our simulations at temperature less than the melting temperatures of the components.

Avoiding fractional electrons in subsystem DFT based ab-initio molecular dynamics yields accurate models for liquid water and solvated OH radical

DOE Office of Scientific and Technical Information (OSTI.GOV)

Genova, Alessandro, E-mail: alessandro.genova@rutgers.edu; Pavanello, Michele, E-mail: m.pavanello@rutgers.edu; Ceresoli, Davide, E-mail: davide.ceresoli@cnr.it

2016-06-21

In this work we achieve three milestones: (1) we present a subsystem DFT method capable of running ab-initio molecular dynamics simulations accurately and efficiently. (2) In order to rid the simulations of inter-molecular self-interaction error, we exploit the ability of semilocal frozen density embedding formulation of subsystem DFT to represent the total electron density as a sum of localized subsystem electron densities that are constrained to integrate to a preset, constant number of electrons; the success of the method relies on the fact that employed semilocal nonadditive kinetic energy functionals effectively cancel out errors in semilocal exchange–correlation potentials that aremore » linked to static correlation effects and self-interaction. (3) We demonstrate this concept by simulating liquid water and solvated OH{sup •} radical. While the bulk of our simulations have been performed on a periodic box containing 64 independent water molecules for 52 ps, we also simulated a box containing 256 water molecules for 22 ps. The results show that, provided one employs an accurate nonadditive kinetic energy functional, the dynamics of liquid water and OH{sup •} radical are in semiquantitative agreement with experimental results or higher-level electronic structure calculations. Our assessments are based upon comparisons of radial and angular distribution functions as well as the diffusion coefficient of the liquid.« less

Avoiding fractional electrons in subsystem DFT based ab-initio molecular dynamics yields accurate models for liquid water and solvated OH radical.

PubMed

Genova, Alessandro; Ceresoli, Davide; Pavanello, Michele

2016-06-21

In this work we achieve three milestones: (1) we present a subsystem DFT method capable of running ab-initio molecular dynamics simulations accurately and efficiently. (2) In order to rid the simulations of inter-molecular self-interaction error, we exploit the ability of semilocal frozen density embedding formulation of subsystem DFT to represent the total electron density as a sum of localized subsystem electron densities that are constrained to integrate to a preset, constant number of electrons; the success of the method relies on the fact that employed semilocal nonadditive kinetic energy functionals effectively cancel out errors in semilocal exchange-correlation potentials that are linked to static correlation effects and self-interaction. (3) We demonstrate this concept by simulating liquid water and solvated OH(•) radical. While the bulk of our simulations have been performed on a periodic box containing 64 independent water molecules for 52 ps, we also simulated a box containing 256 water molecules for 22 ps. The results show that, provided one employs an accurate nonadditive kinetic energy functional, the dynamics of liquid water and OH(•) radical are in semiquantitative agreement with experimental results or higher-level electronic structure calculations. Our assessments are based upon comparisons of radial and angular distribution functions as well as the diffusion coefficient of the liquid.

Quantum mechanical/molecular mechanical/continuum style solvation model: time-dependent density functional theory.

PubMed

Thellamurege, Nandun M; Cui, Fengchao; Li, Hui

2013-08-28

A combined quantum mechanical/molecular mechanical/continuum (QM/MMpol/C) style method is developed for time-dependent density functional theory (TDDFT, including long-range corrected TDDFT) method, induced dipole polarizable force field, and induced surface charge continuum model. Induced dipoles and induced charges are included in the TDDFT equations to solve for the transition energies, relaxed density, and transition density. Analytic gradient is derived and implemented for geometry optimization and molecular dynamics simulation. QM/MMpol/C style DFT and TDDFT methods are used to study the hydrogen bonding of the photoactive yellow protein chromopore in ground state and excited state.

Using molecular dynamics simulations and finite element method to study the mechanical properties of nanotube reinforced polyethylene and polyketone

NASA Astrophysics Data System (ADS)

Rouhi, S.; Alizadeh, Y.; Ansari, R.; Aryayi, M.

2015-09-01

Molecular dynamics simulations are used to study the mechanical behavior of single-walled carbon nanotube reinforced composites. Polyethylene and polyketone are selected as the polymer matrices. The effects of nanotube atomic structure and diameter on the mechanical properties of polymer matrix nanocomposites are investigated. It is shown that although adding nanotube to the polymer matrix raises the longitudinal elastic modulus significantly, the transverse tensile and shear moduli do not experience important change. As the previous finite element models could not be used for polymer matrices with the atom types other than carbon, molecular dynamics simulations are used to propose a finite element model which can be used for any polymer matrices. It is shown that this model can predict Young’s modulus with an acceptable accuracy.

Application of molecular dynamics simulation to predict the compatability between water-insoluble drugs and self-associating poly(ethylene oxide)-b-poly(epsilon-caprolactone) block copolymers.

PubMed

Patel, Sarthak; Lavasanifar, Afsaneh; Choi, Phillip

2008-11-01

In the present work, molecular dynamics (MD) simulation was applied to study the solubility of two water-insoluble drugs, fenofibrate and nimodipine, in a series of micelle-forming PEO-b-PCL block copolymers with combinations of blocks having different molecular weights. The solubility predictions based on the MD results were then compared with those obtained from solubility experiments and by the commonly used group contribution method (GCM). The results showed that Flory-Huggins interaction parameters computed by the MD simulations are consistent with the solubility data of the drug/PEO-b-PCL systems, whereas those calculated by the GCM significantly deviate from the experimental observation. We have also accounted for the possibility of drug solubilization in the PEO block of PEO-b-PCL.

Communication: Quantum molecular dynamics simulation of liquid para-hydrogen by nuclear and electron wave packet approach.

PubMed

Hyeon-Deuk, Kim; Ando, Koji

2014-05-07

Liquid para-hydrogen (p-H2) is a typical quantum liquid which exhibits strong nuclear quantum effects (NQEs) and thus anomalous static and dynamic properties. We propose a real-time simulation method of wave packet (WP) molecular dynamics (MD) based on non-empirical intra- and inter-molecular interactions of non-spherical hydrogen molecules, and apply it to condensed-phase p-H2. The NQEs, such as WP delocalization and zero-point energy, are taken into account without perturbative expansion of prepared model potential functions but with explicit interactions between nuclear and electron WPs. The developed MD simulation for 100 ps with 1200 hydrogen molecules is realized at feasible computational cost, by which basic experimental properties of p-H2 liquid such as radial distribution functions, self-diffusion coefficients, and shear viscosities are all well reproduced.

Effect of gas adsorption on acoustic wave propagation in MFI zeolite membrane materials: experiment and molecular simulation.

PubMed

Manga, Etoungh D; Blasco, Hugues; Da-Costa, Philippe; Drobek, Martin; Ayral, André; Le Clezio, Emmanuel; Despaux, Gilles; Coasne, Benoit; Julbe, Anne

2014-09-02

The present study reports on the development of a characterization method of porous membrane materials which consists of considering their acoustic properties upon gas adsorption. Using acoustic microscopy experiments and atomistic molecular simulations for helium adsorbed in a silicalite-1 zeolite membrane layer, we showed that acoustic wave propagation could be used, in principle, for controlling the membranes operando. Molecular simulations, which were found to fit experimental data, showed that the compressional modulus of the composite system consisting of silicalite-1 with adsorbed He increases linearly with the He adsorbed amount while its shear modulus remains constant in a large range of applied pressures. These results suggest that the longitudinal and Rayleigh wave velocities (VL and VR) depend on the He adsorbed amount whereas the transverse wave velocity VT remains constant.

Density-based clustering of small peptide conformations sampled from a molecular dynamics simulation.

PubMed

Kim, Minkyoung; Choi, Seung-Hoon; Kim, Junhyoung; Choi, Kihang; Shin, Jae-Min; Kang, Sang-Kee; Choi, Yun-Jaie; Jung, Dong Hyun

2009-11-01

This study describes the application of a density-based algorithm to clustering small peptide conformations after a molecular dynamics simulation. We propose a clustering method for small peptide conformations that enables adjacent clusters to be separated more clearly on the basis of neighbor density. Neighbor density means the number of neighboring conformations, so if a conformation has too few neighboring conformations, then it is considered as noise or an outlier and is excluded from the list of cluster members. With this approach, we can easily identify clusters in which the members are densely crowded in the conformational space, and we can safely avoid misclustering individual clusters linked by noise or outliers. Consideration of neighbor density significantly improves the efficiency of clustering of small peptide conformations sampled from molecular dynamics simulations and can be used for predicting peptide structures.

Use of Nonequilibrium Work Methods to Compute Free Energy Differences Between Molecular Mechanical and Quantum Mechanical Representations of Molecular Systems.

PubMed

Hudson, Phillip S; Woodcock, H Lee; Boresch, Stefan

2015-12-03

Carrying out free energy simulations (FES) using quantum mechanical (QM) Hamiltonians remains an attractive, albeit elusive goal. Renewed efforts in this area have focused on using "indirect" thermodynamic cycles to connect "low level" simulation results to "high level" free energies. The main obstacle to computing converged free energy results between molecular mechanical (MM) and QM (ΔA(MM→QM)), as recently demonstrated by us and others, is differences in the so-called "stiff" degrees of freedom (e.g., bond stretching) between the respective energy surfaces. Herein, we demonstrate that this problem can be efficiently circumvented using nonequilibrium work (NEW) techniques, i.e., Jarzynski's and Crooks' equations. Initial applications of computing ΔA(NEW)(MM→QM), for blocked amino acids alanine and serine as well as to generate butane's potentials of mean force via the indirect QM/MM FES method, showed marked improvement over traditional FES approaches.

Protein dynamics in organic media at varying water activity studied by molecular dynamics simulation.

PubMed

Wedberg, Rasmus; Abildskov, Jens; Peters, Günther H

2012-03-01

In nonaqueous enzymology, control of enzyme hydration is commonly approached by fixing the thermodynamic water activity of the medium. In this work, we present a strategy for evaluating the water activity in molecular dynamics simulations of proteins in water/organic solvent mixtures. The method relies on determining the water content of the bulk phase and uses a combination of Kirkwood-Buff theory and free energy calculations to determine corresponding activity coefficients. We apply the method in a molecular dynamics study of Candida antarctica lipase B in pure water and the organic solvents methanol, tert-butyl alcohol, methyl tert-butyl ether, and hexane, each mixture at five different water activities. It is shown that similar water activity yields similar enzyme hydration in the different solvents. However, both solvent and water activity are shown to have profound effects on enzyme structure and flexibility.

Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies.

PubMed

Soler, Miguel A; de Marco, Ario; Fortuna, Sara

2016-10-10

Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies

NASA Astrophysics Data System (ADS)

Soler, Miguel A.; De Marco, Ario; Fortuna, Sara

2016-10-01

Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

Antibody humanization by molecular dynamics simulations-in-silico guided selection of critical backmutations.

PubMed

Margreitter, Christian; Mayrhofer, Patrick; Kunert, Renate; Oostenbrink, Chris

2016-06-01

Monoclonal antibodies represent the fastest growing class of biotherapeutic proteins. However, as they are often initially derived from rodent organisms, there is a severe risk of immunogenic reactions, hampering their applicability. The humanization of these antibodies remains a challenging task in the context of rational drug design. "Superhumanization" describes the direct transfer of the complementarity determining regions to a human germline framework, but this humanization approach often results in loss of binding affinity. In this study, we present a new approach for predicting promising backmutation sites using molecular dynamics simulations of the model antibody Ab2/3H6. The simulation method was developed in close conjunction with novel specificity experiments. Binding properties of mAb variants were evaluated directly from crude supernatants and confirmed using established binding affinity assays for purified antibodies. Our approach provides access to the dynamical features of the actual binding sites of an antibody, based solely on the antibody sequence. Thus we do not need structural data on the antibody-antigen complex and circumvent cumbersome methods to assess binding affinities. © 2016 The Authors Journal of Molecular Recognition Published by John Wiley & Sons Ltd. © 2016 The Authors Journal of Molecular Recognition Published by John Wiley & Sons Ltd.

Sensitivity of electrospray molecular dynamics simulations to long-range Coulomb interaction models

NASA Astrophysics Data System (ADS)

Mehta, Neil A.; Levin, Deborah A.

2018-03-01

Molecular dynamics (MD) electrospray simulations of 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM-BF4) ion liquid were performed with the goal of evaluating the influence of long-range Coulomb models on ion emission characteristics. The direct Coulomb (DC), shifted force Coulomb sum (SFCS), and particle-particle particle-mesh (PPPM) long-range Coulomb models were considered in this work. The DC method with a sufficiently large cutoff radius was found to be the most accurate approach for modeling electrosprays, but, it is computationally expensive. The Coulomb potential energy modeled by the DC method in combination with the radial electric fields were found to be necessary to generate the Taylor cone. The differences observed between the SFCS and the DC in terms of predicting the total ion emission suggest that the former should not be used in MD electrospray simulations. Furthermore, the common assumption of domain periodicity was observed to be detrimental to the accuracy of the capillary-based electrospray simulations.

Unbiased Rare Event Sampling in Spatial Stochastic Systems Biology Models Using a Weighted Ensemble of Trajectories

PubMed Central

Donovan, Rory M.; Tapia, Jose-Juan; Sullivan, Devin P.; Faeder, James R.; Murphy, Robert F.; Dittrich, Markus; Zuckerman, Daniel M.

2016-01-01

The long-term goal of connecting scales in biological simulation can be facilitated by scale-agnostic methods. We demonstrate that the weighted ensemble (WE) strategy, initially developed for molecular simulations, applies effectively to spatially resolved cell-scale simulations. The WE approach runs an ensemble of parallel trajectories with assigned weights and uses a statistical resampling strategy of replicating and pruning trajectories to focus computational effort on difficult-to-sample regions. The method can also generate unbiased estimates of non-equilibrium and equilibrium observables, sometimes with significantly less aggregate computing time than would be possible using standard parallelization. Here, we use WE to orchestrate particle-based kinetic Monte Carlo simulations, which include spatial geometry (e.g., of organelles, plasma membrane) and biochemical interactions among mobile molecular species. We study a series of models exhibiting spatial, temporal and biochemical complexity and show that although WE has important limitations, it can achieve performance significantly exceeding standard parallel simulation—by orders of magnitude for some observables. PMID:26845334

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

PubMed

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.

Sensitivity of electrospray molecular dynamics simulations to long-range Coulomb interaction models.

PubMed

Mehta, Neil A; Levin, Deborah A

2018-03-01

Molecular dynamics (MD) electrospray simulations of 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM-BF_{4}) ion liquid were performed with the goal of evaluating the influence of long-range Coulomb models on ion emission characteristics. The direct Coulomb (DC), shifted force Coulomb sum (SFCS), and particle-particle particle-mesh (PPPM) long-range Coulomb models were considered in this work. The DC method with a sufficiently large cutoff radius was found to be the most accurate approach for modeling electrosprays, but, it is computationally expensive. The Coulomb potential energy modeled by the DC method in combination with the radial electric fields were found to be necessary to generate the Taylor cone. The differences observed between the SFCS and the DC in terms of predicting the total ion emission suggest that the former should not be used in MD electrospray simulations. Furthermore, the common assumption of domain periodicity was observed to be detrimental to the accuracy of the capillary-based electrospray simulations.

Automatic Selection of Order Parameters in the Analysis of Large Scale Molecular Dynamics Simulations.

PubMed

Sultan, Mohammad M; Kiss, Gert; Shukla, Diwakar; Pande, Vijay S

2014-12-09

Given the large number of crystal structures and NMR ensembles that have been solved to date, classical molecular dynamics (MD) simulations have become powerful tools in the atomistic study of the kinetics and thermodynamics of biomolecular systems on ever increasing time scales. By virtue of the high-dimensional conformational state space that is explored, the interpretation of large-scale simulations faces difficulties not unlike those in the big data community. We address this challenge by introducing a method called clustering based feature selection (CB-FS) that employs a posterior analysis approach. It combines supervised machine learning (SML) and feature selection with Markov state models to automatically identify the relevant degrees of freedom that separate conformational states. We highlight the utility of the method in the evaluation of large-scale simulations and show that it can be used for the rapid and automated identification of relevant order parameters involved in the functional transitions of two exemplary cell-signaling proteins central to human disease states.

Rational design of methicillin resistance staphylococcus aureus inhibitors through 3D-QSAR, molecular docking and molecular dynamics simulations.

PubMed

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

2018-04-01

Staphylococcus aureus is a gram positive bacterium. It is the leading cause of skin and respiratory infections, osteomyelitis, Ritter's disease, endocarditis, and bacteraemia in the developed world. We employed combined studies of 3D QSAR, molecular docking which are validated by molecular dynamics simulations and in silico ADME prediction have been performed on Isothiazoloquinolones inhibitors against methicillin resistance Staphylococcus aureus. Three-dimensional quantitative structure-activity relationship (3D-QSAR) study was applied using comparative molecular field analysis (CoMFA) with Q 2 of 0.578, R 2 of 0.988, and comparative molecular similarity indices analysis (CoMSIA) with Q 2 of 0.554, R 2 of 0.975. The predictive ability of these model was determined using a test set of molecules that gave acceptable predictive correlation (r 2 Pred) values 0.55 and 0.57 of CoMFA and CoMSIA respectively. Docking, simulations were employed to position the inhibitors into protein active site to find out the most probable binding mode and most reliable conformations. Developed models and Docking methods provide guidance to design molecules with enhanced activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cation solvation with quantum chemical effects modeled by a size-consistent multi-partitioning quantum mechanics/molecular mechanics method.

PubMed

Watanabe, Hiroshi C; Kubillus, Maximilian; Kubař, Tomáš; Stach, Robert; Mizaikoff, Boris; Ishikita, Hiroshi

2017-07-21

In the condensed phase, quantum chemical properties such as many-body effects and intermolecular charge fluctuations are critical determinants of the solvation structure and dynamics. Thus, a quantum mechanical (QM) molecular description is required for both solute and solvent to incorporate these properties. However, it is challenging to conduct molecular dynamics (MD) simulations for condensed systems of sufficient scale when adapting QM potentials. To overcome this problem, we recently developed the size-consistent multi-partitioning (SCMP) quantum mechanics/molecular mechanics (QM/MM) method and realized stable and accurate MD simulations, using the QM potential to a benchmark system. In the present study, as the first application of the SCMP method, we have investigated the structures and dynamics of Na + , K + , and Ca 2+ solutions based on nanosecond-scale sampling, a sampling 100-times longer than that of conventional QM-based samplings. Furthermore, we have evaluated two dynamic properties, the diffusion coefficient and difference spectra, with high statistical certainty. Furthermore the calculation of these properties has not previously been possible within the conventional QM/MM framework. Based on our analysis, we have quantitatively evaluated the quantum chemical solvation effects, which show distinct differences between the cations.

Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems

DOE PAGES

Radak, Brian K.; Chipot, Christophe; Suh, Donghyuk; ...

2017-11-07

We report that an increasingly important endeavor is to develop computational strategies that enable molecular dynamics (MD) simulations of biomolecular systems with spontaneous changes in protonation states under conditions of constant pH. The present work describes our efforts to implement the powerful constant-pH MD simulation method, based on a hybrid nonequilibrium MD/Monte Carlo (neMD/MC) technique within the highly scalable program NAMD. The constant-pH hybrid neMD/MC method has several appealing features; it samples the correct semigrand canonical ensemble rigorously, the computational cost increases linearly with the number of titratable sites, and it is applicable to explicit solvent simulations. The present implementationmore » of the constant-pH hybrid neMD/MC in NAMD is designed to handle a wide range of biomolecular systems with no constraints on the choice of force field. Furthermore, the sampling efficiency can be adaptively improved on-the-fly by adjusting algorithmic parameters during the simulation. Finally, illustrative examples emphasizing medium- and large-scale applications on next-generation supercomputing architectures are provided.« less

Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radak, Brian K.; Chipot, Christophe; Suh, Donghyuk

We report that an increasingly important endeavor is to develop computational strategies that enable molecular dynamics (MD) simulations of biomolecular systems with spontaneous changes in protonation states under conditions of constant pH. The present work describes our efforts to implement the powerful constant-pH MD simulation method, based on a hybrid nonequilibrium MD/Monte Carlo (neMD/MC) technique within the highly scalable program NAMD. The constant-pH hybrid neMD/MC method has several appealing features; it samples the correct semigrand canonical ensemble rigorously, the computational cost increases linearly with the number of titratable sites, and it is applicable to explicit solvent simulations. The present implementationmore » of the constant-pH hybrid neMD/MC in NAMD is designed to handle a wide range of biomolecular systems with no constraints on the choice of force field. Furthermore, the sampling efficiency can be adaptively improved on-the-fly by adjusting algorithmic parameters during the simulation. Finally, illustrative examples emphasizing medium- and large-scale applications on next-generation supercomputing architectures are provided.« less

How to identify dislocations in molecular dynamics simulations?

NASA Astrophysics Data System (ADS)

Li, Duo; Wang, FengChao; Yang, ZhenYu; Zhao, YaPu

2014-12-01

Dislocations are of great importance in revealing the underlying mechanisms of deformed solid crystals. With the development of computational facilities and technologies, the observations of dislocations at atomic level through numerical simulations are permitted. Molecular dynamics (MD) simulation suggests itself as a powerful tool for understanding and visualizing the creation of dislocations as well as the evolution of crystal defects. However, the numerical results from the large-scale MD simulations are not very illuminating by themselves and there exist various techniques for analyzing dislocations and the deformed crystal structures. Thus, it is a big challenge for the beginners in this community to choose a proper method to start their investigations. In this review, we summarized and discussed up to twelve existing structure characterization methods in MD simulations of deformed crystal solids. A comprehensive comparison was made between the advantages and disadvantages of these typical techniques. We also examined some of the recent advances in the dynamics of dislocations related to the hydraulic fracturing. It was found that the dislocation emission has a significant effect on the propagation and bifurcation of the crack tip in the hydraulic fracturing.

An investigation of molecular dynamics simulation and molecular docking: interaction of citrus flavonoids and bovine β-lactoglobulin in focus.

PubMed

Sahihi, M; Ghayeb, Y

2014-08-01

Citrus flavonoids are natural compounds with important health benefits. The study of their interaction with a transport protein, such as bovine β-lactoglobulin (BLG), at the atomic level could be a valuable factor to control their transport to biological sites. In the present study, molecular docking and molecular dynamics simulation methods were used to investigate the interaction of hesperetin, naringenin, nobiletin and tangeretin as citrus flavonoids and BLG as transport protein. The molecular docking results revealed that these flavonoids bind in the internal cavity of BLG and the BLG affinity for binding the flavonoids follows naringenin>hesperetin>tangeretin>nobiletin. The docking results also indicated that the BLG-flavonoid complexes are stabilized through hydrophobic interactions, hydrogen bond interactions and π-π stacking interactions. The analysis of molecular dynamics (MD) simulation trajectories showed that the root mean square deviation (RMSD) of various systems reaches equilibrium and fluctuates around the mean value at various times. Time evolution of the radius of gyration, total solvent accessible surface of the protein and the second structure of protein showed as well that BLG and BLG-flavonoid complexes were stable around 2500ps, and there was not any conformational change as for BLG-flavonoid complexes. Further, the profiles of atomic fluctuations indicated the rigidity of the ligand binding site during the simulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

A low noise discrete velocity method for the Boltzmann equation with quantized rotational and vibrational energy

NASA Astrophysics Data System (ADS)

Clarke, Peter; Varghese, Philip; Goldstein, David

2018-01-01

A discrete velocity method is developed for gas mixtures of diatomic molecules with both rotational and vibrational energy states. A full quantized model is described, and rotation-translation and vibration-translation energy exchanges are simulated using a Larsen-Borgnakke exchange model. Elastic and inelastic molecular interactions are modeled during every simulated collision to help produce smooth internal energy distributions. The method is verified by comparing simulations of homogeneous relaxation by our discrete velocity method to numerical solutions of the Jeans and Landau-Teller equations, and to direct simulation Monte Carlo. We compute the structure of a 1D shock using this method, and determine how the rotational energy distribution varies with spatial location in the shock and with position in velocity space.

Novel methodology developments in modern molecular simulations

NASA Astrophysics Data System (ADS)

Minary, Peter

The present thesis aims to summarize novel methodological developments and their uses in the rapidly expanding field of molecular simulations. A new formalism designed to treat long range interactions on surfaces/wires, systems which are infinitely replicated in two/one spatial directions but have finite extent in the remaining dimensions, is developed in the first part of this thesis. The method is tested on both model and realistic problems and is found to be accurate, efficient and a marked improvement over existing formulations in speed, accuracy and utility. In the second part of this thesis, a novel ab initio molecular dynamics technique capable of treating metallic systems and highly exothermic chemical reactions is presented. The combination of the aforementioned methods are applied in the next part to study functionalization reactions at the Si(100)-2x1 semiconductor interface. Here, a set of forty finite temperature ab initio molecular dynamics trajectories is employed to investigate the microscopic mechanism of the addition of 1,3-butadiene to the Si(100)-2x1 surface. The detailed study of the trajectories indicate a common non-concerted stepwise mechanism that proceeds via an intermediate carbocation. In the remaining parts of the thesis, a novel set of methods is introduced to significantly enhance conformational sampling in molecular dynamics simulations of biomolecular systems. First, a new set of equations of motion and a reversible, resonance free, integrator are developed which permits step sizes on the order of 100 fs to be used. The new technique provides sufficient sampling to impact studies of the 200--300 residue proteins of greatest interest. Second, it is shown that combining molecular dynamics with novel variable transformations designed to warp configuration space so as to reduce barrier regions and enhance attractive basins lead to substantial gains in conformational sampling efficiency. Here, new transformations designed to overcome barriers induced by intermolecular interactions are introduced. The method is shown to substantially enhance conformational sampling in long alkane chains and in a model protein over standard molecular dynamics as well as parallel tempering.

Predict the glass transition temperature of glycerol-water binary cryoprotectant by molecular dynamic simulation.

PubMed

Li, Dai-Xi; Liu, Bao-Lin; Liu, Yi-shu; Chen, Cheng-lung

2008-04-01

Vitrification is proposed to be the best way for the cryopreservation of organs. The glass transition temperature (T(g)) of vitrification solutions is a critical parameter of fundamental importance for cryopreservation by vitrification. The instruments that can detect the thermodynamic, mechanical and dielectric changes of a substance may be used to determine the glass transition temperature. T(g) is usually measured by using differential scanning calorimetry (DSC). In this study, the T(g) of the glycerol-aqueous solution (60%, wt/%) was determined by isothermal-isobaric molecular dynamic simulation (NPT-MD). The software package Discover in Material Studio with the Polymer Consortium Force Field (PCFF) was used for the simulation. The state parameters of heat capacity at constant pressure (C(p)), density (rho), amorphous cell volume (V(cell)) and specific volume (V(specific)) and radial distribution function (rdf) were obtained by NPT-MD in the temperature range of 90-270K. These parameters showed a discontinuity at a specific temperature in the plot of state parameter versus temperature. The temperature at the discontinuity is taken as the simulated T(g) value for glycerol-water binary solution. The T(g) values determined by simulation method were compared with the values in the literatures. The simulation values of T(g) (160.06-167.51K) agree well with the DSC results (163.60-167.10K) and the DMA results (159.00K). We drew the conclusion that molecular dynamic simulation (MDS) is a potential method for investigating the glass transition temperature (T(g)) of glycerol-water binary cryoprotectants and may be used for other vitrification solutions.

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

NASA Astrophysics Data System (ADS)

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

2012-12-01

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.

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

PubMed

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.

A generalized crystal-cutting method for modeling arbitrarily oriented crystals in 3D periodic simulation cells with applications to crystal-crystal interfaces

NASA Astrophysics Data System (ADS)

Kroonblawd, Matthew P.; Mathew, Nithin; Jiang, Shan; Sewell, Thomas D.

2016-10-01

A Generalized Crystal-Cutting Method (GCCM) is developed that automates construction of three-dimensionally periodic simulation cells containing arbitrarily oriented single crystals and thin films, two-dimensionally (2D) infinite crystal-crystal homophase and heterophase interfaces, and nanostructures with intrinsic N-fold interfaces. The GCCM is based on a simple mathematical formalism that facilitates easy definition of constraints on cut crystal geometries. The method preserves the translational symmetry of all Bravais lattices and thus can be applied to any crystal described by such a lattice including complicated, low-symmetry molecular crystals. Implementations are presented with carefully articulated combinations of loop searches and constraints that drastically reduce computational complexity compared to simple loop searches. Orthorhombic representations of monoclinic and triclinic crystals found using the GCCM overcome some limitations in standard distributions of popular molecular dynamics software packages. Stability of grain boundaries in β-HMX was investigated using molecular dynamics and molecular statics simulations with 2D infinite crystal-crystal homophase interfaces created using the GCCM. The order of stabilities for the four grain boundaries studied is predicted to correlate with the relative prominence of particular crystal faces in lab-grown β-HMX crystals. We demonstrate how nanostructures can be constructed through simple constraints applied in the GCCM framework. Example GCCM constructions are shown that are relevant to some current problems in materials science, including shock sensitivity of explosives, layered electronic devices, and pharmaceuticals.

An accelerated algorithm for discrete stochastic simulation of reaction-diffusion systems using gradient-based diffusion and tau-leaping.

PubMed

Koh, Wonryull; Blackwell, Kim T

2011-04-21

Stochastic simulation of reaction-diffusion systems enables the investigation of stochastic events arising from the small numbers and heterogeneous distribution of molecular species in biological cells. Stochastic variations in intracellular microdomains and in diffusional gradients play a significant part in the spatiotemporal activity and behavior of cells. Although an exact stochastic simulation that simulates every individual reaction and diffusion event gives a most accurate trajectory of the system's state over time, it can be too slow for many practical applications. We present an accelerated algorithm for discrete stochastic simulation of reaction-diffusion systems designed to improve the speed of simulation by reducing the number of time-steps required to complete a simulation run. This method is unique in that it employs two strategies that have not been incorporated in existing spatial stochastic simulation algorithms. First, diffusive transfers between neighboring subvolumes are based on concentration gradients. This treatment necessitates sampling of only the net or observed diffusion events from higher to lower concentration gradients rather than sampling all diffusion events regardless of local concentration gradients. Second, we extend the non-negative Poisson tau-leaping method that was originally developed for speeding up nonspatial or homogeneous stochastic simulation algorithms. This method calculates each leap time in a unified step for both reaction and diffusion processes while satisfying the leap condition that the propensities do not change appreciably during the leap and ensuring that leaping does not cause molecular populations to become negative. Numerical results are presented that illustrate the improvement in simulation speed achieved by incorporating these two new strategies.

Generalized image charge solvation model for electrostatic interactions in molecular dynamics simulations of aqueous solutions

PubMed Central

Deng, Shaozhong; Xue, Changfeng; Baumketner, Andriy; Jacobs, Donald; Cai, Wei

2013-01-01

This paper extends the image charge solvation model (ICSM) [J. Chem. Phys. 131, 154103 (2009)], a hybrid explicit/implicit method to treat electrostatic interactions in computer simulations of biomolecules formulated for spherical cavities, to prolate spheroidal and triaxial ellipsoidal cavities, designed to better accommodate non-spherical solutes in molecular dynamics (MD) simulations. In addition to the utilization of a general truncated octahedron as the MD simulation box, central to the proposed extension is an image approximation method to compute the reaction field for a point charge placed inside such a non-spherical cavity by using a single image charge located outside the cavity. The resulting generalized image charge solvation model (GICSM) is tested in simulations of liquid water, and the results are analyzed in comparison with those obtained from the ICSM simulations as a reference. We find that, for improved computational efficiency due to smaller simulation cells and consequently a less number of explicit solvent molecules, the generalized model can still faithfully reproduce known static and dynamic properties of liquid water at least for systems considered in the present paper, indicating its great potential to become an accurate but more efficient alternative to the ICSM when bio-macromolecules of irregular shapes are to be simulated. PMID:23913979

Excited state X-ray absorption spectroscopy: Probing both electronic and structural dynamics

NASA Astrophysics Data System (ADS)

Neville, Simon P.; Averbukh, Vitali; Ruberti, Marco; Yun, Renjie; Patchkovskii, Serguei; Chergui, Majed; Stolow, Albert; Schuurman, Michael S.

2016-10-01

We investigate the sensitivity of X-ray absorption spectra, simulated using a general method, to properties of molecular excited states. Recently, Averbukh and co-workers [M. Ruberti et al., J. Chem. Phys. 140, 184107 (2014)] introduced an efficient and accurate L 2 method for the calculation of excited state valence photoionization cross-sections based on the application of Stieltjes imaging to the Lanczos pseudo-spectrum of the algebraic diagrammatic construction (ADC) representation of the electronic Hamiltonian. In this paper, we report an extension of this method to the calculation of excited state core photoionization cross-sections. We demonstrate that, at the ADC(2)x level of theory, ground state X-ray absorption spectra may be accurately reproduced, validating the method. Significantly, the calculated X-ray absorption spectra of the excited states are found to be sensitive to both geometric distortions (structural dynamics) and the electronic character (electronic dynamics) of the initial state, suggesting that core excitation spectroscopies will be useful probes of excited state non-adiabatic dynamics. We anticipate that the method presented here can be combined with ab initio molecular dynamics calculations to simulate the time-resolved X-ray spectroscopy of excited state molecular wavepacket dynamics.

Non-adiabatic molecular dynamics by accelerated semiclassical Monte Carlo

DOE PAGES

White, Alexander J.; Gorshkov, Vyacheslav N.; Tretiak, Sergei; ...

2015-07-07

Non-adiabatic dynamics, where systems non-radiatively transition between electronic states, plays a crucial role in many photo-physical processes, such as fluorescence, phosphorescence, and photoisomerization. Methods for the simulation of non-adiabatic dynamics are typically either numerically impractical, highly complex, or based on approximations which can result in failure for even simple systems. Recently, the Semiclassical Monte Carlo (SCMC) approach was developed in an attempt to combine the accuracy of rigorous semiclassical methods with the efficiency and simplicity of widely used surface hopping methods. However, while SCMC was found to be more efficient than other semiclassical methods, it is not yet as efficientmore » as is needed to be used for large molecular systems. Here, we have developed two new methods: the accelerated-SCMC and the accelerated-SCMC with re-Gaussianization, which reduce the cost of the SCMC algorithm up to two orders of magnitude for certain systems. In many cases shown here, the new procedures are nearly as efficient as the commonly used surface hopping schemes, with little to no loss of accuracy. This implies that these modified SCMC algorithms will be of practical numerical solutions for simulating non-adiabatic dynamics in realistic molecular systems.« less

COLLABORATIVE RESEARCH AND DEVELOPMENT (CR&D) Delivery Order 0059: Molecular Dynamics Modeling Support

DTIC Science & Technology

2008-03-01

Molecular Dynamics Simulations 5 Theory: Equilibrium Molecular Dynamics Simulations 6 Theory: Non...Equilibrium Molecular Dynamics Simulations 8 Carbon Nanotube Simulations : Approach and results from equilibrium and non-equilibrium molecular dynamics ...touched from the perspective of molecular dynamics simulations . However, ordered systems such as “Carbon Nanotubes” have been investigated in terms

Exploring transmembrane transport through alpha-hemolysin with grid-steered molecular dynamics.

PubMed

Wells, David B; Abramkina, Volha; Aksimentiev, Aleksei

2007-09-28

The transport of biomolecules across cell boundaries is central to cellular function. While structures of many membrane channels are known, the permeation mechanism is known only for a select few. Molecular dynamics (MD) is a computational method that can provide an accurate description of permeation events at the atomic level, which is required for understanding the transport mechanism. However, due to the relatively short time scales accessible to this method, it is of limited utility. Here, we present a method for all-atom simulation of electric field-driven transport of large solutes through membrane channels, which in tens of nanoseconds can provide a realistic account of a permeation event that would require a millisecond simulation using conventional MD. In this method, the average distribution of the electrostatic potential in a membrane channel under a transmembrane bias of interest is determined first from an all-atom MD simulation. This electrostatic potential, defined on a grid, is subsequently applied to a charged solute to steer its permeation through the membrane channel. We apply this method to investigate permeation of DNA strands, DNA hairpins, and alpha-helical peptides through alpha-hemolysin. To test the accuracy of the method, we computed the relative permeation rates of DNA strands having different sequences and global orientations. The results of the G-SMD simulations were found to be in good agreement in experiment.

Better Than Counting: Density Profiles from Force Sampling

NASA Astrophysics Data System (ADS)

de las Heras, Daniel; Schmidt, Matthias

2018-05-01

Calculating one-body density profiles in equilibrium via particle-based simulation methods involves counting of events of particle occurrences at (histogram-resolved) space points. Here, we investigate an alternative method based on a histogram of the local force density. Via an exact sum rule, the density profile is obtained with a simple spatial integration. The method circumvents the inherent ideal gas fluctuations. We have tested the method in Monte Carlo, Brownian dynamics, and molecular dynamics simulations. The results carry a statistical uncertainty smaller than that of the standard counting method, reducing therefore the computation time.

Recursive Factorization of the Inverse Overlap Matrix in Linear-Scaling Quantum Molecular Dynamics Simulations.

PubMed

Negre, Christian F A; Mniszewski, Susan M; Cawkwell, Marc J; Bock, Nicolas; Wall, Michael E; Niklasson, Anders M N

2016-07-12

We present a reduced complexity algorithm to compute the inverse overlap factors required to solve the generalized eigenvalue problem in a quantum-based molecular dynamics (MD) simulation. Our method is based on the recursive, iterative refinement of an initial guess of Z (inverse square root of the overlap matrix S). The initial guess of Z is obtained beforehand by using either an approximate divide-and-conquer technique or dynamical methods, propagated within an extended Lagrangian dynamics from previous MD time steps. With this formulation, we achieve long-term stability and energy conservation even under the incomplete, approximate, iterative refinement of Z. Linear-scaling performance is obtained using numerically thresholded sparse matrix algebra based on the ELLPACK-R sparse matrix data format, which also enables efficient shared-memory parallelization. As we show in this article using self-consistent density-functional-based tight-binding MD, our approach is faster than conventional methods based on the diagonalization of overlap matrix S for systems as small as a few hundred atoms, substantially accelerating quantum-based simulations even for molecular structures of intermediate size. For a 4158-atom water-solvated polyalanine system, we find an average speedup factor of 122 for the computation of Z in each MD step.

Removing systematic errors in interionic potentials of mean force computed in molecular simulations using reaction-field-based electrostatics

PubMed Central

Baumketner, Andrij

2009-01-01

The performance of reaction-field methods to treat electrostatic interactions is tested in simulations of ions solvated in water. The potential of mean force between sodium chloride pair of ions and between side chains of lysine and aspartate are computed using umbrella sampling and molecular dynamics simulations. It is found that in comparison with lattice sum calculations, the charge-group-based approaches to reaction-field treatments produce a large error in the association energy of the ions that exhibits strong systematic dependence on the size of the simulation box. The atom-based implementation of the reaction field is seen to (i) improve the overall quality of the potential of mean force and (ii) remove the dependence on the size of the simulation box. It is suggested that the atom-based truncation be used in reaction-field simulations of mixed media. PMID:19292522

Molecular dynamics: deciphering the data.

PubMed

Dauber-Osguthorpe, P; Maunder, C M; Osguthorpe, D J

1996-06-01

The dynamic behaviour of molecules is important in determining their activity. Molecular dynamics (MD) simulations give a detailed description of motion, from small fluctuations to conformational transitions, and can include solvent effects. However, extracting useful information about conformational motion from a trajectory is not trivial. We have used digital signal-processing techniques to characterise the motion in MD simulations, including: calculating the frequency distribution, applying filtering functions, and extraction of vectors defining the characteristic motion for each frequency in an MD simulation. We describe here some typical results obtained for peptides and proteins. The nature of the low-frequency modes of motion, as obtained from MD and normal mode (NM) analysis, of Ace-(Ala)31-Nma and of a proline mutant is discussed. Low-frequency modes extracted from the MD trajectories of Rop protein and phospholipase A2 reveal characteristic motions of secondary structure elements, as well as concerned motions that are of significance to the protein's biological activity. MD simulations are also used frequently as a tool for conformational searches and for investigating protein folding/unfolding. We have developed a novel method that uses time-domain filtering to channel energy into conformational motion and thus enhance conformational transitions. The selectively enhanced molecular dynamics method is tested on the small molecule hexane.

Molecular dynamics: Deciphering the data

NASA Astrophysics Data System (ADS)

Dauber-Osguthorpe, Pnina; Maunder, Colette M.; Osguthorpe, David J.

1996-06-01

The dynamic behaviour of molecules is important in determining their activity. Molecular dynamics (MD) simulations give a detailed description of motion, from small fluctuations to conformational transitions, and can include solvent effects. However, extracting useful information about conformational motion from a trajectory is not trivial. We have used digital signal-processing techniques to characterise the motion in MD simulations, including: calculating the frequency distribution, applying filtering functions, and extraction of vectors defining the characteristic motion for each frequency in an MD simulation. We describe here some typical results obtained for peptides and proteins. The nature of the low-frequency modes of motion, as obtained from MD and normal mode (NM) analysis, of Ace-(Ala)31-Nma and of a proline mutant is discussed. Low-frequency modes extracted from the MD trajectories of Rop protein and phospholipase A2 reveal characteristic motions of secondary structure elements, as well as concerted motions that are of significance to the protein's biological activity. MD simulations are also used frequently as a tool for conformational searches and for investigating protein folding/unfolding. We have developed a novel method that uses time-domain filtering to channel energy into conformational motion and thus enhance conformational transitions. The selectively enhanced molecular dynamics method is tested on the small molecule hexane.

Locking the 150-cavity open: in silico design and verification of influenza neuraminidase inhibitors.

PubMed

Han, Nanyu; Mu, Yuguang

2013-01-01

Neuraminidase (NA) of influenza is a key target for virus infection control and the recently discovered open 150-cavity in group-1 NA provides new opportunity for novel inhibitors design. In this study, we used a combination of theoretical methods including fragment docking, molecular linking and molecular dynamics simulations to design ligands that specifically target at the 150-cavity. Through in silico screening of a fragment compound library on the open 150-cavity of NA, a few best scored fragment compounds were selected to link with Zanamivir, one NA-targeting drug. The resultant new ligands may bind both the active site and the 150-cavity of NA simultaneously. Extensive molecular dynamics simulations in explicit solvent were applied to validate the binding between NA and the designed ligands. Moreover, two control systems, a positive control using Zanamivir and a negative control using a low-affinity ligand 3-(p-tolyl) allyl-Neu5Ac2en (ETT, abbreviation reported in the PDB) found in a recent experimental work, were employed to calibrate the simulation method. During the simulations, ETT was observed to detach from NA, on the contrary, both Zanamivir and our designed ligand bind NA firmly. Our study provides a prospective way to design novel inhibitors for controlling the spread of influenza virus.

Consistent View of Protein Fluctuations from All-Atom Molecular Dynamics and Coarse-Grained Dynamics with Knowledge-Based Force-Field.

PubMed

Jamroz, Michal; Orozco, Modesto; Kolinski, Andrzej; Kmiecik, Sebastian

2013-01-08

It is widely recognized that atomistic Molecular Dynamics (MD), a classical simulation method, captures the essential physics of protein dynamics. That idea is supported by a theoretical study showing that various MD force-fields provide a consensus picture of protein fluctuations in aqueous solution [Rueda, M. et al. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 796-801]. However, atomistic MD cannot be applied to most biologically relevant processes due to its limitation to relatively short time scales. Much longer time scales can be accessed by properly designed coarse-grained models. We demonstrate that the aforementioned consensus view of protein dynamics from short (nanosecond) time scale MD simulations is fairly consistent with the dynamics of the coarse-grained protein model - the CABS model. The CABS model employs stochastic dynamics (a Monte Carlo method) and a knowledge-based force-field, which is not biased toward the native structure of a simulated protein. Since CABS-based dynamics allows for the simulation of entire folding (or multiple folding events) in a single run, integration of the CABS approach with all-atom MD promises a convenient (and computationally feasible) means for the long-time multiscale molecular modeling of protein systems with atomistic resolution.

Molecular dynamics force-field refinement against quasi-elastic neutron scattering data

DOE PAGES

Borreguero Calvo, Jose M.; Lynch, Vickie E.

2015-11-23

Quasi-elastic neutron scattering (QENS) is one of the experimental techniques of choice for probing the dynamics at length and time scales that are also in the realm of full-atom molecular dynamics (MD) simulations. This overlap enables extension of current fitting methods that use time-independent equilibrium measurements to new methods fitting against dynamics data. We present an algorithm that fits simulation-derived incoherent dynamical structure factors against QENS data probing the diffusive dynamics of the system. We showcase the difficulties inherent to this type of fitting problem, namely, the disparity between simulation and experiment environment, as well as limitations in the simulationmore » due to incomplete sampling of phase space. We discuss a methodology to overcome these difficulties and apply it to a set of full-atom MD simulations for the purpose of refining the force-field parameter governing the activation energy of methyl rotation in the octa-methyl polyhedral oligomeric silsesquioxane molecule. Our optimal simulated activation energy agrees with the experimentally derived value up to a 5% difference, well within experimental error. We believe the method will find applicability to other types of diffusive motions and other representation of the systems such as coarse-grain models where empirical fitting is essential. In addition, the refinement method can be extended to the coherent dynamic structure factor with no additional effort.« less

Correlation of chemical shifts predicted by molecular dynamics simulations for partially disordered proteins.

PubMed

Karp, Jerome M; Eryilmaz, Ertan; Erylimaz, Ertan; Cowburn, David

2015-01-01

There has been a longstanding interest in being able to accurately predict NMR chemical shifts from structural data. Recent studies have focused on using molecular dynamics (MD) simulation data as input for improved prediction. Here we examine the accuracy of chemical shift prediction for intein systems, which have regions of intrinsic disorder. We find that using MD simulation data as input for chemical shift prediction does not consistently improve prediction accuracy over use of a static X-ray crystal structure. This appears to result from the complex conformational ensemble of the disordered protein segments. We show that using accelerated molecular dynamics (aMD) simulations improves chemical shift prediction, suggesting that methods which better sample the conformational ensemble like aMD are more appropriate tools for use in chemical shift prediction for proteins with disordered regions. Moreover, our study suggests that data accurately reflecting protein dynamics must be used as input for chemical shift prediction in order to correctly predict chemical shifts in systems with disorder.

Characterization of the Interaction between Gallic Acid and Lysozyme by Molecular Dynamics Simulation and Optical Spectroscopy

PubMed Central

Zhan, Minzhong; Guo, Ming; Jiang, Yanke; Wang, Xiaomeng

2015-01-01

The binding interaction between gallic acid (GA) and lysozyme (LYS) was investigated and compared by molecular dynamics (MD) simulation and spectral techniques. The results from spectroscopy indicate that GA binds to LYS to generate a static complex. The binding constants and thermodynamic parameters were calculated. MD simulation revealed that the main driving forces for GA binding to LYS are hydrogen bonding and hydrophobic interactions. The root-mean-square deviation verified that GA and LYS bind to form a stable complex, while the root-mean-square fluctuation results showed that the stability of the GA-LYS complex at 298 K was higher than that at 310 K. The calculated free binding energies from the molecular mechanics/Poisson-Boltzmann surface area method showed that van der Waals forces and electrostatic interactions are the predominant intermolecular forces. The MD simulation was consistent with the spectral experiments. This study provides a reference for future study of the pharmacological mechanism of GA. PMID:26140374

Characterization of the Interaction between Gallic Acid and Lysozyme by Molecular Dynamics Simulation and Optical Spectroscopy.

PubMed

Zhan, Minzhong; Guo, Ming; Jiang, Yanke; Wang, Xiaomeng

2015-07-01

The binding interaction between gallic acid (GA) and lysozyme (LYS) was investigated and compared by molecular dynamics (MD) simulation and spectral techniques. The results from spectroscopy indicate that GA binds to LYS to generate a static complex. The binding constants and thermodynamic parameters were calculated. MD simulation revealed that the main driving forces for GA binding to LYS are hydrogen bonding and hydrophobic interactions. The root-mean-square deviation verified that GA and LYS bind to form a stable complex, while the root-mean-square fluctuation results showed that the stability of the GA-LYS complex at 298 K was higher than that at 310 K. The calculated free binding energies from the molecular mechanics/Poisson-Boltzmann surface area method showed that van der Waals forces and electrostatic interactions are the predominant intermolecular forces. The MD simulation was consistent with the spectral experiments. This study provides a reference for future study of the pharmacological mechanism of GA.

Coarse-grained simulations of protein-protein association: an energy landscape perspective.

PubMed

Ravikumar, Krishnakumar M; Huang, Wei; Yang, Sichun

2012-08-22

Understanding protein-protein association is crucial in revealing the molecular basis of many biological processes. Here, we describe a theoretical simulation pipeline to study protein-protein association from an energy landscape perspective. First, a coarse-grained model is implemented and its applications are demonstrated via molecular dynamics simulations for several protein complexes. Second, an enhanced search method is used to efficiently sample a broad range of protein conformations. Third, multiple conformations are identified and clustered from simulation data and further projected on a three-dimensional globe specifying protein orientations and interacting energies. Results from several complexes indicate that the crystal-like conformation is favorable on the energy landscape even if the landscape is relatively rugged with metastable conformations. A closer examination on molecular forces shows that the formation of associated protein complexes can be primarily electrostatics-driven, hydrophobics-driven, or a combination of both in stabilizing specific binding interfaces. Taken together, these results suggest that the coarse-grained simulations and analyses provide an alternative toolset to study protein-protein association occurring in functional biomolecular complexes. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Coarse-Grained Simulations of Protein-Protein Association: An Energy Landscape Perspective

PubMed Central

Ravikumar, Krishnakumar M.; Huang, Wei; Yang, Sichun

2012-01-01

Understanding protein-protein association is crucial in revealing the molecular basis of many biological processes. Here, we describe a theoretical simulation pipeline to study protein-protein association from an energy landscape perspective. First, a coarse-grained model is implemented and its applications are demonstrated via molecular dynamics simulations for several protein complexes. Second, an enhanced search method is used to efficiently sample a broad range of protein conformations. Third, multiple conformations are identified and clustered from simulation data and further projected on a three-dimensional globe specifying protein orientations and interacting energies. Results from several complexes indicate that the crystal-like conformation is favorable on the energy landscape even if the landscape is relatively rugged with metastable conformations. A closer examination on molecular forces shows that the formation of associated protein complexes can be primarily electrostatics-driven, hydrophobics-driven, or a combination of both in stabilizing specific binding interfaces. Taken together, these results suggest that the coarse-grained simulations and analyses provide an alternative toolset to study protein-protein association occurring in functional biomolecular complexes. PMID:22947945

Error correction in multi-fidelity molecular dynamics simulations using functional uncertainty quantification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reeve, Samuel Temple; Strachan, Alejandro, E-mail: strachan@purdue.edu

We use functional, Fréchet, derivatives to quantify how thermodynamic outputs of a molecular dynamics (MD) simulation depend on the potential used to compute atomic interactions. Our approach quantifies the sensitivity of the quantities of interest with respect to the input functions as opposed to its parameters as is done in typical uncertainty quantification methods. We show that the functional sensitivity of the average potential energy and pressure in isothermal, isochoric MD simulations using Lennard–Jones two-body interactions can be used to accurately predict those properties for other interatomic potentials (with different functional forms) without re-running the simulations. This is demonstrated undermore » three different thermodynamic conditions, namely a crystal at room temperature, a liquid at ambient pressure, and a high pressure liquid. The method provides accurate predictions as long as the change in potential can be reasonably described to first order and does not significantly affect the region in phase space explored by the simulation. The functional uncertainty quantification approach can be used to estimate the uncertainties associated with constitutive models used in the simulation and to correct predictions if a more accurate representation becomes available.« less

Simulation of wave packet tunneling of interacting identical particles

NASA Astrophysics Data System (ADS)

Lozovik, Yu. E.; Filinov, A. V.; Arkhipov, A. S.

2003-02-01

We demonstrate a different method of simulation of nonstationary quantum processes, considering the tunneling of two interacting identical particles, represented by wave packets. The used method of quantum molecular dynamics (WMD) is based on the Wigner representation of quantum mechanics. In the context of this method ensembles of classical trajectories are used to solve quantum Wigner-Liouville equation. These classical trajectories obey Hamiltonian-like equations, where the effective potential consists of the usual classical term and the quantum term, which depends on the Wigner function and its derivatives. The quantum term is calculated using local distribution of trajectories in phase space, therefore, classical trajectories are not independent, contrary to classical molecular dynamics. The developed WMD method takes into account the influence of exchange and interaction between particles. The role of direct and exchange interactions in tunneling is analyzed. The tunneling times for interacting particles are calculated.

Prediction of drug-packaging interactions via molecular dynamics (MD) simulations.

PubMed

Feenstra, Peter; Brunsteiner, Michael; Khinast, Johannes

2012-07-15

The interaction between packaging materials and drug products is an important issue for the pharmaceutical industry, since during manufacturing, processing and storage a drug product is continuously exposed to various packaging materials. The experimental investigation of a great variety of different packaging material-drug product combinations in terms of efficacy and safety can be a costly and time-consuming task. In our work we used molecular dynamics (MD) simulations in order to evaluate the applicability of such methods to pre-screening of the packaging material-solute compatibility. The solvation free energy and the free energy of adsorption of diverse solute/solvent/solid systems were estimated. The results of our simulations agree with experimental values previously published in the literature, which indicates that the methods in question can be used to semi-quantitatively reproduce the solid-liquid interactions of the investigated systems. Copyright © 2012 Elsevier B.V. All rights reserved.

Penetration of Gold Nanoparticles through Human Skin: Unraveling Its Mechanisms at the Molecular Scale.

PubMed

Gupta, Rakesh; Rai, Beena

2016-07-28

Recent experimental studies suggest that nanosized gold nanoparticles (AuNPs) are able to penetrate into the deeper layer (epidermis and dermis) of rat and human skin. However, the mechanisms by which these AuNPs penetrate and disrupt the skin's lipid matrix are not well understood. In this study, we have used computer simulations to explore the translocation and the permeation of AuNPs through the model skin lipid membrane using both unconstrained and constrained coarse-grained molecular dynamics simulations. Each AuNP (1-6 nm) disrupted the bilayer packing and entered the interior of the bilayer rapidly (within 100 ns). It created a hydrophobic vacancy in the bilayer, which was mostly filled by skin constituents. Bigger AuNPs induced changes in the bilayer structure, and undulations were observed in the bilayer. The bilayer exhibited self-healing properties; it retained its original form once the simulation was run further after the removal of the AuNPs. Constrained simulation results showed that there was a trade-off between the kinetics and thermodynamics of AuNP permeation at a molecular scale. The combined effect of both resulted in a high permeation of small-sized AuNPs. The molecular-level information obtained through our simulations offers a very convenient method to design novel drug delivery systems and effective cosmetics.

Molecular simulations of lipid systems: Edge stability and structure in pure and mixed bilayers

NASA Astrophysics Data System (ADS)

Jiang, Yong

2007-12-01

Understanding the structural, mechanical and dynamical properties of lipid self-assembled systems is fundamental to understand the behavior of the cell membrane. This thesis has investigated the equilibrium properties of lipid systems with edge defects through various molecular simulation techniques. The overall goal of this study is to understand the free energy terms of the edges and to develop efficient methods to sample equilibrium distributions of mixed-lipid systems. In the first main part of my thesis, an atomistic molecular model is used to study lipid ribbon which has two edges on both sides. Details of the edge structures, such as area per lipid and tail torsional statistics are presented. Line tension, calculated from pressure tensor in MD simulation has good agreement with result from other sources. To further investigate edge properties on a longer timescale and larger length scale, we have applied a coarse-grained forcefield on mixed lipid systems and try to interpret the edge fluctuations in terms of free energy parameters such as line tension and bending modulus. We have identified two regimes with quite different edge behavior: a high line tension regime and a low line tension regime. The last part of this thesis focuses on a hybrid Molecular dynamics and Configurational-bias Monte Carlo (MCMD) simulation method in which molecules can change their type by growing and shrinking the terminal acyl united carbon atoms. A two-step extension of the MCMD method has been developed to allow for a larger difference in the components' tail lengths. Results agreed well with previous one-step mutation results for a mixture with a length difference of four carbons. The current method can efficiently sample mixtures with a length difference of eight carbons, with a small portion of lipids of intermediate tail length. Preliminary results are obtained for "bicelle"-type (DMPC/DHPC) ribbons.

ms 2: A molecular simulation tool for thermodynamic properties, release 3.0

NASA Astrophysics Data System (ADS)

Rutkai, Gábor; Köster, Andreas; Guevara-Carrion, Gabriela; Janzen, Tatjana; Schappals, Michael; Glass, Colin W.; Bernreuther, Martin; Wafai, Amer; Stephan, Simon; Kohns, Maximilian; Reiser, Steffen; Deublein, Stephan; Horsch, Martin; Hasse, Hans; Vrabec, Jadran

2017-12-01

A new version release (3.0) of the molecular simulation tool ms 2 (Deublein et al., 2011; Glass et al. 2014) is presented. Version 3.0 of ms 2 features two additional ensembles, i.e. microcanonical (NVE) and isobaric-isoenthalpic (NpH), various Helmholtz energy derivatives in the NVE ensemble, thermodynamic integration as a method for calculating the chemical potential, the osmotic pressure for calculating the activity of solvents, the six Maxwell-Stefan diffusion coefficients of quaternary mixtures, statistics for sampling hydrogen bonds, smooth-particle mesh Ewald summation as well as the ability to carry out molecular dynamics runs for an arbitrary number of state points in a single program execution.

Comparison of MM/GBSA calculations based on explicit and implicit solvent simulations.

PubMed

Godschalk, Frithjof; Genheden, Samuel; Söderhjelm, Pär; Ryde, Ulf

2013-05-28

Molecular mechanics with generalised Born and surface area solvation (MM/GBSA) is a popular method to calculate the free energy of the binding of ligands to proteins. It involves molecular dynamics (MD) simulations with an explicit solvent of the protein-ligand complex to give a set of snapshots for which energies are calculated with an implicit solvent. This change in the solvation method (explicit → implicit) would strictly require that the energies are reweighted with the implicit-solvent energies, which is normally not done. In this paper we calculate MM/GBSA energies with two generalised Born models for snapshots generated by the same methods or by explicit-solvent simulations for five synthetic N-acetyllactosamine derivatives binding to galectin-3. We show that the resulting energies are very different both in absolute and relative terms, showing that the change in the solvent model is far from innocent and that standard MM/GBSA is not a consistent method. The ensembles generated with the various solvent models are quite different with root-mean-square deviations of 1.2-1.4 Å. The ensembles can be converted to each other by performing short MD simulations with the new method, but the convergence is slow, showing mean absolute differences in the calculated energies of 6-7 kJ mol(-1) after 2 ps simulations. Minimisations show even slower convergence and there are strong indications that the energies obtained from minimised structures are different from those obtained by MD.

Hamiltonian adaptive resolution molecular dynamics simulation of infrared dielectric functions of liquids

NASA Astrophysics Data System (ADS)

Wang, C. C.; Tan, J. Y.; Liu, L. H.

2018-05-01

Hamiltonian adaptive resolution scheme (H-AdResS), which allows to simulate materials by treating different domains of the system at different levels of resolution, is a recently proposed atomistic/coarse-grained multiscale model. In this work, a scheme to calculate the dielectric functions of liquids on account of H-AdResS is presented. In the proposed H-AdResS dielectric-function calculation scheme (DielectFunctCalS), the corrected molecular dipole moments are calculated by multiplying molecular dipole moment by the weighting fraction of the molecular mapping point. As the widths of all-atom and hybrid regions show different degrees of influence on the dielectric functions, a prefactor is multiplied to eliminate the effects of all-atom and hybrid region widths. Since one goal of using the H-AdResS method is to reduce computational costs, widths of the all-atom region and the hybrid region can be reduced considering that the coarse-grained simulation is much more timesaving compared to atomistic simulation. Liquid water and ethanol are taken as test cases to validate the DielectFunctCalS. The H-AdResS DielectFunctCalS results are in good agreement with all-atom molecular dynamics simulations. The accuracy of the H-AdResS results, together with all-atom molecular dynamics results, depends heavily on the choice of the force field and force field parameters. The H-AdResS DielectFunctCalS allows us to calculate the dielectric functions of macromolecule systems with high efficiency and makes the dielectric function calculations of large biomolecular systems possible.

Bottom-up derivation of conservative and dissipative interactions for coarse-grained molecular liquids with the conditional reversible work method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deichmann, Gregor; Marcon, Valentina; Vegt, Nico F. A. van der, E-mail: vandervegt@csi.tu-darmstadt.de

Molecular simulations of soft matter systems have been performed in recent years using a variety of systematically coarse-grained models. With these models, structural or thermodynamic properties can be quite accurately represented while the prediction of dynamic properties remains difficult, especially for multi-component systems. In this work, we use constraint molecular dynamics simulations for calculating dissipative pair forces which are used together with conditional reversible work (CRW) conservative forces in dissipative particle dynamics (DPD) simulations. The combined CRW-DPD approach aims to extend the representability of CRW models to dynamic properties and uses a bottom-up approach. Dissipative pair forces are derived frommore » fluctuations of the direct atomistic forces between mapped groups. The conservative CRW potential is obtained from a similar series of constraint dynamics simulations and represents the reversible work performed to couple the direct atomistic interactions between the mapped atom groups. Neopentane, tetrachloromethane, cyclohexane, and n-hexane have been considered as model systems. These molecular liquids are simulated with atomistic molecular dynamics, coarse-grained molecular dynamics, and DPD. We find that the CRW-DPD models reproduce the liquid structure and diffusive dynamics of the liquid systems in reasonable agreement with the atomistic models when using single-site mapping schemes with beads containing five or six heavy atoms. For a two-site representation of n-hexane (3 carbons per bead), time scale separation can no longer be assumed and the DPD approach consequently fails to reproduce the atomistic dynamics.« less

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

PubMed

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.

Designing Free Energy Surfaces That Match Experimental Data with Metadynamics

DOE PAGES

White, Andrew D.; Dama, James F.; Voth, Gregory A.

2015-04-30

Creating models that are consistent with experimental data is essential in molecular modeling. This is often done by iteratively tuning the molecular force field of a simulation to match experimental data. An alternative method is to bias a simulation, leading to a hybrid model composed of the original force field and biasing terms. Previously we introduced such a method called experiment directed simulation (EDS). EDS minimally biases simulations to match average values. We also introduce a new method called experiment directed metadynamics (EDM) that creates minimal biases for matching entire free energy surfaces such as radial distribution functions and phi/psimore » angle free energies. It is also possible with EDM to create a tunable mixture of the experimental data and free energy of the unbiased ensemble with explicit ratios. EDM can be proven to be convergent, and we also present proof, via a maximum entropy argument, that the final bias is minimal and unique. Examples of its use are given in the construction of ensembles that follow a desired free energy. Finally, the example systems studied include a Lennard-Jones fluid made to match a radial distribution function, an atomistic model augmented with bioinformatics data, and a three-component electrolyte solution where ab initio simulation data is used to improve a classical empirical model.« less

Designing free energy surfaces that match experimental data with metadynamics.

PubMed

White, Andrew D; Dama, James F; Voth, Gregory A

2015-06-09

Creating models that are consistent with experimental data is essential in molecular modeling. This is often done by iteratively tuning the molecular force field of a simulation to match experimental data. An alternative method is to bias a simulation, leading to a hybrid model composed of the original force field and biasing terms. We previously introduced such a method called experiment directed simulation (EDS). EDS minimally biases simulations to match average values. In this work, we introduce a new method called experiment directed metadynamics (EDM) that creates minimal biases for matching entire free energy surfaces such as radial distribution functions and phi/psi angle free energies. It is also possible with EDM to create a tunable mixture of the experimental data and free energy of the unbiased ensemble with explicit ratios. EDM can be proven to be convergent, and we also present proof, via a maximum entropy argument, that the final bias is minimal and unique. Examples of its use are given in the construction of ensembles that follow a desired free energy. The example systems studied include a Lennard-Jones fluid made to match a radial distribution function, an atomistic model augmented with bioinformatics data, and a three-component electrolyte solution where ab initio simulation data is used to improve a classical empirical model.

Understanding the influence of solvent field and fluctuations on the stability of photo-induced charge-separated state in molecular triad

NASA Astrophysics Data System (ADS)

Balamurugan, D.; Aquino, Adelia; Lischka, Hans; Dios, Francis; Flores, Lionel; Cheung, Margaret

2013-03-01

Molecular triad composed of fullerene, porphyrin, and carotene is an artificial analogue of natural photosynthetic system and is considered for applications in solar energy conversion because of its ability to produce long-lived photo-induced charge separated state. The goal of the present multiscale simulation is to understand how the stability of photo-induced charge-separated state in molecular triad is influenced by a polar organic solvent, namely tetrahydrofuran (THF). The multiscale approach is based on combined quantum, classical molecular dynamics, and statistical physics calculations. The quantum chemical calculations were performed on the triad using the second order algebraic diagrammatic perturbation and time-dependent density functional theory. Molecular dynamics simulations were performed on triad in a box of THF solvent with the replica exchange method. The two methods on different length and time scales are bridged through an important sampling technique. We have analyzed the free energy landscape, structural fluctuations, and the long- range electrostatic interactions between triad and solvent molecules. The results suggest that the polarity and re-organization of the solvent is critical in stabilization of charge-separated state in triad. Supported by DOE (DE-FG02-10ER16175)

Some connections between importance sampling and enhanced sampling methods in molecular dynamics.

PubMed

Lie, H C; Quer, J

2017-11-21

In molecular dynamics, enhanced sampling methods enable the collection of better statistics of rare events from a reference or target distribution. We show that a large class of these methods is based on the idea of importance sampling from mathematical statistics. We illustrate this connection by comparing the Hartmann-Schütte method for rare event simulation (J. Stat. Mech. Theor. Exp. 2012, P11004) and the Valsson-Parrinello method of variationally enhanced sampling [Phys. Rev. Lett. 113, 090601 (2014)]. We use this connection in order to discuss how recent results from the Monte Carlo methods literature can guide the development of enhanced sampling methods.

Some connections between importance sampling and enhanced sampling methods in molecular dynamics

NASA Astrophysics Data System (ADS)

Lie, H. C.; Quer, J.

2017-11-01

In molecular dynamics, enhanced sampling methods enable the collection of better statistics of rare events from a reference or target distribution. We show that a large class of these methods is based on the idea of importance sampling from mathematical statistics. We illustrate this connection by comparing the Hartmann-Schütte method for rare event simulation (J. Stat. Mech. Theor. Exp. 2012, P11004) and the Valsson-Parrinello method of variationally enhanced sampling [Phys. Rev. Lett. 113, 090601 (2014)]. We use this connection in order to discuss how recent results from the Monte Carlo methods literature can guide the development of enhanced sampling methods.

Identification of Rare Lewis Oligosaccharide Conformers in Aqueous Solution Using Enhanced Sampling Molecular Dynamics.

PubMed

Alibay, Irfan; Burusco, Kepa K; Bruce, Neil J; Bryce, Richard A

2018-03-08

Determining the conformations accessible to carbohydrate ligands in aqueous solution is important for understanding their biological action. In this work, we evaluate the conformational free-energy surfaces of Lewis oligosaccharides in explicit aqueous solvent using a multidimensional variant of the swarm-enhanced sampling molecular dynamics (msesMD) method; we compare with multi-microsecond unbiased MD simulations, umbrella sampling, and accelerated MD approaches. For the sialyl Lewis A tetrasaccharide, msesMD simulations in aqueous solution predict conformer landscapes in general agreement with the other biased methods and with triplicate unbiased 10 μs trajectories; these simulations find a predominance of closed conformer and a range of low-occupancy open forms. The msesMD simulations also suggest closed-to-open transitions in the tetrasaccharide are facilitated by changes in ring puckering of its GlcNAc residue away from the 4 C 1 form, in line with previous work. For sialyl Lewis X tetrasaccharide, msesMD simulations predict a minor population of an open form in solution corresponding to a rare lectin-bound pose observed crystallographically. Overall, from comparison with biased MD calculations, we find that triplicate 10 μs unbiased MD simulations may not be enough to fully sample glycan conformations in aqueous solution. However, the computational efficiency and intuitive approach of the msesMD method suggest potential for its application in glycomics as a tool for analysis of oligosaccharide conformation.

Acceleration of Lateral Equilibration in Mixed Lipid Bilayers Using Replica Exchange with Solute Tempering

PubMed Central

2015-01-01

The lateral heterogeneity of cellular membranes plays an important role in many biological functions such as signaling and regulating membrane proteins. This heterogeneity can result from preferential interactions between membrane components or interactions with membrane proteins. One major difficulty in molecular dynamics simulations aimed at studying the membrane heterogeneity is that lipids diffuse slowly and collectively in bilayers, and therefore, it is difficult to reach equilibrium in lateral organization in bilayer mixtures. Here, we propose the use of the replica exchange with solute tempering (REST) approach to accelerate lateral relaxation in heterogeneous bilayers. REST is based on the replica exchange method but tempers only the solute, leaving the temperature of the solvent fixed. Since the number of replicas in REST scales approximately only with the degrees of freedom in the solute, REST enables us to enhance the configuration sampling of lipid bilayers with fewer replicas, in comparison with the temperature replica exchange molecular dynamics simulation (T-REMD) where the number of replicas scales with the degrees of freedom of the entire system. We apply the REST method to a cholesterol and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer mixture and find that the lateral distribution functions of all molecular pair types converge much faster than in the standard MD simulation. The relative diffusion rate between molecules in REST is, on average, an order of magnitude faster than in the standard MD simulation. Although REST was initially proposed to study protein folding and its efficiency in protein folding is still under debate, we find a unique application of REST to accelerate lateral equilibration in mixed lipid membranes and suggest a promising way to probe membrane lateral heterogeneity through molecular dynamics simulation. PMID:25328493

Covalent dye attachment influences the dynamics and conformational properties of flexible peptides

PubMed Central

Crevenna, Alvaro H.; Bomblies, Rainer; Lamb, Don C.

2017-01-01

Fluorescence spectroscopy techniques like Förster resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS) have become important tools for the in vitro and in vivo investigation of conformational dynamics in biomolecules. These methods rely on the distance-dependent quenching of the fluorescence signal of a donor fluorophore either by a fluorescent acceptor fluorophore (FRET) or a non-fluorescent quencher, as used in FCS with photoinduced electron transfer (PET). The attachment of fluorophores to the molecule of interest can potentially alter the molecular properties and may affect the relevant conformational states and dynamics especially of flexible biomolecules like intrinsically disordered proteins (IDP). Using the intrinsically disordered S-peptide as a model system, we investigate the impact of terminal fluorescence labeling on the molecular properties. We perform extensive molecular dynamics simulations on the labeled and unlabeled peptide and compare the results with in vitro PET-FCS measurements. Experimental and simulated timescales of end-to-end fluctuations were found in excellent agreement. Comparison between simulations with and without labels reveal that the π-stacking interaction between the fluorophore labels traps the conformation of S-peptide in a single dominant state, while the unlabeled peptide undergoes continuous conformational rearrangements. Furthermore, we find that the open to closed transition rate of S-peptide is decreased by at least one order of magnitude by the fluorophore attachment. Our approach combining experimental and in silico methods provides a benchmark for the simulations and reveals the significant effect that fluorescence labeling can have on the conformational dynamics of small biomolecules, at least for inherently flexible short peptides. The presented protocol is not only useful for comparing PET-FCS experiments with simulation results but provides a strategy to minimize the influence on molecular properties when chosing labeling positions for fluorescence experiments. PMID:28542243

Acceleration of Lateral Equilibration in Mixed Lipid Bilayers Using Replica Exchange with Solute Tempering.

PubMed

Huang, Kun; García, Angel E

2014-10-14

The lateral heterogeneity of cellular membranes plays an important role in many biological functions such as signaling and regulating membrane proteins. This heterogeneity can result from preferential interactions between membrane components or interactions with membrane proteins. One major difficulty in molecular dynamics simulations aimed at studying the membrane heterogeneity is that lipids diffuse slowly and collectively in bilayers, and therefore, it is difficult to reach equilibrium in lateral organization in bilayer mixtures. Here, we propose the use of the replica exchange with solute tempering (REST) approach to accelerate lateral relaxation in heterogeneous bilayers. REST is based on the replica exchange method but tempers only the solute, leaving the temperature of the solvent fixed. Since the number of replicas in REST scales approximately only with the degrees of freedom in the solute, REST enables us to enhance the configuration sampling of lipid bilayers with fewer replicas, in comparison with the temperature replica exchange molecular dynamics simulation (T-REMD) where the number of replicas scales with the degrees of freedom of the entire system. We apply the REST method to a cholesterol and 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC) bilayer mixture and find that the lateral distribution functions of all molecular pair types converge much faster than in the standard MD simulation. The relative diffusion rate between molecules in REST is, on average, an order of magnitude faster than in the standard MD simulation. Although REST was initially proposed to study protein folding and its efficiency in protein folding is still under debate, we find a unique application of REST to accelerate lateral equilibration in mixed lipid membranes and suggest a promising way to probe membrane lateral heterogeneity through molecular dynamics simulation.

Formation of young massive clusters from turbulent molecular clouds

NASA Astrophysics Data System (ADS)

Fujii, Michiko; Portegies Zwart, Simon

2015-08-01

We simulate the formation and evolution of young star clusters using smoothed-particle hydrodynamics (SPH) and direct N-body methods. We start by performing SPH simulations of the giant molecular cloud with a turbulent velocity field, a mass of 10^4 to 10^6 M_sun, and a density between 17 and 1700 cm^-3. We continue the SPH simulations for a free-fall time scale, and analyze the resulting structure of the collapsed cloud. We subsequently replace a density-selected subset of SPH particles with stars. As a consequence, the local star formation efficiency exceeds 30 per cent, whereas globally only a few per cent of the gas is converted to stars. The stellar distribution is very clumpy with typically a dozen bound conglomerates that consist of 100 to 10000 stars. We continue to evolve the stars dynamically using the collisional N-body method, which accurately treats all pairwise interactions, stellar collisions and stellar evolution. We analyze the results of the N-body simulations at 2 Myr and 10 Myr. From dense massive molecular clouds, massive clusters grow via hierarchical merging of smaller clusters. The shape of the cluster mass function that originates from an individual molecular cloud is consistent with a Schechter function with a power-law slope of beta = -1.73 at 2 Myr and beta = -1.67 at 10 Myr, which fits to observed cluster mass function of the Carina region. The superposition of mass functions have a power-law slope of < -2, which fits the observed mass function of star clusters in the Milky Way, M31 and M83. We further find that the mass of the most massive cluster formed in a single molecular cloud with a mass of M_g scales with 6.1 M_g^0.51 which also agrees with recent observation in M51. The molecular clouds which can form massive clusters are much denser than those typical in the Milky Way. The velocity dispersion of such molecular clouds reaches 20 km/s and it is consistent with the relative velocity of the molecular clouds observed near NGC 3603 and Westerlund 2, for which a triggered star formation by cloud-cloud collisions is suggested.

Bond breaking in epoxy systems: A combined QM/MM approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barr, Stephen A.; Ecker, Allison M.; Berry, Rajiv J., E-mail: Rajiv.Berry@us.af.mil

2016-06-28

A novel method to combine quantum mechanics (QM) and molecular mechanics has been developed to accurately and efficiently account for covalent bond breaking in polymer systems under high strain without the use of predetermined break locations. Use of this method will provide a better fundamental understanding of the mechano-chemical origins of fracture in thermosets. Since classical force fields cannot accurately account for bond breaking, and QM is too demanding to simulate large systems, a hybrid approach is required. In the method presented here, strain is applied to the system using a classical force field, and all bond lengths are monitored.more » When a bond is stretched past a threshold value, a zone surrounding the bond is used in a QM energy minimization to determine which, if any, bonds break. The QM results are then used to reconstitute the system to continue the classical simulation at progressively larger strain until another QM calculation is triggered. In this way, a QM calculation is only computed when and where needed, allowing for efficient simulations. A robust QM method for energy minimization has been determined, as well as appropriate values for the QM zone size and the threshold bond length. Compute times do not differ dramatically from classical molecular mechanical simulations.« less

Mesoscale energy deposition footprint model for kiloelectronvolt cluster bombardment of solids.

PubMed

Russo, Michael F; Garrison, Barbara J

2006-10-15

Molecular dynamics simulations have been performed to model 5-keV C60 and Au3 projectile bombardment of an amorphous water substrate. The goal is to obtain detailed insights into the dynamics of motion in order to develop a straightforward and less computationally demanding model of the process of ejection. The molecular dynamics results provide the basis for the mesoscale energy deposition footprint model. This model provides a method for predicting relative yields based on information from less than 1 ps of simulation time.

Exploring Hamiltonian dielectric solvent molecular dynamics

NASA Astrophysics Data System (ADS)

Bauer, Sebastian; Tavan, Paul; Mathias, Gerald

2014-09-01

Hamiltonian dielectric solvent (HADES) is a recent method [7,25], which enables Hamiltonian molecular dynamics (MD) simulations of peptides and proteins in dielectric continua. Sample simulations of an α-helical decapeptide with and without explicit solvent demonstrate the high efficiency of HADES-MD. Addressing the folding of this peptide by replica exchange MD we study the properties of HADES by comparing melting curves, secondary structure motifs and salt bridges with explicit solvent results. Despite the unoptimized ad hoc parametrization of HADES, calculated reaction field energies correlate well with numerical grid solutions of the dielectric Poisson equation.

Sensitivity Analysis and Uncertainty Quantification for the LAMMPS Molecular Dynamics Simulation Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Picard, Richard Roy; Bhat, Kabekode Ghanasham

2017-07-18

We examine sensitivity analysis and uncertainty quantification for molecular dynamics simulation. Extreme (large or small) output values for the LAMMPS code often occur at the boundaries of input regions, and uncertainties in those boundary values are overlooked by common SA methods. Similarly, input values for which code outputs are consistent with calibration data can also occur near boundaries. Upon applying approaches in the literature for imprecise probabilities (IPs), much more realistic results are obtained than for the complacent application of standard SA and code calibration.

Prediction of solubility parameters and miscibility of pharmaceutical compounds by molecular dynamics simulations.

PubMed

Gupta, Jasmine; Nunes, Cletus; Vyas, Shyam; Jonnalagadda, Sriramakamal

2011-03-10

The objectives of this study were (i) to develop a computational model based on molecular dynamics technique to predict the miscibility of indomethacin in carriers (polyethylene oxide, glucose, and sucrose) and (ii) to experimentally verify the in silico predictions by characterizing the drug-carrier mixtures using thermoanalytical techniques. Molecular dynamics (MD) simulations were performed using the COMPASS force field, and the cohesive energy density and the solubility parameters were determined for the model compounds. The magnitude of difference in the solubility parameters of drug and carrier is indicative of their miscibility. The MD simulations predicted indomethacin to be miscible with polyethylene oxide and to be borderline miscible with sucrose and immiscible with glucose. The solubility parameter values obtained using the MD simulations values were in reasonable agreement with those calculated using group contribution methods. Differential scanning calorimetry showed melting point depression of polyethylene oxide with increasing levels of indomethacin accompanied by peak broadening, confirming miscibility. In contrast, thermal analysis of blends of indomethacin with sucrose and glucose verified general immiscibility. The findings demonstrate that molecular modeling is a powerful technique for determining the solubility parameters and predicting miscibility of pharmaceutical compounds. © 2011 American Chemical Society

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

PubMed

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.

Molecular Docking Simulation of Neuraminidase Influenza A Subtype H1N1 with Potential Inhibitor of Disulfide Cyclic Peptide (DNY, NNY, LRL)

NASA Astrophysics Data System (ADS)

Putra, R. P.; Imaniastuti, R.; Nasution, M. A. F.; Kerami, Djati; Tambunan, U. S. F.

2018-04-01

Oseltamivir resistance as an inhibitor of neuraminidase influenza A virus subtype H1N1 has been reported lately. Therefore, to solve this problem, several kinds of research has been conducted to design and discover disulfide cyclic peptide ligands through molecular docking method, to find the potential inhibitors for neuraminidase H1N1 which then can disturb the virus replication. This research was studied and evaluated the interaction of ligands toward enzyme using molecular docking simulation, which was performed on three disulfide cyclic peptide inhibitors (DNY, LRL, and NNT), along with oseltamivir and zanamivir as the standard ligands using MOE 2008.10 software. The docking simulation shows that all disulfide cyclic peptide ligands have lower Gibbs free binding energies (ΔGbinding) than the standard ligands, with DNY ligand has the lowest ΔGbinding at -7.8544 kcal/mol. Furthermore, these ligands were also had better molecular interactions with neuraminidase than the standards, owing by the hydrogen bonds that were formed during the docking simulation. In the end, we concluded that DNY, LRL and NNT ligands have the potential to be developed as the inhibitor of neuraminidase H1N1.

Atomistic Monte Carlo Simulation of Lipid Membranes

PubMed Central

Wüstner, Daniel; Sklenar, Heinz

2014-01-01

Biological membranes are complex assemblies of many different molecules of which analysis demands a variety of experimental and computational approaches. In this article, we explain challenges and advantages of atomistic Monte Carlo (MC) simulation of lipid membranes. We provide an introduction into the various move sets that are implemented in current MC methods for efficient conformational sampling of lipids and other molecules. In the second part, we demonstrate for a concrete example, how an atomistic local-move set can be implemented for MC simulations of phospholipid monomers and bilayer patches. We use our recently devised chain breakage/closure (CBC) local move set in the bond-/torsion angle space with the constant-bond-length approximation (CBLA) for the phospholipid dipalmitoylphosphatidylcholine (DPPC). We demonstrate rapid conformational equilibration for a single DPPC molecule, as assessed by calculation of molecular energies and entropies. We also show transition from a crystalline-like to a fluid DPPC bilayer by the CBC local-move MC method, as indicated by the electron density profile, head group orientation, area per lipid, and whole-lipid displacements. We discuss the potential of local-move MC methods in combination with molecular dynamics simulations, for example, for studying multi-component lipid membranes containing cholesterol. PMID:24469314

Direct Quantum Dynamics Using Grid-Based Wave Function Propagation and Machine-Learned Potential Energy Surfaces.

PubMed

Richings, Gareth W; Habershon, Scott

2017-09-12

We describe a method for performing nuclear quantum dynamics calculations using standard, grid-based algorithms, including the multiconfiguration time-dependent Hartree (MCTDH) method, where the potential energy surface (PES) is calculated "on-the-fly". The method of Gaussian process regression (GPR) is used to construct a global representation of the PES using values of the energy at points distributed in molecular configuration space during the course of the wavepacket propagation. We demonstrate this direct dynamics approach for both an analytical PES function describing 3-dimensional proton transfer dynamics in malonaldehyde and for 2- and 6-dimensional quantum dynamics simulations of proton transfer in salicylaldimine. In the case of salicylaldimine we also perform calculations in which the PES is constructed using Hartree-Fock calculations through an interface to an ab initio electronic structure code. In all cases, the results of the quantum dynamics simulations are in excellent agreement with previous simulations of both systems yet do not require prior fitting of a PES at any stage. Our approach (implemented in a development version of the Quantics package) opens a route to performing accurate quantum dynamics simulations via wave function propagation of many-dimensional molecular systems in a direct and efficient manner.

An Introduction to Computational Physics

NASA Astrophysics Data System (ADS)

Pang, Tao

2010-07-01

Preface to first edition; Preface; Acknowledgements; 1. Introduction; 2. Approximation of a function; 3. Numerical calculus; 4. Ordinary differential equations; 5. Numerical methods for matrices; 6. Spectral analysis; 7. Partial differential equations; 8. Molecular dynamics simulations; 9. Modeling continuous systems; 10. Monte Carlo simulations; 11. Genetic algorithm and programming; 12. Numerical renormalization; References; Index.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biyikli, Emre; To, Albert C., E-mail: albertto@pitt.edu

Atomistic/continuum coupling methods combine accurate atomistic methods and efficient continuum methods to simulate the behavior of highly ordered crystalline systems. Coupled methods utilize the advantages of both approaches to simulate systems at a lower computational cost, while retaining the accuracy associated with atomistic methods. Many concurrent atomistic/continuum coupling methods have been proposed in the past; however, their true computational efficiency has not been demonstrated. The present work presents an efficient implementation of a concurrent coupling method called the Multiresolution Molecular Mechanics (MMM) for serial, parallel, and adaptive analysis. First, we present the features of the software implemented along with themore » associated technologies. The scalability of the software implementation is demonstrated, and the competing effects of multiscale modeling and parallelization are discussed. Then, the algorithms contributing to the efficiency of the software are presented. These include algorithms for eliminating latent ghost atoms from calculations and measurement-based dynamic balancing of parallel workload. The efficiency improvements made by these algorithms are demonstrated by benchmark tests. The efficiency of the software is found to be on par with LAMMPS, a state-of-the-art Molecular Dynamics (MD) simulation code, when performing full atomistic simulations. Speed-up of the MMM method is shown to be directly proportional to the reduction of the number of the atoms visited in force computation. Finally, an adaptive MMM analysis on a nanoindentation problem, containing over a million atoms, is performed, yielding an improvement of 6.3–8.5 times in efficiency, over the full atomistic MD method. For the first time, the efficiency of a concurrent atomistic/continuum coupling method is comprehensively investigated and demonstrated.« less

Communication: Multiple atomistic force fields in a single enhanced sampling simulation

NASA Astrophysics Data System (ADS)

Hoang Viet, Man; Derreumaux, Philippe; Nguyen, Phuong H.

2015-07-01

The main concerns of biomolecular dynamics simulations are the convergence of the conformational sampling and the dependence of the results on the force fields. While the first issue can be addressed by employing enhanced sampling techniques such as simulated tempering or replica exchange molecular dynamics, repeating these simulations with different force fields is very time consuming. Here, we propose an automatic method that includes different force fields into a single advanced sampling simulation. Conformational sampling using three all-atom force fields is enhanced by simulated tempering and by formulating the weight parameters of the simulated tempering method in terms of the energy fluctuations, the system is able to perform random walk in both temperature and force field spaces. The method is first demonstrated on a 1D system and then validated by the folding of the 10-residue chignolin peptide in explicit water.

SLTCAP: A Simple Method for Calculating the Number of Ions Needed for MD Simulation.

PubMed

Schmit, Jeremy D; Kariyawasam, Nilusha L; Needham, Vince; Smith, Paul E

2018-04-10

An accurate depiction of electrostatic interactions in molecular dynamics requires the correct number of ions in the simulation box to capture screening effects. However, the number of ions that should be added to the box is seldom given by the bulk salt concentration because a charged biomolecule solute will perturb the local solvent environment. We present a simple method for calculating the number of ions that requires only the total solute charge, solvent volume, and bulk salt concentration as inputs. We show that the most commonly used method for adding salt to a simulation results in an effective salt concentration that is too high. These findings are confirmed using simulations of lysozyme. We have established a web server where these calculations can be readily performed to aid simulation setup.

Computer Simulations of Intrinsically Disordered Proteins

NASA Astrophysics Data System (ADS)

Chong, Song-Ho; Chatterjee, Prathit; Ham, Sihyun

2017-05-01

The investigation of intrinsically disordered proteins (IDPs) is a new frontier in structural and molecular biology that requires a new paradigm to connect structural disorder to function. Molecular dynamics simulations and statistical thermodynamics potentially offer ideal tools for atomic-level characterizations and thermodynamic descriptions of this fascinating class of proteins that will complement experimental studies. However, IDPs display sensitivity to inaccuracies in the underlying molecular mechanics force fields. Thus, achieving an accurate structural characterization of IDPs via simulations is a challenge. It is also daunting to perform a configuration-space integration over heterogeneous structural ensembles sampled by IDPs to extract, in particular, protein configurational entropy. In this review, we summarize recent efforts devoted to the development of force fields and the critical evaluations of their performance when applied to IDPs. We also survey recent advances in computational methods for protein configurational entropy that aim to provide a thermodynamic link between structural disorder and protein activity.

Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes revealed by molecular simulations

PubMed Central

Tan, Cheng; Takada, Shoji

2017-01-01

While nucleosome positioning on eukaryotic genome play important roles for genetic regulation, molecular mechanisms of nucleosome positioning and sliding along DNA are not well understood. Here we investigated thermally-activated spontaneous nucleosome sliding mechanisms developing and applying a coarse-grained molecular simulation method that incorporates both long-range electrostatic and short-range hydrogen-bond interactions between histone octamer and DNA. The simulations revealed two distinct sliding modes depending on the nucleosomal DNA sequence. A uniform DNA sequence showed frequent sliding with one base pair step in a rotation-coupled manner, akin to screw-like motions. On the contrary, a strong positioning sequence, the so-called 601 sequence, exhibits rare, abrupt transitions of five and ten base pair steps without rotation. Moreover, we evaluated the importance of hydrogen bond interactions on the sliding mode, finding that strong and weak bonds favor respectively the rotation-coupled and -uncoupled sliding movements. PMID:29194442

Ultrafast fragmentation dynamics of triply charged carbon dioxide: Vibrational-mode-dependent molecular bond breakage

NASA Astrophysics Data System (ADS)

Yang, HongJiang; Wang, Enliang; Dong, WenXiu; Gong, Maomao; Shen, Zhenjie; Tang, Yaguo; Shan, Xu; Chen, Xiangjun

2018-05-01

The a b i n i t i o molecular dynamics (MD) simulations using an atom-centered density matrix propagation method have been carried out to investigate the fragmentation of the ground-state triply charged carbon dioxide, CO23 +→C+ + Oa+ + Ob+ . Ten thousands of trajectories have been simulated. By analyzing the momentum correlation of the final fragments, it is demonstrated that the sequential fragmentation dominates in the three-body dissociation, consistent with our experimental observations which were performed by electron collision at impact energy of 1500 eV. Furthermore, the MD simulations allow us to have detailed insight into the ultrafast evolution of the molecular bond breakage at a very early stage, within several tens of femtoseconds, and the result shows that the initial nuclear vibrational mode plays a decisive role in switching the dissociation pathways.

Kinetics from Replica Exchange Molecular Dynamics Simulations.

PubMed

Stelzl, Lukas S; Hummer, Gerhard

2017-08-08

Transitions between metastable states govern many fundamental processes in physics, chemistry and biology, from nucleation events in phase transitions to the folding of proteins. The free energy surfaces underlying these processes can be obtained from simulations using enhanced sampling methods. However, their altered dynamics makes kinetic and mechanistic information difficult or impossible to extract. Here, we show that, with replica exchange molecular dynamics (REMD), one can not only sample equilibrium properties but also extract kinetic information. For systems that strictly obey first-order kinetics, the procedure to extract rates is rigorous. For actual molecular systems whose long-time dynamics are captured by kinetic rate models, accurate rate coefficients can be determined from the statistics of the transitions between the metastable states at each replica temperature. We demonstrate the practical applicability of the procedure by constructing master equation (Markov state) models of peptide and RNA folding from REMD simulations.

Tube Visualization and Properties from Isoconfigurational Averaging

NASA Astrophysics Data System (ADS)

Qin, Jian; Bisbee, Windsor; Milner, Scott

2012-02-01

We introduce a simulation method to visualize the confining tube in polymer melts and measure its properties. We studied bead-spring ring polymers, which conveniently suppresses constraint release and contour length fluctuations. We allow molecules to cross and reach topologically equilibrated states by invoking various molecular rebridging moves in Monte Carlo simulations. To reveal the confining tube, we start with a well equilibrated configuration, turn off rebridging moves, and run molecular dynamics simulation multiple times, each with different initial velocities. The resulting set of ``movies'' of molecular trajectories defines an isoconfigurational ensemble, with the bead positions at different times and in different ``movies'' giving rise to a cloud. The cloud shows the shape, range and strength of the tube confinement, which enables us to study the statistical properties of tube. Using this approach, we studied the effects of free surface, and found that the tube diameter near the surface is greater than the bulk value by about 25%.

Communication: Quantum molecular dynamics simulation of liquid para-hydrogen by nuclear and electron wave packet approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hyeon-Deuk, Kim, E-mail: kim@kuchem.kyoto-u.ac.jp; Japan Science and Technology Agency, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012; Ando, Koji

2014-05-07

Liquid para-hydrogen (p-H{sub 2}) is a typical quantum liquid which exhibits strong nuclear quantum effects (NQEs) and thus anomalous static and dynamic properties. We propose a real-time simulation method of wave packet (WP) molecular dynamics (MD) based on non-empirical intra- and inter-molecular interactions of non-spherical hydrogen molecules, and apply it to condensed-phase p-H{sub 2}. The NQEs, such as WP delocalization and zero-point energy, are taken into account without perturbative expansion of prepared model potential functions but with explicit interactions between nuclear and electron WPs. The developed MD simulation for 100 ps with 1200 hydrogen molecules is realized at feasible computationalmore » cost, by which basic experimental properties of p-H{sub 2} liquid such as radial distribution functions, self-diffusion coefficients, and shear viscosities are all well reproduced.« less

Vibrational cross-angles in condensed molecules: a structural tool.

PubMed

Chen, Hailong; Zhang, Yufan; Li, Jiebo; Liu, Hongjun; Jiang, De-En; Zheng, Junrong

2013-09-05

The fluctuations of three-dimensional molecular conformations of a molecule in different environments play critical roles in many important chemical and biological processes. X-ray diffraction (XRD) techniques and nuclear magnetic resonance (NMR) methods are routinely applied to monitor the molecular conformations in condensed phases. However, some special requirements of the methods have prevented them from exploring many molecular phenomena at the current stage. Here, we introduce another method to resolve molecular conformations based on an ultrafast MIR/T-Hz multiple-dimensional vibrational spectroscopic technique. The model molecule (4'-methyl-2'-nitroacetanilide, MNA) is prepared in two of its crystalline forms and liquid samples. Two polarized ultrafast infrared pulses are then used to determine the cross-angles of vibrational transition moment directions by exciting one vibrational band and detecting the induced response on another vibrational band of the molecule. The vibrational cross-angles are then converted into molecular conformations with the aid of calculations. The molecular conformations determined by the method are supported by X-ray diffraction and molecular dynamics simulation results. The experimental results suggest that thermodynamic interactions with solvent molecules are not altering the molecular conformations of MNA in the solutions to control their ultimate conformations in the crystals.

ReaxFF based molecular dynamics simulations of ignition front propagation in hydrocarbon/oxygen mixtures under high temperature and pressure conditions.

PubMed

Ashraf, Chowdhury; Jain, Abhishek; Xuan, Yuan; van Duin, Adri C T

2017-02-15

In this paper, we present the first atomistic-scale based method for calculating ignition front propagation speed and hypothesize that this quantity is related to laminar flame speed. This method is based on atomistic-level molecular dynamics (MD) simulations with the ReaxFF reactive force field. Results reported in this study are for supercritical (P = 55 MPa and T u = 1800 K) combustion of hydrocarbons as elevated pressure and temperature are required to accelerate the dynamics for reactive MD simulations. These simulations are performed for different types of hydrocarbons, including alkyne, alkane, and aromatic, and are able to successfully reproduce the experimental trend of reactivity of these hydrocarbons. Moreover, our results indicate that the ignition front propagation speed under supercritical conditions has a strong dependence on equivalence ratio, similar to experimentally measured flame speeds at lower temperatures and pressures which supports our hypothesis that ignition front speed is a related quantity to laminar flame speed. In addition, comparisons between results obtained from ReaxFF simulation and continuum simulations performed under similar conditions show good qualitative, and reasonable quantitative agreement. This demonstrates that ReaxFF based MD-simulations are a promising tool to study flame speed/ignition front speed in supercritical hydrocarbon combustion.

Method for construction of a biased potential for hyperdynamic simulation of atomic systems

NASA Astrophysics Data System (ADS)

Duda, E. V.; Kornich, G. V.

2017-10-01

An approach to constructing a biased potential for hyperdynamic simulation of atomic systems is considered. Using this approach, the diffusion of an atom adsorbed on the surface of a two-dimensional crystal and a vacancy in the bulk of the crystal are simulated. The influence of the variation in the potential barriers due to thermal vibrations of atoms on the results of calculations is discussed. It is shown that the bias of the potential in the hyperdynamic simulation makes it possible to obtain statistical samples of transitions of atomic systems between states, similar to those given by classical molecular dynamics. However, hyperdynamics significantly accelerates computations in comparison with molecular dynamics in the case of temperature-activated transitions and the associated processes in atomic systems.

Surface-Tension Replica-Exchange Molecular Dynamics Method for Enhanced Sampling of Biological Membrane Systems.

PubMed

Mori, Takaharu; Jung, Jaewoon; Sugita, Yuji

2013-12-10

Conformational sampling is fundamentally important for simulating complex biomolecular systems. The generalized-ensemble algorithm, especially the temperature replica-exchange molecular dynamics method (T-REMD), is one of the most powerful methods to explore structures of biomolecules such as proteins, nucleic acids, carbohydrates, and also of lipid membranes. T-REMD simulations have focused on soluble proteins rather than membrane proteins or lipid bilayers, because explicit membranes do not keep their structural integrity at high temperature. Here, we propose a new generalized-ensemble algorithm for membrane systems, which we call the surface-tension REMD method. Each replica is simulated in the NPγT ensemble, and surface tensions in a pair of replicas are exchanged at certain intervals to enhance conformational sampling of the target membrane system. We test the method on two biological membrane systems: a fully hydrated DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine) lipid bilayer and a WALP23-POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) membrane system. During these simulations, a random walk in surface tension space is realized. Large-scale lateral deformation (shrinking and stretching) of the membranes takes place in all of the replicas without collapse of the lipid bilayer structure. There is accelerated lateral diffusion of DPPC lipid molecules compared with conventional MD simulation, and a much wider range of tilt angle of the WALP23 peptide is sampled due to large deformation of the POPC lipid bilayer and through peptide-lipid interactions. Our method could be applicable to a wide variety of biological membrane systems.

Charge-leveling and proper treatment of long-range electrostatics in all-atom molecular dynamics at constant pH.

PubMed

Wallace, Jason A; Shen, Jana K

2012-11-14

Recent development of constant pH molecular dynamics (CpHMD) methods has offered promise for adding pH-stat in molecular dynamics simulations. However, until now the working pH molecular dynamics (pHMD) implementations are dependent in part or whole on implicit-solvent models. Here we show that proper treatment of long-range electrostatics and maintaining charge neutrality of the system are critical for extending the continuous pHMD framework to the all-atom representation. The former is achieved here by adding forces to titration coordinates due to long-range electrostatics based on the generalized reaction field method, while the latter is made possible by a charge-leveling technique that couples proton titration with simultaneous ionization or neutralization of a co-ion in solution. We test the new method using the pH-replica-exchange CpHMD simulations of a series of aliphatic dicarboxylic acids with varying carbon chain length. The average absolute deviation from the experimental pK(a) values is merely 0.18 units. The results show that accounting for the forces due to extended electrostatics removes the large random noise in propagating titration coordinates, while maintaining charge neutrality of the system improves the accuracy in the calculated electrostatic interaction between ionizable sites. Thus, we believe that the way is paved for realizing pH-controlled all-atom molecular dynamics in the near future.

Charge-leveling and proper treatment of long-range electrostatics in all-atom molecular dynamics at constant pH

PubMed Central

Wallace, Jason A.; Shen, Jana K.

2012-01-01

Recent development of constant pH molecular dynamics (CpHMD) methods has offered promise for adding pH-stat in molecular dynamics simulations. However, until now the working pH molecular dynamics (pHMD) implementations are dependent in part or whole on implicit-solvent models. Here we show that proper treatment of long-range electrostatics and maintaining charge neutrality of the system are critical for extending the continuous pHMD framework to the all-atom representation. The former is achieved here by adding forces to titration coordinates due to long-range electrostatics based on the generalized reaction field method, while the latter is made possible by a charge-leveling technique that couples proton titration with simultaneous ionization or neutralization of a co-ion in solution. We test the new method using the pH-replica-exchange CpHMD simulations of a series of aliphatic dicarboxylic acids with varying carbon chain length. The average absolute deviation from the experimental pKa values is merely 0.18 units. The results show that accounting for the forces due to extended electrostatics removes the large random noise in propagating titration coordinates, while maintaining charge neutrality of the system improves the accuracy in the calculated electrostatic interaction between ionizable sites. Thus, we believe that the way is paved for realizing pH-controlled all-atom molecular dynamics in the near future. PMID:23163362

Application of principal component analysis in protein unfolding: an all-atom molecular dynamics simulation study.

PubMed

Das, Atanu; Mukhopadhyay, Chaitali

2007-10-28

We have performed molecular dynamics (MD) simulation of the thermal denaturation of one protein and one peptide-ubiquitin and melittin. To identify the correlation in dynamics among various secondary structural fragments and also the individual contribution of different residues towards thermal unfolding, principal component analysis method was applied in order to give a new insight to protein dynamics by analyzing the contribution of coefficients of principal components. The cross-correlation matrix obtained from MD simulation trajectory provided important information regarding the anisotropy of backbone dynamics that leads to unfolding. Unfolding of ubiquitin was found to be a three-state process, while that of melittin, though smaller and mostly helical, is more complicated.

Application of principal component analysis in protein unfolding: An all-atom molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Das, Atanu; Mukhopadhyay, Chaitali

2007-10-01

We have performed molecular dynamics (MD) simulation of the thermal denaturation of one protein and one peptide—ubiquitin and melittin. To identify the correlation in dynamics among various secondary structural fragments and also the individual contribution of different residues towards thermal unfolding, principal component analysis method was applied in order to give a new insight to protein dynamics by analyzing the contribution of coefficients of principal components. The cross-correlation matrix obtained from MD simulation trajectory provided important information regarding the anisotropy of backbone dynamics that leads to unfolding. Unfolding of ubiquitin was found to be a three-state process, while that of melittin, though smaller and mostly helical, is more complicated.

Selectivity trend of gas separation through nanoporous graphene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Hongjun; Chen, Zhongfang; Dai, Sheng

2014-01-29

We demonstrate that porous graphene can efficiently separate gases according to their molecular sizes using molecular dynamic (MD) simulations,. The flux sequence from the classical MD simulation is H 2>CO 2>>N 2>Ar>CH 4, which generally follows the trend in the kinetic diameters. Moreover, this trend is also confirmed from the fluxes based on the computed free energy barriers for gas permeation using the umbrella sampling method and kinetic theory of gases. Both brute-force MD simulations and free-energy calcualtions lead to the flux trend consistent with experiments. Case studies of two compositions of CO 2/N 2 mixtures further demonstrate the separationmore » capability of nanoporous graphene.« less

Molecular dynamic simulation for nanometric cutting of single-crystal face-centered cubic metals.

PubMed

Huang, Yanhua; Zong, Wenjun

2014-01-01

In this work, molecular dynamics simulations are performed to investigate the influence of material properties on the nanometric cutting of single crystal copper and aluminum with a diamond cutting tool. The atomic interactions in the two metallic materials are modeled by two sets of embedded atom method (EAM) potential parameters. Simulation results show that although the plastic deformation of the two materials is achieved by dislocation activities, the deformation behavior and related physical phenomena, such as the machining forces, machined surface quality, and chip morphology, are significantly different for different materials. Furthermore, the influence of material properties on the nanometric cutting has a strong dependence on the operating temperature.

A systematic petri net approach for multiple-scale modeling and simulation of biochemical processes.

PubMed

Chen, Ming; Hu, Minjie; Hofestädt, Ralf

2011-06-01

A method to exploit hybrid Petri nets for modeling and simulating biochemical processes in a systematic way was introduced. Both molecular biology and biochemical engineering aspects are manipulated. With discrete and continuous elements, the hybrid Petri nets can easily handle biochemical factors such as metabolites concentration and kinetic behaviors. It is possible to translate both molecular biological behavior and biochemical processes workflow into hybrid Petri nets in a natural manner. As an example, penicillin production bioprocess is modeled to illustrate the concepts of the methodology. Results of the dynamic of production parameters in the bioprocess were simulated and observed diagrammatically. Current problems and post-genomic perspectives were also discussed.

Molecular dynamics simulations on PGLa using NMR orientational constraints.

PubMed

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.

Identification of the hot spot residues for pyridine derivative inhibitor CCT251455 and ATP substrate binding on monopolar spindle 1 (MPS1) kinase by molecular dynamic simulation.

PubMed

Chen, Kai; Duan, Wenxiu; Han, Qianqian; Sun, Xuan; Li, Wenqian; Hu, Shuangyun; Wan, Jiajia; Wu, Jiang; Ge, Yushu; Liu, Dan

2018-03-08

Protein kinase monopolar spindle 1 plays an important role in spindle assembly checkpoint at the onset of mitosis. Over expression of MPS1 correlated with a wide range of human tumors makes it an attractive target for finding an effective and specific inhibitor. In this work, we performed molecular dynamics simulations of protein MPS1 itself as well as protein bound systems with the inhibitor and natural substrate based on crystal structures. The reported orally bioavailable 1 h-pyrrolo [3,2-c] pyridine inhibitors of MPS1 maintained stable binding in the catalytic site, while natural substrate ATP could not stay. Comparative study of stability and flexibility of three systems reveals position shifting of β-sheet region within the catalytic site, which indicates inhibition mechanism was through stabilizing the β-sheet region. Binding free energies calculated with MM-GB/PBSA method shows different binding affinity for inhibitor and ATP. Finally, interactions between protein and inhibitor during molecular dynamic simulations were measured and counted. Residue Gly605 and Leu654 were suggested as important hot spots for stable binding of inhibitor by molecular dynamic simulation. Our results reveal an important position shifting within catalytic site for non-inhibited proteins. Together with hot spots found by molecular dynamic simulation, the results provide important information of inhibition mechanism and will be referenced for designing novel inhibitors.

Accelerating Monte Carlo molecular simulations by reweighting and reconstructing Markov chains: Extrapolation of canonical ensemble averages and second derivatives to different temperature and density conditions

NASA Astrophysics Data System (ADS)

Kadoura, Ahmad; Sun, Shuyu; Salama, Amgad

2014-08-01

Accurate determination of thermodynamic properties of petroleum reservoir fluids is of great interest to many applications, especially in petroleum engineering and chemical engineering. Molecular simulation has many appealing features, especially its requirement of fewer tuned parameters but yet better predicting capability; however it is well known that molecular simulation is very CPU expensive, as compared to equation of state approaches. We have recently introduced an efficient thermodynamically consistent technique to regenerate rapidly Monte Carlo Markov Chains (MCMCs) at different thermodynamic conditions from the existing data points that have been pre-computed with expensive classical simulation. This technique can speed up the simulation more than a million times, making the regenerated molecular simulation almost as fast as equation of state approaches. In this paper, this technique is first briefly reviewed and then numerically investigated in its capability of predicting ensemble averages of primary quantities at different neighboring thermodynamic conditions to the original simulated MCMCs. Moreover, this extrapolation technique is extended to predict second derivative properties (e.g. heat capacity and fluid compressibility). The method works by reweighting and reconstructing generated MCMCs in canonical ensemble for Lennard-Jones particles. In this paper, system's potential energy, pressure, isochoric heat capacity and isothermal compressibility along isochors, isotherms and paths of changing temperature and density from the original simulated points were extrapolated. Finally, an optimized set of Lennard-Jones parameters (ε, σ) for single site models were proposed for methane, nitrogen and carbon monoxide.

A method of solid-solid phase equilibrium calculation by molecular dynamics

NASA Astrophysics Data System (ADS)

Karavaev, A. V.; Dremov, V. V.

2016-12-01

A method for evaluation of solid-solid phase equilibrium curves in molecular dynamics simulation for a given model of interatomic interaction is proposed. The method allows to calculate entropies of crystal phases and provides an accuracy comparable with that of the thermodynamic integration method by Frenkel and Ladd while it is much simpler in realization and less intense computationally. The accuracy of the proposed method was demonstrated in MD calculations of entropies for EAM potential for iron and for MEAM potential for beryllium. The bcc-hcp equilibrium curves for iron calculated for the EAM potential by the thermodynamic integration method and by the proposed one agree quite well.

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

NASA Astrophysics Data System (ADS)

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.

Ab Initio Simulation Beryllium in Solid Molecular Hydrogen: Elastic Constant

NASA Astrophysics Data System (ADS)

Guerrero, Carlo L.; Perlado, Jose M.

2016-03-01

In systems of inertial confinement fusion targets Deuterium-Tritium are manufactured with a solid layer, it must have specific properties to increase the efficiency of ignition. Currently there have been some proposals to model the phases of hydrogen isotopes and hence their high pressure, but these works do not allow explaining some of the structures present at the solid phase change effect of increased pressure. By means of simulation with first principles methods and Quantum Molecular Dynamics, we compare the structural difference of solid molecular hydrogen pure and solid molecular hydrogen with beryllium, watching beryllium inclusion in solid hydrogen matrix, we obtain several differences in mechanical properties, in particular elastic constants. For C11 the difference between hydrogen and hydrogen with beryllium is 37.56%. This may produce a non-uniform initial compression and decreased efficiency of ignition.

Molecular simulation of the water-triolein-oleic acid mixture: Local structure and thermodynamic properties

NASA Astrophysics Data System (ADS)

Couallier, E.; Riaublanc, A.; David Briand, E.; Rousseau, B.

2018-05-01

An artificial oil-in-water emulsion analogous to those found in bioresources or food matrices is simulated and studied experimentally. It is composed of one of the major natural free fatty acids (the oleic acid, OA) and the corresponding triacylglyceride (trioleic glyceride, or triolein, GTO). Because of the large time and length scales involved, the molecular simulations are done with the Martini force field, a coarse-grained model. This allowed us to study the water-OA-GTO system at different compositions with more than 20 000 molecules and up to 2 μs. Interfacial tension was measured using the pendant drop method and compared with molecular simulation results. We observe very good agreement at high OA concentrations and deviations up to 15% at low OA concentrations. The water solubility in the lipid phase is in fair agreement with experiments, between 0.03 and 0.32 mol/l, rising with the OA content. The area occupied by OA and GTO at the interface between water and the pure product fitted with experimental data (AOA = 36.6 Å2 and AGTO = 152.1 Å2). The consistency between simulation and experimental results allowed a structural analysis of the interface. A bilayer structure of the lipids at the water/oil interface is proposed, containing preferentially oleic acid but also triolein. Through all these results, the usefulness of coarse-grained simulation for the description of water-oil interfacial organization is demonstrated. This method will be used later to bring local information on the organization of target compounds, necessary in biomass fractionation processes or food additive formulations, for example.

Using polarized Raman spectroscopy and the pseudospectral method to characterize molecular structure and function

NASA Astrophysics Data System (ADS)

Weisman, Andrew L.

Electronic structure calculation is an essential approach for determining the structure and function of molecules and is therefore of critical interest to physics, chemistry, and materials science. Of the various algorithms for calculating electronic structure, the pseudospectral method is among the fastest. However, the trade-off for its speed is more up-front programming and testing, and as a result, applications using the pseudospectral method currently lag behind those using other methods. In Part I of this dissertation, we first advance the pseudospectral method by optimizing it for an important application, polarized Raman spectroscopy, which is a well-established tool used to characterize molecular properties. This is an application of particular importance because often the easiest and most economical way to obtain the polarized Raman spectrum of a material is to simulate it; thus, utilization of the pseudospectral method for this purpose will accelerate progress in the determination of molecular properties. We demonstrate that our implementation of Raman spectroscopy using the pseudospectral method results in spectra that are just as accurate as those calculated using the traditional analytic method, and in the process, we derive the most comprehensive formulation to date of polarized Raman intensity formulas, applicable to both crystalline and isotropic systems. Next, we apply our implementation to determine the orientations of crystalline oligothiophenes -- a class of materials important in the field of organic electronics -- achieving excellent agreement with experiment and demonstrating the general utility of polarized Raman spectroscopy for the determination of crystal orientation. In addition, we derive from first-principles a method for using polarized Raman spectra to establish unambiguously whether a uniform region of a material is crystalline or isotropic. Finally, we introduce free, open-source software that allows a user to determine any of a number of polarized Raman properties of a sample given common output from electronic structure calculations. In Part II, we apply the pseudospectral method to other areas of scientific importance requiring a deeper understanding of molecular structure and function. First, we use it to accurately determine the frequencies of vibrational tags on biomolecules that can be detected in real-time using stimulated Raman spectroscopy. Next, we evaluate the performance of the pseudospectral method for calculating excited-state energies and energy gradients of large molecules -- another new application of the pseudospectral method -- showing that the calculations run much more quickly than those using the analytic method. Finally, we use the pseudospectral method to simulate the bottleneck process of a solar cell used for water splitting, a promising technology for converting the sun's energy into hydrogen fuel. We apply the speed of the pseudospectral method by modeling the relevant part of the system as a large, explicitly passivated titanium dioxide nanoparticle and simulating it realistically using hybrid density functional theory with an implicit solvent model, yielding insight into the physical nature of the rate-limiting step of water splitting. These results further validate the particularly fast and accurate simulation methodologies used, opening the door to efficient and realistic cluster-based, fully quantum-mechanical simulations of the bottleneck process of a promising technology for clean solar energy conversion. Taken together, we show how both polarized Raman spectroscopy and the pseudospectral method are effective tools for analyzing the structure and function of important molecular systems.

Kinetic Monte Carlo Method for Rule-based Modeling of Biochemical Networks

PubMed Central

Yang, Jin; Monine, Michael I.; Faeder, James R.; Hlavacek, William S.

2009-01-01

We present a kinetic Monte Carlo method for simulating chemical transformations specified by reaction rules, which can be viewed as generators of chemical reactions, or equivalently, definitions of reaction classes. A rule identifies the molecular components involved in a transformation, how these components change, conditions that affect whether a transformation occurs, and a rate law. The computational cost of the method, unlike conventional simulation approaches, is independent of the number of possible reactions, which need not be specified in advance or explicitly generated in a simulation. To demonstrate the method, we apply it to study the kinetics of multivalent ligand-receptor interactions. We expect the method will be useful for studying cellular signaling systems and other physical systems involving aggregation phenomena. PMID:18851068

Continuum description of solvent dielectrics in molecular-dynamics simulations of proteins

NASA Astrophysics Data System (ADS)

Egwolf, Bernhard; Tavan, Paul

2003-02-01

We present a continuum approach for efficient and accurate calculation of reaction field forces and energies in classical molecular-dynamics (MD) simulations of proteins in water. The derivation proceeds in two steps. First, we reformulate the electrostatics of an arbitrarily shaped molecular system, which contains partially charged atoms and is embedded in a dielectric continuum representing the water. A so-called fuzzy partition is used to exactly decompose the system into partial atomic volumes. The reaction field is expressed by means of dipole densities localized at the atoms. Since these densities cannot be calculated analytically for general systems, we introduce and carefully analyze a set of approximations in a second step. These approximations allow us to represent the dipole densities by simple dipoles localized at the atoms. We derive a system of linear equations for these dipoles, which can be solved numerically by iteration. After determining the two free parameters of our approximate method we check its quality by comparisons (i) with an analytical solution, which is available for a perfectly spherical system, (ii) with forces obtained from a MD simulation of a soluble protein in water, and (iii) with reaction field energies of small molecules calculated by a finite difference method.

Combined quantum mechanics and molecular mechanics simulation of Ca2+/ammonia solution based on the ONIOM-XS method: Octahedral coordination and implication to biology

NASA Astrophysics Data System (ADS)

Kerdcharoen, Teerakiat; Morokuma, Keiji

2003-05-01

An extension of the ONIOM (Own N-layered Integrated molecular Orbital and molecular Mechanics) method [M. Svensson, S. Humbel, R. D. J. Froese, T. Mutsubara, S. Sieber, and K. Morokuma, J. Phys. Chem. 100, 19357 (1996)] for simulation in the condensed phase, called ONIOM-XS (XS=eXtension to Solvation) [T. Kerdcharoen and K. Morokuma, Chem. Phys. Lett. 355, 257 (2002)], was applied to investigate the coordination of Ca2+ in liquid ammonia. A coordination number of 6 is found. Previous simulations based on pair potential or pair potential plus three-body correction gave values of 9 and 8.2, respectively. The new value is the same as the coordination number most frequently listed in the Cambridge Structural Database (CSD) and Protein Data Bank (PDB). N-Ca-N angular distribution reveals a near-octahedral coordination structure. Inclusion of many-body interactions (which amounts to 25% of the pair interactions) into the potential energy surface is essential for obtaining reasonable coordination number. Analyses of the metal coordination in water, water-ammonia mixture, and in proteins reveals that cation/ammonia solution can be used to approximate the coordination environment in proteins.

Molecular Dynamics Simulations of Hydration Effects on Solvation, Diffusivity, and Permeability in Chitosan/Chitin Films.

PubMed

McDonnell, Marshall T; Greeley, Duncan A; Kit, Kevin M; Keffer, David J

2016-09-01

The effects of hydration on the solvation, diffusivity, solubility, and permeability of oxygen molecules in sustainable, biodegradable chitosan/chitin food packaging films were studied via molecular dynamics and confined random walk simulations. With increasing hydration, the membrane has a more homogeneous water distribution with the polymer chains being fully solvated. The diffusivity increased by a factor of 4 for oxygen molecules and by an order of magnitude for water with increasing the humidity. To calculate the Henry's constant and solubility of oxygen in the membranes with changing hydration, the excess chemical potential was calculated via free energy perturbation, thermodynamic integration and direct particle deletion methods. The simulations predicted a higher solubility and permeability for the lower humidity, in contradiction to experimental results. All three methods for calculating the solubility were in good agreement. It was found that the Coulombic interactions in the potential caused the oxygen to bind too strongly to the protonated amine group. Insight from this work will help guide molecular modeling of chitosan/chitin membranes, specifically permeability measurements for small solute molecules. Efforts to chemically tailor chitosan/chitin membranes to favor discrete as opposed to continuous aqueous domains could reduce oxygen permeability.

Insights into the functional role of protonation states in the HIV-1 protease-BEA369 complex: molecular dynamics simulations and free energy calculations.

PubMed

Chen, Jianzhong; Yang, Maoyou; Hu, Guodong; Shi, Shuhua; Yi, Changhong; Zhang, Qinggang

2009-10-01

The molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method combined with molecular dynamics (MD) simulations were used to investigate the functional role of protonation in human immunodeficiency virus type 1 (HIV-1) protease complexed with the inhibitor BEA369. Our results demonstrate that protonation of two aspartic acids (Asp25/Asp25') has a strong influence on the dynamics behavior of the complex, the binding free energy of BEA369, and inhibitor-residue interactions. Relative binding free energies calculated using the MM-PBSA method show that protonation of Asp25 results in the strongest binding of BEA369 to HIV-1 protease. Inhibitor-residue interactions computed by the theory of free energy decomposition also indicate that protonation of Asp25 has the most favorable effect on binding of BEA369. In addition, hydrogen-bond analysis based on the trajectories of the MD simulations shows that protonation of Asp25 strongly influences the water-mediated link of a conserved water molecule, Wat301. We expect that the results of this study will contribute significantly to binding calculations for BEA369, and to the design of high affinity inhibitors.

Finding the best density functional approximation to describe interaction energies and structures of ionic liquids in molecular dynamics studies

NASA Astrophysics Data System (ADS)

Perlt, Eva; Ray, Promit; Hansen, Andreas; Malberg, Friedrich; Grimme, Stefan; Kirchner, Barbara

2018-05-01

Ionic liquids raise interesting but complicated questions for theoretical investigations due to the fact that a number of different inter-molecular interactions, e.g., hydrogen bonding, long-range Coulomb interactions, and dispersion interactions, need to be described properly. Here, we present a detailed study on the ionic liquids ethylammonium nitrate and 1-ethyl-3-methylimidazolium acetate, in which we compare different dispersion corrected density functional approximations to accurate local coupled cluster data in static calculations on ionic liquid clusters. The efficient new composite method B97-3c is tested and has been implemented in CP2K for future studies. Furthermore, tight-binding based approaches which may be used in large scale simulations are assessed. Subsequently, ab initio as well as classical molecular dynamics simulations are conducted and structural analyses are presented in order to shed light on the different short- and long-range structural patterns depending on the method and the system size considered in the simulation. Our results indicate the presence of strong hydrogen bonds in ionic liquids as well as the aggregation of alkyl side chains due to dispersion interactions.

Hydrogen-vacancy-dislocation interactions in α-Fe

NASA Astrophysics Data System (ADS)

Tehranchi, A.; Zhang, X.; Lu, G.; Curtin, W. A.

2017-02-01

Atomistic simulations of the interactions between dislocations, hydrogen atoms, and vacancies are studied to assess the viability of a recently proposed mechanism for the formation of nanoscale voids in Fe-based steels in the presence of hydrogen. Quantum-mechanics/molecular-mechanics method calculations confirm molecular statics simulations based on embedded atom method (EAM) potential showing that individual vacancies on the compressive side of an edge dislocation can be transported with the dislocation as it glides. Molecular dynamics simulations based on EAM potential then show, however, that vacancy clusters in the glide plane of an approaching dislocation are annihilated or reduced in size by the creation of a double-jog/climb process that is driven by the huge reduction in energy accompanying vacancy annihilation. The effectiveness of annihilation/reduction processes is not reduced by the presence of hydrogen in the vacancy clusters because typical V-H cluster binding energies are much lower than the vacancy formation energy, except at very high hydrogen content in the cluster. Analysis of a range of configurations indicates that hydrogen plays no special role in stabilizing nanovoids against jog formation processes that shrink voids. Experimental observations of nanovoids on the fracture surfaces of steels must be due to as-yet undetermined processes.

Insights from molecular dynamics simulations for computational protein design.

PubMed

Childers, Matthew Carter; Daggett, Valerie

2017-02-01

A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics. Here, we review how insights into protein dynamics derived from MD simulations have influenced the design of proteins. One of the greatest strengths of MD is its capacity to reveal information beyond what is available in the static structures deposited in the Protein Data Bank. In this regard simulations can be used to directly guide protein design by providing atomistic details of the dynamic molecular interactions contributing to protein stability and function. MD simulations can also be used as a virtual screening tool to rank, select, identify, and assess potential designs. MD is uniquely poised to inform protein design efforts where the application requires realistic models of protein dynamics and atomic level descriptions of the relationship between dynamics and function. Here, we review cases where MD simulations was used to modulate protein stability and protein function by providing information regarding the conformation(s), conformational transitions, interactions, and dynamics that govern stability and function. In addition, we discuss cases where conformations from protein folding/unfolding simulations have been exploited for protein design, yielding novel outcomes that could not be obtained from static structures.

Multiscale simulations of patchy particle systems combining Molecular Dynamics, Path Sampling and Green's Function Reaction Dynamics

NASA Astrophysics Data System (ADS)

Bolhuis, Peter

Important reaction-diffusion processes, such as biochemical networks in living cells, or self-assembling soft matter, span many orders in length and time scales. In these systems, the reactants' spatial dynamics at mesoscopic length and time scales of microns and seconds is coupled to the reactions between the molecules at microscopic length and time scales of nanometers and milliseconds. This wide range of length and time scales makes these systems notoriously difficult to simulate. While mean-field rate equations cannot describe such processes, the mesoscopic Green's Function Reaction Dynamics (GFRD) method enables efficient simulation at the particle level provided the microscopic dynamics can be integrated out. Yet, many processes exhibit non-trivial microscopic dynamics that can qualitatively change the macroscopic behavior, calling for an atomistic, microscopic description. The recently developed multiscale Molecular Dynamics Green's Function Reaction Dynamics (MD-GFRD) approach combines GFRD for simulating the system at the mesocopic scale where particles are far apart, with microscopic Molecular (or Brownian) Dynamics, for simulating the system at the microscopic scale where reactants are in close proximity. The association and dissociation of particles are treated with rare event path sampling techniques. I will illustrate the efficiency of this method for patchy particle systems. Replacing the microscopic regime with a Markov State Model avoids the microscopic regime completely. The MSM is then pre-computed using advanced path-sampling techniques such as multistate transition interface sampling. I illustrate this approach on patchy particle systems that show multiple modes of binding. MD-GFRD is generic, and can be used to efficiently simulate reaction-diffusion systems at the particle level, including the orientational dynamics, opening up the possibility for large-scale simulations of e.g. protein signaling networks.

Insights from molecular dynamics simulations for computational protein design

PubMed Central

Childers, Matthew Carter; Daggett, Valerie

2017-01-01

A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics. Here, we review how insights into protein dynamics derived from MD simulations have influenced the design of proteins. One of the greatest strengths of MD is its capacity to reveal information beyond what is available in the static structures deposited in the Protein Data Bank. In this regard simulations can be used to directly guide protein design by providing atomistic details of the dynamic molecular interactions contributing to protein stability and function. MD simulations can also be used as a virtual screening tool to rank, select, identify, and assess potential designs. MD is uniquely poised to inform protein design efforts where the application requires realistic models of protein dynamics and atomic level descriptions of the relationship between dynamics and function. Here, we review cases where MD simulations was used to modulate protein stability and protein function by providing information regarding the conformation(s), conformational transitions, interactions, and dynamics that govern stability and function. In addition, we discuss cases where conformations from protein folding/unfolding simulations have been exploited for protein design, yielding novel outcomes that could not be obtained from static structures. PMID:28239489

Predicting the equilibrium solubility of solid polycyclic aromatic hydrocarbons and dibenzothiophene using a combination of MOSCED plus molecular simulation or electronic structure calculations

NASA Astrophysics Data System (ADS)

Phifer, Jeremy R.; Cox, Courtney E.; da Silva, Larissa Ferreira; Nogueira, Gabriel Gonçalves; Barbosa, Ana Karolyne Pereira; Ley, Ryan T.; Bozada, Samantha M.; O'Loughlin, Elizabeth J.; Paluch, Andrew S.

2017-06-01

Methods to predict the equilibrium solubility of non-electrolyte solids are important for the design of novel separation processes. Here we demonstrate how conventional molecular simulation free energy calculations or electronic structure calculations in a continuum solvent, here SMD or SM8, can be used to predict parameters for the MOdified Separation of Cohesive Energy Density (MOSCED) method. The method is applied to the solutes naphthalene, anthracene, phenanthrene, pyrene and dibenzothiophene, compounds of interested to the petroleum industry and for environmental remediation. Adopting the melting point temperature and enthalpy of fusion of these compounds from experiment, we are able to predict equilibrium solubilities. Comparing to a total of 422 non-aqueous and 193 aqueous experimental solubilities, we find the proposed method is able to well correlate the data. The use of MOSCED is additionally advantageous as it is a solubility parameter-based method useful for intuitive solvent selection and formulation.

Liquid li structure and dynamics: A comparison between OFDFT and second nearest-neighbor embedded-atom method

DOE PAGES

Chen, Mohan; Vella, Joseph R.; Panagiotopoulos, Athanassios Z.; ...

2015-04-08

The structure and dynamics of liquid lithium are studied using two simulation methods: orbital-free (OF) first-principles molecular dynamics (MD), which employs OF density functional theory (DFT), and classical MD utilizing a second nearest-neighbor embedded-atom method potential. The properties we studied include the dynamic structure factor, the self-diffusion coefficient, the dispersion relation, the viscosity, and the bond angle distribution function. Our simulation results were compared to available experimental data when possible. Each method has distinct advantages and disadvantages. For example, OFDFT gives better agreement with experimental dynamic structure factors, yet is more computationally demanding than classical simulations. Classical simulations can accessmore » a broader temperature range and longer time scales. The combination of first-principles and classical simulations is a powerful tool for studying properties of liquid lithium.« less

On the statistical equivalence of restrained-ensemble simulations with the maximum entropy method

PubMed Central

Roux, Benoît; Weare, Jonathan

2013-01-01

An issue of general interest in computer simulations is to incorporate information from experiments into a structural model. An important caveat in pursuing this goal is to avoid corrupting the resulting model with spurious and arbitrary biases. While the problem of biasing thermodynamic ensembles can be formulated rigorously using the maximum entropy method introduced by Jaynes, the approach can be cumbersome in practical applications with the need to determine multiple unknown coefficients iteratively. A popular alternative strategy to incorporate the information from experiments is to rely on restrained-ensemble molecular dynamics simulations. However, the fundamental validity of this computational strategy remains in question. Here, it is demonstrated that the statistical distribution produced by restrained-ensemble simulations is formally consistent with the maximum entropy method of Jaynes. This clarifies the underlying conditions under which restrained-ensemble simulations will yield results that are consistent with the maximum entropy method. PMID:23464140