Comparative Investigation of Normal Modes and Molecular Dynamics of Hepatitis C NS5B Protein

NASA Astrophysics Data System (ADS)

Asafi, M. S.; Yildirim, A.; Tekpinar, M.

2016-04-01

Understanding dynamics of proteins has many practical implications in terms of finding a cure for many protein related diseases. Normal mode analysis and molecular dynamics methods are widely used physics-based computational methods for investigating dynamics of proteins. In this work, we studied dynamics of Hepatitis C NS5B protein with molecular dynamics and normal mode analysis. Principal components obtained from a 100 nanoseconds molecular dynamics simulation show good overlaps with normal modes calculated with a coarse-grained elastic network model. Coarse-grained normal mode analysis takes at least an order of magnitude shorter time. Encouraged by this good overlaps and short computation times, we analyzed further low frequency normal modes of Hepatitis C NS5B. Motion directions and average spatial fluctuations have been analyzed in detail. Finally, biological implications of these motions in drug design efforts against Hepatitis C infections have been elaborated.

Adaptively biased molecular dynamics for free energy calculations

NASA Astrophysics Data System (ADS)

Babin, Volodymyr; Roland, Christopher; Sagui, Celeste

2008-04-01

We present an adaptively biased molecular dynamics (ABMD) method for the computation of the free energy surface of a reaction coordinate using nonequilibrium dynamics. The ABMD method belongs to the general category of umbrella sampling methods with an evolving biasing potential and is inspired by the metadynamics method. The ABMD method has several useful features, including a small number of control parameters and an O(t ) numerical cost with molecular dynamics time t. The ABMD method naturally allows for extensions based on multiple walkers and replica exchange, where different replicas can have different temperatures and/or collective variables. This is beneficial not only in terms of the speed and accuracy of a calculation, but also in terms of the amount of useful information that may be obtained from a given simulation. The workings of the ABMD method are illustrated via a study of the folding of the Ace-GGPGGG-Nme peptide in a gaseous and solvated environment.

Shock waves simulated using the dual domain material point method combined with molecular dynamics

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

Zhang, Duan Z.; Dhakal, Tilak Raj

Here in this work we combine the dual domain material point method with molecular dynamics in an attempt to create a multiscale numerical method to simulate materials undergoing large deformations with high strain rates. In these types of problems, the material is often in a thermodynamically nonequilibrium state, and conventional constitutive relations or equations of state are often not available. In this method, the closure quantities, such as stress, at each material point are calculated from a molecular dynamics simulation of a group of atoms surrounding the material point. Rather than restricting the multiscale simulation in a small spatial region,more » such as phase interfaces, or crack tips, this multiscale method can be used to consider nonequilibrium thermodynamic effects in a macroscopic domain. This method takes the advantage that the material points only communicate with mesh nodes, not among themselves; therefore molecular dynamics simulations for material points can be performed independently in parallel. The dual domain material point method is chosen for this multiscale method because it can be used in history dependent problems with large deformation without generating numerical noise as material points move across cells, and also because of its convergence and conservation properties. In conclusion, to demonstrate the feasibility and accuracy of this method, we compare the results of a shock wave propagation in a cerium crystal calculated using the direct molecular dynamics simulation with the results from this combined multiscale calculation.« less

Shock waves simulated using the dual domain material point method combined with molecular dynamics

DOE PAGES

Zhang, Duan Z.; Dhakal, Tilak Raj

2017-01-17

Here in this work we combine the dual domain material point method with molecular dynamics in an attempt to create a multiscale numerical method to simulate materials undergoing large deformations with high strain rates. In these types of problems, the material is often in a thermodynamically nonequilibrium state, and conventional constitutive relations or equations of state are often not available. In this method, the closure quantities, such as stress, at each material point are calculated from a molecular dynamics simulation of a group of atoms surrounding the material point. Rather than restricting the multiscale simulation in a small spatial region,more » such as phase interfaces, or crack tips, this multiscale method can be used to consider nonequilibrium thermodynamic effects in a macroscopic domain. This method takes the advantage that the material points only communicate with mesh nodes, not among themselves; therefore molecular dynamics simulations for material points can be performed independently in parallel. The dual domain material point method is chosen for this multiscale method because it can be used in history dependent problems with large deformation without generating numerical noise as material points move across cells, and also because of its convergence and conservation properties. In conclusion, to demonstrate the feasibility and accuracy of this method, we compare the results of a shock wave propagation in a cerium crystal calculated using the direct molecular dynamics simulation with the results from this combined multiscale calculation.« less

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

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.

Molecular dynamics based enhanced sampling of collective variables with very large time steps.

PubMed

Chen, Pei-Yang; Tuckerman, Mark E

2018-01-14

Enhanced sampling techniques that target a set of collective variables and that use molecular dynamics as the driving engine have seen widespread application in the computational molecular sciences as a means to explore the free-energy landscapes of complex systems. The use of molecular dynamics as the fundamental driver of the sampling requires the introduction of a time step whose magnitude is limited by the fastest motions in a system. While standard multiple time-stepping methods allow larger time steps to be employed for the slower and computationally more expensive forces, the maximum achievable increase in time step is limited by resonance phenomena, which inextricably couple fast and slow motions. Recently, we introduced deterministic and stochastic resonance-free multiple time step algorithms for molecular dynamics that solve this resonance problem and allow ten- to twenty-fold gains in the large time step compared to standard multiple time step algorithms [P. Minary et al., Phys. Rev. Lett. 93, 150201 (2004); B. Leimkuhler et al., Mol. Phys. 111, 3579-3594 (2013)]. These methods are based on the imposition of isokinetic constraints that couple the physical system to Nosé-Hoover chains or Nosé-Hoover Langevin schemes. In this paper, we show how to adapt these methods for collective variable-based enhanced sampling techniques, specifically adiabatic free-energy dynamics/temperature-accelerated molecular dynamics, unified free-energy dynamics, and by extension, metadynamics, thus allowing simulations employing these methods to employ similarly very large time steps. The combination of resonance-free multiple time step integrators with free-energy-based enhanced sampling significantly improves the efficiency of conformational exploration.

Molecular dynamics based enhanced sampling of collective variables with very large time steps

NASA Astrophysics Data System (ADS)

Chen, Pei-Yang; Tuckerman, Mark E.

2018-01-01

Enhanced sampling techniques that target a set of collective variables and that use molecular dynamics as the driving engine have seen widespread application in the computational molecular sciences as a means to explore the free-energy landscapes of complex systems. The use of molecular dynamics as the fundamental driver of the sampling requires the introduction of a time step whose magnitude is limited by the fastest motions in a system. While standard multiple time-stepping methods allow larger time steps to be employed for the slower and computationally more expensive forces, the maximum achievable increase in time step is limited by resonance phenomena, which inextricably couple fast and slow motions. Recently, we introduced deterministic and stochastic resonance-free multiple time step algorithms for molecular dynamics that solve this resonance problem and allow ten- to twenty-fold gains in the large time step compared to standard multiple time step algorithms [P. Minary et al., Phys. Rev. Lett. 93, 150201 (2004); B. Leimkuhler et al., Mol. Phys. 111, 3579-3594 (2013)]. These methods are based on the imposition of isokinetic constraints that couple the physical system to Nosé-Hoover chains or Nosé-Hoover Langevin schemes. In this paper, we show how to adapt these methods for collective variable-based enhanced sampling techniques, specifically adiabatic free-energy dynamics/temperature-accelerated molecular dynamics, unified free-energy dynamics, and by extension, metadynamics, thus allowing simulations employing these methods to employ similarly very large time steps. The combination of resonance-free multiple time step integrators with free-energy-based enhanced sampling significantly improves the efficiency of conformational exploration.

Fragmentation-based QM/MM simulations: length dependence of chain dynamics and hydrogen bonding of polyethylene oxide and polyethylene in aqueous solutions.

PubMed

Li, Hui; Li, Wei; Li, Shuhua; Ma, Jing

2008-06-12

Molecular fragmentation quantum mechanics (QM) calculations have been combined with molecular mechanics (MM) to construct the fragmentation QM/MM method for simulations of dilute solutions of macromolecules. We adopt the electrostatics embedding QM/MM model, where the low-cost generalized energy-based fragmentation calculations are employed for the QM part. Conformation energy calculations, geometry optimizations, and Born-Oppenheimer molecular dynamics simulations of poly(ethylene oxide), PEO(n) (n = 6-20), and polyethylene, PE(n) ( n = 9-30), in aqueous solution have been performed within the framework of both fragmentation and conventional QM/MM methods. The intermolecular hydrogen bonding and chain configurations obtained from the fragmentation QM/MM simulations are consistent with the conventional QM/MM method. The length dependence of chain conformations and dynamics of PEO and PE oligomers in aqueous solutions is also investigated through the fragmentation QM/MM molecular dynamics simulations.

Ab initio molecular dynamics in a finite homogeneous electric field.

PubMed

Umari, P; Pasquarello, Alfredo

2002-10-07

We treat homogeneous electric fields within density functional calculations with periodic boundary conditions. A nonlocal energy functional depending on the applied field is used within an ab initio molecular dynamics scheme. The reliability of the method is demonstrated in the case of bulk MgO for the Born effective charges, and the high- and low-frequency dielectric constants. We evaluate the static dielectric constant by performing a damped molecular dynamics in an electric field and avoiding the calculation of the dynamical matrix. Application of this method to vitreous silica shows good agreement with experiment and illustrates its potential for systems of large size.

Solution NMR structure of a designed metalloprotein and complementary molecular dynamics refinement.

PubMed

Calhoun, Jennifer R; Liu, Weixia; Spiegel, Katrin; Dal Peraro, Matteo; Klein, Michael L; Valentine, Kathleen G; Wand, A Joshua; DeGrado, William F

2008-02-01

We report the solution NMR structure of a designed dimetal-binding protein, di-Zn(II) DFsc, along with a secondary refinement step employing molecular dynamics techniques. Calculation of the initial NMR structural ensemble by standard methods led to distortions in the metal-ligand geometries at the active site. Unrestrained molecular dynamics using a nonbonded force field for the metal shell, followed by quantum mechanical/molecular mechanical dynamics of DFsc, were used to relax local frustrations at the dimetal site that were apparent in the initial NMR structure and provide a more realistic description of the structure. The MD model is consistent with NMR restraints, and in good agreement with the structural and functional properties expected for DF proteins. This work demonstrates that NMR structures of metalloproteins can be further refined using classical and first-principles molecular dynamics methods in the presence of explicit solvent to provide otherwise unavailable insight into the geometry of the metal center.

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

PubMed

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

2012-01-01

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

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.

Genetic Algorithms and Their Application to the Protein Folding Problem

DTIC Science & Technology

1993-12-01

and symbolic methods, random methods such as Monte Carlo simulation and simulated annealing, distance geometry, and molecular dynamics. Many of these...calculated energies with those obtained using the molecular simulation software package called CHARMm. 10 9) Test both the simple and parallel simpie genetic...homology-based, and simplification techniques. 3.21 Molecular Dynamics. Perhaps the most natural approach is to actually simulate the folding process. This

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.

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)

Variational path integral molecular dynamics and hybrid Monte Carlo algorithms using a fourth order propagator with applications to molecular systems

NASA Astrophysics Data System (ADS)

Kamibayashi, Yuki; Miura, Shinichi

2016-08-01

In the present study, variational path integral molecular dynamics and associated hybrid Monte Carlo (HMC) methods have been developed on the basis of a fourth order approximation of a density operator. To reveal various parameter dependence of physical quantities, we analytically solve one dimensional harmonic oscillators by the variational path integral; as a byproduct, we obtain the analytical expression of the discretized density matrix using the fourth order approximation for the oscillators. Then, we apply our methods to realistic systems like a water molecule and a para-hydrogen cluster. In the HMC, we adopt two level description to avoid the time consuming Hessian evaluation. For the systems examined in this paper, the HMC method is found to be about three times more efficient than the molecular dynamics method if appropriate HMC parameters are adopted; the advantage of the HMC method is suggested to be more evident for systems described by many body interaction.

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

Enhanced conformational sampling via novel variable transformations and very large time-step molecular dynamics

NASA Astrophysics Data System (ADS)

Tuckerman, Mark

2006-03-01

One of the computational grand challenge problems is to develop methodology capable of sampling conformational equilibria in systems with rough energy landscapes. If met, many important problems, most notably protein folding, could be significantly impacted. In this talk, two new approaches for addressing this problem will be presented. First, it will be shown how molecular dynamics can be combined with a novel variable transformation designed to warp configuration space in such a way that barriers are reduced and attractive basins stretched. This method rigorously preserves equilibrium properties while leading to very large enhancements in sampling efficiency. Extensions of this approach to the calculation/exploration of free energy surfaces will be discussed. Next, a new very large time-step molecular dynamics method will be introduced that overcomes the resonances which plague many molecular dynamics algorithms. The performance of the methods is demonstrated on a variety of systems including liquid water, long polymer chains simple protein models, and oligopeptides.

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 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

Selective IR multiphoton dissociation of molecules in a pulsed gas-dynamically cooled molecular flow interacting with a solid surface as an alternative to low-energy methods of molecular laser isotope separation

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

Makarov, G N; Petin, A N

2016-03-31

We report the results of studies on the isotope-selective infrared multiphoton dissociation (IR MFD) of SF{sub 6} and CF{sub 3}I molecules in a pulsed, gas-dynamically cooled molecular flow interacting with a solid surface. The productivity of this method in the conditions of a specific experiment (by the example of SF{sub 6} molecules) is evaluated. A number of low-energy methods of molecular laser isotope separation based on the use of infrared lasers for selective excitation of molecules are analysed and their productivity is estimated. The methods are compared with those of selective dissociation of molecules in the flow interacting with amore » surface. The advantages of this method compared to the low-energy methods of molecular laser isotope separation and the IR MPD method in the unperturbed jets and flows are shown. It is concluded that this method could be a promising alternative to the low-energy methods of molecular laser isotope separation. (laser separation of isotopes)« less

Nonadiabatic electron wavepacket dynamics behind molecular autoionization

NASA Astrophysics Data System (ADS)

Matsuoka, Takahide; Takatsuka, Kazuo

2018-01-01

A theoretical method for real-time dynamics of nonadiabatic reorganization of electronic configurations in molecules is developed, with dual aim that the intramolecular electron dynamics can be probed by means of direct and/or indirect photoionizations and that the physical origins behind photoionization signals attained in the time domain can be identified in terms of the language of time-dependent quantum chemistry. In doing so, we first formulate and implement a new computational scheme for nonadiabatic electron dynamics associated with molecular ionization, which well fits in the general theory of nonadiabatic electron dynamics. In this method, the total nonadiabatic electron wavepackets are propagated in time directly with complex natural orbitals without referring to Hartree-Fock molecular orbitals, and the amount of electron flux from a molecular region leading to ionization is evaluated in terms of the relevant complex natural orbitals. In the second half of this paper, we apply the method to electron dynamics in the elementary processes consisting of the Auger decay to demonstrate the methodological significance. An illustrative example is taken from an Auger decay starting from the 2a1 orbital hole-state of H2O+. The roles of nuclear momentum (kinetic) couplings in electronic-state mixing during the decay process are analyzed in terms of complex natural orbitals, which are schematically represented in the conventional language of molecular symmetry of the Hartree-Fock orbitals.

Quantum dynamics of light-driven chiral molecular motors.

PubMed

Yamaki, Masahiro; Nakayama, Shin-ichiro; Hoki, Kunihito; Kono, Hirohiko; Fujimura, Yuichi

2009-03-21

The results of theoretical studies on quantum dynamics of light-driven molecular motors with internal rotation are presented. Characteristic features of chiral motors driven by a non-helical, linearly polarized electric field of light are explained on the basis of symmetry argument. The rotational potential of the chiral motor is characterized by a ratchet form. The asymmetric potential determines the directional motion: the rotational direction is toward the gentle slope of the asymmetric potential. This direction is called the intuitive direction. To confirm the unidirectional rotational motion, results of quantum dynamical calculations of randomly-oriented molecular motors are presented. A theoretical design of the smallest light-driven molecular machine is presented. The smallest chiral molecular machine has an optically driven engine and a running propeller on its body. The mechanisms of transmission of driving forces from the engine to the propeller are elucidated by using a quantum dynamical treatment. The results provide a principle for control of optically-driven molecular bevel gears. Temperature effects are discussed using the density operator formalism. An effective method for ultrafast control of rotational motions in any desired direction is presented with the help of a quantum control theory. In this method, visible or UV light pulses are applied to drive the motor via an electronic excited state. A method for driving a large molecular motor consisting of an aromatic hydrocarbon is presented. The molecular motor is operated by interactions between the induced dipole of the molecular motor and the electric field of light pulses.

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.

Coupled wave-packets for non-adiabatic molecular dynamics: a generalization of Gaussian wave-packet dynamics to multiple potential energy surfaces

DOE PAGES

White, Alexander James; Tretiak, Sergei; Mozyrsky, Dima V.

2016-04-25

Accurate simulation of the non-adiabatic dynamics of molecules in excited electronic states is key to understanding molecular photo-physical processes. Here we present a novel method, based on a semiclassical approximation, that is as efficient as the commonly used mean field Ehrenfest or ad hoc surface hopping methods and properly accounts for interference and decoherence effects. This novel method is an extension of Heller's thawed Gaussian wave-packet dynamics that includes coupling between potential energy surfaces. By studying several standard test problems we demonstrate that the accuracy of the method can be systematically improved while maintaining high efficiency. The method is suitablemore » for investigating the role of quantum coherence in the non-adiabatic dynamics of many-atom molecules.« less

Photonic-plasmonic hybrid single-molecule nanosensor measures the effect of fluorescent labels on DNA-protein dynamics

PubMed Central

Liang, Feng; Guo, Yuzheng; Hou, Shaocong; Quan, Qimin

2017-01-01

Current methods to study molecular interactions require labeling the subject molecules with fluorescent reporters. However, the effect of the fluorescent reporters on molecular dynamics has not been quantified because of a lack of alternative methods. We develop a hybrid photonic-plasmonic antenna-in-a-nanocavity single-molecule biosensor to study DNA-protein dynamics without using fluorescent labels. Our results indicate that the fluorescein and fluorescent protein labels decrease the interaction between a single DNA and a protein due to weakened electrostatic interaction. Although the study is performed on the DNA-XPA system, the conclusion has a general implication that the traditional fluorescent labeling methods might be misestimating the molecular interactions. PMID:28560341

Combined multireference configuration interaction/ molecular dynamics approach for calculating solvatochromic shifts: application to the n(O) --> pi* electronic transition of formaldehyde.

PubMed

Xu, ZongRong; Matsika, Spiridoula

2006-11-02

A combined quantum mechanics/molecular mechanics method is described here for considering the solvatochromic shift of excited states in solution. The quantum mechanical solute is described using high level multireference configuration interaction methods (MRCI), while molecular dynamics is used for obtaining the structure of the solvent around the solute. The electrostatic effect of the solvent is included in the quantum description of the solute in an averaged way. This method is used to study solvent effects on the n(O) --> pi* electronic transition of formaldehyde in aqueous solution. The effects of solute polarization, basis sets, and dynamical correlation on the solvatochromic shift, and on dipole moments, have been investigated.

Multiscale Modeling of Multiphase Fluid Flow

DTIC Science & Technology

2016-08-01

the disparate time and length scales involved in modeling fluid flow and heat transfer. Molecular dynamics simulations were carried out to provide a...fluid dynamics methods were used to investigate the heat transfer process in open-cell micro-foam with phase change material; enhancement of natural...Computational fluid dynamics, Heat transfer, Phase change material in Micro-foam, Molecular Dynamics, Multiphase flow, Multiscale modeling, Natural

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,…

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.

Nonadiabatic ab initio molecular dynamics with PME-ONIOM scheme of photoisomerization reaction between 1,3-cyclohexadiene and 1,3,5-cis-hexatriene in solution phase

NASA Astrophysics Data System (ADS)

Ohta, Ayumi; Kobayashi, Osamu; Danielache, Sebastian O.; Nanbu, Shinkoh

2017-03-01

The ultra-fast photoisomerization reactions between 1,3-cyclohexadiene (CHD) and 1,3,5-cis-hexatriene (HT) in both hexane and ethanol solvents were revealed by nonadiabatic ab initio molecular dynamics (AI-MD) with a particle-mesh Ewald summation method and our Own N-layered Integrated molecular Orbital and molecular Mechanics model (PME-ONIOM) scheme. Zhu-Nakamura version trajectory surface hopping method (ZN-TSH) was employed to treat the ultra-fast nonadiabatic decaying process. The results for hexane and ethanol simulations reasonably agree with experimental data. The high nonpolar-nonpolar affinity between CHD and the solvent was observed in hexane solvent, which definitely affected the excited state lifetimes, the product branching ratio of CHD:HT, and solute (CHD) dynamics. In ethanol solvent, however, the CHD solute was isomerized in the solvent cage caused by the first solvation shell. The photochemical dynamics in ethanol solvent results in the similar property to the process appeared in vacuo (isolated CHD dynamics).

A reduced basis method for molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Vincent-Finley, Rachel Elisabeth

In this dissertation, we develop a method for molecular simulation based on principal component analysis (PCA) of a molecular dynamics trajectory and least squares approximation of a potential energy function. Molecular dynamics (MD) simulation is a computational tool used to study molecular systems as they evolve through time. With respect to protein dynamics, local motions, such as bond stretching, occur within femtoseconds, while rigid body and large-scale motions, occur within a range of nanoseconds to seconds. To capture motion at all levels, time steps on the order of a femtosecond are employed when solving the equations of motion and simulations must continue long enough to capture the desired large-scale motion. To date, simulations of solvated proteins on the order of nanoseconds have been reported. It is typically the case that simulations of a few nanoseconds do not provide adequate information for the study of large-scale motions. Thus, the development of techniques that allow longer simulation times can advance the study of protein function and dynamics. In this dissertation we use principal component analysis (PCA) to identify the dominant characteristics of an MD trajectory and to represent the coordinates with respect to these characteristics. We augment PCA with an updating scheme based on a reduced representation of a molecule and consider equations of motion with respect to the reduced representation. We apply our method to butane and BPTI and compare the results to standard MD simulations of these molecules. Our results indicate that the molecular activity with respect to our simulation method is analogous to that observed in the standard MD simulation with simulations on the order of picoseconds.

A centroid molecular dynamics study of liquid para-hydrogen and ortho-deuterium.

PubMed

Hone, Tyler D; Voth, Gregory A

2004-10-01

Centroid molecular dynamics (CMD) is applied to the study of collective and single-particle dynamics in liquid para-hydrogen at two state points and liquid ortho-deuterium at one state point. The CMD results are compared with the results of classical molecular dynamics, quantum mode coupling theory, a maximum entropy analytic continuation approach, pair-product forward- backward semiclassical dynamics, and available experimental results. The self-diffusion constants are in excellent agreement with the experimental measurements for all systems studied. Furthermore, it is shown that the method is able to adequately describe both the single-particle and collective dynamics of quantum liquids. (c) 2004 American Institute of Physics

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.

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

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.

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.

Protonation-induced stereoisomerism in nicotine: Conformational studies using classical (AMBER) and ab initio (Car Parrinello) molecular dynamics

NASA Astrophysics Data System (ADS)

Hammond, Philip S.; Wu, Yudong; Harris, Rebecca; Minehardt, Todd J.; Car, Roberto; Schmitt, Jeffrey D.

2005-01-01

A variety of biologically active small molecules contain prochiral tertiary amines, which become chiral centers upon protonation. S-nicotine, the prototypical nicotinic acetylcholine receptor agonist, produces two diastereomers on protonation. Results, using both classical (AMBER) and ab initio (Car-Parrinello) molecular dynamical studies, illustrate the significant differences in conformational space explored by each diastereomer. As is expected, this phenomenon has an appreciable effect on nicotine's energy hypersurface and leads to differentiation in molecular shape and divergent sampling. Thus, protonation induced isomerism can produce dynamic effects that may influence the behavior of a molecule in its interaction with a target protein. We also examine differences in the conformational dynamics for each diastereomer as quantified by both molecular dynamics methods.

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,.

Molecular dynamics study of the structural and dynamic characteristics of the polyextremophilic short-chain dehydrogenase from the Thermococcus sibiricus archaeon and its homologues

NASA Astrophysics Data System (ADS)

Popinako, Anna V.; Antonov, Mikhail Yu.; Bezsudnova, Ekaterina Yu.; Prokopiev, Georgiy A.; Popov, Vladimir O.

2017-11-01

The study of structural adaptations of proteins from polyextremophilic organisms using computational molecular dynamics method is appealing because the obtained knowledge can be applied to construction of synthetic proteins with high activity and stability in polyextreme media which is useful for many industrial applications. To investigate molecular adaptations to high temperature, we have focused on a superthermostable short-chain dehydrogenase TsAdh319 from the Thermococcus sibiricus polyextremophilic archaeon and its closest structural homologues. Molecular dynamics method is widely used for molecular structure refinement, investigation of biological macromolecules motion, and, consequently, for interpreting the results of certain biophysical experiments. We performed molecular dynamics simulations of the proteins at different temperatures. Comparison of root mean square fluctuations (RMSF) of the atoms in thermophilic alcohol dehydrogenases (ADHs) at 300 K and 358 K revealed the existence of stable residues at 358 K. These residues surround the active site and form a "nucleus of rigidity" in thermophilic ADHs. The results of our studies suggest that the existence of the "nucleus of rigidity" is crucial for the stability of TsAdh319. Absence of the "nucleus of rigidity" in non-thermally stable proteins causes fluctuations throughout the protein, especially on the surface, triggering the process of denaturation at high temperatures.

Crossed Molecular Beam Studies and Dynamics of Decomposition of Chemically Activated Radicals

DOE R&D Accomplishments Database

Lee, Y. T.

1973-09-01

The power of the crossed molecular beams method in the investigation of the dynamics of chemical reactions lies mainly in the direct observation of the consequences of single collisions of well controlled reactant molecules. The primary experimental observations which provide information on reaction dynamics are the measurements of angular and velocity distributions of reaction products.

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

Thermal quantum time-correlation functions from classical-like dynamics

NASA Astrophysics Data System (ADS)

Hele, Timothy J. H.

2017-07-01

Thermal quantum time-correlation functions are of fundamental importance in quantum dynamics, allowing experimentally measurable properties such as reaction rates, diffusion constants and vibrational spectra to be computed from first principles. Since the exact quantum solution scales exponentially with system size, there has been considerable effort in formulating reliable linear-scaling methods involving exact quantum statistics and approximate quantum dynamics modelled with classical-like trajectories. Here, we review recent progress in the field with the development of methods including centroid molecular dynamics , ring polymer molecular dynamics (RPMD) and thermostatted RPMD (TRPMD). We show how these methods have recently been obtained from 'Matsubara dynamics', a form of semiclassical dynamics which conserves the quantum Boltzmann distribution. We also apply the Matsubara formalism to reaction rate theory, rederiving t → 0+ quantum transition-state theory (QTST) and showing that Matsubara-TST, like RPMD-TST, is equivalent to QTST. We end by surveying areas for future progress.

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

Multiscale Modeling for the Analysis for Grain-Scale Fracture Within Aluminum Microstructures

NASA Technical Reports Server (NTRS)

Glaessgen, Edward H.; Phillips, Dawn R.; Yamakov, Vesselin; Saether, Erik

2005-01-01

Multiscale modeling methods for the analysis of metallic microstructures are discussed. Both molecular dynamics and the finite element method are used to analyze crack propagation and stress distribution in a nanoscale aluminum bicrystal model subjected to hydrostatic loading. Quantitative similarity is observed between the results from the two very different analysis methods. A bilinear traction-displacement relationship that may be embedded into cohesive zone finite elements is extracted from the nanoscale molecular dynamics results.

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.

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

From Geometry Optimization to Time Dependent Molecular Structure Modeling: Method Developments, ab initio Theories and Applications

NASA Astrophysics Data System (ADS)

Liang, Wenkel

This dissertation consists of two general parts: (I) developments of optimization algorithms (both nuclear and electronic degrees of freedom) for time-independent molecules and (II) novel methods, first-principle theories and applications in time dependent molecular structure modeling. In the first part, we discuss in specific two new algorithms for static geometry optimization, the eigenspace update (ESU) method in nonredundant internal coordinate that exhibits an enhanced performace with up to a factor of 3 savings in computational cost for large-sized molecular systems; the Car-Parrinello density matrix search (CP-DMS) method that enables direct minimization of the SCF energy as an effective alternative to conventional diagonalization approach. For the second part, we consider the time dependence and first presents two nonadiabatic dynamic studies that model laser controlled molecular photo-dissociation for qualitative understandings of intense laser-molecule interaction, using ab initio direct Ehrenfest dynamics scheme implemented with real-time time-dependent density functional theory (RT-TDDFT) approach developed in our group. Furthermore, we place our special interest on the nonadiabatic electronic dynamics in the ultrafast time scale, and presents (1) a novel technique that can not only obtain energies but also the electron densities of doubly excited states within a single determinant framework, by combining methods of CP-DMS with RT-TDDFT; (2) a solvated first-principles electronic dynamics method by incorporating the polarizable continuum solvation model (PCM) to RT-TDDFT, which is found to be very effective in describing the dynamical solvation effect in the charge transfer process and yields a consistent absorption spectrum in comparison to the conventional linear response results in solution. (3) applications of the PCM-RT-TDDFT method to study the intramolecular charge-transfer (CT) dynamics in a C60 derivative. Such work provides insights into the characteristics of ultrafast dynamics in photoexcited fullerene derivatives, and aids in the rational design for pre-dissociative exciton in the intramolecular CT process in organic solar cells.

Interaction sorting method for molecular dynamics on multi-core SIMD CPU architecture.

PubMed

Matvienko, Sergey; Alemasov, Nikolay; Fomin, Eduard

2015-02-01

Molecular dynamics (MD) is widely used in computational biology for studying binding mechanisms of molecules, molecular transport, conformational transitions, protein folding, etc. The method is computationally expensive; thus, the demand for the development of novel, much more efficient algorithms is still high. Therefore, the new algorithm designed in 2007 and called interaction sorting (IS) clearly attracted interest, as it outperformed the most efficient MD algorithms. In this work, a new IS modification is proposed which allows the algorithm to utilize SIMD processor instructions. This paper shows that the improvement provides an additional gain in performance, 9% to 45% in comparison to the original IS method.

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.

Geometric analysis characterizes molecular rigidity in generic and non-generic protein configurations

PubMed Central

Budday, Dominik; Leyendecker, Sigrid; van den Bedem, Henry

2015-01-01

Proteins operate and interact with partners by dynamically exchanging between functional substates of a conformational ensemble on a rugged free energy landscape. Understanding how these substates are linked by coordinated, collective motions requires exploring a high-dimensional space, which remains a tremendous challenge. While molecular dynamics simulations can provide atomically detailed insight into the dynamics, computational demands to adequately sample conformational ensembles of large biomolecules and their complexes often require tremendous resources. Kinematic models can provide high-level insights into conformational ensembles and molecular rigidity beyond the reach of molecular dynamics by reducing the dimensionality of the search space. Here, we model a protein as a kinematic linkage and present a new geometric method to characterize molecular rigidity from the constraint manifold Q and its tangent space Q at the current configuration q. In contrast to methods based on combinatorial constraint counting, our method is valid for both generic and non-generic, e.g., singular configurations. Importantly, our geometric approach provides an explicit basis for collective motions along floppy modes, resulting in an efficient procedure to probe conformational space. An atomically detailed structural characterization of coordinated, collective motions would allow us to engineer or allosterically modulate biomolecules by selectively stabilizing conformations that enhance or inhibit function with broad implications for human health. PMID:26213417

Geometric analysis characterizes molecular rigidity in generic and non-generic protein configurations

NASA Astrophysics Data System (ADS)

Budday, Dominik; Leyendecker, Sigrid; van den Bedem, Henry

2015-10-01

Proteins operate and interact with partners by dynamically exchanging between functional substates of a conformational ensemble on a rugged free energy landscape. Understanding how these substates are linked by coordinated, collective motions requires exploring a high-dimensional space, which remains a tremendous challenge. While molecular dynamics simulations can provide atomically detailed insight into the dynamics, computational demands to adequately sample conformational ensembles of large biomolecules and their complexes often require tremendous resources. Kinematic models can provide high-level insights into conformational ensembles and molecular rigidity beyond the reach of molecular dynamics by reducing the dimensionality of the search space. Here, we model a protein as a kinematic linkage and present a new geometric method to characterize molecular rigidity from the constraint manifold Q and its tangent space Tq Q at the current configuration q. In contrast to methods based on combinatorial constraint counting, our method is valid for both generic and non-generic, e.g., singular configurations. Importantly, our geometric approach provides an explicit basis for collective motions along floppy modes, resulting in an efficient procedure to probe conformational space. An atomically detailed structural characterization of coordinated, collective motions would allow us to engineer or allosterically modulate biomolecules by selectively stabilizing conformations that enhance or inhibit function with broad implications for human health.

Modelling and enhanced molecular dynamics to steer structure-based drug discovery.

PubMed

Kalyaanamoorthy, Subha; Chen, Yi-Ping Phoebe

2014-05-01

The ever-increasing gap between the availabilities of the genome sequences and the crystal structures of proteins remains one of the significant challenges to the modern drug discovery efforts. The knowledge of structure-dynamics-functionalities of proteins is important in order to understand several key aspects of structure-based drug discovery, such as drug-protein interactions, drug binding and unbinding mechanisms and protein-protein interactions. This review presents a brief overview on the different state of the art computational approaches that are applied for protein structure modelling and molecular dynamics simulations of biological systems. We give an essence of how different enhanced sampling molecular dynamics approaches, together with regular molecular dynamics methods, assist in steering the structure based drug discovery processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

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.

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.

Modeling of diatomic molecule using the Morse potential and the Verlet algorithm

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

Fidiani, Elok

Performing molecular modeling usually uses special software for Molecular Dynamics (MD) such as: GROMACS, NAMD, JMOL etc. Molecular dynamics is a computational method to calculate the time dependent behavior of a molecular system. In this work, MATLAB was used as numerical method for a simple modeling of some diatomic molecules: HCl, H{sub 2} and O{sub 2}. MATLAB is a matrix based numerical software, in order to do numerical analysis, all the functions and equations describing properties of atoms and molecules must be developed manually in MATLAB. In this work, a Morse potential was generated to describe the bond interaction betweenmore » the two atoms. In order to analyze the simultaneous motion of molecules, the Verlet Algorithm derived from Newton’s Equations of Motion (classical mechanics) was operated. Both the Morse potential and the Verlet algorithm were integrated using MATLAB to derive physical properties and the trajectory of the molecules. The data computed by MATLAB is always in the form of a matrix. To visualize it, Visualized Molecular Dynamics (VMD) was performed. Such method is useful for development and testing some types of interaction on a molecular scale. Besides, this can be very helpful for describing some basic principles of molecular interaction for educational purposes.« 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.

Ion-ion dynamic structure factor of warm dense mixtures

DOE PAGES

Gill, N. M.; Heinonen, R. A.; Starrett, C. E.; ...

2015-06-25

In this study, the ion-ion dynamic structure factor of warm dense matter is determined using the recently developed pseudoatom molecular dynamics method [Starrett et al., Phys. Rev. E 91, 013104 (2015)]. The method uses density functional theory to determine ion-ion pair interaction potentials that have no free parameters. These potentials are used in classical molecular dynamics simulations. This constitutes a computationally efficient and realistic model of dense plasmas. Comparison with recently published simulations of the ion-ion dynamic structure factor and sound speed of warm dense aluminum finds good to reasonable agreement. Using this method, we make predictions of the ion-ionmore » dynamical structure factor and sound speed of a warm dense mixture—equimolar carbon-hydrogen. This material is commonly used as an ablator in inertial confinement fusion capsules, and our results are amenable to direct experimental measurement.« less

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.

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.

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.

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.

Leveraging Gibbs Ensemble Molecular Dynamics and Hybrid Monte Carlo/Molecular Dynamics for Efficient Study of Phase Equilibria.

PubMed

Gartner, Thomas E; Epps, Thomas H; Jayaraman, Arthi

2016-11-08

We describe an extension of the Gibbs ensemble molecular dynamics (GEMD) method for studying phase equilibria. Our modifications to GEMD allow for direct control over particle transfer between phases and improve the method's numerical stability. Additionally, we found that the modified GEMD approach had advantages in computational efficiency in comparison to a hybrid Monte Carlo (MC)/MD Gibbs ensemble scheme in the context of the single component Lennard-Jones fluid. We note that this increase in computational efficiency does not compromise the close agreement of phase equilibrium results between the two methods. However, numerical instabilities in the GEMD scheme hamper GEMD's use near the critical point. We propose that the computationally efficient GEMD simulations can be used to map out the majority of the phase window, with hybrid MC/MD used as a follow up for conditions under which GEMD may be unstable (e.g., near-critical behavior). In this manner, we can capitalize on the contrasting strengths of these two methods to enable the efficient study of phase equilibria for systems that present challenges for a purely stochastic GEMC method, such as dense or low temperature systems, and/or those with complex molecular topologies.

A Practical Quantum Mechanics Molecular Mechanics Method for the Dynamical Study of Reactions in Biomolecules.

PubMed

Mendieta-Moreno, Jesús I; Marcos-Alcalde, Iñigo; Trabada, Daniel G; Gómez-Puertas, Paulino; Ortega, José; Mendieta, Jesús

2015-01-01

Quantum mechanics/molecular mechanics (QM/MM) methods are excellent tools for the modeling of biomolecular reactions. Recently, we have implemented a new QM/MM method (Fireball/Amber), which combines an efficient density functional theory method (Fireball) and a well-recognized molecular dynamics package (Amber), offering an excellent balance between accuracy and sampling capabilities. Here, we present a detailed explanation of the Fireball method and Fireball/Amber implementation. We also discuss how this tool can be used to analyze reactions in biomolecules using steered molecular dynamics simulations. The potential of this approach is shown by the analysis of a reaction catalyzed by the enzyme triose-phosphate isomerase (TIM). The conformational space and energetic landscape for this reaction are analyzed without a priori assumptions about the protonation states of the different residues during the reaction. The results offer a detailed description of the reaction and reveal some new features of the catalytic mechanism. In particular, we find a new reaction mechanism that is characterized by the intramolecular proton transfer from O1 to O2 and the simultaneous proton transfer from Glu 165 to C2. Copyright © 2015 Elsevier Inc. All rights reserved.

Increasing the power of accelerated molecular dynamics methods and plans to exploit the coming exascale

NASA Astrophysics Data System (ADS)

Voter, Arthur

Many important materials processes take place on time scales that far exceed the roughly one microsecond accessible to molecular dynamics simulation. Typically, this long-time evolution is characterized by a succession of thermally activated infrequent events involving defects in the material. In the accelerated molecular dynamics (AMD) methodology, known characteristics of infrequent-event systems are exploited to make reactive events take place more frequently, in a dynamically correct way. For certain processes, this approach has been remarkably successful, offering a view of complex dynamical evolution on time scales of microseconds, milliseconds, and sometimes beyond. We have recently made advances in all three of the basic AMD methods (hyperdynamics, parallel replica dynamics, and temperature accelerated dynamics (TAD)), exploiting both algorithmic advances and novel parallelization approaches. I will describe these advances, present some examples of our latest results, and discuss what should be possible when exascale computing arrives in roughly five years. Funded by the U.S. Department of Energy, Office of Basic Energy Sciences, Materials Sciences and Engineering Division, and by the Los Alamos Laboratory Directed Research and Development program.

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.

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.

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.

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

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.

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.

Search for Length Dependent Stable Structures of Polyglutamaine Proteins with Replica Exchange Molecular Dynamic

NASA Astrophysics Data System (ADS)

Kluber, Alexander; Hayre, Robert; Cox, Daniel

2012-02-01

Motivated by the need to find beta-structure aggregation nuclei for the polyQ diseases such as Huntington's, we have undertaken a search for length dependent structure in model polyglutamine proteins. We use the Onufriev-Bashford-Case (OBC) generalized Born implicit solvent GPU based AMBER11 molecular dynamics with the parm96 force field coupled with a replica exchange method to characterize monomeric strands of polyglutamine as a function of chain length and temperature. This force field and solvation method has been shown among other methods to accurately reproduce folded metastability in certain small peptides, and to yield accurately de novo folded structures in a millisecond time-scale protein. Using GPU molecular dynamics we can sample out into the microsecond range. Additionally, explicit solvent runs will be used to verify results from the implicit solvent runs. We will assess order using measures of secondary structure and hydrogen bond content.

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.

Biodiversity and dynamics of meat fermentations: the contribution of molecular methods for a better comprehension of a complex ecosystem.

PubMed

Cocolin, Luca; Dolci, Paola; Rantsiou, Kalliopi

2011-11-01

The ecology of fermented sausages is complex and includes different species and strains of bacteria, yeasts and molds. The developments in the field of molecular biology, allowed for new methods to become available, which could be applied to better understand dynamics and diversity of the microorganisms involved in the production of sausages. Methods, such as denaturing gradient gel electrophoresis (DGGE), employed as a culture-independent approach, allow to define the microbial dynamics during the fermentation and ripening. Such approach has highlighted that two main species of lactic acid bacteria, namely Lactobacillus sakei and Lb. curvatus, are involved in the transformation process and that they are accompanied by Staphylococcus xylosus, as representative of the coagulase-negative cocci. These findings were repeatedly confirmed in different regions of the world, mainly in the Mediterranean countries where dry fermented sausages have a long tradition and history. The application of molecular methods for the identification and characterization of isolated strains from fermentations highlighted a high degree of diversity within the species mentioned above, underlining the need to better follow strain dynamics during the transformation process. While there is an important number of papers dealing with bacterial ecology by using molecular methods, studies on mycobiota of fermented sausages are just a few. This review reports on how the application of molecular methods made possible a better comprehension of the sausage fermentations, opening up new fields of research that in the near future will allow to unravel the connection between sensory properties and co-presence of multiple strains of the same species. Copyright © 2011 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.

Molecular dynamics simulation of a needle-sphere binary mixture

NASA Astrophysics Data System (ADS)

Raghavan, Karthik

This paper investigates the dynamic behaviour of a hard needle-sphere binary system using a novel numerical technique called the Newton homotopy continuation (NHC) method. This mixture is representative of a polymer melt where both long chain molecules and monomers coexist. Since the intermolecular forces are generated from hard body interactions, the consequence of missed collisions or incorrect collision sequences have a significant bearing on the dynamic properties of the fluid. To overcome this problem, in earlier work NHC was chosen over traditional Newton-Raphson methods to solve the hard body dynamics of a needle fluid in random media composed of overlapping spheres. Furthermore, the simplicity of interactions and dynamics allows us to focus our research directly on the effects of particle shape and density on the transport behaviour of the mixture. These studies are also compared with earlier works that examined molecular chains in porous media primarily to understand the differences in molecular transport in the bulk versus porous 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.

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.

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.

Complementary study of molecular dynamics and domain sizes in heterogenous nanocomposites PBT/DA-C{sub 60} and PBT/TCNEO-C{sub 60}

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

Woźniak-Braszak, A., E-mail: abraszak@amu.edu.pl; Baranowski, M.; Jurga, K.

2014-05-28

A comprehensive study of molecular dynamics and structure in new heterogenous nanocomposites based on poly(butylene terephthalate) and nanoparticles C{sub 60} modified by n-decylamine or tetracyanoethylene oxide has been performed. The domain structure of new nanocomposites has been investigated by Fourier transform infrared spectroscopy, wide-angle X-ray scattering, and differential scanning calorimetry techniques. Solid-state {sup 1}H NMR techniques were used to study molecular dynamics and domain sizes in new nanocomposites. Information about the electronic properties of these nanocomposites was obtained by means of electron paramagnetic resonance method. It was shown that the structure and molecular dynamics of new nanocomposites were strongly dependentmore » on the properties and concentration of fullerene derivates.« less

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.

Free energy calculations of short peptide chains using Adaptively Biased Molecular Dynamics

NASA Astrophysics Data System (ADS)

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

2008-10-01

We performed a computational study of monomer peptides composed of methionine, alanine, leucine, glutamate, lysine (all amino acids with a helix-forming propensities); and proline, glycine tyrosine, serine, arginine (which all have poor helix-forming propensities). The free energy landscapes as a function of the handedness and radius of gyration have been calculated using the recently introduced Adaptively Biased Molecular Dynamics (ABMD) method, combined with replica exchange, multiple walkers, and post-processing Umbrella Correction (UC). Minima that correspond to some of the left- and right-handed 310-, α- and π-helixes were identified by secondary structure assignment methods (DSSP, Stride). The resulting free energy surface (FES) and the subsequent steered molecular dynamics (SMD) simulation results are in agreement with the empirical evidence of preferred secondary structures for the peptide chains considered.

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.

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.

Data-Driven Model Reduction and Transfer Operator Approximation

NASA Astrophysics Data System (ADS)

Klus, Stefan; Nüske, Feliks; Koltai, Péter; Wu, Hao; Kevrekidis, Ioannis; Schütte, Christof; Noé, Frank

2018-06-01

In this review paper, we will present different data-driven dimension reduction techniques for dynamical systems that are based on transfer operator theory as well as methods to approximate transfer operators and their eigenvalues, eigenfunctions, and eigenmodes. The goal is to point out similarities and differences between methods developed independently by the dynamical systems, fluid dynamics, and molecular dynamics communities such as time-lagged independent component analysis, dynamic mode decomposition, and their respective generalizations. As a result, extensions and best practices developed for one particular method can be carried over to other related methods.

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.

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

Molecular Dynamics Information Improves cis-Peptide-Based Function Annotation of Proteins.

PubMed

Das, Sreetama; Bhadra, Pratiti; Ramakumar, Suryanarayanarao; Pal, Debnath

2017-08-04

cis-Peptide bonds, whose occurrence in proteins is rare but evolutionarily conserved, are implicated to play an important role in protein function. This has led to their previous use in a homology-independent, fragment-match-based protein function annotation method. However, proteins are not static molecules; dynamics is integral to their activity. This is nicely epitomized by the geometric isomerization of cis-peptide to trans form for molecular activity. Hence we have incorporated both static (cis-peptide) and dynamics information to improve the prediction of protein molecular function. Our results show that cis-peptide information alone cannot detect functional matches in cases where cis-trans isomerization exists but 3D coordinates have been obtained for only the trans isomer or when the cis-peptide bond is incorrectly assigned as trans. On the contrary, use of dynamics information alone includes false-positive matches for cases where fragments with similar secondary structure show similar dynamics, but the proteins do not share a common function. Combining the two methods reduces errors while detecting the true matches, thereby enhancing the utility of our method in function annotation. A combined approach, therefore, opens up new avenues of improving existing automated function annotation methodologies.

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.

Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors β

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

Li, Xiaolin; Ye, Li; Wang, Xiaoxiang

2012-12-15

Several recent reports suggested that hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural features for thyroid hormone activity of HO-PBDEs and the binding mode between HO-PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO-PBDEs to thyroid receptors β was studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor-based 3D-QSAR models were obtained using Comparative Molecular Similarity Index Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded satisfactory statistical results: leave-one-out cross-validation correlation coefficient (q{sup 2}) was 0.571 andmore » non-cross-validation correlation coefficient (r{sup 2}) was 0.951. Furthermore, the results of internal validation such as bootstrapping, leave-many-out cross-validation, and progressive scrambling as well as external validation indicated the rationality and good predictive ability of the best model. In addition, molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket, MD simulation further determined the binding process and validated the rationality of docking results. -- Highlights: ► The thyroid hormone activities of HO-PBDEs were studied by 3D-QSAR. ► The binding modes between HO-PBDEs and TRβ were explored. ► 3D-QSAR, molecular docking, and molecular dynamics (MD) methods were performed.« less

Pipeline for inferring protein function from dynamics using coarse-grained molecular mechanics forcefield.

PubMed

Bhadra, Pratiti; Pal, Debnath

2017-04-01

Dynamics is integral to the function of proteins, yet the use of molecular dynamics (MD) simulation as a technique remains under-explored for molecular function inference. This is more important in the context of genomics projects where novel proteins are determined with limited evolutionary information. Recently we developed a method to match the query protein's flexible segments to infer function using a novel approach combining analysis of residue fluctuation-graphs and auto-correlation vectors derived from coarse-grained (CG) MD trajectory. The method was validated on a diverse dataset with sequence identity between proteins as low as 3%, with high function-recall rates. Here we share its implementation as a publicly accessible web service, named DynFunc (Dynamics Match for Function) to query protein function from ≥1 µs long CG dynamics trajectory information of protein subunits. Users are provided with the custom-developed coarse-grained molecular mechanics (CGMM) forcefield to generate the MD trajectories for their protein of interest. On upload of trajectory information, the DynFunc web server identifies specific flexible regions of the protein linked to putative molecular function. Our unique application does not use evolutionary information to infer molecular function from MD information and can, therefore, work for all proteins, including moonlighting and the novel ones, whenever structural information is available. Our pipeline is expected to be of utility to all structural biologists working with novel proteins and interested in moonlighting functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reprogrammable Assembly of Molecular Motor on Solid Surfaces via Dynamic Bonds.

PubMed

Yu, Li; Sun, Jian; Wang, Qian; Guan, Yan; Zhou, Le; Zhang, Jingxuan; Zhang, Lanying; Yang, Huai

2017-06-01

Controllable assembly of molecular motors on solid surfaces is a fundamental issue for providing them to perform physical tasks. However, it can hardly be achieved by most previous methods due to their inherent limitations. Here, a general strategy is designed for the reprogrammable assembly of molecular motors on solid surfaces based on dynamic bonds. In this method, molecular motors with disulfide bonds can be remotely, reversibly, and precisely attached to solid surfaces with disulfide bonds, regardless of their chemical composition and microstructure. More importantly, it not only allows encoding geometric information referring to a pattern of molecular motors, but also enables erasing and re-encoding of geometric information via hemolytic photocleavage and recombination of disulfide bonds. Thus, solid surfaces can be regarded as "computer hardware", where molecular motors can be reformatted and reprogramed as geometric information. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Communication: On the consistency of approximate quantum dynamics simulation methods for vibrational spectra in the condensed phase.

PubMed

Rossi, Mariana; Liu, Hanchao; Paesani, Francesco; Bowman, Joel; Ceriotti, Michele

2014-11-14

Including quantum mechanical effects on the dynamics of nuclei in the condensed phase is challenging, because the complexity of exact methods grows exponentially with the number of quantum degrees of freedom. Efforts to circumvent these limitations can be traced down to two approaches: methods that treat a small subset of the degrees of freedom with rigorous quantum mechanics, considering the rest of the system as a static or classical environment, and methods that treat the whole system quantum mechanically, but using approximate dynamics. Here, we perform a systematic comparison between these two philosophies for the description of quantum effects in vibrational spectroscopy, taking the Embedded Local Monomer model and a mixed quantum-classical model as representatives of the first family of methods, and centroid molecular dynamics and thermostatted ring polymer molecular dynamics as examples of the latter. We use as benchmarks D2O doped with HOD and pure H2O at three distinct thermodynamic state points (ice Ih at 150 K, and the liquid at 300 K and 600 K), modeled with the simple q-TIP4P/F potential energy and dipole moment surfaces. With few exceptions the different techniques yield IR absorption frequencies that are consistent with one another within a few tens of cm(-1). Comparison with classical molecular dynamics demonstrates the importance of nuclear quantum effects up to the highest temperature, and a detailed discussion of the discrepancies between the various methods let us draw some (circumstantial) conclusions about the impact of the very different approximations that underlie them. Such cross validation between radically different approaches could indicate a way forward to further improve the state of the art in simulations of condensed-phase quantum dynamics.

Multiscale simulations of anisotropic particles combining molecular dynamics and Green's function reaction dynamics

NASA Astrophysics Data System (ADS)

Vijaykumar, Adithya; Ouldridge, Thomas E.; ten Wolde, Pieter Rein; Bolhuis, Peter G.

2017-03-01

The modeling of complex reaction-diffusion processes in, for instance, cellular biochemical networks or self-assembling soft matter can be tremendously sped up by employing a multiscale algorithm which combines the mesoscopic Green's Function Reaction Dynamics (GFRD) method with explicit stochastic Brownian, Langevin, or deterministic molecular dynamics to treat reactants at the microscopic scale [A. Vijaykumar, P. G. Bolhuis, and P. R. ten Wolde, J. Chem. Phys. 143, 214102 (2015)]. Here we extend this multiscale MD-GFRD approach to include the orientational dynamics that is crucial to describe the anisotropic interactions often prevalent in biomolecular systems. We present the novel algorithm focusing on Brownian dynamics only, although the methodology is generic. We illustrate the novel algorithm using a simple patchy particle model. After validation of the algorithm, we discuss its performance. The rotational Brownian dynamics MD-GFRD multiscale method will open up the possibility for large scale simulations of protein signalling networks.

Graph Theory and Ion and Molecular Aggregation in Aqueous Solutions.

PubMed

Choi, Jun-Ho; Lee, Hochan; Choi, Hyung Ran; Cho, Minhaeng

2018-04-20

In molecular and cellular biology, dissolved ions and molecules have decisive effects on chemical and biological reactions, conformational stabilities, and functions of small to large biomolecules. Despite major efforts, the current state of understanding of the effects of specific ions, osmolytes, and bioprotecting sugars on the structure and dynamics of water H-bonding networks and proteins is not yet satisfactory. Recently, to gain deeper insight into this subject, we studied various aggregation processes of ions and molecules in high-concentration salt, osmolyte, and sugar solutions with time-resolved vibrational spectroscopy and molecular dynamics simulation methods. It turns out that ions (or solute molecules) have a strong propensity to self-assemble into large and polydisperse aggregates that affect both local and long-range water H-bonding structures. In particular, we have shown that graph-theoretical approaches can be used to elucidate morphological characteristics of large aggregates in various aqueous salt, osmolyte, and sugar solutions. When ion and molecular aggregates in such aqueous solutions are treated as graphs, a variety of graph-theoretical properties, such as graph spectrum, degree distribution, clustering coefficient, minimum path length, and graph entropy, can be directly calculated by considering an ensemble of configurations taken from molecular dynamics trajectories. Here we show percolating behavior exhibited by ion and molecular aggregates upon increase in solute concentration in high solute concentrations and discuss compelling evidence of the isomorphic relation between percolation transitions of ion and molecular aggregates and water H-bonding networks. We anticipate that the combination of graph theory and molecular dynamics simulation methods will be of exceptional use in achieving a deeper understanding of the fundamental physical chemistry of dissolution and in describing the interplay between the self-aggregation of solute molecules and the structure and dynamics of water.

Graph Theory and Ion and Molecular Aggregation in Aqueous Solutions

NASA Astrophysics Data System (ADS)

Choi, Jun-Ho; Lee, Hochan; Choi, Hyung Ran; Cho, Minhaeng

2018-04-01

In molecular and cellular biology, dissolved ions and molecules have decisive effects on chemical and biological reactions, conformational stabilities, and functions of small to large biomolecules. Despite major efforts, the current state of understanding of the effects of specific ions, osmolytes, and bioprotecting sugars on the structure and dynamics of water H-bonding networks and proteins is not yet satisfactory. Recently, to gain deeper insight into this subject, we studied various aggregation processes of ions and molecules in high-concentration salt, osmolyte, and sugar solutions with time-resolved vibrational spectroscopy and molecular dynamics simulation methods. It turns out that ions (or solute molecules) have a strong propensity to self-assemble into large and polydisperse aggregates that affect both local and long-range water H-bonding structures. In particular, we have shown that graph-theoretical approaches can be used to elucidate morphological characteristics of large aggregates in various aqueous salt, osmolyte, and sugar solutions. When ion and molecular aggregates in such aqueous solutions are treated as graphs, a variety of graph-theoretical properties, such as graph spectrum, degree distribution, clustering coefficient, minimum path length, and graph entropy, can be directly calculated by considering an ensemble of configurations taken from molecular dynamics trajectories. Here we show percolating behavior exhibited by ion and molecular aggregates upon increase in solute concentration in high solute concentrations and discuss compelling evidence of the isomorphic relation between percolation transitions of ion and molecular aggregates and water H-bonding networks. We anticipate that the combination of graph theory and molecular dynamics simulation methods will be of exceptional use in achieving a deeper understanding of the fundamental physical chemistry of dissolution and in describing the interplay between the self-aggregation of solute molecules and the structure and dynamics of water.

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.

Quantum Spectra and Dynamics

NASA Astrophysics Data System (ADS)

Arce, Julio Cesar

1992-01-01

This work focuses on time-dependent quantum theory and methods for the study of the spectra and dynamics of atomic and molecular systems. Specifically, we have addressed the following two problems: (i) Development of a time-dependent spectral method for the construction of spectra of simple quantum systems--This includes the calculation of eigenenergies, the construction of bound and continuum eigenfunctions, and the calculation of photo cross-sections. Computational applications include the quadrupole photoabsorption spectra and dissociation cross-sections of molecular hydrogen from various vibrational states in its ground electronic potential -energy curve. This method is seen to provide an advantageous alternative, both from the computational and conceptual point of view, to existing standard methods. (ii) Explicit time-dependent formulation of photoabsorption processes --Analytical solutions of the time-dependent Schrodinger equation are constructed and employed for the calculation of probability densities, momentum distributions, fluxes, transition rates, expectation values and correlation functions. These quantities are seen to establish the link between the dynamics and the calculated, or measured, spectra and cross-sections, and to clarify the dynamical nature of the excitation, transition and ejection processes. Numerical calculations on atomic and molecular hydrogen corroborate and complement the previous results, allowing the identification of different regimes during the photoabsorption process.

A method for the direct measurement of electronic site populations in a molecular aggregate using two-dimensional electronic-vibrational spectroscopy

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

Lewis, Nicholas H. C.; Dong, Hui; Oliver, Thomas A. A.

2015-09-28

Two dimensional electronic spectroscopy has proven to be a valuable experimental technique to reveal electronic excitation dynamics in photosynthetic pigment-protein complexes, nanoscale semiconductors, organic photovoltaic materials, and many other types of systems. It does not, however, provide direct information concerning the spatial structure and dynamics of excitons. 2D infrared spectroscopy has become a widely used tool for studying structural dynamics but is incapable of directly providing information concerning electronic excited states. 2D electronic-vibrational (2DEV) spectroscopy provides a link between these domains, directly connecting the electronic excitation with the vibrational structure of the system under study. In this work, we derivemore » response functions for the 2DEV spectrum of a molecular dimer and propose a method by which 2DEV spectra could be used to directly measure the electronic site populations as a function of time following the initial electronic excitation. We present results from the response function simulations which show that our proposed approach is substantially valid. This method provides, to our knowledge, the first direct experimental method for measuring the electronic excited state dynamics in the spatial domain, on the molecular scale.« less

A method for the direct measurement of electronic site populations in a molecular aggregate using two-dimensional electronic-vibrational spectroscopy

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

Lewis, Nicholas H. C.; Dong, Hui; Oliver, Thomas A. A.

2015-09-28

Two dimensional electronic spectroscopy has proved to be a valuable experimental technique to reveal electronic excitation dynamics in photosynthetic pigment-protein complexes, nanoscale semiconductors, organic photovoltaic materials, and many other types of systems. It does not, however, provide direct information concerning the spatial structure and dynamics of excitons. 2D infrared spectroscopy has become a widely used tool for studying structural dynamics but is incapable of directly providing information concerning electronic excited states. 2D electronic-vibrational (2DEV) spectroscopy provides a link between these domains, directly connecting the electronic excitation with the vibrational structure of the system under study. In this work, we derivemore » response functions for the 2DEV spectrum of a molecular dimer and propose a method by which 2DEV spectra could be used to directly measure the electronic site populations as a function of time following the initial electronic excitation. We present results from the response function simulations which show that our proposed approach is substantially valid. This method provides, to our knowledge, the first direct experimental method for measuring the electronic excited state dynamics in the spatial domain, on the molecular scale.« less

A method for the direct measurement of electronic site populations in a molecular aggregate using two-dimensional electronic-vibrational spectroscopy.

PubMed

Lewis, Nicholas H C; Dong, Hui; Oliver, Thomas A A; Fleming, Graham R

2015-09-28

Two dimensional electronic spectroscopy has proved to be a valuable experimental technique to reveal electronic excitation dynamics in photosynthetic pigment-protein complexes, nanoscale semiconductors, organic photovoltaic materials, and many other types of systems. It does not, however, provide direct information concerning the spatial structure and dynamics of excitons. 2D infrared spectroscopy has become a widely used tool for studying structural dynamics but is incapable of directly providing information concerning electronic excited states. 2D electronic-vibrational (2DEV) spectroscopy provides a link between these domains, directly connecting the electronic excitation with the vibrational structure of the system under study. In this work, we derive response functions for the 2DEV spectrum of a molecular dimer and propose a method by which 2DEV spectra could be used to directly measure the electronic site populations as a function of time following the initial electronic excitation. We present results from the response function simulations which show that our proposed approach is substantially valid. This method provides, to our knowledge, the first direct experimental method for measuring the electronic excited state dynamics in the spatial domain, on the molecular scale.

Detecting transitions in protein dynamics using a recurrence quantification analysis based bootstrap method.

PubMed

Karain, Wael I

2017-11-28

Proteins undergo conformational transitions over different time scales. These transitions are closely intertwined with the protein's function. Numerous standard techniques such as principal component analysis are used to detect these transitions in molecular dynamics simulations. In this work, we add a new method that has the ability to detect transitions in dynamics based on the recurrences in the dynamical system. It combines bootstrapping and recurrence quantification analysis. We start from the assumption that a protein has a "baseline" recurrence structure over a given period of time. Any statistically significant deviation from this recurrence structure, as inferred from complexity measures provided by recurrence quantification analysis, is considered a transition in the dynamics of the protein. We apply this technique to a 132 ns long molecular dynamics simulation of the β-Lactamase Inhibitory Protein BLIP. We are able to detect conformational transitions in the nanosecond range in the recurrence dynamics of the BLIP protein during the simulation. The results compare favorably to those extracted using the principal component analysis technique. The recurrence quantification analysis based bootstrap technique is able to detect transitions between different dynamics states for a protein over different time scales. It is not limited to linear dynamics regimes, and can be generalized to any time scale. It also has the potential to be used to cluster frames in molecular dynamics trajectories according to the nature of their recurrence dynamics. One shortcoming for this method is the need to have large enough time windows to insure good statistical quality for the recurrence complexity measures needed to detect the transitions.

Drama in Dynamics: Boom, Splash, and Speed

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

Netzloff, Heather Marie

2004-12-19

The full nature of chemistry and physics cannot be captured by static calculations alone. Dynamics calculations allow the simulation of time-dependent phenomena. This facilitates both comparisons with experimental data and the prediction and interpretation of details not easily obtainable from experiments. Simulations thus provide a direct link between theory and experiment, between microscopic details of a system and macroscopic observed properties. Many types of dynamics calculations exist. The most important distinction between the methods and the decision of which method to use can be described in terms of the size and type of molecule/reaction under consideration and the type andmore » level of accuracy required in the final properties of interest. These considerations must be balanced with available computational codes and resources as simulations to mimic ''real-life'' may require many time steps. As indicated in the title, the theme of this thesis is dynamics. The goal is to utilize the best type of dynamics for the system under study while trying to perform dynamics in the most accurate way possible. As a quantum chemist, this involves some level of first principles calculations by default. Very accurate calculations of small molecules and molecular systems are now possible with relatively high-level ab initio quantum chemistry. For example, a quantum chemical potential energy surface (PES) can be developed ''on-the-fly'' with dynamic reaction path (DRP) methods. In this way a classical trajectory is developed without prior knowledge of the PES. In order to treat solvation processes and the condensed phase, large numbers of molecules are required, especially in predicting bulk behavior. The Effective Fragment Potential (EFP) method for solvation decreases the cost of a fully quantum mechanical calculation by dividing a chemical system into an ab initio region that contains the solute and an ''effective fragment'' region that contains the remaining solvent molecules. But, despite the reduced cost relative to fully QM calculations, the EFP method, due to its complex, QM-based potential, does require more computation time than simple interaction potentials, especially when the method is used for large scale molecular dynamics simulations. Thus, the EFP method was parallelized to facilitate these calculations within the quantum chemistry program GAMESS. The EFP method provides relative energies and structures that are in excellent agreement with the analogous fully quantum results for small water clusters. The ability of the method to predict bulk water properties with a comparable accuracy is assessed by performing EFP molecular dynamics simulations. Molecular dynamics simulations can provide properties that are directly comparable with experimental results, for example radial distribution functions. The molecular PES is a fundamental starting point for chemical reaction dynamics. Many methods can be used to obtain a PES; for example, assuming a global functional form for the PES or, as mentioned above, performing ''on-the-fly'' dynamics with Al or semi-empirical calculations at every molecular configuration. But as the size of the system grows, using electronic structure theory to build a PES and, therefore, study reaction dynamics becomes virtually impossible. The program Grow builds a PES as an interpolation of Al data; the goal is to attempt to produce an accurate PES with the smallest number of Al calculations. The Grow-GAMESS interface was developed to obtain the Al data from GAMESS. Classical or quantum dynamics can be performed on the resulting surface. The interface includes the novel capability to build multi-reference PESs; these types of calculations are applicable to problems ranging from atmospheric chemistry to photochemical reaction mechanisms in organic and inorganic chemistry to fundamental biological phenomena such as photosynthesis.« less

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.

Nanomechanics of Carbon and CxByNz Nanotubes: Via a Quantum Molecular Dynamics Method

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Menon, M.; Cho, Kyeong Jae; Saini, Subhash (Technical Monitor)

1999-01-01

Nanomechanics of single-wall C, BN and BC$_3$ and B doped C nanotubes under axial compression and tension are investigated through a generalized tight-binding molecular dynamics (GTBMD) and {\\it ab-initio} electronic structure methods. The dynamic strength of BN, BC$_3$ and B doped C nanotubes for small axial strain are comparable to each other. The main difference is in the critical strain at which structural collapse occurs. For example, even a shallow doping with B lowers the value of critical strain for C nanotubes. The critical strain for BN nanotube is found to be more than that for the similar C nanotube. Once the structural collapse starts to occur we find that carbon nanotubes irreversibly go into plastic deformation regime via the formation of tetrahedral (four-fold coordinated) bonds at the location of sharp pinches or kinks. This finding is considerably different from the classical MD (molecular dynamics) simulation results known so far. The energetics and electronic densities of states of the collapsed structures, investigated with {\\it ab-initio) methods, will also be discussed.

Exploring oxidative ageing behaviour of hydrocarbons using ab initio molecular dynamics analysis

NASA Astrophysics Data System (ADS)

Pan, Tongyan; Cheng, Cheng

2016-06-01

With a proper approximate solution to the Schrödinger Equation of a multi-electron system, the method of ab initio molecular dynamics (AIMD) performs first-principles molecular dynamics analysis without pre-defining interatomic potentials as are mandatory in traditional molecular dynamics analyses. The objective of this study is to determine the oxidative-ageing pathway of petroleum asphalt as a typical hydrocarbon system, using the AIMD method. This objective was accomplished in three steps, including (1) identifying a group of representative asphalt molecules to model, (2) determining an atomistic modelling method that can effectively simulate the production of critical functional groups in oxidative ageing of hydrocarbons and (3) evaluating the oxidative-ageing pathway of a hydrocarbon system. The determination of oxidative-ageing pathway of hydrocarbons was done by tracking the generations of critical functional groups in the course of oxidative ageing. The chemical elements of carbon, nitrogen and sulphur all experience oxidative reactions, producing polarised functional groups such as ketones, aldehydes or carboxylic acids, pyrrolic groups and sulphoxides. The electrostatic forces of the polarised groups generated in oxidation are responsible for the behaviour of aged hydrocarbons. The developed AIMD model can be used for modelling the ageing of generic hydrocarbon polymers and developing antioxidants without running expensive experiments.

Exploring high dimensional free energy landscapes: Temperature accelerated sliced sampling

NASA Astrophysics Data System (ADS)

Awasthi, Shalini; Nair, Nisanth N.

2017-03-01

Biased sampling of collective variables is widely used to accelerate rare events in molecular simulations and to explore free energy surfaces. However, computational efficiency of these methods decreases with increasing number of collective variables, which severely limits the predictive power of the enhanced sampling approaches. Here we propose a method called Temperature Accelerated Sliced Sampling (TASS) that combines temperature accelerated molecular dynamics with umbrella sampling and metadynamics to sample the collective variable space in an efficient manner. The presented method can sample a large number of collective variables and is advantageous for controlled exploration of broad and unbound free energy basins. TASS is also shown to achieve quick free energy convergence and is practically usable with ab initio molecular dynamics techniques.

Energy conserving, linear scaling Born-Oppenheimer molecular dynamics.

PubMed

Cawkwell, M J; Niklasson, Anders M N

2012-10-07

Born-Oppenheimer molecular dynamics simulations with long-term conservation of the total energy and a computational cost that scales linearly with system size have been obtained simultaneously. Linear scaling with a low pre-factor is achieved using density matrix purification with sparse matrix algebra and a numerical threshold on matrix elements. The extended Lagrangian Born-Oppenheimer molecular dynamics formalism [A. M. N. Niklasson, Phys. Rev. Lett. 100, 123004 (2008)] yields microcanonical trajectories with the approximate forces obtained from the linear scaling method that exhibit no systematic drift over hundreds of picoseconds and which are indistinguishable from trajectories computed using exact forces.

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.

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.

Capillary waves' dynamics at the nanoscale

NASA Astrophysics Data System (ADS)

Delgado-Buscalioni, Rafael; Chacón, Enrique; Tarazona, Pedro

2008-12-01

We study the dynamics of thermally excited capillary waves (CW) at molecular scales, using molecular dynamics simulations of simple liquid slabs. The analysis is based on the Fourier modes of the liquid surface, constructed via the intrinsic sampling method (Chacón and Tarazona 2003 Phys. Rev. Lett. 91 166103). We obtain the time autocorrelation of the Fourier modes to get the frequency and damping rate Γd(q) of each mode, with wavenumber q. Continuum hydrodynamics predicts \\Gamma (q) \\propto q\\gamma (q) and thus provides a dynamic measure of the q-dependent surface tension, γd(q). The dynamical estimation is much more robust than the structural prediction based on the amplitude of the Fourier mode, γs(q). Using the optimal estimation of the intrinsic surface, we obtain quantitative agreement between the structural and dynamic pictures. Quite surprisingly, the hydrodynamic prediction for CW remains valid up to wavelengths of about four molecular diameters. Surface tension hydrodynamics break down at shorter scales, whereby a transition to a molecular diffusion regime is observed.

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.

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.

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.

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.

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

Analysis of Serial and Parallel Algorithms for Use in Molecular Dynamics.. Review and Proposals

NASA Astrophysics Data System (ADS)

Mazzone, A. M.

This work analyzes the stability and accuracy of multistep methods, either for serial or parallel calculations, applied to molecular dynamics simulations. Numerical testing is made by evaluating the equilibrium configurations of mono-elemental crystalline lattices of metallic and semiconducting type (Ag and Si, respectively) and of a cubic CuY compound.

Exploring warm dense matter using quantum molecular dynamics

NASA Astrophysics Data System (ADS)

Clérouin, J.; Mazevet, S.

2006-06-01

For dense plasmas produced in shock experiments, the influence of the media on the isolated atomic properties can no longer be treated as a perturbation and conventional atomic physics approaches usually fail. Recently, quantum molecular dynamics (QMD) has been used to successfully predict static, dynamical and optical properties in this regime within the framework of a first principle method. In this short report, we illustrate the usefulness of the method for dense plasmas with a few selected examples: the equation of state of liquid deuterium, the electrical properties of expanded metals, the optical properties of shocked insulators, and the interaction of femto-second lasers with gold thin films.

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.

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.

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.

Molecular nonlinear dynamics and protein thermal uncertainty quantification

PubMed Central

Xia, Kelin; Wei, Guo-Wei

2014-01-01

This work introduces molecular nonlinear dynamics (MND) as a new approach for describing protein folding and aggregation. By using a mode system, we show that the MND of disordered proteins is chaotic while that of folded proteins exhibits intrinsically low dimensional manifolds (ILDMs). The stability of ILDMs is found to strongly correlate with protein energies. We propose a novel method for protein thermal uncertainty quantification based on persistently invariant ILDMs. Extensive comparison with experimental data and the state-of-the-art methods in the field validate the proposed new method for protein B-factor prediction. PMID:24697365

Free-energy analyses of a proton transfer reaction by simulated-tempering umbrella sampling and first-principles molecular dynamics simulations.

PubMed

Mori, Yoshiharu; Okamoto, Yuko

2013-02-01

A simulated tempering method, which is referred to as simulated-tempering umbrella sampling, for calculating the free energy of chemical reactions is proposed. First principles molecular dynamics simulations with this simulated tempering were performed to study the intramolecular proton transfer reaction of malonaldehyde in an aqueous solution. Conformational sampling in reaction coordinate space can be easily enhanced with this method, and the free energy along a reaction coordinate can be calculated accurately. Moreover, the simulated-tempering umbrella sampling provides trajectory data more efficiently than the conventional umbrella sampling method.

Advances in modelling of biomimetic fluid flow at different scales

PubMed Central

2011-01-01

The biomimetic flow at different scales has been discussed at length. The need of looking into the biological surfaces and morphologies and both geometrical and physical similarities to imitate the technological products and processes has been emphasized. The complex fluid flow and heat transfer problems, the fluid-interface and the physics involved at multiscale and macro-, meso-, micro- and nano-scales have been discussed. The flow and heat transfer simulation is done by various CFD solvers including Navier-Stokes and energy equations, lattice Boltzmann method and molecular dynamics method. Combined continuum-molecular dynamics method is also reviewed. PMID:21711847

Molecular dynamics for dense matter

NASA Astrophysics Data System (ADS)

Maruyama, Toshiki; Watanabe, Gentaro; Chiba, Satoshi

2012-08-01

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

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.

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.

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.

General Formalism of Mass Scaling Approach for Replica-Exchange Molecular Dynamics and its Application

NASA Astrophysics Data System (ADS)

Nagai, Tetsuro

2017-01-01

Replica-exchange molecular dynamics (REMD) has demonstrated its efficiency by combining trajectories of a wide range of temperatures. As an extension of the method, the author formalizes the mass-manipulating replica-exchange molecular dynamics (MMREMD) method that allows for arbitrary mass scaling with respect to temperature and individual particles. The formalism enables the versatile application of mass-scaling approaches to the REMD method. The key change introduced in the novel formalism is the generalized rules for the velocity and momentum scaling after accepted replica-exchange attempts. As an application of this general formalism, the refinement of the viscosity-REMD (V-REMD) method [P. H. Nguyen, J. Chem. Phys. 132, 144109 (2010)] is presented. Numerical results are provided using a pilot system, demonstrating easier and more optimized applicability of the new version of V-REMD as well as the importance of adherence to the generalized velocity scaling rules. With the new formalism, more sound and efficient simulations will be performed.

POLYANA-A tool for the calculation of molecular radial distribution functions based on Molecular Dynamics trajectories

NASA Astrophysics Data System (ADS)

Dimitroulis, Christos; Raptis, Theophanes; Raptis, Vasilios

2015-12-01

We present an application for the calculation of radial distribution functions for molecular centres of mass, based on trajectories generated by molecular simulation methods (Molecular Dynamics, Monte Carlo). When designing this application, the emphasis was placed on ease of use as well as ease of further development. In its current version, the program can read trajectories generated by the well-known DL_POLY package, but it can be easily extended to handle other formats. It is also very easy to 'hack' the program so it can compute intermolecular radial distribution functions for groups of interaction sites rather than whole molecules.

Enhanced sampling of molecular dynamics simulation of peptides and proteins by double coupling to thermal bath.

PubMed

Chen, Changjun; Huang, Yanzhao; Xiao, Yi

2013-01-01

Low sampling efficiency in conformational space is the well-known problem for conventional molecular dynamics. It greatly increases the difficulty for molecules to find the transition path to native state, and costs amount of CPU time. To accelerate the sampling, in this paper, we re-couple the critical degrees of freedom in the molecule to environment temperature, like dihedrals in generalized coordinates or nonhydrogen atoms in Cartesian coordinate. After applying to ALA dipeptide model, we find that this modified molecular dynamics greatly enhances the sampling behavior in the conformational space and provides more information about the state-to-state transition, while conventional molecular dynamics fails to do so. Moreover, from the results of 16 independent 100 ns simulations by the new method, it shows that trpzip2 has one-half chances to reach the naive state in all the trajectories, which is greatly higher than conventional molecular dynamics. Such an improvement would provide a potential way for searching the conformational space or predicting the most stable states of peptides and proteins.

Impact of anisotropy on the structure and dynamics of ionic liquids: A computational study of 1-butyl-3-methyl-imidazolium trifluoroacetate

NASA Astrophysics Data System (ADS)

Schröder, C.; Rudas, T.; Neumayr, G.; Gansterer, W.; Steinhauser, O.

2007-07-01

The complex ionic network of 1-butyl-3-methyl-imidazolium trifluoroacetate was simulated by means of the molecular dynamics methods over a time period of 100ns. The influence of the anisotropy of the shape and charge distribution of both the cations and the anions on the local (molecular) and global (collective) structure and dynamics is analyzed. The distance-dependent g coefficients of the orientational probability function g(r,Ω) were found to be an excellent way to interpret local structure. Thereby, the combination and interrelation of individual g coefficients elucidate the mutual orientation. Dynamics at the molecular level is characterized by the time correlation function of the center-of-mass corrected molecular dipole moment μcm. Upon uniting the set of molecular dipoles to a single collective rotational dipole moment, MD, dynamics on a global level is studied. Decomposing into subsets of cations and anions respective self terms as well as the prominent cross term can be extracted. This decomposition also enables a detailed peak assignment in dielectric spectra.

Impact of anisotropy on the structure and dynamics of ionic liquids: a computational study of 1-butyl-3-methyl-imidazolium trifluoroacetate.

PubMed

Schröder, C; Rudas, T; Neumayr, G; Gansterer, W; Steinhauser, O

2007-07-28

The complex ionic network of 1-butyl-3-methyl-imidazolium trifluoroacetate was simulated by means of the molecular dynamics methods over a time period of 100 ns. The influence of the anisotropy of the shape and charge distribution of both the cations and the anions on the local (molecular) and global (collective) structure and dynamics is analyzed. The distance-dependent g coefficients of the orientational probability function g(r,Omega) were found to be an excellent way to interpret local structure. Thereby, the combination and interrelation of individual g coefficients elucidate the mutual orientation. Dynamics at the molecular level is characterized by the time correlation function of the center-of-mass corrected molecular dipole moment mucm. Upon uniting the set of molecular dipoles to a single collective rotational dipole moment, MD, dynamics on a global level is studied. Decomposing into subsets of cations and anions respective self terms as well as the prominent cross term can be extracted. This decomposition also enables a detailed peak assignment in dielectric spectra.

Overcoming potential energy distortions in constrained internal coordinate molecular dynamics simulations.

PubMed

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

2016-01-28

The Internal Coordinate Molecular Dynamics (ICMD) method is an attractive molecular dynamics (MD) method for studying the dynamics of bonded systems such as proteins and polymers. It offers a simple venue for coarsening the dynamics model of a system at multiple hierarchical levels. For example, large scale protein dynamics can be studied using torsional dynamics, where large domains or helical structures can be treated as rigid bodies and the loops connecting them as flexible torsions. ICMD with such a dynamic model of the protein, combined with enhanced conformational sampling method such as temperature replica exchange, allows the sampling of large scale domain motion involving high energy barrier transitions. Once these large scale conformational transitions are sampled, all-torsion, or even all-atom, MD simulations can be carried out for the low energy conformations sampled via coarse grained ICMD to calculate the energetics of distinct conformations. Such hierarchical MD simulations can be carried out with standard all-atom forcefields without the need for compromising on the accuracy of the forces. Using constraints to treat bond lengths and bond angles as rigid can, however, distort the potential energy landscape of the system and reduce the number of dihedral transitions as well as conformational sampling. We present here a two-part solution to overcome such distortions of the potential energy landscape with ICMD models. To alleviate the intrinsic distortion that stems from the reduced phase space in torsional MD, we use the Fixman compensating potential. To additionally alleviate the extrinsic distortion that arises from the coupling between the dihedral angles and bond angles within a force field, we propose a hybrid ICMD method that allows the selective relaxing of bond angles. This hybrid ICMD method bridges the gap between all-atom MD and torsional MD. We demonstrate with examples that these methods together offer a solution to eliminate the potential energy distortions encountered in constrained ICMD simulations of peptide molecules.

Overcoming potential energy distortions in constrained internal coordinate molecular dynamics simulations

NASA Astrophysics Data System (ADS)

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

2016-01-01

The Internal Coordinate Molecular Dynamics (ICMD) method is an attractive molecular dynamics (MD) method for studying the dynamics of bonded systems such as proteins and polymers. It offers a simple venue for coarsening the dynamics model of a system at multiple hierarchical levels. For example, large scale protein dynamics can be studied using torsional dynamics, where large domains or helical structures can be treated as rigid bodies and the loops connecting them as flexible torsions. ICMD with such a dynamic model of the protein, combined with enhanced conformational sampling method such as temperature replica exchange, allows the sampling of large scale domain motion involving high energy barrier transitions. Once these large scale conformational transitions are sampled, all-torsion, or even all-atom, MD simulations can be carried out for the low energy conformations sampled via coarse grained ICMD to calculate the energetics of distinct conformations. Such hierarchical MD simulations can be carried out with standard all-atom forcefields without the need for compromising on the accuracy of the forces. Using constraints to treat bond lengths and bond angles as rigid can, however, distort the potential energy landscape of the system and reduce the number of dihedral transitions as well as conformational sampling. We present here a two-part solution to overcome such distortions of the potential energy landscape with ICMD models. To alleviate the intrinsic distortion that stems from the reduced phase space in torsional MD, we use the Fixman compensating potential. To additionally alleviate the extrinsic distortion that arises from the coupling between the dihedral angles and bond angles within a force field, we propose a hybrid ICMD method that allows the selective relaxing of bond angles. This hybrid ICMD method bridges the gap between all-atom MD and torsional MD. We demonstrate with examples that these methods together offer a solution to eliminate the potential energy distortions encountered in constrained ICMD simulations of peptide molecules.

Multiple time step integrators in ab initio molecular dynamics.

PubMed

Luehr, Nathan; Markland, Thomas E; Martínez, Todd J

2014-02-28

Multiple time-scale algorithms exploit the natural separation of time-scales in chemical systems to greatly accelerate the efficiency of molecular dynamics simulations. Although the utility of these methods in systems where the interactions are described by empirical potentials is now well established, their application to ab initio molecular dynamics calculations has been limited by difficulties associated with splitting the ab initio potential into fast and slowly varying components. Here we present two schemes that enable efficient time-scale separation in ab initio calculations: one based on fragment decomposition and the other on range separation of the Coulomb operator in the electronic Hamiltonian. We demonstrate for both water clusters and a solvated hydroxide ion that multiple time-scale molecular dynamics allows for outer time steps of 2.5 fs, which are as large as those obtained when such schemes are applied to empirical potentials, while still allowing for bonds to be broken and reformed throughout the dynamics. This permits computational speedups of up to 4.4x, compared to standard Born-Oppenheimer ab initio molecular dynamics with a 0.5 fs time step, while maintaining the same energy conservation and accuracy.

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

Semiclassical Monte Carlo: A first principles approach to non-adiabatic molecular dynamics

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

White, Alexander J.; Center for Nonlinear Studies; Gorshkov, Vyacheslav N.

2014-11-14

Modeling the dynamics of photophysical and (photo)chemical reactions in extended molecular systems is a new frontier for quantum chemistry. Many dynamical phenomena, such as intersystem crossing, non-radiative relaxation, and charge and energy transfer, require a non-adiabatic description which incorporate transitions between electronic states. Additionally, these dynamics are often highly sensitive to quantum coherences and interference effects. Several methods exist to simulate non-adiabatic dynamics; however, they are typically either too expensive to be applied to large molecular systems (10's-100's of atoms), or they are based on ad hoc schemes which may include severe approximations due to inconsistencies in classical and quantummore » mechanics. We present, in detail, an algorithm based on Monte Carlo sampling of the semiclassical time-dependent wavefunction that involves running simple surface hopping dynamics, followed by a post-processing step which adds little cost. The method requires only a few quantities from quantum chemistry calculations, can systematically be improved, and provides excellent agreement with exact quantum mechanical results. Here we show excellent agreement with exact solutions for scattering results of standard test problems. Additionally, we find that convergence of the wavefunction is controlled by complex valued phase factors, the size of the non-adiabatic coupling region, and the choice of sampling function. These results help in determining the range of applicability of the method, and provide a starting point for further improvement.« less

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

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.

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.

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.

Exciton dynamics of C60-based single-photon emitters explored by Hanbury Brown-Twiss scanning tunnelling microscopy.

PubMed

Merino, P; Große, C; Rosławska, A; Kuhnke, K; Kern, K

2015-09-29

Exciton creation and annihilation by charges are crucial processes for technologies relying on charge-exciton-photon conversion. Improvement of organic light sources or dye-sensitized solar cells requires methods to address exciton dynamics at the molecular scale. Near-field techniques have been instrumental for this purpose; however, characterizing exciton recombination with molecular resolution remained a challenge. Here, we study exciton dynamics by using scanning tunnelling microscopy to inject current with sub-molecular precision and Hanbury Brown-Twiss interferometry to measure photon correlations in the far-field electroluminescence. Controlled injection allows us to generate excitons in solid C60 and let them interact with charges during their lifetime. We demonstrate electrically driven single-photon emission from localized structural defects and determine exciton lifetimes in the picosecond range. Monitoring lifetime shortening and luminescence saturation for increasing carrier injection rates provides access to charge-exciton annihilation dynamics. Our approach introduces a unique way to study single quasi-particle dynamics on the ultimate molecular scale.

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.

Evaluation of enhanced sampling provided by accelerated molecular dynamics with Hamiltonian replica exchange methods.

PubMed

Roe, Daniel R; Bergonzo, Christina; Cheatham, Thomas E

2014-04-03

Many problems studied via molecular dynamics require accurate estimates of various thermodynamic properties, such as the free energies of different states of a system, which in turn requires well-converged sampling of the ensemble of possible structures. Enhanced sampling techniques are often applied to provide faster convergence than is possible with traditional molecular dynamics simulations. Hamiltonian replica exchange molecular dynamics (H-REMD) is a particularly attractive method, as it allows the incorporation of a variety of enhanced sampling techniques through modifications to the various Hamiltonians. In this work, we study the enhanced sampling of the RNA tetranucleotide r(GACC) provided by H-REMD combined with accelerated molecular dynamics (aMD), where a boosting potential is applied to torsions, and compare this to the enhanced sampling provided by H-REMD in which torsion potential barrier heights are scaled down to lower force constants. We show that H-REMD and multidimensional REMD (M-REMD) combined with aMD does indeed enhance sampling for r(GACC), and that the addition of the temperature dimension in the M-REMD simulations is necessary to efficiently sample rare conformations. Interestingly, we find that the rate of convergence can be improved in a single H-REMD dimension by simply increasing the number of replicas from 8 to 24 without increasing the maximum level of bias. The results also indicate that factors beyond replica spacing, such as round trip times and time spent at each replica, must be considered in order to achieve optimal sampling efficiency.

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.

Quantum wavepacket ab initio molecular dynamics: an approach for computing dynamically averaged vibrational spectra including critical nuclear quantum effects.

PubMed

Sumner, Isaiah; Iyengar, Srinivasan S

2007-10-18

We have introduced a computational methodology to study vibrational spectroscopy in clusters inclusive of critical nuclear quantum effects. This approach is based on the recently developed quantum wavepacket ab initio molecular dynamics method that combines quantum wavepacket dynamics with ab initio molecular dynamics. The computational efficiency of the dynamical procedure is drastically improved (by several orders of magnitude) through the utilization of wavelet-based techniques combined with the previously introduced time-dependent deterministic sampling procedure measure to achieve stable, picosecond length, quantum-classical dynamics of electrons and nuclei in clusters. The dynamical information is employed to construct a novel cumulative flux/velocity correlation function, where the wavepacket flux from the quantized particle is combined with classical nuclear velocities to obtain the vibrational density of states. The approach is demonstrated by computing the vibrational density of states of [Cl-H-Cl]-, inclusive of critical quantum nuclear effects, and our results are in good agreement with experiment. A general hierarchical procedure is also provided, based on electronic structure harmonic frequencies, classical ab initio molecular dynamics, computation of nuclear quantum-mechanical eigenstates, and employing quantum wavepacket ab initio dynamics to understand vibrational spectroscopy in hydrogen-bonded clusters that display large degrees of anharmonicities.

Dynamic load balancing algorithm for molecular dynamics based on Voronoi cells domain decompositions

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

Fattebert, J.-L.; Richards, D.F.; Glosli, J.N.

2012-12-01

We present a new algorithm for automatic parallel load balancing in classical molecular dynamics. It assumes a spatial domain decomposition of particles into Voronoi cells. It is a gradient method which attempts to minimize a cost function by displacing Voronoi sites associated with each processor/sub-domain along steepest descent directions. Excellent load balance has been obtained for quasi-2D and 3D practical applications, with up to 440·10 6 particles on 65,536 MPI tasks.

Theoretical studies on a carbonaceous molecular bearing: association thermodynamics and dual-mode rolling dynamics† †Electronic supplementary information (ESI) available: Supplementary figures, tables and atomic coordinates of representative geometries. See DOI: 10.1039/c5sc00335k

PubMed Central

Nakamura, Kosuke; Hitosugi, Shunpei; Sato, Sota; Tokoyama, Hiroaki; Yamakado, Hideo; Ohno, Koichi

2015-01-01

The thermodynamics and dynamics of a carbonaceous molecular bearing comprising a belt-persistent tubular molecule and a fullerene molecule have been investigated using density functional theory (DFT). Among ten representative methods, two DFT methods afforded an association energy that reasonably reproduced the experimental enthalpy of –12.5 kcal mol–1 at the unique curved π-interface. The dynamics of the molecular bearing, which was assembled solely with van der Waals interactions, exhibited small energy barriers with maximum values of 2–3 kcal mol–1 for the rolling motions. The dynamic motions responded sensitively to the steric environment and resulted in two distinct motions, precession and spin, which explained the unique NMR observations that were not clarified in previous experimental studies. PMID:29142679

A stochastic thermostat algorithm for coarse-grained thermomechanical modeling of large-scale soft matters: Theory and application to microfilaments

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

Li, Tong; Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au

As all-atom molecular dynamics method is limited by its enormous computational cost, various coarse-grained strategies have been developed to extend the length scale of soft matters in the modeling of mechanical behaviors. However, the classical thermostat algorithm in highly coarse-grained molecular dynamics method would underestimate the thermodynamic behaviors of soft matters (e.g. microfilaments in cells), which can weaken the ability of materials to overcome local energy traps in granular modeling. Based on all-atom molecular dynamics modeling of microfilament fragments (G-actin clusters), a new stochastic thermostat algorithm is developed to retain the representation of thermodynamic properties of microfilaments at extra coarse-grainedmore » level. The accuracy of this stochastic thermostat algorithm is validated by all-atom MD simulation. This new stochastic thermostat algorithm provides an efficient way to investigate the thermomechanical properties of large-scale soft matters.« 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.

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

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.

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.

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.

Isobaric molecular dynamics version of the generalized replica exchange method (gREM): Liquid–vapor equilibrium

DOE PAGES

Malolepsza, Edyta; Secor, Maxim; Keyes, Tom

2015-09-23

A prescription for sampling isobaric generalized ensembles with molecular dynamics is presented and applied to the generalized replica exchange method (gREM), which was designed for simulating first-order phase transitions. The properties of the isobaric gREM ensemble are discussed and a study is presented of the liquid-vapor equilibrium of the guest molecules given for gas hydrate formation with the mW water model. As a result, phase diagrams, critical parameters, and a law of corresponding states are obtained.

Recent Advances and Perspectives on Nonadiabatic Mixed Quantum-Classical Dynamics.

PubMed

Crespo-Otero, Rachel; Barbatti, Mario

2018-05-16

Nonadiabatic mixed quantum-classical (NA-MQC) dynamics methods form a class of computational theoretical approaches in quantum chemistry tailored to investigate the time evolution of nonadiabatic phenomena in molecules and supramolecular assemblies. NA-MQC is characterized by a partition of the molecular system into two subsystems: one to be treated quantum mechanically (usually but not restricted to electrons) and another to be dealt with classically (nuclei). The two subsystems are connected through nonadiabatic couplings terms to enforce self-consistency. A local approximation underlies the classical subsystem, implying that direct dynamics can be simulated, without needing precomputed potential energy surfaces. The NA-MQC split allows reducing computational costs, enabling the treatment of realistic molecular systems in diverse fields. Starting from the three most well-established methods-mean-field Ehrenfest, trajectory surface hopping, and multiple spawning-this review focuses on the NA-MQC dynamics methods and programs developed in the last 10 years. It stresses the relations between approaches and their domains of application. The electronic structure methods most commonly used together with NA-MQC dynamics are reviewed as well. The accuracy and precision of NA-MQC simulations are critically discussed, and general guidelines to choose an adequate method for each application are delivered.

Molecular dynamics simulation of nonlinear spectroscopies of intermolecular motions in liquid water.

PubMed

Yagasaki, Takuma; Saito, Shinji

2009-09-15

Water is the most extensively studied of liquids because of both its ubiquity and its anomalous thermodynamic and dynamic properties. The properties of water are dominated by hydrogen bonds and hydrogen bond network rearrangements. Fundamental information on the dynamics of liquid water has been provided by linear infrared (IR), Raman, and neutron-scattering experiments; molecular dynamics simulations have also provided insights. Recently developed higher-order nonlinear spectroscopies open new windows into the study of the hydrogen bond dynamics of liquid water. For example, the vibrational lifetimes of stretches and a bend, intramolecular features of water dynamics, can be accurately measured and are found to be on the femtosecond time scale at room temperature. Higher-order nonlinear spectroscopy is expressed by a multitime correlation function, whereas traditional linear spectroscopy is given by a one-time correlation function. Thus, nonlinear spectroscopy yields more detailed information on the dynamics of condensed media than linear spectroscopy. In this Account, we describe the theoretical background and methods for calculating higher order nonlinear spectroscopy; equilibrium and nonequilibrium molecular dynamics simulations, and a combination of both, are used. We also present the intermolecular dynamics of liquid water revealed by fifth-order two-dimensional (2D) Raman spectroscopy and third-order IR spectroscopy. 2D Raman spectroscopy is sensitive to couplings between modes; the calculated 2D Raman signal of liquid water shows large anharmonicity in the translational motion and strong coupling between the translational and librational motions. Third-order IR spectroscopy makes it possible to examine the time-dependent couplings. The 2D IR spectra and three-pulse photon echo peak shift show the fast frequency modulation of the librational motion. A significant effect of the translational motion on the fast frequency modulation of the librational motion is elucidated by introducing the "translation-free" molecular dynamics simulation. The isotropic pump-probe signal and the polarization anisotropy decay show fast transfer of the librational energy to the surrounding water molecules, followed by relaxation to the hot ground state. These theoretical methods do not require frequently used assumptions and can thus be called ab initio methods; together with multidimensional nonlinear spectroscopies, they provide powerful methods for examining the inter- and intramolecular details of water dynamics.

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

Conformation and dynamics of the ligand shell of a water-soluble Au102 nanoparticle.

PubMed

Salorinne, Kirsi; Malola, Sami; Wong, O Andrea; Rithner, Christopher D; Chen, Xi; Ackerson, Christopher J; Häkkinen, Hannu

2016-01-21

Inorganic nanoparticles, stabilized by a passivating layer of organic molecules, form a versatile class of nanostructured materials with potential applications in material chemistry, nanoscale physics, nanomedicine and structural biology. While the structure of the nanoparticle core is often known to atomic precision, gaining precise structural and dynamical information on the organic layer poses a major challenge. Here we report a full assignment of (1)H and (13)C NMR shifts to all ligands of a water-soluble, atomically precise, 102-atom gold nanoparticle stabilized by 44 para-mercaptobenzoic acid ligands in solution, by using a combination of multidimensional NMR methods, density functional theory calculations and molecular dynamics simulations. Molecular dynamics simulations augment the data by giving information about the ligand disorder and visualization of possible distinct ligand conformations of the most dynamic ligands. The method demonstrated here opens a way to controllable strategies for functionalization of ligated nanoparticles for applications.

Conformation and dynamics of the ligand shell of a water-soluble Au102 nanoparticle

PubMed Central

Salorinne, Kirsi; Malola, Sami; Wong, O. Andrea; Rithner, Christopher D.; Chen, Xi; Ackerson, Christopher J.; Häkkinen, Hannu

2016-01-01

Inorganic nanoparticles, stabilized by a passivating layer of organic molecules, form a versatile class of nanostructured materials with potential applications in material chemistry, nanoscale physics, nanomedicine and structural biology. While the structure of the nanoparticle core is often known to atomic precision, gaining precise structural and dynamical information on the organic layer poses a major challenge. Here we report a full assignment of 1H and 13C NMR shifts to all ligands of a water-soluble, atomically precise, 102-atom gold nanoparticle stabilized by 44 para-mercaptobenzoic acid ligands in solution, by using a combination of multidimensional NMR methods, density functional theory calculations and molecular dynamics simulations. Molecular dynamics simulations augment the data by giving information about the ligand disorder and visualization of possible distinct ligand conformations of the most dynamic ligands. The method demonstrated here opens a way to controllable strategies for functionalization of ligated nanoparticles for applications. PMID:26791253

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.

Nanoscale methods for single-molecule electrochemistry.

PubMed

Mathwig, Klaus; Aartsma, Thijs J; Canters, Gerard W; Lemay, Serge G

2014-01-01

The development of experiments capable of probing individual molecules has led to major breakthroughs in fields ranging from molecular electronics to biophysics, allowing direct tests of knowledge derived from macroscopic measurements and enabling new assays that probe population heterogeneities and internal molecular dynamics. Although still somewhat in their infancy, such methods are also being developed for probing molecular systems in solution using electrochemical transduction mechanisms. Here we outline the present status of this emerging field, concentrating in particular on optical methods, metal-molecule-metal junctions, and electrochemical nanofluidic devices.

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.

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.

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

Laser-enhanced dynamics in molecular rate processes

NASA Technical Reports Server (NTRS)

George, T. F.; Zimmerman, I. H.; Devries, P. L.; Yuan, J.-M.; Lam, K.-S.; Bellum, J. C.; Lee, H.-W.; Slutsky, M. S.

1978-01-01

The present discussion deals with some theoretical aspects associated with the description of molecular rate processes in the presence of intense laser radiation, where the radiation actually interacts with the molecular dynamics. Whereas for weak and even moderately intense radiation, the absorption and stimulated emission of photons by a molecular system can be described by perturbative methods, for intense radiation, perturbation theory is usually not adequate. Limiting the analysis to the gas phase, an attempt is made to describe nonperturbative approaches applicable to the description of such processes (in the presence of intense laser radiation) as electronic energy transfer in molecular (in particular atom-atom) collisions; collision-induced ionization and emission; and unimolecular dissociation.

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.

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.

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.

QTAIM and Stress Tensor Characterization of Intramolecular Interactions Along Dynamics Trajectories of a Light-Driven Rotary Molecular Motor.

PubMed

Wang, Lingling; Huan, Guo; Momen, Roya; Azizi, Alireza; Xu, Tianlv; Kirk, Steven R; Filatov, Michael; Jenkins, Samantha

2017-06-29

A quantum theory of atoms in molecules (QTAIM) and stress tensor analysis was applied to analyze intramolecular interactions influencing the photoisomerization dynamics of a light-driven rotary molecular motor. For selected nonadiabatic molecular dynamics trajectories characterized by markedly different S 1 state lifetimes, the electron densities were obtained using the ensemble density functional theory method. The analysis revealed that torsional motion of the molecular motor blades from the Franck-Condon point to the S 1 energy minimum and the S 1 /S 0 conical intersection is controlled by two factors: greater numbers of intramolecular bonds before the hop-time and unusually strongly coupled bonds between the atoms of the rotor and the stator blades. This results in the effective stalling of the progress along the torsional path for an extended period of time. This finding suggests a possibility of chemical tuning of the speed of photoisomerization of molecular motors and related molecular switches by reshaping their molecular backbones to decrease or increase the degree of coupling and numbers of intramolecular bond critical points as revealed by the QTAIM/stress tensor analysis of the electron density. Additionally, the stress tensor scalar and vector analysis was found to provide new methods to follow the trajectories, and from this, new insight was gained into the behavior of the S 1 state in the vicinity of the conical intersection.

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

PubMed

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

2017-03-14

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

The fluctuating ribosome: thermal molecular dynamics characterized by neutron scattering

NASA Astrophysics Data System (ADS)

Zaccai, Giuseppe; Natali, Francesca; Peters, Judith; Řihová, Martina; Zimmerman, Ella; Ollivier, J.; Combet, J.; Maurel, Marie-Christine; Bashan, Anat; Yonath, Ada

2016-11-01

Conformational changes associated with ribosome function have been identified by X-ray crystallography and cryo-electron microscopy. These methods, however, inform poorly on timescales. Neutron scattering is well adapted for direct measurements of thermal molecular dynamics, the ‘lubricant’ for the conformational fluctuations required for biological activity. The method was applied to compare water dynamics and conformational fluctuations in the 30 S and 50 S ribosomal subunits from Haloarcula marismortui, under high salt, stable conditions. Similar free and hydration water diffusion parameters are found for both subunits. With respect to the 50 S subunit, the 30 S is characterized by a softer force constant and larger mean square displacements (MSD), which would facilitate conformational adjustments required for messenger and transfer RNA binding. It has been shown previously that systems from mesophiles and extremophiles are adapted to have similar MSD under their respective physiological conditions. This suggests that the results presented are not specific to halophiles in high salt but a general property of ribosome dynamics under corresponding, active conditions. The current study opens new perspectives for neutron scattering characterization of component functional molecular dynamics within the ribosome.

Communication: Influence of external static and alternating electric fields on water from long-time non-equilibrium ab initio molecular dynamics

NASA Astrophysics Data System (ADS)

Futera, Zdenek; English, Niall J.

2017-07-01

The response of water to externally applied electric fields is of central relevance in the modern world, where many extraneous electric fields are ubiquitous. Historically, the application of external fields in non-equilibrium molecular dynamics has been restricted, by and large, to relatively inexpensive, more or less sophisticated, empirical models. Here, we report long-time non-equilibrium ab initio molecular dynamics in both static and oscillating (time-dependent) external electric fields, therefore opening up a new vista in rigorous studies of electric-field effects on dynamical systems with the full arsenal of electronic-structure methods. In so doing, we apply this to liquid water with state-of-the-art non-local treatment of dispersion, and we compute a range of field effects on structural and dynamical properties, such as diffusivities and hydrogen-bond kinetics.

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.

A classical phase r-centroid approach to molecular wave packet dynamics illustrating the danger of using an incomplete set of initial states for thermal averaging

NASA Astrophysics Data System (ADS)

Hansson, Tony

1999-08-01

An inexpensive semiclassical method to simulate time-resolved pump-probe spectroscopy on molecular wave packets is applied to NaK molecules at high temperature. The method builds on the introduction of classical phase factors related to the r-centroids for vibronic transitions and assumes instantaneous laser-molecule interaction. All observed quantum mechanical features are reproduced - for short times where experimental data are available even quantitatively. Furthermore, it is shown that fully quantum dynamical molecular wave packet calculations on molecules at elevated temperatures, which do not include all rovibrational states, must be regarded with caution, as they easily might yield even qualitatively incorrect results.

Using VMD - An Introductory Tutorial

PubMed Central

Hsin, Jen; Arkhipov, Anton; Yin, Ying; Stone, John E.; Schulten, Klaus

2010-01-01

VMD (Visual Molecular Dynamics) is a molecular visualization and analysis program designed for biological systems such as proteins, nucleic acids, lipid bilayer assemblies, etc. This unit will serve as an introductory VMD tutorial. We will present several step-by-step examples of some of VMD’s most popular features, including visualizing molecules in three dimensions with different drawing and coloring methods, rendering publication-quality figures, animate and analyze the trajectory of a molecular dynamics simulation, scripting in the text-based Tcl/Tk interface, and analyzing both sequence and structure data for proteins. PMID:19085979

Quantum Mechanical Modeling: A Tool for the Understanding of Enzyme Reactions

PubMed Central

Náray-Szabó, Gábor; Oláh, Julianna; Krámos, Balázs

2013-01-01

Most enzyme reactions involve formation and cleavage of covalent bonds, while electrostatic effects, as well as dynamics of the active site and surrounding protein regions, may also be crucial. Accordingly, special computational methods are needed to provide an adequate description, which combine quantum mechanics for the reactive region with molecular mechanics and molecular dynamics describing the environment and dynamic effects, respectively. In this review we intend to give an overview to non-specialists on various enzyme models as well as established computational methods and describe applications to some specific cases. For the treatment of various enzyme mechanisms, special approaches are often needed to obtain results, which adequately refer to experimental data. As a result of the spectacular progress in the last two decades, most enzyme reactions can be quite precisely treated by various computational methods. PMID:24970187

Leap-dynamics: efficient sampling of conformational space of proteins and peptides in solution.

PubMed

Kleinjung, J; Bayley, P; Fraternali, F

2000-03-31

A molecular simulation scheme, called Leap-dynamics, that provides efficient sampling of protein conformational space in solution is presented. The scheme is a combined approach using a fast sampling method, imposing conformational 'leaps' to force the system over energy barriers, and molecular dynamics (MD) for refinement. The presence of solvent is approximated by a potential of mean force depending on the solvent accessible surface area. The method has been successfully applied to N-acetyl-L-alanine-N-methylamide (alanine dipeptide), sampling experimentally observed conformations inaccessible to MD alone under the chosen conditions. The method predicts correctly the increased partial flexibility of the mutant Y35G compared to native bovine pancreatic trypsin inhibitor. In particular, the improvement over MD consists of the detection of conformational flexibility that corresponds closely to slow motions identified by nuclear magnetic resonance techniques.

Temperature dependent effective potential method for accurate free energy calculations of solids

NASA Astrophysics Data System (ADS)

Hellman, Olle; Steneteg, Peter; Abrikosov, I. A.; Simak, S. I.

2013-03-01

We have developed a thorough and accurate method of determining anharmonic free energies, the temperature dependent effective potential technique (TDEP). It is based on ab initio molecular dynamics followed by a mapping onto a model Hamiltonian that describes the lattice dynamics. The formalism and the numerical aspects of the technique are described in detail. A number of practical examples are given, and results are presented, which confirm the usefulness of TDEP within ab initio and classical molecular dynamics frameworks. In particular, we examine from first principles the behavior of force constants upon the dynamical stabilization of the body centered phase of Zr, and show that they become more localized. We also calculate the phase diagram for 4He modeled with the Aziz potential and obtain results which are in favorable agreement both with respect to experiment and established techniques.

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.

A LAMMPS implementation of volume-temperature replica exchange molecular dynamics

NASA Astrophysics Data System (ADS)

Liu, Liang-Chun; Kuo, Jer-Lai

2015-04-01

A driver module for executing volume-temperature replica exchange molecular dynamics (VTREMD) was developed for the LAMMPS package. As a patch code, the VTREMD module performs classical molecular dynamics (MD) with Monte Carlo (MC) decisions between MD runs. The goal of inserting the MC step was to increase the breadth of sampled configurational space. In this method, states receive better sampling by making temperature or density swaps with their neighboring states. As an accelerated sampling method, VTREMD is particularly useful to explore states at low temperatures, where systems are easily trapped in local potential wells. As functional examples, TIP4P/Ew and TIP4P/2005 water models were analyzed using VTREMD. The phase diagram in this study covered the deeply supercooled regime, and this test served as a suitable demonstration of the usefulness of VTREMD in overcoming the slow dynamics problem. To facilitate using the current code, attention was also paid on how to optimize the exchange efficiency by using grid allocation. VTREMD was useful for studying systems with rough energy landscapes, such as those with numerous local minima or multiple characteristic time scales.

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.

Exact dynamic properties of molecular motors

NASA Astrophysics Data System (ADS)

Boon, N. J.; Hoyle, R. B.

2012-08-01

Molecular motors play important roles within a biological cell, performing functions such as intracellular transport and gene transcription. Recent experimental work suggests that there are many plausible biochemical mechanisms that molecules such as myosin-V could use to achieve motion. To account for the abundance of possible discrete-stochastic frameworks that can arise when modeling molecular motor walks, a generalized and straightforward graphical method for calculating their dynamic properties is presented. It allows the calculation of the velocity, dispersion, and randomness ratio for any proposed system through analysis of its structure. This article extends work of King and Altman ["A schematic method of deriving the rate laws of enzyme-catalyzed reactions," J. Phys. Chem. 60, 1375-1378 (1956)], 10.1021/j150544a010 on networks of enzymatic reactions by calculating additional dynamic properties for spatially hopping systems. Results for n-state systems are presented: single chain, parallel pathway, divided pathway, and divided pathway with a chain. A novel technique for combining multiple system architectures coupled at a reference state is also demonstrated. Four-state examples illustrate the effectiveness and simplicity of these methods.

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

Evaluation of Enhanced Sampling Provided by Accelerated Molecular Dynamics with Hamiltonian Replica Exchange Methods

PubMed Central

2015-01-01

Many problems studied via molecular dynamics require accurate estimates of various thermodynamic properties, such as the free energies of different states of a system, which in turn requires well-converged sampling of the ensemble of possible structures. Enhanced sampling techniques are often applied to provide faster convergence than is possible with traditional molecular dynamics simulations. Hamiltonian replica exchange molecular dynamics (H-REMD) is a particularly attractive method, as it allows the incorporation of a variety of enhanced sampling techniques through modifications to the various Hamiltonians. In this work, we study the enhanced sampling of the RNA tetranucleotide r(GACC) provided by H-REMD combined with accelerated molecular dynamics (aMD), where a boosting potential is applied to torsions, and compare this to the enhanced sampling provided by H-REMD in which torsion potential barrier heights are scaled down to lower force constants. We show that H-REMD and multidimensional REMD (M-REMD) combined with aMD does indeed enhance sampling for r(GACC), and that the addition of the temperature dimension in the M-REMD simulations is necessary to efficiently sample rare conformations. Interestingly, we find that the rate of convergence can be improved in a single H-REMD dimension by simply increasing the number of replicas from 8 to 24 without increasing the maximum level of bias. The results also indicate that factors beyond replica spacing, such as round trip times and time spent at each replica, must be considered in order to achieve optimal sampling efficiency. PMID:24625009

An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis.

PubMed

Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F; Cohen, Itay; Henin, Rachel D; Hockla, Alexandra; Soares, Alexei S; Papo, Niv; Caulfield, Thomas R; Radisky, Evette S

2016-12-16

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. Although considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here, we examine the importance of substrate dynamics in the cleavage of Kunitz-bovine pancreatic trypsin inhibitor protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4-Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals a dramatic conformational change in the substrate upon proteolysis. By using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning 3 orders of magnitude, we identify global and local dynamic features of substrates on the nanosecond-microsecond time scale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substrate-like and product-like states, linking substrate dynamics on the nanosecond-microsecond time scale with large collective substrate motions on the much slower time scale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Path-space variational inference for non-equilibrium coarse-grained systems

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

Harmandaris, Vagelis, E-mail: harman@uoc.gr; Institute of Applied and Computational Mathematics; Kalligiannaki, Evangelia, E-mail: ekalligian@tem.uoc.gr

In this paper we discuss information-theoretic tools for obtaining optimized coarse-grained molecular models for both equilibrium and non-equilibrium molecular simulations. The latter are ubiquitous in physicochemical and biological applications, where they are typically associated with coupling mechanisms, multi-physics and/or boundary conditions. In general the non-equilibrium steady states are not known explicitly as they do not necessarily have a Gibbs structure. The presented approach can compare microscopic behavior of molecular systems to parametric and non-parametric coarse-grained models using the relative entropy between distributions on the path space and setting up a corresponding path-space variational inference problem. The methods can become entirelymore » data-driven when the microscopic dynamics are replaced with corresponding correlated data in the form of time series. Furthermore, we present connections and generalizations of force matching methods in coarse-graining with path-space information methods. We demonstrate the enhanced transferability of information-based parameterizations to different observables, at a specific thermodynamic point, due to information inequalities. We discuss methodological connections between information-based coarse-graining of molecular systems and variational inference methods primarily developed in the machine learning community. However, we note that the work presented here addresses variational inference for correlated time series due to the focus on dynamics. The applicability of the proposed methods is demonstrated on high-dimensional stochastic processes given by overdamped and driven Langevin dynamics of interacting particles.« less

Approximate Quantum Dynamics using Ab Initio Classical Separable Potentials: Spectroscopic Applications.

PubMed

Hirshberg, Barak; Sagiv, Lior; Gerber, R Benny

2017-03-14

Algorithms for quantum molecular dynamics simulations that directly use ab initio methods have many potential applications. In this article, the ab initio classical separable potentials (AICSP) method is proposed as the basis for approximate algorithms of this type. The AICSP method assumes separability of the total time-dependent wave function of the nuclei and employs mean-field potentials that govern the dynamics of each degree of freedom. In the proposed approach, the mean-field potentials are determined by classical ab initio molecular dynamics simulations. The nuclear wave function can thus be propagated in time using the effective potentials generated "on the fly". As a test of the method for realistic systems, calculations of the stationary anharmonic frequencies of hydrogen stretching modes were carried out for several polyatomic systems, including three amino acids and the guanine-cytosine pair of nucleobases. Good agreement with experiments was found. The method scales very favorably with the number of vibrational modes and should be applicable for very large molecules, e.g., peptides. The method should also be applicable for properties such as vibrational line widths and line shapes. Work in these directions is underway.

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.

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.

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.

Performance of multiple docking and refinement methods in the pose prediction D3R prospective Grand Challenge 2016

NASA Astrophysics Data System (ADS)

Fradera, Xavier; Verras, Andreas; Hu, Yuan; Wang, Deping; Wang, Hongwu; Fells, James I.; Armacost, Kira A.; Crespo, Alejandro; Sherborne, Brad; Wang, Huijun; Peng, Zhengwei; Gao, Ying-Duo

2018-01-01

We describe the performance of multiple pose prediction methods for the D3R 2016 Grand Challenge. The pose prediction challenge includes 36 ligands, which represent 4 chemotypes and some miscellaneous structures against the FXR ligand binding domain. In this study we use a mix of fully automated methods as well as human-guided methods with considerations of both the challenge data and publicly available data. The methods include ensemble docking, colony entropy pose prediction, target selection by molecular similarity, molecular dynamics guided pose refinement, and pose selection by visual inspection. We evaluated the success of our predictions by method, chemotype, and relevance of publicly available data. For the overall data set, ensemble docking, visual inspection, and molecular dynamics guided pose prediction performed the best with overall mean RMSDs of 2.4, 2.2, and 2.2 Å respectively. For several individual challenge molecules, the best performing method is evaluated in light of that particular ligand. We also describe the protein, ligand, and public information data preparations that are typical of our binding mode prediction workflow.

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.

Modeling Molecules

NASA Technical Reports Server (NTRS)

2000-01-01

The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

Long-time atomistic dynamics through a new self-adaptive accelerated molecular dynamics method

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

Gao, N.; Yang, L.; Gao, F.

2017-02-27

A self-adaptive accelerated molecular dynamics method is developed to model infrequent atomic- scale events, especially those events that occur on a rugged free-energy surface. Key in the new development is the use of the total displacement of the system at a given temperature to construct a boost-potential, which is slowly increased to accelerate the dynamics. The temperature is slowly increased to accelerate the dynamics. By allowing the system to evolve from one steady-state con guration to another by overcoming the transition state, this self-evolving approach makes it possible to explore the coupled motion of species that migrate on vastly differentmore » time scales. The migrations of single vacancy (V) and small He-V clusters, and the growth of nano-sized He-V clusters in Fe for times in the order of seconds are studied by this new method. An interstitial- assisted mechanism is rst explored for the migration of a helium-rich He-V cluster, while a new two-component Ostwald ripening mechanism is suggested for He-V cluster growth.« less

Molecular structures and intramolecular dynamics of pentahalides

NASA Astrophysics Data System (ADS)

Ischenko, A. A.

2017-03-01

This paper reviews advances of modern gas electron diffraction (GED) method combined with high-resolution spectroscopy and quantum chemical calculations in studies of the impact of intramolecular dynamics in free molecules of pentahalides. Some recently developed approaches to the electron diffraction data interpretation, based on direct incorporation of the adiabatic potential energy surface parameters to the diffraction intensity are described. In this way, complementary data of different experimental and computational methods can be directly combined for solving problems of the molecular structure and its dynamics. The possibility to evaluate some important parameters of the adiabatic potential energy surface - barriers to pseudorotation and saddle point of intermediate configuration from diffraction intensities in solving the inverse GED problem is demonstrated on several examples. With increasing accuracy of the electron diffraction intensities and the development of the theoretical background of electron scattering and data interpretation, it has become possible to investigate complex nuclear dynamics in fluxional systems by the GED method. Results of other research groups are also included in the discussion.

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.

An Analog Macroscopic Technique for Studying Molecular Hydrodynamic Processes in Dense Gases and Liquids.

PubMed

Dahlberg, Jerry; Tkacik, Peter T; Mullany, Brigid; Fleischhauer, Eric; Shahinian, Hossein; Azimi, Farzad; Navare, Jayesh; Owen, Spencer; Bisel, Tucker; Martin, Tony; Sholar, Jodie; Keanini, Russell G

2017-12-04

An analog, macroscopic method for studying molecular-scale hydrodynamic processes in dense gases and liquids is described. The technique applies a standard fluid dynamic diagnostic, particle image velocimetry (PIV), to measure: i) velocities of individual particles (grains), extant on short, grain-collision time-scales, ii) velocities of systems of particles, on both short collision-time- and long, continuum-flow-time-scales, iii) collective hydrodynamic modes known to exist in dense molecular fluids, and iv) short- and long-time-scale velocity autocorrelation functions, central to understanding particle-scale dynamics in strongly interacting, dense fluid systems. The basic system is composed of an imaging system, light source, vibrational sensors, vibrational system with a known media, and PIV and analysis software. Required experimental measurements and an outline of the theoretical tools needed when using the analog technique to study molecular-scale hydrodynamic processes are highlighted. The proposed technique provides a relatively straightforward alternative to photonic and neutron beam scattering methods traditionally used in molecular hydrodynamic studies.

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

EDITORIAL: 18th European Conference on Dynamics of Molecular Systems 18th European Conference on Dynamics of Molecular Systems

NASA Astrophysics Data System (ADS)

Varandas, A. J. C.

2011-08-01

This special section of Comments on Atomic, Molecular and Optical Physics (CAMOP) in Physica Scripta collects some of the papers that have been presented at the 18th European Conference on Dynamics of Molecular Systems MOLEC 2010 held in September 2010 in Curia, Portugal, as part of a series of biennial MOLEC conferences. This started in 1976 in Trento, Italy, and has continued, visiting 17 cities in 11 countries, namely Denmark, The Netherlands, Israel, France, Italy, Germany, Czech Republic, Spain, United Kingdom, Turkey and Russia. Following the MOLEC tradition, the scientific programme of the Curia meeting focused on experimental and theoretical studies of molecular interactions, collision dynamics, spectroscopy, and related fields. It included invited speakers from 22 countries, who were asked to summarize the problems reported in their presentations with the objective of revealing the current thinking of leading researchers in atomic, molecular and optical physics. It is hoped that their authoritative contributions presented in this CAMOP special section will also appeal to non-specialists through their clear and broad introductions to the field as well as references to the accessible literature. This CAMOP special section comprises ten contributions, which cover theoretical studies on the electronic structure of molecules and clusters as well as dynamics of elastic, inelastic and reactive encounters between atoms, molecules, ions, clusters and surfaces. Specifically, it includes electronic structure calculations using the traditional coupled-cluster method (Barreto et al 028111), the electron-attached equation-of-motion coupled cluster method (Hansen et al 028110), the diffusion Monte Carlo method (López-Durán et al 028107) and the path-integral Monte Carlo method (Barragán et al 028109). The contributions on molecular dynamics include on-the-fly quasi-classical trajectories on a five-atom molecule (Yu 028104), quantum reaction dynamics on triatomics (Bovino et al 028103, and Hankel et al 028102) and statistical reaction dynamics using a model based on the long-range interaction potential (McCarroll 028106). A contribution on gas-surface interactions is also included (Sahoo et al 028105) as well as first-principles ab initio calculations to explore the hydrogen-graphene interaction (Irving et al 028108). These articles reflect the recent progress made in this field and constructively build on work described in the previous three MOLEC special sections of CAMOP published in Physica Scripta. I thank, on behalf of the scientific organizing committee of MOLEC, all the authors who contributed and Physica Scripta for providing a platform for the publication of this special section dedicated to MOLEC 2010. A special thanks goes to the CAMOP Editor, Harold Linarz, for the excellent guidance in handling the editorial work. I hope that the articles catalyze the attention of the readers towards the topics covered and contribute in attracting them to attend MOLEC 2012 in Oxford, UK.

Non-equilibrium dynamics from RPMD and CMD.

PubMed

Welsch, Ralph; Song, Kai; Shi, Qiang; Althorpe, Stuart C; Miller, Thomas F

2016-11-28

We investigate the calculation of approximate non-equilibrium quantum time correlation functions (TCFs) using two popular path-integral-based molecular dynamics methods, ring-polymer molecular dynamics (RPMD) and centroid molecular dynamics (CMD). It is shown that for the cases of a sudden vertical excitation and an initial momentum impulse, both RPMD and CMD yield non-equilibrium TCFs for linear operators that are exact for high temperatures, in the t = 0 limit, and for harmonic potentials; the subset of these conditions that are preserved for non-equilibrium TCFs of non-linear operators is also discussed. Furthermore, it is shown that for these non-equilibrium initial conditions, both methods retain the connection to Matsubara dynamics that has previously been established for equilibrium initial conditions. Comparison of non-equilibrium TCFs from RPMD and CMD to Matsubara dynamics at short times reveals the orders in time to which the methods agree. Specifically, for the position-autocorrelation function associated with sudden vertical excitation, RPMD and CMD agree with Matsubara dynamics up to O(t 4 ) and O(t 1 ), respectively; for the position-autocorrelation function associated with an initial momentum impulse, RPMD and CMD agree with Matsubara dynamics up to O(t 5 ) and O(t 2 ), respectively. Numerical tests using model potentials for a wide range of non-equilibrium initial conditions show that RPMD and CMD yield non-equilibrium TCFs with an accuracy that is comparable to that for equilibrium TCFs. RPMD is also used to investigate excited-state proton transfer in a system-bath model, and it is compared to numerically exact calculations performed using a recently developed version of the Liouville space hierarchical equation of motion approach; again, similar accuracy is observed for non-equilibrium and equilibrium initial conditions.

Single Molecules as Optical Probes for Structure and Dynamics

NASA Astrophysics Data System (ADS)

Orrit, Michel

Single molecules and single nanoparticles are convenient links between the nanoscale world and the laboratory. We discuss the limits for their optical detection by three different methods: fluorescence, direct absorption, and photothermal detection. We briefly review some recent illustrations of qualitatively new information gathered from single-molecule signals: intermittency of the fluorescence intensity, acoustic vibrations of nanoparticles (1-100 GHz) or of extended defects in molecular crystals (0.1-1 MHz), and dynamical heterogeneity in glass-forming molecular liquids. We conclude with an outlook of future uses of single-molecule methods in physical chemistry, soft matter, and material science.

Activity coefficients from molecular simulations using the OPAS method

NASA Astrophysics Data System (ADS)

Kohns, Maximilian; Horsch, Martin; Hasse, Hans

2017-10-01

A method for determining activity coefficients by molecular dynamics simulations is presented. It is an extension of the OPAS (osmotic pressure for the activity of the solvent) method in previous work for studying the solvent activity in electrolyte solutions. That method is extended here to study activities of all components in mixtures of molecular species. As an example, activity coefficients in liquid mixtures of water and methanol are calculated for 298.15 K and 323.15 K at 1 bar using molecular models from the literature. These dense and strongly interacting mixtures pose a significant challenge to existing methods for determining activity coefficients by molecular simulation. It is shown that the new method yields accurate results for the activity coefficients which are in agreement with results obtained with a thermodynamic integration technique. As the partial molar volumes are needed in the proposed method, the molar excess volume of the system water + methanol is also investigated.

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

Multiscale Reactive Molecular Dynamics

DTIC Science & Technology

2012-08-15

biology cannot be described without considering electronic and nuclear-level dynamics and their coupling to slower, cooperative motions of the system ...coupling to slower, cooperative motions of the system . These inherently multiscale problems require computationally efficient and accurate methods to...condensed phase systems with computational efficiency orders of magnitudes greater than currently possible with ab initio simulation methods, thus

Extended Lagrangian Excited State Molecular Dynamics

DOE PAGES

Bjorgaard, Josiah August; Sheppard, Daniel Glen; Tretiak, Sergei; ...

2018-01-09

In this work, an extended Lagrangian framework for excited state molecular dynamics (XL-ESMD) using time-dependent self-consistent field theory is proposed. The formulation is a generalization of the extended Lagrangian formulations for ground state Born–Oppenheimer molecular dynamics [Phys. Rev. Lett. 2008 100, 123004]. The theory is implemented, demonstrated, and evaluated using a time-dependent semiempirical model, though it should be generally applicable to ab initio theory. The simulations show enhanced energy stability and a significantly reduced computational cost associated with the iterative solutions of both the ground state and the electronically excited states. Relaxed convergence criteria can therefore be used both formore » the self-consistent ground state optimization and for the iterative subspace diagonalization of the random phase approximation matrix used to calculate the excited state transitions. In conclusion, the XL-ESMD approach is expected to enable numerically efficient excited state molecular dynamics for such methods as time-dependent Hartree–Fock (TD-HF), Configuration Interactions Singles (CIS), and time-dependent density functional theory (TD-DFT).« less

Extended Lagrangian Excited State Molecular Dynamics

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

Bjorgaard, Josiah August; Sheppard, Daniel Glen; Tretiak, Sergei

In this work, an extended Lagrangian framework for excited state molecular dynamics (XL-ESMD) using time-dependent self-consistent field theory is proposed. The formulation is a generalization of the extended Lagrangian formulations for ground state Born–Oppenheimer molecular dynamics [Phys. Rev. Lett. 2008 100, 123004]. The theory is implemented, demonstrated, and evaluated using a time-dependent semiempirical model, though it should be generally applicable to ab initio theory. The simulations show enhanced energy stability and a significantly reduced computational cost associated with the iterative solutions of both the ground state and the electronically excited states. Relaxed convergence criteria can therefore be used both formore » the self-consistent ground state optimization and for the iterative subspace diagonalization of the random phase approximation matrix used to calculate the excited state transitions. In conclusion, the XL-ESMD approach is expected to enable numerically efficient excited state molecular dynamics for such methods as time-dependent Hartree–Fock (TD-HF), Configuration Interactions Singles (CIS), and time-dependent density functional theory (TD-DFT).« less

Extended Lagrangian Excited State Molecular Dynamics.

PubMed

Bjorgaard, J A; Sheppard, D; Tretiak, S; Niklasson, A M N

2018-02-13

An extended Lagrangian framework for excited state molecular dynamics (XL-ESMD) using time-dependent self-consistent field theory is proposed. The formulation is a generalization of the extended Lagrangian formulations for ground state Born-Oppenheimer molecular dynamics [Phys. Rev. Lett. 2008 100, 123004]. The theory is implemented, demonstrated, and evaluated using a time-dependent semiempirical model, though it should be generally applicable to ab initio theory. The simulations show enhanced energy stability and a significantly reduced computational cost associated with the iterative solutions of both the ground state and the electronically excited states. Relaxed convergence criteria can therefore be used both for the self-consistent ground state optimization and for the iterative subspace diagonalization of the random phase approximation matrix used to calculate the excited state transitions. The XL-ESMD approach is expected to enable numerically efficient excited state molecular dynamics for such methods as time-dependent Hartree-Fock (TD-HF), Configuration Interactions Singles (CIS), and time-dependent density functional theory (TD-DFT).

Gaussian Accelerated Molecular Dynamics: Theory, Implementation, and Applications

PubMed Central

Miao, Yinglong; McCammon, J. Andrew

2018-01-01

A novel Gaussian Accelerated Molecular Dynamics (GaMD) method has been developed for simultaneous unconstrained enhanced sampling and free energy calculation of biomolecules. Without the need to set predefined reaction coordinates, GaMD enables unconstrained enhanced sampling of the biomolecules. Furthermore, by constructing a boost potential that follows a Gaussian distribution, accurate reweighting of GaMD simulations is achieved via cumulant expansion to the second order. The free energy profiles obtained from GaMD simulations allow us to identify distinct low energy states of the biomolecules and characterize biomolecular structural dynamics quantitatively. In this chapter, we present the theory of GaMD, its implementation in the widely used molecular dynamics software packages (AMBER and NAMD), and applications to the alanine dipeptide biomolecular model system, protein folding, biomolecular large-scale conformational transitions and biomolecular recognition. PMID:29720925

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.

Real-Time Single Molecule Visualization of SH2 Domain Membrane Recruitment in Growth Factor Stimulated Cells.

PubMed

Oh, Dongmyung

2017-01-01

In the last decade, single molecule tracking (SMT) techniques have emerged as a versatile tool for molecular cell biology research. This approach allows researchers to monitor the real-time behavior of individual molecules in living cells with nanometer and millisecond resolution. As a result, it is possible to visualize biological processes as they occur at a molecular level in real time. Here we describe a method for the real-time visualization of SH2 domain membrane recruitment from the cytoplasm to epidermal growth factor (EGF) induced phosphotyrosine sites on the EGF receptor. Further, we describe methods that utilize SMT data to define SH2 domain membrane dynamics parameters such as binding (τ), dissociation (k d ), and diffusion (D) rates. Together these methods may allow us to gain greater understanding of signal transduction dynamics and the molecular basis of disease-related aberrant pathways.

A practical method to avoid zero-point leak in molecular dynamics calculations: application to the water dimer.

PubMed

Czakó, Gábor; Kaledin, Alexey L; Bowman, Joel M

2010-04-28

We report the implementation of a previously suggested method to constrain a molecular system to have mode-specific vibrational energy greater than or equal to the zero-point energy in quasiclassical trajectory calculations [J. M. Bowman et al., J. Chem. Phys. 91, 2859 (1989); W. H. Miller et al., J. Chem. Phys. 91, 2863 (1989)]. The implementation is made practical by using a technique described recently [G. Czako and J. M. Bowman, J. Chem. Phys. 131, 244302 (2009)], where a normal-mode analysis is performed during the course of a trajectory and which gives only real-valued frequencies. The method is applied to the water dimer, where its effectiveness is shown by computing mode energies as a function of integration time. Radial distribution functions are also calculated using constrained quasiclassical and standard classical molecular dynamics at low temperature and at 300 K and compared to rigorous quantum path integral calculations.

The fast multipole method and point dipole moment polarizable force fields.

PubMed

Coles, Jonathan P; Masella, Michel

2015-01-14

We present an implementation of the fast multipole method for computing Coulombic electrostatic and polarization forces from polarizable force-fields based on induced point dipole moments. We demonstrate the expected O(N) scaling of that approach by performing single energy point calculations on hexamer protein subunits of the mature HIV-1 capsid. We also show the long time energy conservation in molecular dynamics at the nanosecond scale by performing simulations of a protein complex embedded in a coarse-grained solvent using a standard integrator and a multiple time step integrator. Our tests show the applicability of fast multipole method combined with state-of-the-art chemical models in molecular dynamical systems.

Unconstrained Enhanced Sampling for Free Energy Calculations of Biomolecules: A Review

PubMed Central

Miao, Yinglong; McCammon, J. Andrew

2016-01-01

Free energy calculations are central to understanding the structure, dynamics and function of biomolecules. Yet insufficient sampling of biomolecular configurations is often regarded as one of the main sources of error. Many enhanced sampling techniques have been developed to address this issue. Notably, enhanced sampling methods based on biasing collective variables (CVs), including the widely used umbrella sampling, adaptive biasing force and metadynamics, have been discussed in a recent excellent review (Abrams and Bussi, Entropy, 2014). Here, we aim to review enhanced sampling methods that do not require predefined system-dependent CVs for biomolecular simulations and as such do not suffer from the hidden energy barrier problem as encountered in the CV-biasing methods. These methods include, but are not limited to, replica exchange/parallel tempering, self-guided molecular/Langevin dynamics, essential energy space random walk and accelerated molecular dynamics. While it is overwhelming to describe all details of each method, we provide a summary of the methods along with the applications and offer our perspectives. We conclude with challenges and prospects of the unconstrained enhanced sampling methods for accurate biomolecular free energy calculations. PMID:27453631

Unconstrained Enhanced Sampling for Free Energy Calculations of Biomolecules: A Review.

PubMed

Miao, Yinglong; McCammon, J Andrew

Free energy calculations are central to understanding the structure, dynamics and function of biomolecules. Yet insufficient sampling of biomolecular configurations is often regarded as one of the main sources of error. Many enhanced sampling techniques have been developed to address this issue. Notably, enhanced sampling methods based on biasing collective variables (CVs), including the widely used umbrella sampling, adaptive biasing force and metadynamics, have been discussed in a recent excellent review (Abrams and Bussi, Entropy, 2014). Here, we aim to review enhanced sampling methods that do not require predefined system-dependent CVs for biomolecular simulations and as such do not suffer from the hidden energy barrier problem as encountered in the CV-biasing methods. These methods include, but are not limited to, replica exchange/parallel tempering, self-guided molecular/Langevin dynamics, essential energy space random walk and accelerated molecular dynamics. While it is overwhelming to describe all details of each method, we provide a summary of the methods along with the applications and offer our perspectives. We conclude with challenges and prospects of the unconstrained enhanced sampling methods for accurate biomolecular free energy calculations.

On the accuracy of the LSC-IVR approach for excitation energy transfer in molecular aggregates

NASA Astrophysics Data System (ADS)

Teh, Hung-Hsuan; Cheng, Yuan-Chung

2017-04-01

We investigate the applicability of the linearized semiclassical initial value representation (LSC-IVR) method to excitation energy transfer (EET) problems in molecular aggregates by simulating the EET dynamics of a dimer model in a wide range of parameter regime and comparing the results to those obtained from a numerically exact method. It is found that the LSC-IVR approach yields accurate population relaxation rates and decoherence rates in a broad parameter regime. However, the classical approximation imposed by the LSC-IVR method does not satisfy the detailed balance condition, generally leading to incorrect equilibrium populations. Based on this observation, we propose a post-processing algorithm to solve the long time equilibrium problem and demonstrate that this long-time correction method successfully removed the deviations from exact results for the LSC-IVR method in all of the regimes studied in this work. Finally, we apply the LSC-IVR method to simulate EET dynamics in the photosynthetic Fenna-Matthews-Olson complex system, demonstrating that the LSC-IVR method with long-time correction provides excellent description of coherent EET dynamics in this typical photosynthetic pigment-protein complex.

Earle K. Plyler Prize Lecture: The Three Pillars of Ultrafast Molecular Science - Time, Phase, Intensity

NASA Astrophysics Data System (ADS)

Stolow, Albert

We discuss the probing and control of molecular wavepacket dynamics in the context of three main `pillars' of light-matter interaction: time, phase, intensity. Time: Using short, coherent laser pulses and perturbative matter-field interactions, we study molecular wavepackets with a focus on the ultrafast non-Born-Oppenheimer dynamics, that is, the coupling of electronic and nuclear motions. Time-Resolved Photoelectron Spectroscopy (TRPES) is a powerful ultrafast probe of these processes in polyatomic molecules because it is sensitive both electronic and vibrational dynamics. Ideally, one would like to observe these ultrafast processes from the molecule's point of view - the Molecular Frame - thereby avoiding loss of information due to orientational averaging. This can be achieved by Time-Resolved Coincidence Imaging Spectroscopy (TRCIS) which images 3D recoil vectors of both photofragments and photoelectrons, in coincidence and as a function of time, permitting direct Molecular Frame imaging of valence electronic dynamics during a molecular dynamics. Phase: Using intermediate strength non-perturbative interactions, we apply the second order (polarizability) Non-Resonant Dynamic Stark Effect (NRDSE) to control molecular dynamics without any net absorption of light. NRDSE is also the interaction underlying molecular alignment and applies to field-free 1D of linear molecules and field-free 3D alignment of general (asymmetric) molecules. Using laser alignment, we can transiently fix a molecule in space, yielding a more general approach to direct Molecular Frame imaging of valence electronic dynamics during a chemical reaction. Intensity: In strong (ionizing) laser fields, a new laser-matter physics emerges for polyatomic systems wherein both the single active electron picture and the adiabatic electron response, both implicit in the standard 3-step models, can fail dramatically. This has important consequences for all attosecond strong field spectroscopies of polyatomic molecules, including high harmonic generation (HHG). We discuss an experimental method, Channel-Resolved Above Threshold Ionization (CRATI), which directly unveils the electronic channels participating in the attosecond molecular strong field ionization response [10]. This work was supported by the National Research Council of Canada and the Natural Sciences & Engineering Research Council.

Molecular modelling of protein-protein/protein-solvent interactions

NASA Astrophysics Data System (ADS)

Luchko, Tyler

The inner workings of individual cells are based on intricate networks of protein-protein interactions. However, each of these individual protein interactions requires a complex physical interaction between proteins and their aqueous environment at the atomic scale. In this thesis, molecular dynamics simulations are used in three theoretical studies to gain insight at the atomic scale about protein hydration, protein structure and tubulin-tubulin (protein-protein) interactions, as found in microtubules. Also presented, in a fourth project, is a molecular model of solvation coupled with the Amber molecular modelling package, to facilitate further studies without the need of explicitly modelled water. Basic properties of a minimally solvated protein were calculated through an extended study of myoglobin hydration with explicit solvent, directly investigating water and protein polarization. Results indicate a close correlation between polarization of both water and protein and the onset of protein function. The methodology of explicit solvent molecular dynamics was further used to study tubulin and microtubules. Extensive conformational sampling of the carboxy-terminal tails of 8-tubulin was performed via replica exchange molecular dynamics, allowing the characterisation of the flexibility, secondary structure and binding domains of the C-terminal tails through statistical analysis methods. Mechanical properties of tubulin and microtubules were calculated with adaptive biasing force molecular dynamics. The function of the M-loop in microtubule stability was demonstrated in these simulations. The flexibility of this loop allowed constant contacts between the protofilaments to be maintained during simulations while the smooth deformation provided a spring-like restoring force. Additionally, calculating the free energy profile between the straight and bent tubulin configurations was used to test the proposed conformational change in tubulin, thought to cause microtubule destabilization. No conformational change was observed but a nucleotide dependent 'softening' of the interaction was found instead, suggesting that an entropic force in a microtubule configuration could be the mechanism of microtubule collapse. Finally, to overcome much of the computational costs associated with explicit soIvent calculations, a new combination of molecular dynamics with the 3D-reference interaction site model (3D-RISM) of solvation was integrated into the Amber molecular dynamics package. Our implementation of 3D-RISM shows excellent agreement with explicit solvent free energy calculations. Several optimisation techniques, including a new multiple time step method, provide a nearly 100 fold performance increase, giving similar computational performance to explicit solvent.

Study of methods of improving the performance of the Langley Research Center Transonic Dynamics Tunnel (TDT)

NASA Technical Reports Server (NTRS)

1973-01-01

A study has been made of possible ways to improve the performance of the Langley Research Center's Transonic Dynamics Tunnel (TDT). The major effort was directed toward obtaining increased dynamic pressure in the Mach number range from 0.8 to 1.2, but methods to increase Mach number capability were also considered. Methods studied for increasing dynamic pressure capability were higher total pressure, auxiliary suction, reducing circuit losses, reduced test medium temperature, smaller test section and higher molecular weight test medium. Increased Mach number methods investigated were nozzle block inserts, variable geometry nozzle, changes in test section wall configuration, and auxiliary suction.

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

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.

Towards fast, rigorous and efficient conformational sampling of biomolecules: Advances in accelerated molecular dynamics.

PubMed

Doshi, Urmi; Hamelberg, Donald

2015-05-01

Accelerated molecular dynamics (aMD) has been proven to be a powerful biasing method for enhanced sampling of biomolecular conformations on general-purpose computational platforms. Biologically important long timescale events that are beyond the reach of standard molecular dynamics can be accessed without losing the detailed atomistic description of the system in aMD. Over other biasing methods, aMD offers the advantages of tuning the level of acceleration to access the desired timescale without any advance knowledge of the reaction coordinate. Recent advances in the implementation of aMD and its applications to small peptides and biological macromolecules are reviewed here along with a brief account of all the aMD variants introduced in the last decade. In comparison to the original implementation of aMD, the recent variant in which all the rotatable dihedral angles are accelerated (RaMD) exhibits faster convergence rates and significant improvement in statistical accuracy of retrieved thermodynamic properties. RaMD in conjunction with accelerating diffusive degrees of freedom, i.e. dual boosting, has been rigorously tested for the most difficult conformational sampling problem, protein folding. It has been shown that RaMD with dual boosting is capable of efficiently sampling multiple folding and unfolding events in small fast folding proteins. RaMD with the dual boost approach opens exciting possibilities for sampling multiple timescales in biomolecules. While equilibrium properties can be recovered satisfactorily from aMD-based methods, directly obtaining dynamics and kinetic rates for larger systems presents a future challenge. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

Time-dependent theoretical treatments of the dynamics of electrons and nuclei in molecular systems

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

Deumens, E.; Diz, A.; Longo, R.

1994-07-01

An overview is presented of methods for time-dependent treatments of molecules as systems of electrons and nuclei. The theoretical details of these methods are reviewed and contrasted in the light of a recently developed time-dependent method called electron-nuclear dynamics. Electron-nuclear dynamics (END) is a formulation of the complete dynamics of electrons and nuclei of a molecular system that eliminates the necessity of constructing potential-energy surfaces. Because of its general formulation, it encompasses many aspects found in other formulations and can serve as a didactic device for clarifying many of the principles and approximations relevant in time-dependent treatments of molecular systems.more » The END equations are derived from the time-dependent variational principle applied to a chosen family of efficiently parametrized approximate state vectors. A detailed analysis of the END equations is given for the case of a single-determinantal state for the electrons and a classical treatment of the nuclei. The approach leads to a simple formulation of the fully nonlinear time-dependent Hartree-Fock theory including nuclear dynamics. The nonlinear END equations with the [ital ab] [ital initio] Coulomb Hamiltonian have been implemented at this level of theory in a computer program, ENDyne, and have been shown feasible for the study of small molecular systems. Implementation of the Austin Model 1 semiempirical Hamiltonian is discussed as a route to large molecular systems. The linearized END equations at this level of theory are shown to lead to the random-phase approximation for the coupled system of electrons and nuclei. The qualitative features of the general nonlinear solution are analyzed using the results of the linearized equations as a first approximation. Some specific applications of END are presented, and the comparison with experiment and other theoretical approaches is discussed.« less

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.

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.

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.

Nonequilibrium ab initio molecular dynamics determination of Ti monovacancy migration rates in B 1 TiN

NASA Astrophysics Data System (ADS)

Gambino, D.; Sangiovanni, D. G.; Alling, B.; Abrikosov, I. A.

2017-09-01

We use the color diffusion (CD) algorithm in nonequilibrium (accelerated) ab initio molecular dynamics simulations to determine Ti monovacancy jump frequencies in NaCl-structure titanium nitride (TiN), at temperatures ranging from 2200 to 3000 K. Our results show that the CD method extended beyond the linear-fitting rate-versus-force regime [Sangiovanni et al., Phys. Rev. B 93, 094305 (2016), 10.1103/PhysRevB.93.094305] can efficiently determine metal vacancy migration rates in TiN, despite the low mobilities of lattice defects in this type of ceramic compound. We propose a computational method based on gamma-distribution statistics, which provides unambiguous definition of nonequilibrium and equilibrium (extrapolated) vacancy jump rates with corresponding statistical uncertainties. The acceleration-factor achieved in our implementation of nonequilibrium molecular dynamics increases dramatically for decreasing temperatures from 500 for T close to the melting point Tm, up to 33 000 for T ≈0.7 Tm .

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.

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.

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.

Molecular modeling of polycarbonate materials: Glass transition and mechanical properties

NASA Astrophysics Data System (ADS)

Palczynski, Karol; Wilke, Andreas; Paeschke, Manfred; Dzubiella, Joachim

2017-09-01

Linking the experimentally accessible macroscopic properties of thermoplastic polymers to their microscopic static and dynamic properties is a key requirement for targeted material design. Classical molecular dynamics simulations enable us to study the structural and dynamic behavior of molecules on microscopic scales, and statistical physics provides a framework for relating these properties to the macroscopic properties. We take a first step toward creating an automated workflow for the theoretical prediction of thermoplastic material properties by developing an expeditious method for parameterizing a simple yet surprisingly powerful coarse-grained bisphenol-A polycarbonate model which goes beyond previous coarse-grained models and successfully reproduces the thermal expansion behavior, the glass transition temperature as a function of the molecular weight, and several elastic properties.

High pressure study of molecular dynamics of protic ionic liquid lidocaine hydrochloride.

PubMed

Swiety-Pospiech, A; Wojnarowska, Z; Pionteck, J; Pawlus, S; Grzybowski, A; Hensel-Bielowka, S; Grzybowska, K; Szulc, A; Paluch, M

2012-06-14

In this paper, we investigate the effect of pressure on the molecular dynamics of protic ionic liquid lidocaine hydrochloride, a commonly used pharmaceutical, by means of dielectric spectroscopy and pressure-temperature-volume methods. We observed that near T(g) the pressure dependence of conductivity relaxation times reveals a peculiar behavior, which can be treated as a manifestation of decoupling between ion migration and structural relaxation times. Moreover, we discuss the validity of thermodynamic scaling in lidocaine HCl. We also employed the temperature-volume Avramov model to determine the value of pressure coefficient of glass transition temperature, dT(g)/dP|(P = 0.1). Finally, we investigate the role of thermal and density fluctuations in controlling of molecular dynamics of the examined compound.

Performance of a docking/molecular dynamics protocol for virtual screening of nutlin-class inhibitors of Mdmx.

PubMed

Bharatham, Nagakumar; Finch, Kristin E; Min, Jaeki; Mayasundari, Anand; Dyer, Michael A; Guy, R Kiplin; Bashford, Donald

2017-06-01

A virtual screening protocol involving docking and molecular dynamics has been tested against the results of fluorescence polarization assays testing the potency of a series of compounds of the nutlin class for inhibition of the interaction between p53 and Mdmx, an interaction identified as a driver of certain cancers. The protocol uses a standard docking method (AutoDock) with a cutoff based on the AutoDock score (ADscore), followed by molecular dynamics simulation with a cutoff based on root-mean-square-deviation (RMSD) from the docked pose. An analysis of the experimental and computational results shows modest performance of ADscore alone, but dramatically improved performance when RMSD is also used. Published by Elsevier Inc.

Investigating the Structural Impacts of I64T and P311S Mutations in APE1-DNA Complex: A Molecular Dynamics Approach

PubMed Central

Doss, C. George Priya; NagaSundaram, N.

2012-01-01

Background Elucidating the molecular dynamic behavior of Protein-DNA complex upon mutation is crucial in current genomics. Molecular dynamics approach reveals the changes on incorporation of variants that dictate the structure and function of Protein-DNA complexes. Deleterious mutations in APE1 protein modify the physicochemical property of amino acids that affect the protein stability and dynamic behavior. Further, these mutations disrupt the binding sites and prohibit the protein to form complexes with its interacting DNA. Principal Findings In this study, we developed a rapid and cost-effective method to analyze variants in APE1 gene that are associated with disease susceptibility and evaluated their impacts on APE1-DNA complex dynamic behavior. Initially, two different in silico approaches were used to identify deleterious variants in APE1 gene. Deleterious scores that overlap in these approaches were taken in concern and based on it, two nsSNPs with IDs rs61730854 (I64T) and rs1803120 (P311S) were taken further for structural analysis. Significance Different parameters such as RMSD, RMSF, salt bridge, H-bonds and SASA applied in Molecular dynamic study reveals that predicted deleterious variants I64T and P311S alters the structure as well as affect the stability of APE1-DNA interacting functions. This study addresses such new methods for validating functional polymorphisms of human APE1 which is critically involved in causing deficit in repair capacity, which in turn leads to genetic instability and carcinogenesis. PMID:22384055

Light induced kickoff of magnetic domain walls in Ising chains

NASA Astrophysics Data System (ADS)

Bogani, Lapo

2012-02-01

Controlling the speed at which systems evolve is a challenge shared by all disciplines, and otherwise unrelated areas use common theoretical frameworks towards this goal. A particularly widespread model is Glauber dynamics, which describes the time evolution of the Ising model and can be applied to any binary system. Here we show, using molecular nanowires under irradiation, that Glauber dynamics can be controlled by a novel domain-wall kickoff mechanism. Contrary to known processes, the kickoff has unambiguous fingerprints, slowing down the spin-flip attempt rate by several orders of magnitude, and following a scaling law. The required irradiation power is very low, a substantial improvement over present methods of magnetooptical switching: in our experimental demonstration we switched molecular nanowires with light, using powers thousands of times lower than in previous optical switching methods. This manipulation of stochastic dynamic processes is extremely clean, leading to fingerprint signatures and scaling laws. These observations can be used, in material science, to better study domain-wall displacements and solitons in discrete lattices. These results provide a new way to control and study stochastic dynamic processes. Being general for Glauber dynamics, they can be extended to different kinds of magnetic nanowires and to a myriad of fields, ranging from social evolution to neural networks and chemical reactivity. For nanoelectronics and molecular spintronics the kickoff affords external control of molecular spin-valves and a magnetic fingerprint in single molecule measurements. It can also be applied to the dynamics of mechanical switches and the related study of phasons and order-disorder transitions.

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.

Concise NMR approach for molecular dynamics characterizations in organic solids.

PubMed

Aliev, Abil E; Courtier-Murias, Denis

2013-08-22

Molecular dynamics characterisations in solids can be carried out selectively using dipolar-dephasing experiments. Here we show that the introduction of a sum of Lorentzian and Gaussian functions greatly improve fittings of the "intensity versus time" data for protonated carbons in dipolar-dephasing experiments. The Lorentzian term accounts for remote intra- and intermolecular (1)H-(13)C dipole-dipole interactions, which vary from one molecule to another or for different carbons within the same molecule. Thus, by separating contributions from weak remote interactions, more accurate Gaussian decay constants, T(dd), can be extracted for directly bonded (1)H-(13)C dipole-dipole interactions. Reorientations of the (1)H-(13)C bonds lead to the increase of T(dd), and by measuring dipolar-dephasing constants, insight can be gained into dynamics in solids. We have demonstrated advantages of the method using comparative dynamics studies in the α and γ polymorphs of glycine, cyclic amino acids L-proline, DL-proline and trans-4-hydroxy-L-proline, the Ala residue in different dipeptides, as well as adamantane and hexamethylenetetramine. It was possible to distinguish subtle differences in dynamics of different carbon sites within a molecule in polymorphs and in L- and DL-forms. The presence of overall molecular motions is shown to lead to particularly large differences in dipolar-dephasing experiments. The differences in dynamics can be attributed to differences in noncovalent interactions. In the case of hexamethylenetetramine, for example, the presence of C-H···N interactions leads to nearly rigid molecules. Overall, the method allows one to gain insight into the role of noncovalent interactions in solids and their influence on the molecular dynamics.

Free Energy Computations by Minimization of Kullback-Leibler Divergence: An Efficient Adaptive Biasing Potential Method for Sparse Representations

DTIC Science & Technology

2011-10-14

landscapes. It is motivated by statistical learning arguments and unifies the tasks of biasing the molecular dynamics to escape free energy wells and...statistical learning arguments and unifies the tasks of biasing the molecular dynamics to escape free energy wells and estimating the free energy...experimentally, to characterize global changes as well as investigate relative stabilities. In most applications, a brute- force computation based on

Surface Structure of Liquid Li and Na: An ab initio Molecular Dynamics Study

NASA Astrophysics Data System (ADS)

González, D. J.; González, L. E.; Stott, M. J.

2004-02-01

Molecular dynamics simulations of the liquid-vapor interfaces of liquid metals have been performed using first principles methods. Results are presented for liquid lithium and sodium near their respective triple points, for samples of 2000 particles in a slab geometry. The atomic density profiles show a pronounced stratification extending several atomic diameters into the bulk, which is similar to that already experimentally observed in liquid K, Ga, In, and Hg.

Symplectic integration of closed chain rigid body dynamics with internal coordinate equations of motion

NASA Astrophysics Data System (ADS)

Mazur, Alexey K.

1999-07-01

Internal coordinate molecular dynamics (ICMD) is a recent efficient method for modeling polymer molecules which treats them as chains of rigid bodies rather than ensembles of point particles as in Cartesian MD. Unfortunately, it is readily applicable only to linear or tree topologies without closed flexible loops. Important examples violating this condition are sugar rings of nucleic acids, proline residues in proteins, and also disulfide bridges. This paper presents the first complete numerical solution of the chain closure problem within the context of ICMD. The method combines natural implicit fixation of bond lengths and bond angles by the choice of internal coordinates with explicit constraints similar to Cartesian dynamics used to maintain the chain closure. It is affordable for large molecules and makes possible 3-5 times faster dynamics simulations of molecular systems with flexible rings, including important biological objects like nucleic acids and disulfide-bonded proteins.

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

PubMed

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

2012-11-28

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

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).

Phosphorylation effects on cis/trans isomerization and the backbone conformation of serine-proline motifs: accelerated molecular dynamics analysis.

PubMed

Hamelberg, Donald; Shen, Tongye; McCammon, J Andrew

2005-02-16

The presence of serine/threonine-proline motifs in proteins provides a conformational switching mechanism of the backbone through the cis/trans isomerization of the peptidyl-prolyl (omega) bond. The reversible phosphorylation of the serine/threonine modulates this switching in regulatory proteins to alter signaling and transcription. However, the mechanism is not well understood. This is partly because cis/trans isomerization is a very slow process and, hence, difficult to study. We have used our accelerated molecular dynamics method to study the cis/trans proline isomerization, preferred backbone conformation of a serine-proline motif, and the effects of phosphorylation of the serine residue. We demonstrate that, unlike normal molecular dynamics, the accelerated molecular dynamics allows for the system to escape very easily from the trans isomer to cis isomer, and vice versa. Moreover, for both the unphosphorylated and phosphorylated peptides, the statistical thermodynamic properties are recaptured, and the results are consistent with experimental values. Isomerization of the proline omega bond is shown to be asymmetric and strongly dependent on the psi backbone angle before and after phosphorylation. The rates of escape decrease after phosphorylation. Also, the alpha-helical backbone conformation is more favored after phosphorylation. This accelerated molecular dynamics approach provides a general approach for enhancing the conformational transitions of molecular systems without having prior knowledge of the location of the minima and barriers on the potential-energy landscape.

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

Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F.

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. While considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here in this paper, we examine the importance of substrate dynamics in the cleavage of Kunitz-BPTI protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4 Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals amore » dramatic conformational change in the substrate upon proteolysis. Using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning three orders of magnitude, we identify global and local dynamic features of substrates on the ns-μs timescale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substratelike and product-like states, linking substrate dynamics on the ns-μs timescale with large collective substrate motions on the much slower timescale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis.« less

Linking time-series of single-molecule experiments with molecular dynamics simulations by machine learning

PubMed Central

Matsunaga, Yasuhiro

2018-01-01

Single-molecule experiments and molecular dynamics (MD) simulations are indispensable tools for investigating protein conformational dynamics. The former provide time-series data, such as donor-acceptor distances, whereas the latter give atomistic information, although this information is often biased by model parameters. Here, we devise a machine-learning method to combine the complementary information from the two approaches and construct a consistent model of conformational dynamics. It is applied to the folding dynamics of the formin-binding protein WW domain. MD simulations over 400 μs led to an initial Markov state model (MSM), which was then "refined" using single-molecule Förster resonance energy transfer (FRET) data through hidden Markov modeling. The refined or data-assimilated MSM reproduces the FRET data and features hairpin one in the transition-state ensemble, consistent with mutation experiments. The folding pathway in the data-assimilated MSM suggests interplay between hydrophobic contacts and turn formation. Our method provides a general framework for investigating conformational transitions in other proteins. PMID:29723137

Markov State Models of gene regulatory networks.

PubMed

Chu, Brian K; Tse, Margaret J; Sato, Royce R; Read, Elizabeth L

2017-02-06

Gene regulatory networks with dynamics characterized by multiple stable states underlie cell fate-decisions. Quantitative models that can link molecular-level knowledge of gene regulation to a global understanding of network dynamics have the potential to guide cell-reprogramming strategies. Networks are often modeled by the stochastic Chemical Master Equation, but methods for systematic identification of key properties of the global dynamics are currently lacking. The method identifies the number, phenotypes, and lifetimes of long-lived states for a set of common gene regulatory network models. Application of transition path theory to the constructed Markov State Model decomposes global dynamics into a set of dominant transition paths and associated relative probabilities for stochastic state-switching. In this proof-of-concept study, we found that the Markov State Model provides a general framework for analyzing and visualizing stochastic multistability and state-transitions in gene networks. Our results suggest that this framework-adopted from the field of atomistic Molecular Dynamics-can be a useful tool for quantitative Systems Biology at the network scale.

Linking time-series of single-molecule experiments with molecular dynamics simulations by machine learning.

PubMed

Matsunaga, Yasuhiro; Sugita, Yuji

2018-05-03

Single-molecule experiments and molecular dynamics (MD) simulations are indispensable tools for investigating protein conformational dynamics. The former provide time-series data, such as donor-acceptor distances, whereas the latter give atomistic information, although this information is often biased by model parameters. Here, we devise a machine-learning method to combine the complementary information from the two approaches and construct a consistent model of conformational dynamics. It is applied to the folding dynamics of the formin-binding protein WW domain. MD simulations over 400 μs led to an initial Markov state model (MSM), which was then "refined" using single-molecule Förster resonance energy transfer (FRET) data through hidden Markov modeling. The refined or data-assimilated MSM reproduces the FRET data and features hairpin one in the transition-state ensemble, consistent with mutation experiments. The folding pathway in the data-assimilated MSM suggests interplay between hydrophobic contacts and turn formation. Our method provides a general framework for investigating conformational transitions in other proteins. © 2018, Matsunaga et al.

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.

Transitioning NWChem to the Next Generation of Manycore Machines

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

Bylaska, Eric J.; Apra, Edoardo; Kowalski, Karol

The NorthWest Chemistry (NWChem) modeling software is a popular molecular chemistry simulation software that was designed from the start to work on massively parallel processing supercomputers[6, 28, 49]. It contains an umbrella of modules that today includes Self Consistent Field (SCF), second order Mller-Plesset perturbation theory (MP2), Coupled Cluster, multi-conguration selfconsistent eld (MCSCF), selected conguration interaction (CI), tensor contraction engine (TCE) many body methods, density functional theory (DFT), time-dependent density functional theory (TDDFT), real time time-dependent density functional theory, pseudopotential plane-wave density functional theory (PSPW), band structure (BAND), ab initio molecular dynamics, Car-Parrinello molecular dynamics, classical molecular dynamics (MD), QM/MM,more » AIMD/MM, GIAO NMR, COSMO, COSMO-SMD, and RISM solvation models, free energy simulations, reaction path optimization, parallel in time, among other capabilities[ 22]. Moreover new capabilities continue to be added with each new release.« 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.

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.

Kernel optimization for short-range molecular dynamics

NASA Astrophysics Data System (ADS)

Hu, Changjun; Wang, Xianmeng; Li, Jianjiang; He, Xinfu; Li, Shigang; Feng, Yangde; Yang, Shaofeng; Bai, He

2017-02-01

To optimize short-range force computations in Molecular Dynamics (MD) simulations, multi-threading and SIMD optimizations are presented in this paper. With respect to multi-threading optimization, a Partition-and-Separate-Calculation (PSC) method is designed to avoid write conflicts caused by using Newton's third law. Serial bottlenecks are eliminated with no additional memory usage. The method is implemented by using the OpenMP model. Furthermore, the PSC method is employed on Intel Xeon Phi coprocessors in both native and offload models. We also evaluate the performance of the PSC method under different thread affinities on the MIC architecture. In the SIMD execution, we explain the performance influence in the PSC method, considering the "if-clause" of the cutoff radius check. The experiment results show that our PSC method is relatively more efficient compared to some traditional methods. In double precision, our 256-bit SIMD implementation is about 3 times faster than the scalar version.

An Evaluation of Explicit Receptor Flexibility in Molecular Docking Using Molecular Dynamics and Torsion Angle Molecular Dynamics.

PubMed

Armen, Roger S; Chen, Jianhan; Brooks, Charles L

2009-10-13

Incorporating receptor flexibility into molecular docking should improve results for flexible proteins. However, the incorporation of explicit all-atom flexibility with molecular dynamics for the entire protein chain may also introduce significant error and "noise" that could decrease docking accuracy and deteriorate the ability of a scoring function to rank native-like poses. We address this apparent paradox by comparing the success of several flexible receptor models in cross-docking and multiple receptor ensemble docking for p38α mitogen-activated protein (MAP) kinase. Explicit all-atom receptor flexibility has been incorporated into a CHARMM-based molecular docking method (CDOCKER) using both molecular dynamics (MD) and torsion angle molecular dynamics (TAMD) for the refinement of predicted protein-ligand binding geometries. These flexible receptor models have been evaluated, and the accuracy and efficiency of TAMD sampling is directly compared to MD sampling. Several flexible receptor models are compared, encompassing flexible side chains, flexible loops, multiple flexible backbone segments, and treatment of the entire chain as flexible. We find that although including side chain and some backbone flexibility is required for improved docking accuracy as expected, docking accuracy also diminishes as additional and unnecessary receptor flexibility is included into the conformational search space. Ensemble docking results demonstrate that including protein flexibility leads to to improved agreement with binding data for 227 active compounds. This comparison also demonstrates that a flexible receptor model enriches high affinity compound identification without significantly increasing the number of false positives from low affinity compounds.

An Evaluation of Explicit Receptor Flexibility in Molecular Docking Using Molecular Dynamics and Torsion Angle Molecular Dynamics

PubMed Central

Armen, Roger S.; Chen, Jianhan; Brooks, Charles L.

2009-01-01

Incorporating receptor flexibility into molecular docking should improve results for flexible proteins. However, the incorporation of explicit all-atom flexibility with molecular dynamics for the entire protein chain may also introduce significant error and “noise” that could decrease docking accuracy and deteriorate the ability of a scoring function to rank native-like poses. We address this apparent paradox by comparing the success of several flexible receptor models in cross-docking and multiple receptor ensemble docking for p38α mitogen-activated protein (MAP) kinase. Explicit all-atom receptor flexibility has been incorporated into a CHARMM-based molecular docking method (CDOCKER) using both molecular dynamics (MD) and torsion angle molecular dynamics (TAMD) for the refinement of predicted protein-ligand binding geometries. These flexible receptor models have been evaluated, and the accuracy and efficiency of TAMD sampling is directly compared to MD sampling. Several flexible receptor models are compared, encompassing flexible side chains, flexible loops, multiple flexible backbone segments, and treatment of the entire chain as flexible. We find that although including side chain and some backbone flexibility is required for improved docking accuracy as expected, docking accuracy also diminishes as additional and unnecessary receptor flexibility is included into the conformational search space. Ensemble docking results demonstrate that including protein flexibility leads to to improved agreement with binding data for 227 active compounds. This comparison also demonstrates that a flexible receptor model enriches high affinity compound identification without significantly increasing the number of false positives from low affinity compounds. PMID:20160879

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

Lu, Chun-Yaung; Perez, Danny; Voter, Arthur F., E-mail: afv@lanl.gov

Nuclear quantum effects are important for systems containing light elements, and the effects are more prominent in the low temperature regime where the dynamics also becomes sluggish. We show that parallel replica (ParRep) dynamics, an accelerated molecular dynamics approach for infrequent-event systems, can be effectively combined with ring-polymer molecular dynamics, a semiclassical trajectory approach that gives a good approximation to zero-point and tunneling effects in activated escape processes. The resulting RP-ParRep method is a powerful tool for reaching long time scales in complex infrequent-event systems where quantum dynamics are important. Two illustrative examples, symmetric Eckart barrier crossing and interstitial heliummore » diffusion in Fe and Fe–Cr alloy, are presented to demonstrate the accuracy and long-time scale capability of this approach.« less

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.

Reconstruction of fluorophore concentration variation in dynamic fluorescence molecular tomography.

PubMed

Zhang, Xuanxuan; Liu, Fei; Zuo, Simin; Shi, Junwei; Zhang, Guanglei; Bai, Jing; Luo, Jianwen

2015-01-01

Dynamic fluorescence molecular tomography (DFMT) is a potential approach for drug delivery, tumor detection, diagnosis, and staging. The purpose of DFMT is to quantify the changes of fluorescent agents in the bodies, which offer important information about the underlying physiological processes. However, the conventional method requires that the fluorophore concentrations to be reconstructed are stationary during the data collection period. As thus, it cannot offer the dynamic information of fluorophore concentration variation within the data collection period. In this paper, a method is proposed to reconstruct the fluorophore concentration variation instead of the fluorophore concentration through a linear approximation. The fluorophore concentration variation rate is introduced by the linear approximation as a new unknown term to be reconstructed and is used to obtain the time courses of fluorophore concentration. Simulation and phantom studies are performed to validate the proposed method. The results show that the method is able to reconstruct the fluorophore concentration variation rates and the time courses of fluorophore concentration with relative errors less than 0.0218.

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.

A classical molecular dynamics investigation of the free energy and structure of short polyproline conformers

NASA Astrophysics Data System (ADS)

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

2010-09-01

Folded polyproline peptides can exist as either left-(PPII) or right-handed (PPI) helices, depending on their environment. In this work, we have characterized the conformations and the free energy landscapes of Ace-(Pro)n-Nme, n =2,3,…,9, and 13 peptides both in vacuo and in an implicit solvent environment. In order to enhance the sampling provided by regular molecular dynamics simulations, we have used the recently developed adaptively biased molecular dynamics method—which provides an accurate description of the free energy landscapes in terms of a set of relevant collective variables—combined with Hamiltonian and temperature replica exchange molecular dynamics methods. The collective variables, which are chosen so as to reflect the stable structures and the "slow modes" of the polyproline system, were based primarily on properties of length and of the cis/trans isomerization associated with the prolyl bonds. Results indicate that the space of peptide structures is characterized not just by pure PPII and PPI structures, but rather by a broad distribution of stable minima with similar free energies. These results are in agreement with recent experimental work. In addition, we have used steered molecular dynamics methods in order to quantitatively estimate the free energy difference of PPI and PPII for peptides of the length n =2,…,5 in vacuo and implicit water and qualitatively investigate transition pathways and mechanisms for the PPII to PPI transitions. A zipper-like mechanism, starting from either the center of the peptide or the amidated end, appear to be the most likely mechanisms for the PPII→PPI transition for the longer peptides.

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.

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.

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.

Transitioning NWChem to the Next Generation of Manycore Machines

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

Bylaska, Eric J.; Apra, E; Kowalski, Karol

The NorthWest chemistry (NWChem) modeling software is a popular molecular chemistry simulation software that was designed from the start to work on massively parallel processing supercomputers [1-3]. It contains an umbrella of modules that today includes self-consistent eld (SCF), second order Møller-Plesset perturbation theory (MP2), coupled cluster (CC), multiconguration self-consistent eld (MCSCF), selected conguration interaction (CI), tensor contraction engine (TCE) many body methods, density functional theory (DFT), time-dependent density functional theory (TDDFT), real-time time-dependent density functional theory, pseudopotential plane-wave density functional theory (PSPW), band structure (BAND), ab initio molecular dynamics (AIMD), Car-Parrinello molecular dynamics (MD), classical MD, hybrid quantum mechanicsmore » molecular mechanics (QM/MM), hybrid ab initio molecular dynamics molecular mechanics (AIMD/MM), gauge independent atomic orbital nuclear magnetic resonance (GIAO NMR), conductor like screening solvation model (COSMO), conductor-like screening solvation model based on density (COSMO-SMD), and reference interaction site model (RISM) solvation models, free energy simulations, reaction path optimization, parallel in time, among other capabilities [4]. Moreover, new capabilities continue to be added with each new release.« less

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.

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.

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.

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

Raman Optical Activity Spectra from Density Functional Perturbation Theory and Density-Functional-Theory-Based Molecular Dynamics.

PubMed

Luber, Sandra

2017-03-14

We describe the calculation of Raman optical activity (ROA) tensors from density functional perturbation theory, which has been implemented into the CP2K software package. Using the mixed Gaussian and plane waves method, ROA spectra are evaluated in the double-harmonic approximation. Moreover, an approach for the calculation of ROA spectra by means of density functional theory-based molecular dynamics is derived and used to obtain an ROA spectrum via time correlation functions, which paves the way for the calculation of ROA spectra taking into account anharmonicities and dynamic effects at ambient conditions.

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.

Molecular dynamics at low time resolution.

PubMed

Faccioli, P

2010-10-28

The internal dynamics of macromolecular systems is characterized by widely separated time scales, ranging from fraction of picoseconds to nanoseconds. In ordinary molecular dynamics simulations, the elementary time step Δt used to integrate the equation of motion needs to be chosen much smaller of the shortest time scale in order not to cut-off physical effects. We show that in systems obeying the overdamped Langevin equation, it is possible to systematically correct for such discretization errors. This is done by analytically averaging out the fast molecular dynamics which occurs at time scales smaller than Δt, using a renormalization group based technique. Such a procedure gives raise to a time-dependent calculable correction to the diffusion coefficient. The resulting effective Langevin equation describes by construction the same long-time dynamics, but has a lower time resolution power, hence it can be integrated using larger time steps Δt. We illustrate and validate this method by studying the diffusion of a point-particle in a one-dimensional toy model and the denaturation of a protein.

Atomistic characterization of the active-site solvation dynamics of a model photocatalyst

DOE PAGES

van Driel, Tim B.; Kjær, Kasper S.; Hartsock, Robert W.; ...

2016-11-28

The interactions between the reactive excited state of molecular photocatalysts and surrounding solvent dictate reaction mechanisms and pathways, but are not readily accessible to conventional optical spectroscopic techniques. Here we report an investigation of the structural and solvation dynamics following excitation of a model photocatalytic molecular system [Ir 2(dimen) 4] 2+, where dimen is para-diisocyanomenthane. The time-dependent structural changes in this model photocatalyst, as well as the changes in the solvation shell structure, have been measured with ultrafast diffuse X-ray scattering and simulated with Born-Oppenheimer Molecular Dynamics. Both methods provide direct access to the solute–solvent pair distribution function, enabling themore » solvation dynamics around the catalytically active iridium sites to be robustly characterized. Our results provide evidence for the coordination of the iridium atoms by the acetonitrile solvent and demonstrate the viability of using diffuse X-ray scattering at free-electron laser sources for studying the dynamics of photocatalysis.« less

Toward an Enhanced Sampling Molecular Dynamics Method for Studying Ligand-Induced Conformational Changes in Proteins.

PubMed

Andersen, Ole Juul; Grouleff, Julie; Needham, Perri; Walker, Ross C; Jensen, Frank

2015-11-19

Current enhanced sampling molecular dynamics methods for studying large conformational changes in proteins suffer from certain limitations. These include, among others, the need for user defined collective variables, the prerequisite of both start and end point structures of the conformational change, and the need for a priori knowledge of the amount by which to boost specific parts of the potential. In this paper, a framework is proposed for a molecular dynamics method for studying ligand-induced conformational changes, in which the nonbonded interactions between the ligand and the protein are used to calculate a biasing force. The method requires only a single input structure, and does not entail the use of collective variables. We provide a proof-of-concept for accelerating conformational changes in three simple test molecules, as well as promising results for two proteins known to undergo domain closure upon ligand binding. For the ribose-binding protein, backbone root-mean-square deviations as low as 0.75 Å compared to the crystal structure of the closed conformation are obtained within 50 ns simulations, whereas no domain closures are observed in unbiased simulations. A skewed closed structure is obtained for the glutamine-binding protein at high bias values, indicating that specific protein-ligand interactions might suppress important protein-protein interactions.

Exploration of structural stability in deleterious nsSNPs of the XPA gene: A molecular dynamics approach.

PubMed

Nagasundaram, N; Priya Doss, C George

2011-01-01

Distinguishing the deleterious from the massive number of non-functional nsSNPs that occur within a single genome is a considerable challenge in mutation research. In this approach, we have used the existing in silico methods to explore the mutation-structure-function relationship in the XPAgene. We used the Sorting Intolerant From Tolerant (SIFT), Polymorphism Phenotyping (PolyPhen), I-Mutant 2.0, and the Protein Analysis THrough Evolutionary Relationships methods to predict the effects of deleterious nsSNPs on protein function and evaluated the impact of mutation on protein stability by Molecular Dynamics simulations. By comparing the scores of all the four in silico methods, nsSNP with an ID rs104894131 at position C108F was predicted to be highly deleterious. We extended our Molecular dynamics approach to gain insight into the impact of this non-synonymous polymorphism on structural changes that may affect the activity of the XPAgene. Based on the in silico methods score, potential energy, root-mean-square deviation, and root-mean-square fluctuation, we predict that deleterious nsSNP at position C108F would play a significant role in causing disease by the XPA gene. Our approach would present the application of in silicotools in understanding the functional variation from the perspective of structure, evolution, and phenotype.

Recipes for free energy calculations in biomolecular systems.

PubMed

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

2013-01-01

During the last decade, several methods for sampling phase space and calculating various free energies in biomolecular systems have been devised or refined for molecular dynamics (MD) simulations. Thus, state-of-the-art methodology and the ever increasing computer power allow calculations that were forbidden a decade ago. These calculations, however, are not trivial as they require knowledge of the methods, insight into the system under study, and, quite often, an artful combination of different methodologies in order to avoid the various traps inherent in an unknown free energy landscape. In this chapter, we illustrate some of these concepts with two relatively simple systems, a sugar ring and proline oligopeptides, whose free energy landscapes still offer considerable challenges. In order to explore the configurational space of these systems, and to surmount the various free energy barriers, we combine three complementary methods: a nonequilibrium umbrella sampling method (adaptively biased MD, or ABMD), replica-exchange molecular dynamics (REMD), and steered molecular dynamics (SMD). In particular, ABMD is used to compute the free energy surface of a set of collective variables; REMD is used to improve the performance of ABMD, to carry out sampling in space complementary to the collective variables, and to sample equilibrium configurations directly; and SMD is used to study different transition mechanisms.

Quantum nuclear effects in water using centroid molecular dynamics

NASA Astrophysics Data System (ADS)

Kondratyuk, N. D.; Norman, G. E.; Stegailov, V. V.

2018-01-01

The quantum nuclear effects are studied in water using the method of centroid molecular dynamics (CMD). The aim is the calibration of CMD implementation in LAMMPS. The calculated intramolecular energy, atoms gyration radii and radial distribution functions are shown in comparison with previous works. The work is assumed to be the step toward to solution of the discrepancy between the simulation results and the experimental data of liquid n-alkane properties in our previous works.

Molecular dynamics of individual alpha-helices of bacteriorhodopsin in dimyristol phosphatidylocholine. I. Structure and dynamics.

PubMed

Woolf, T B

1997-11-01

Understanding the role of the lipid bilayer in membrane protein structure and dynamics is needed for tertiary structure determination methods. However, the molecular details are not well understood. Molecular dynamics computer calculations can provide insight into these molecular details of protein:lipid interactions. This paper reports on 10 simulations of individual alpha-helices in explicit lipid bilayers. The 10 helices were selected from the bacteriorhodopsin structure as representative alpha-helical membrane folding components. The bilayer is constructed of dimyristoyl phosphatidylcholine molecules. The only major difference between simulations is the primary sequence of the alpha-helix. The results show dramatic differences in motional behavior between alpha-helices. For example, helix A has much smaller root-mean-squared deviations than does helix D. This can be understood in terms of the presence of aromatic residues at the interface for helix A that are not present in helix D. Additional motions are possible for the helices that contain proline side chains relative to other amino acids. The results thus provide insight into the types of motion and the average structures possible for helices within the bilayer setting and demonstrate the strength of molecular simulations in providing molecular details that are not directly visualized in experiments.

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.

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.

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).

Comparison of electron transport calculations in warm dense matter using the Ziman formula

DOE PAGES

Burrill, D. J.; Feinblum, D. V.; Charest, M. R. J.; ...

2016-02-10

The Ziman formulation of electrical conductivity is tested in warm and hot dense matter using the pseudo-atom molecular dynamics method. Several implementation options that have been widely used in the literature are systematically tested through a comparison to the accurate, but expensive Kohn–Sham density functional theory molecular dynamics (KS-DFT-MD) calculations. As a result, the comparison is made for several elements and mixtures and for a wide range of temperatures and densities, and reveals a preferred method that generally gives very good agreement with the KS-DFT-MD results, but at a fraction of the computational cost.

Self-diffusion and conductivity in an ultracold strongly coupled plasma: Calculation by the method of molecular dynamics

NASA Astrophysics Data System (ADS)

Zelener, B. B.; Zelener, B. V.; Manykin, E. A.; Bronin, S. Ya; Bobrov, A. A.; Khikhlukha, D. R.

2018-01-01

We present results of calculations by the method of molecular dynamics of self-diffusion and conductivity of electron and ion components of ultracold plasma in a comparison with available theoretical and experimental data. For the ion self-diffusion coefficient, good agreement was obtained with experiments on ultracold plasma. The results of the calculation of self-diffusion also agree well with other calculations performed for the same values of the coupling parameter, but at high temperatures. The difference in the results of the conductivity calculations on the basis of the current autocorrelation function and on the basis of the diffusion coefficient is discussed.

PREFMD: a web server for protein structure refinement via molecular dynamics simulations.

PubMed

Heo, Lim; Feig, Michael

2018-03-15

Refinement of protein structure models is a long-standing problem in structural bioinformatics. Molecular dynamics-based methods have emerged as an avenue to achieve consistent refinement. The PREFMD web server implements an optimized protocol based on the method successfully tested in CASP11. Validation with recent CASP refinement targets shows consistent and more significant improvement in global structure accuracy over other state-of-the-art servers. PREFMD is freely available as a web server at http://feiglab.org/prefmd. Scripts for running PREFMD as a stand-alone package are available at https://github.com/feiglab/prefmd.git. feig@msu.edu. Supplementary data are available at Bioinformatics online.

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.

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.

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

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.

Direct reconstruction of pharmacokinetic parameters in dynamic fluorescence molecular tomography by the augmented Lagrangian method

NASA Astrophysics Data System (ADS)

Zhu, Dianwen; Zhang, Wei; Zhao, Yue; Li, Changqing

2016-03-01

Dynamic fluorescence molecular tomography (FMT) has the potential to quantify physiological or biochemical information, known as pharmacokinetic parameters, which are important for cancer detection, drug development and delivery etc. To image those parameters, there are indirect methods, which are easier to implement but tend to provide images with low signal-to-noise ratio, and direct methods, which model all the measurement noises together and are statistically more efficient. The direct reconstruction methods in dynamic FMT have attracted a lot of attention recently. However, the coupling of tomographic image reconstruction and nonlinearity of kinetic parameter estimation due to the compartment modeling has imposed a huge computational burden to the direct reconstruction of the kinetic parameters. In this paper, we propose to take advantage of both the direct and indirect reconstruction ideas through a variable splitting strategy under the augmented Lagrangian framework. Each iteration of the direct reconstruction is split into two steps: the dynamic FMT image reconstruction and the node-wise nonlinear least squares fitting of the pharmacokinetic parameter images. Through numerical simulation studies, we have found that the proposed algorithm can achieve good reconstruction results within a small amount of time. This will be the first step for a combined dynamic PET and FMT imaging in the future.

Shock melting method to determine melting curve by molecular dynamics: Cu, Pd, and Al.

PubMed

Liu, Zhong-Li; Zhang, Xiu-Lu; Cai, Ling-Cang

2015-09-21

A melting simulation method, the shock melting (SM) method, is proposed and proved to be able to determine the melting curves of materials accurately and efficiently. The SM method, which is based on the multi-scale shock technique, determines melting curves by preheating and/or prepressurizing materials before shock. This strategy was extensively verified using both classical and ab initio molecular dynamics (MD). First, the SM method yielded the same satisfactory melting curve of Cu with only 360 atoms using classical MD, compared to the results from the Z-method and the two-phase coexistence method. Then, it also produced a satisfactory melting curve of Pd with only 756 atoms. Finally, the SM method combined with ab initio MD cheaply achieved a good melting curve of Al with only 180 atoms, which agrees well with the experimental data and the calculated results from other methods. It turned out that the SM method is an alternative efficient method for calculating the melting curves of materials.

Shock melting method to determine melting curve by molecular dynamics: Cu, Pd, and Al

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

Liu, Zhong-Li, E-mail: zl.liu@163.com; Zhang, Xiu-Lu; Cai, Ling-Cang

A melting simulation method, the shock melting (SM) method, is proposed and proved to be able to determine the melting curves of materials accurately and efficiently. The SM method, which is based on the multi-scale shock technique, determines melting curves by preheating and/or prepressurizing materials before shock. This strategy was extensively verified using both classical and ab initio molecular dynamics (MD). First, the SM method yielded the same satisfactory melting curve of Cu with only 360 atoms using classical MD, compared to the results from the Z-method and the two-phase coexistence method. Then, it also produced a satisfactory melting curvemore » of Pd with only 756 atoms. Finally, the SM method combined with ab initio MD cheaply achieved a good melting curve of Al with only 180 atoms, which agrees well with the experimental data and the calculated results from other methods. It turned out that the SM method is an alternative efficient method for calculating the melting curves of materials.« less

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.

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.

Hard Sphere Simulation by Event-Driven Molecular Dynamics: Breakthrough, Numerical Difficulty, and Overcoming the issues

NASA Astrophysics Data System (ADS)

Isobe, Masaharu

Hard sphere/disk systems are among the simplest models and have been used to address numerous fundamental problems in the field of statistical physics. The pioneering numerical works on the solid-fluid phase transition based on Monte Carlo (MC) and molecular dynamics (MD) methods published in 1957 represent historical milestones, which have had a significant influence on the development of computer algorithms and novel tools to obtain physical insights. This chapter addresses the works of Alder's breakthrough regarding hard sphere/disk simulation: (i) event-driven molecular dynamics, (ii) long-time tail, (iii) molasses tail, and (iv) two-dimensional melting/crystallization. From a numerical viewpoint, there are serious issues that must be overcome for further breakthrough. Here, we present a brief review of recent progress in this area.

Combining NMR and Molecular Dynamics Studies for Insights into the Allostery of Small GTPase–Protein Interactions

PubMed Central

Zhang, Liqun; Bouguet-Bonnet, Sabine; Buck, Matthias

2014-01-01

Combinations of experimentally derived data from nuclear magnetic resonance spectroscopy and analyses of molecular dynamics trajectories increasingly allow us to obtain a detailed description of the molecular mechanisms by which proteins function in signal transduction. This chapter provides an introduction into these two methodologies, illustrated by example of a small GTPase–effector interaction. It is increasingly becoming clear that new insights are provided by the combination of experimental and computational methods. Understanding the structural and protein dynamical contributions to allostery will be useful for the engineering of new binding interfaces and protein functions, as well as for the design/in silico screening of chemical agents that can manipulate the function of small GTPase–protein interactions in diseases such as cancer. PMID:22052494

Integrating protein structural dynamics and evolutionary analysis with Bio3D.

PubMed

Skjærven, Lars; Yao, Xin-Qiu; Scarabelli, Guido; Grant, Barry J

2014-12-10

Popular bioinformatics approaches for studying protein functional dynamics include comparisons of crystallographic structures, molecular dynamics simulations and normal mode analysis. However, determining how observed displacements and predicted motions from these traditionally separate analyses relate to each other, as well as to the evolution of sequence, structure and function within large protein families, remains a considerable challenge. This is in part due to the general lack of tools that integrate information of molecular structure, dynamics and evolution. Here, we describe the integration of new methodologies for evolutionary sequence, structure and simulation analysis into the Bio3D package. This major update includes unique high-throughput normal mode analysis for examining and contrasting the dynamics of related proteins with non-identical sequences and structures, as well as new methods for quantifying dynamical couplings and their residue-wise dissection from correlation network analysis. These new methodologies are integrated with major biomolecular databases as well as established methods for evolutionary sequence and comparative structural analysis. New functionality for directly comparing results derived from normal modes, molecular dynamics and principal component analysis of heterogeneous experimental structure distributions is also included. We demonstrate these integrated capabilities with example applications to dihydrofolate reductase and heterotrimeric G-protein families along with a discussion of the mechanistic insight provided in each case. The integration of structural dynamics and evolutionary analysis in Bio3D enables researchers to go beyond a prediction of single protein dynamics to investigate dynamical features across large protein families. The Bio3D package is distributed with full source code and extensive documentation as a platform independent R package under a GPL2 license from http://thegrantlab.org/bio3d/ .

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.

Performance evaluation of the zero-multipole summation method in modern molecular dynamics software.

PubMed

Sakuraba, Shun; Fukuda, Ikuo

2018-05-04

The zero-multiple summation method (ZMM) is a cutoff-based method for calculating electrostatic interactions in molecular dynamics simulations, utilizing an electrostatic neutralization principle as a physical basis. Since the accuracies of the ZMM have been revealed to be sufficient in previous studies, it is highly desirable to clarify its practical performance. In this paper, the performance of the ZMM is compared with that of the smooth particle mesh Ewald method (SPME), where the both methods are implemented in molecular dynamics software package GROMACS. Extensive performance comparisons against a highly optimized, parameter-tuned SPME implementation are performed for various-sized water systems and two protein-water systems. We analyze in detail the dependence of the performance on the potential parameters and the number of CPU cores. Even though the ZMM uses a larger cutoff distance than the SPME does, the performance of the ZMM is comparable to or better than that of the SPME. This is because the ZMM does not require a time-consuming electrostatic convolution and because the ZMM gains short neighbor-list distances due to the smooth damping feature of the pairwise potential function near the cutoff length. We found, in particular, that the ZMM with quadrupole or octupole cancellation and no damping factor is an excellent candidate for the fast calculation of electrostatic interactions. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

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.

Exploration of structural stability in deleterious nsSNPs of the XPA gene: A molecular dynamics approach

PubMed Central

NagaSundaram, N; Priya Doss, C George

2011-01-01

Background: Distinguishing the deleterious from the massive number of non-functional nsSNPs that occur within a single genome is a considerable challenge in mutation research. In this approach, we have used the existing in silico methods to explore the mutation-structure-function relationship in the XPAgene. Materials and Methods: We used the Sorting Intolerant From Tolerant (SIFT), Polymorphism Phenotyping (PolyPhen), I-Mutant 2.0, and the Protein Analysis THrough Evolutionary Relationships methods to predict the effects of deleterious nsSNPs on protein function and evaluated the impact of mutation on protein stability by Molecular Dynamics simulations. Results: By comparing the scores of all the four in silico methods, nsSNP with an ID rs104894131 at position C108F was predicted to be highly deleterious. We extended our Molecular dynamics approach to gain insight into the impact of this non-synonymous polymorphism on structural changes that may affect the activity of the XPAgene. Conclusion: Based on the in silico methods score, potential energy, root-mean-square deviation, and root-mean-square fluctuation, we predict that deleterious nsSNP at position C108F would play a significant role in causing disease by the XPA gene. Our approach would present the application of in silicotools in understanding the functional variation from the perspective of structure, evolution, and phenotype. PMID:22190868

An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis*

PubMed Central

Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F.; Cohen, Itay; Henin, Rachel D.; Hockla, Alexandra; Soares, Alexei S.; Papo, Niv; Caulfield, Thomas R.; Radisky, Evette S.

2016-01-01

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. Although considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here, we examine the importance of substrate dynamics in the cleavage of Kunitz-bovine pancreatic trypsin inhibitor protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4-Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals a dramatic conformational change in the substrate upon proteolysis. By using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning 3 orders of magnitude, we identify global and local dynamic features of substrates on the nanosecond-microsecond time scale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substrate-like and product-like states, linking substrate dynamics on the nanosecond-microsecond time scale with large collective substrate motions on the much slower time scale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis. PMID:27810896

An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis

DOE PAGES

Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F.; ...

2016-11-03

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. While considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here in this paper, we examine the importance of substrate dynamics in the cleavage of Kunitz-BPTI protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4 Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals amore » dramatic conformational change in the substrate upon proteolysis. Using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning three orders of magnitude, we identify global and local dynamic features of substrates on the ns-μs timescale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substratelike and product-like states, linking substrate dynamics on the ns-μs timescale with large collective substrate motions on the much slower timescale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis.« less

Agent-Based Modeling in Molecular Systems Biology.

PubMed

Soheilypour, Mohammad; Mofrad, Mohammad R K

2018-07-01

Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

The effect of various quantum mechanically derived partial atomic charges on the bulk properties of chloride-based ionic liquids

NASA Astrophysics Data System (ADS)

Zolghadr, Amin Reza; Ghatee, Mohammad Hadi; Moosavi, Fatemeh

2016-08-01

Partial atomic charges using various quantum mechanical calculations for [Cnmim]Cl (n = 1, 4) ionic liquids (ILs) are obtained and used for development of molecular dynamics simulation (MD) force fields. The isolated ion pairs are optimized using HF, B3LYP, and MP2 methods for electronic structure with 6-311++G(d,p) basis set. Partial atomic charges are assigned to the atomic center with CHELPG and NBO methods. The effect of these sets of partial charges on the static and dynamic properties of ILs is evaluated by performing a series of MD simulations and comparing the essential thermodynamic properties with the available experimental data and available molecular dynamics simulation results. In contrast to the general trends reported for ionic liquids with BF4, PF6, and iodide anions (in which restrained electrostatic potential (RESP) charges are preferred), partial charges derived by B3LYP-NBO method are relatively good in prediction of the structural, dynamical, and thermodynamic energetic properties of the chloride based ILs.

Peridynamic Multiscale Finite Element Methods

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

Costa, Timothy; Bond, Stephen D.; Littlewood, David John

The problem of computing quantum-accurate design-scale solutions to mechanics problems is rich with applications and serves as the background to modern multiscale science research. The prob- lem can be broken into component problems comprised of communicating across adjacent scales, which when strung together create a pipeline for information to travel from quantum scales to design scales. Traditionally, this involves connections between a) quantum electronic structure calculations and molecular dynamics and between b) molecular dynamics and local partial differ- ential equation models at the design scale. The second step, b), is particularly challenging since the appropriate scales of molecular dynamic andmore » local partial differential equation models do not overlap. The peridynamic model for continuum mechanics provides an advantage in this endeavor, as the basic equations of peridynamics are valid at a wide range of scales limiting from the classical partial differential equation models valid at the design scale to the scale of molecular dynamics. In this work we focus on the development of multiscale finite element methods for the peridynamic model, in an effort to create a mathematically consistent channel for microscale information to travel from the upper limits of the molecular dynamics scale to the design scale. In particular, we first develop a Nonlocal Multiscale Finite Element Method which solves the peridynamic model at multiple scales to include microscale information at the coarse-scale. We then consider a method that solves a fine-scale peridynamic model to build element-support basis functions for a coarse- scale local partial differential equation model, called the Mixed Locality Multiscale Finite Element Method. Given decades of research and development into finite element codes for the local partial differential equation models of continuum mechanics there is a strong desire to couple local and nonlocal models to leverage the speed and state of the art of local models with the flexibility and accuracy of the nonlocal peridynamic model. In the mixed locality method this coupling occurs across scales, so that the nonlocal model can be used to communicate material heterogeneity at scales inappropriate to local partial differential equation models. Additionally, the computational burden of the weak form of the peridynamic model is reduced dramatically by only requiring that the model be solved on local patches of the simulation domain which may be computed in parallel, taking advantage of the heterogeneous nature of next generation computing platforms. Addition- ally, we present a novel Galerkin framework, the 'Ambulant Galerkin Method', which represents a first step towards a unified mathematical analysis of local and nonlocal multiscale finite element methods, and whose future extension will allow the analysis of multiscale finite element methods that mix models across scales under certain assumptions of the consistency of those models.« less

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

Thermal conductance at atomically clean and disordered silicon/aluminum interfaces: A molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Ih Choi, Woon; Kim, Kwiseon; Narumanchi, Sreekant

2012-09-01

Thermal resistance between layers impedes effective heat dissipation in electronics packaging applications. Thermal conductance for clean and disordered interfaces between silicon (Si) and aluminum (Al) was computed using realistic Si/Al interfaces and classical molecular dynamics with the modified embedded atom method potential. These realistic interfaces, which include atomically clean as well as disordered interfaces, were obtained using density functional theory. At 300 K, the magnitude of interfacial conductance due to phonon-phonon scattering obtained from the classical molecular dynamics simulations was approximately five times higher than the conductance obtained using analytical elastic diffuse mismatch models. Interfacial disorder reduced the thermal conductance due to increased phonon scattering with respect to the atomically clean interface. Also, the interfacial conductance, due to electron-phonon scattering at the interface, was greater than the conductance due to phonon-phonon scattering. This indicates that phonon-phonon scattering is the bottleneck for interfacial transport at the semiconductor/metal interfaces. The molecular dynamics modeling predictions for interfacial thermal conductance for a 5-nm disordered interface between Si/Al were in-line with recent experimental data in the literature.

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

Dynamic Histogram Analysis To Determine Free Energies and Rates from Biased Simulations.

PubMed

Stelzl, Lukas S; Kells, Adam; Rosta, Edina; Hummer, Gerhard

2017-12-12

We present an algorithm to calculate free energies and rates from molecular simulations on biased potential energy surfaces. As input, it uses the accumulated times spent in each state or bin of a histogram and counts of transitions between them. Optimal unbiased equilibrium free energies for each of the states/bins are then obtained by maximizing the likelihood of a master equation (i.e., first-order kinetic rate model). The resulting free energies also determine the optimal rate coefficients for transitions between the states or bins on the biased potentials. Unbiased rates can be estimated, e.g., by imposing a linear free energy condition in the likelihood maximization. The resulting "dynamic histogram analysis method extended to detailed balance" (DHAMed) builds on the DHAM method. It is also closely related to the transition-based reweighting analysis method (TRAM) and the discrete TRAM (dTRAM). However, in the continuous-time formulation of DHAMed, the detailed balance constraints are more easily accounted for, resulting in compact expressions amenable to efficient numerical treatment. DHAMed produces accurate free energies in cases where the common weighted-histogram analysis method (WHAM) for umbrella sampling fails because of slow dynamics within the windows. Even in the limit of completely uncorrelated data, where WHAM is optimal in the maximum-likelihood sense, DHAMed results are nearly indistinguishable. We illustrate DHAMed with applications to ion channel conduction, RNA duplex formation, α-helix folding, and rate calculations from accelerated molecular dynamics. DHAMed can also be used to construct Markov state models from biased or replica-exchange molecular dynamics simulations. By using binless WHAM formulated as a numerical minimization problem, the bias factors for the individual states can be determined efficiently in a preprocessing step and, if needed, optimized globally afterward.

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.

Multiple Point Dynamic Gas Density Measurements Using Molecular Rayleigh Scattering

NASA Technical Reports Server (NTRS)

Seasholtz, Richard; Panda, Jayanta

1999-01-01

A nonintrusive technique for measuring dynamic gas density properties is described. Molecular Rayleigh scattering is used to measure the time-history of gas density simultaneously at eight spatial locations at a 50 kHz sampling rate. The data are analyzed using the Welch method of modified periodograms to reduce measurement uncertainty. Cross-correlations, power spectral density functions, cross-spectral density functions, and coherence functions may be obtained from the data. The technique is demonstrated using low speed co-flowing jets with a heated inner jet.

Lattice Strain Due to an Atomic Vacancy

PubMed Central

Li, Shidong; Sellers, Michael S.; Basaran, Cemal; Schultz, Andrew J.; Kofke, David A.

2009-01-01

Volumetric strain can be divided into two parts: strain due to bond distance change and strain due to vacancy sources and sinks. In this paper, efforts are focused on studying the atomic lattice strain due to a vacancy in an FCC metal lattice with molecular dynamics simulation (MDS). The result has been compared with that from a continuum mechanics method. It is shown that using a continuum mechanics approach yields constitutive results similar to the ones obtained based purely on molecular dynamics considerations. PMID:19582230

Chemisorption and Diffusion of H on a Graphene Sheet and Single-Wall Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Dzegilenko, Fedor; Menon, Madhu

2000-01-01

Recent experiments on hydrogen storage in single wall nanotubes and nanotube bundles have reported large fractional weight of stored molecular hydrogen which are not in agreement with theoretical estimates based of simulation of hydrogen storage by physisorption mechanisms. Hydrogen storage in catalytically doped nanotube bundles indicate that atomic H might undergo chemisorption changing the basic nature of the storage mechanism under investigation by many groups. Using a generalized tight-binding molecular dynamics (GTBMD) method for reactive C-H dynamics, we investigate chemisorption and diffusion of atomic H on graphene sheet and C nanotubes. Effective potential energy surfaces (EPS) for chemisorption and diffusion are calculated for graphene sheet and nanotubes of different curvatures. Analysis of the activation barriers and quantum rate constants, computed via wave-packet dynamics method, will be discussed in this presentation.

Path Integral Computation of Quantum Free Energy Differences Due to Alchemical Transformations Involving Mass and Potential.

PubMed

Pérez, Alejandro; von Lilienfeld, O Anatole

2011-08-09

Thermodynamic integration, perturbation theory, and λ-dynamics methods were applied to path integral molecular dynamics calculations to investigate free energy differences due to "alchemical" transformations. Several estimators were formulated to compute free energy differences in solvable model systems undergoing changes in mass and/or potential. Linear and nonlinear alchemical interpolations were used for the thermodynamic integration. We find improved convergence for the virial estimators, as well as for the thermodynamic integration over nonlinear interpolation paths. Numerical results for the perturbative treatment of changes in mass and electric field strength in model systems are presented. We used thermodynamic integration in ab initio path integral molecular dynamics to compute the quantum free energy difference of the isotope transformation in the Zundel cation. The performance of different free energy methods is discussed.

Analyzing DNA curvature and its impact on the ionic environment: application to molecular dynamics simulations of minicircles

PubMed Central

Pasi, Marco; Zakrzewska, Krystyna; Maddocks, John H.

2017-01-01

Abstract We propose a method for analyzing the magnitude and direction of curvature within nucleic acids, based on the curvilinear helical axis calculated by Curves+. The method is applied to analyzing curvature within minicircles constructed with varying degrees of over- or under-twisting. Using the molecular dynamics trajectories of three different minicircles, we are able to quantify how curvature varies locally both in space and in time. We also analyze how curvature influences the local environment of the minicircles, notably via increased heterogeneity in the ionic distributions surrounding the double helix. The approach we propose has been integrated into Curves+ and the utilities Canal (time trajectory analysis) and Canion (environmental analysis) and can be used to study a wide variety of static and dynamic structural data on nucleic acids. PMID:28180333

Spectral densities for Frenkel exciton dynamics in molecular crystals: A TD-DFTB approach

NASA Astrophysics Data System (ADS)

Plötz, Per-Arno; Megow, Jörg; Niehaus, Thomas; Kühn, Oliver

2017-02-01

Effects of thermal fluctuations on the electronic excitation energies and intermonomeric Coulomb couplings are investigated for a perylene-tetracarboxylic-diimide crystal. To this end, time dependent density functional theory based tight binding (TD-DFTB) in the linear response formulation is used in combination with electronic ground state classical molecular dynamics. As a result, a parametrized Frenkel exciton Hamiltonian is obtained, with the effect of exciton-vibrational coupling being described by spectral densities. Employing dynamically defined normal modes, these spectral densities are analyzed in great detail, thus providing insight into the effect of specific intramolecular motions on excitation energies and Coulomb couplings. This distinguishes the present method from approaches using fixed transition densities. The efficiency by which intramolecular contributions to the spectral density can be calculated is a clear advantage of this method as compared with standard TD-DFT.

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.

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

Rossi, Mariana; Manolopoulos, David E.; Ceriotti, Michele

Two of the most successful methods that are presently available for simulating the quantum dynamics of condensed phase systems are centroid molecular dynamics (CMD) and ring polymer molecular dynamics (RPMD). Despite their conceptual differences, practical implementations of these methods differ in just two respects: the choice of the Parrinello-Rahman mass matrix and whether or not a thermostat is applied to the internal modes of the ring polymer during the dynamics. Here, we explore a method which is halfway between the two approximations: we keep the path integral bead masses equal to the physical particle masses but attach a Langevin thermostatmore » to the internal modes of the ring polymer during the dynamics. We justify this by showing analytically that the inclusion of an internal mode thermostat does not affect any of the established features of RPMD: thermostatted RPMD is equally valid with respect to everything that has actually been proven about the method as RPMD itself. In particular, because of the choice of bead masses, the resulting method is still optimum in the short-time limit, and the transition state approximation to its reaction rate theory remains closely related to the semiclassical instanton approximation in the deep quantum tunneling regime. In effect, there is a continuous family of methods with these properties, parameterised by the strength of the Langevin friction. Here, we explore numerically how the approximation to quantum dynamics depends on this friction, with a particular emphasis on vibrational spectroscopy. We find that a broad range of frictions approaching optimal damping give similar results, and that these results are immune to both the resonance problem of RPMD and the curvature problem of CMD.« less

Novel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies.

PubMed

Wang, Jialu; Zhao, Fang; Liu, Rui; Chen, Jingjing; Zhang, Qinghua; Lao, Ruijuan; Wang, Ze; Jin, Xin; Liu, Changxiao

2017-01-01

The purpose of this study was to prepare, optimize, and characterize a cationic lipid nanoparticle (CLN) system containing multicomponent drugs using a molecular dynamics model as a novel method of evaluating formulations. Puerarin (PUE) and scutellarin (SCU) were used as model drugs. CLNs were successfully prepared using melt-emulsion ultrasonication and low temperature-solidification technique. The properties of CLNs such as morphology, particle size, zeta potential, entrapment efficiency (EE), drug loading (DL), and drug release behavior were investigated. The CLNs were evaluated by corneal permeation, preocular retention time, and pharmacokinetics in the aqueous humor. Additionally, a molecular dynamics model was used to evaluate the formulation. Electron microscopy results showed that the nanoparticles were approximately spherical in shape. The EE (%) and DL (%) values of PUE and SCU in the optimal formulation were 56.60±3.73, 72.31±1.96 and 1.68±0.17, 2.44±1.14, respectively. The pharmacokinetic study in the aqueous humor showed that compared with the PUE and SCU solution, the area under the concentration-time curve (AUC) value of PUE was enhanced by 2.33-fold for PUE-SCU CLNs ( p <0.01), and the SCU AUC was enhanced by 2.32-fold ( p <0.01). In the molecular dynamics model, PUE and SCU passed through the POPC bilayer, with an obvious difference in the free energy well depth. It was found that the maximum free energy required for PUE and SCU transmembrane movement was ~15 and 88 kJ·mol -1 , respectively. These findings indicated that compared with SCU, PUE easily passed through the membrane. The diffusion coefficient for PUE and SCU were 4.1×10 -3 ±0.0027 and 1.0×10 -3 ±0.0006 e -5 cm 2 ·s -1 , respectively. Data from the molecular dynamics model were consistent with the experimental data. All data indicated that CLNs have a great potential for ocular administration and can be used as an ocular delivery system for multicomponent drugs. Moreover, the molecular dynamics model can also be used as a novel method for evaluating formulations.

Molecular-dynamics study on characteristics of energy and tangential momentum accommodation coefficients

NASA Astrophysics Data System (ADS)

Yamaguchi, Hiroki; Matsuda, Yu; Niimi, Tomohide

2017-07-01

Gas-surface interaction is studied by the molecular dynamics method to investigate qualitatively characteristics of accommodation coefficients. A large number of trajectories of gas molecules colliding to and scattering from a surface are statistically analyzed to calculate the energy (thermal) accommodation coefficient (EAC) and the tangential momentum accommodation coefficient (TMAC). Considering experimental measurements of the accommodation coefficients, the incident velocities are stochastically sampled to represent a bulk condition. The accommodation coefficients for noble gases show qualitative coincidence with experimental values. To investigate characteristics of these accommodation coefficients in detail, the gas-surface interaction is parametrically studied by varying the molecular mass of gas, the gas-surface interaction strength, and the molecular size of gas, one by one. EAC increases with increasing every parameter, while TMAC increases with increasing the interaction strength, but decreases with increasing the molecular mass and the molecular size. Thus, contradictory results in experimentally measured TMAC for noble gases could result from the difference between the surface conditions employed in the measurements in the balance among the effective parameters of molecular mass, interaction strength, and molecular size, due to surface roughness and/or adsorbed molecules. The accommodation coefficients for a thermo-fluid dynamics field with a temperature difference between gas and surface and a bulk flow at the same time are also investigated.

Interfacing the Ab initio multiple spawning method with electronic structure methods in GAMESS: Photodecay of trans-Azomethane

DOE PAGES

Gaenko, Alexander; DeFusco, Albert; Varganov, Sergey A.; ...

2014-10-20

This work presents a nonadiabatic molecular dynamics study of the nonradiative decay of photoexcited trans-azomethane, using the ab initio multiple spawning (AIMS) program that has been interfaced with the General Atomic and Molecular Electronic Structure System (GAMESS) quantum chemistry package for on-the-fly electronic structure evaluation. The interface strategy is discussed, and the capabilities of the combined programs are demonstrated with a nonadiabatic molecular dynamics study of the nonradiative decay of photoexcited trans-azomethane. Energies, gradients, and nonadiabatic coupling matrix elements were obtained with the state-averaged complete active space self-consistent field method, as implemented in GAMESS. The influence of initial vibrational excitationmore » on the outcome of the photoinduced isomerization is explored. Increased vibrational excitation in the CNNC torsional mode shortens the excited state lifetime. Depending on the degree of vibrational excitation, the excited state lifetime varies from ~60–200 fs. As a result, these short lifetimes are in agreement with time-resolved photoionization mass spectroscopy experiments.« less

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.

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.

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

Fundamental limits on dynamic inference from single-cell snapshots

PubMed Central

Weinreb, Caleb; Tusi, Betsabeh K.; Socolovsky, Merav

2018-01-01

Single-cell expression profiling reveals the molecular states of individual cells with unprecedented detail. Because these methods destroy cells in the process of analysis, they cannot measure how gene expression changes over time. However, some information on dynamics is present in the data: the continuum of molecular states in the population can reflect the trajectory of a typical cell. Many methods for extracting single-cell dynamics from population data have been proposed. However, all such attempts face a common limitation: for any measured distribution of cell states, there are multiple dynamics that could give rise to it, and by extension, multiple possibilities for underlying mechanisms of gene regulation. Here, we describe the aspects of gene expression dynamics that cannot be inferred from a static snapshot alone and identify assumptions necessary to constrain a unique solution for cell dynamics from static snapshots. We translate these constraints into a practical algorithmic approach, population balance analysis (PBA), which makes use of a method from spectral graph theory to solve a class of high-dimensional differential equations. We use simulations to show the strengths and limitations of PBA, and then apply it to single-cell profiles of hematopoietic progenitor cells (HPCs). Cell state predictions from this analysis agree with HPC fate assays reported in several papers over the past two decades. By highlighting the fundamental limits on dynamic inference faced by any method, our framework provides a rigorous basis for dynamic interpretation of a gene expression continuum and clarifies best experimental designs for trajectory reconstruction from static snapshot measurements. PMID:29463712

Role of Molecular Dynamics and Related Methods in Drug Discovery.

PubMed

De Vivo, Marco; Masetti, Matteo; Bottegoni, Giovanni; Cavalli, Andrea

2016-05-12

Molecular dynamics (MD) and related methods are close to becoming routine computational tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate estimate of the thermodynamics and kinetics associated with drug-target recognition and binding, as better algorithms and hardware architectures increase their use. Here, we review the theoretical background of MD and enhanced sampling methods, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding. We discuss unbiased MD simulations that nowadays allow the observation of unsupervised ligand-target binding, assessing how these approaches help optimizing target affinity and drug residence time toward improved drug efficacy. Further issues discussed include allosteric modulation and the role of water molecules in ligand binding and optimization. We conclude by calling for more prospective studies to attest to these methods' utility in discovering novel drug candidates.

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

A review of theoretical study of graphene chemical vapor deposition synthesis on metals: nucleation, growth, and the role of hydrogen and oxygen

NASA Astrophysics Data System (ADS)

Rezwan Habib, Mohammad; Liang, Tao; Yu, Xuegong; Pi, Xiaodong; Liu, Yingchun; Xu, Mingsheng

2018-03-01

Graphene has attracted intense research interest due to its extraordinary properties and great application potential. Various methods have been proposed for the synthesis of graphene, among which chemical vapor deposition has drawn a great deal of attention for synthesizing large-area and high-quality graphene. Theoretical understanding of the synthesis mechanism is crucial for optimizing the experimental design for desired graphene production. In this review, we discuss the three fundamental steps of graphene synthesis in details, i.e. (1) decomposition of carbon feedstocks and formation of various active carbon species, (2) nucleation, and (3) attachment and extension. We provide a complete scenario of graphene synthesis on metal surfaces at atomistic level by means of density functional theory, molecular dynamics (MD), Monte Carlo (MC) and their combination and interface with other simulation methods such as quantum mechanical molecular dynamics, density functional tight binding molecular dynamics, and combination of MD and MC. We also address the latest investigation of the influences of the hydrogen and oxygen on the synthesis and the quality of the synthesized graphene.

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.

Development of reactive force fields using ab initio molecular dynamics simulation minimally biased to experimental data

NASA Astrophysics Data System (ADS)

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

2017-10-01

Incorporation of quantum mechanical electronic structure data is necessary to properly capture the physics of many chemical processes. Proton hopping in water, which involves rearrangement of chemical and hydrogen bonds, is one such example of an inherently quantum mechanical process. Standard ab initio molecular dynamics (AIMD) methods, however, do not yet accurately predict the structure of water and are therefore less than optimal for developing force fields. We have instead utilized a recently developed method which minimally biases AIMD simulations to match limited experimental data to develop novel multiscale reactive molecular dynamics (MS-RMD) force fields by using relative entropy minimization. In this paper, we present two new MS-RMD models using such a parameterization: one which employs water with harmonic internal vibrations and another which uses anharmonic water. We show that the newly developed MS-RMD models very closely reproduce the solvation structure of the hydrated excess proton in the target AIMD data. We also find that the use of anharmonic water increases proton hopping, thereby increasing the proton diffusion constant.

Modeling of metal thin film growth: Linking angstrom-scale molecular dynamics results to micron-scale film topographies

NASA Astrophysics Data System (ADS)

Hansen, U.; Rodgers, S.; Jensen, K. F.

2000-07-01

A general method for modeling ionized physical vapor deposition is presented. As an example, the method is applied to growth of an aluminum film in the presence of an ionized argon flux. Molecular dynamics techniques are used to examine the surface adsorption, reflection, and sputter reactions taking place during ionized physical vapor deposition. We predict their relative probabilities and discuss their dependence on energy and incident angle. Subsequently, we combine the information obtained from molecular dynamics with a line of sight transport model in a two-dimensional feature, incorporating all effects of reemission and resputtering. This provides a complete growth rate model that allows inclusion of energy- and angular-dependent reaction rates. Finally, a level-set approach is used to describe the morphology of the growing film. We thus arrive at a computationally highly efficient and accurate scheme to model the growth of thin films. We demonstrate the capabilities of the model predicting the major differences on Al film topographies between conventional and ionized sputter deposition techniques studying thin film growth under ionized physical vapor deposition conditions with different Ar fluxes.

Equation of state of paramagnetic CrN from ab initio molecular dynamics

NASA Astrophysics Data System (ADS)

Steneteg, Peter; Alling, Björn; Abrikosov, Igor A.

2012-04-01

The equation of state for chromium nitride has been debated in the literature in connection with a proposed collapse of its bulk modulus following the pressure-induced transition from the paramagnetic cubic phase to the antiferromagnetic orthorhombic phase [F. Rivadulla , Nature Mater.1476-112210.1038/nmat2549 8, 947 (2009); B. Alling , Nature Mater.1476-112210.1038/nmat2722 9, 283 (2010)]. Experimentally the measurements are complicated due to the low transition pressure, while theoretically the simulation of magnetic disorder represents a major challenge. Here a first-principles method is suggested for the calculation of thermodynamic properties of magnetic materials in their high-temperature paramagnetic phase. It is based on ab initio molecular dynamics and simultaneous redistributions of the disordered but finite local magnetic moments. We apply this disordered local moments molecular dynamics method to the case of CrN and simulate its equation of state. In particular the debated bulk modulus is calculated in the paramagnetic cubic phase and is shown to be very similar to that of the antiferromagnetic orthorhombic CrN phase for all considered temperatures.

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

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.

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

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.

Fast and accurate quantum molecular dynamics of dense plasmas across temperature regimes

DOE PAGES

Sjostrom, Travis; Daligault, Jerome

2014-10-10

Here, we develop and implement a new quantum molecular dynamics approximation that allows fast and accurate simulations of dense plasmas from cold to hot conditions. The method is based on a carefully designed orbital-free implementation of density functional theory. The results for hydrogen and aluminum are in very good agreement with Kohn-Sham (orbital-based) density functional theory and path integral Monte Carlo calculations for microscopic features such as the electron density as well as the equation of state. The present approach does not scale with temperature and hence extends to higher temperatures than is accessible in the Kohn-Sham method and lowermore » temperatures than is accessible by path integral Monte Carlo calculations, while being significantly less computationally expensive than either of those two 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.

A Graphics Processing Unit Implementation of Coulomb Interaction in Molecular Dynamics.

PubMed

Jha, Prateek K; Sknepnek, Rastko; Guerrero-García, Guillermo Iván; Olvera de la Cruz, Monica

2010-10-12

We report a GPU implementation in HOOMD Blue of long-range electrostatic interactions based on the orientation-averaged Ewald sum scheme, introduced by Yakub and Ronchi (J. Chem. Phys. 2003, 119, 11556). The performance of the method is compared to an optimized CPU version of the traditional Ewald sum available in LAMMPS, in the molecular dynamics of electrolytes. Our GPU implementation is significantly faster than the CPU implementation of the Ewald method for small to a sizable number of particles (∼10(5)). Thermodynamic and structural properties of monovalent and divalent hydrated salts in the bulk are calculated for a wide range of ionic concentrations. An excellent agreement between the two methods was found at the level of electrostatic energy, heat capacity, radial distribution functions, and integrated charge of the electrolytes.

Boolean Networks in Inference and Dynamic Modeling of Biological Systems at the Molecular and Physiological Level

NASA Astrophysics Data System (ADS)

Thakar, Juilee; Albert, Réka

The following sections are included: * Introduction * Boolean Network Concepts and History * Extensions of the Classical Boolean Framework * Boolean Inference Methods and Examples in Biology * Dynamic Boolean Models: Examples in Plant Biology, Developmental Biology and Immunology * Conclusions * References

Structure, dynamics and stability of water/scCO2/mineral interfaces from ab initio molecular dynamics simulations.

PubMed

Lee, Mal-Soon; Peter McGrail, B; Rousseau, Roger; Glezakou, Vassiliki-Alexandra

2015-10-12

The boundary layer at solid-liquid interfaces is a unique reaction environment that poses significant scientific challenges to characterize and understand by experimentation alone. Using ab initio molecular dynamics (AIMD) methods, we report on the structure and dynamics of boundary layer formation, cation mobilization and carbonation under geologic carbon sequestration scenarios (T = 323 K and P = 90 bar) on a prototypical anorthite (001) surface. At low coverage, water film formation is enthalpically favored, but entropically hindered. Simulated adsorption isotherms show that a water monolayer will form even at the low water concentrations of water-saturated scCO2. Carbonation reactions readily occur at electron-rich terminal Oxygen sites adjacent to cation vacancies that readily form in the presence of a water monolayer. These results point to a carbonation mechanism that does not require prior carbonic acid formation in the bulk liquid. This work also highlights the modern capabilities of theoretical methods to address structure and reactivity at interfaces of high chemical complexity.

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.

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.

Molecular dynamics simulation of ZnO wurtzite phase under high and low pressures and temperatures

NASA Astrophysics Data System (ADS)

Chergui, Y.; Aouaroun, T.; Hadley, M. J.; Belkada, R.; Chemam, R.; Mekki, D. E.

2017-11-01

Isothermal and isobaric ensembles behaviours of ZnO wurtzite phase have been investigated, by parallel molecular dynamics method and using Buckingham potential, which contains long-range Coulomb, repulsive exponential, and attractive dispersion terms. To conduct our calculations, we have used dl_poly 4 software, under which the method is implemented. We have examined the influence of the temperature and pressure on molar volume in the ranges of 300-3000 K and 0-200 GPa. Isothermal-isobaric relationships, fluctuations, standard error, equilibrium time, molar volume and its variation versus time are predicted and analyzed. Our results are close to available experimental data and theoretical results.

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 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.

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.

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.

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.

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.

Dynamic Responses and Initial Decomposition under Shock Loading: A DFTB Calculation Combined with MSST Method for β-HMX with Molecular Vacancy.

PubMed

He, Zheng-Hua; Chen, Jun; Ji, Guang-Fu; Liu, Li-Min; Zhu, Wen-Jun; Wu, Qiang

2015-08-20

Despite extensive efforts on studying the decomposition mechanism of HMX under extreme condition, an intrinsic understanding of mechanical and chemical response processes, inducing the initial chemical reaction, is not yet achieved. In this work, the microscopic dynamic response and initial decomposition of β-HMX with (1 0 0) surface and molecular vacancy under shock condition, were explored by means of the self-consistent-charge density-functional tight-binding method (SCC-DFTB) in conjunction with multiscale shock technique (MSST). The evolutions of various bond lengths and charge transfers were analyzed to explore and understand the initial reaction mechanism of HMX. Our results discovered that the C-N bond close to major axes had less compression sensitivity and higher stretch activity. The charge was transferred mainly from the N-NO2 group along the minor axes and H atom to C atom during the early compression process. The first reaction of HMX primarily initiated with the fission of the molecular ring at the site of the C-N bond close to major axes. Further breaking of the molecular ring enhanced intermolecular interactions and promoted the cleavage of C-H and N-NO2 bonds. More significantly, the dynamic response behavior clearly depended on the angle between chemical bond and shock direction.

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.

A concurrent multiscale micromorphic molecular dynamics

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

Li, Shaofan, E-mail: shaofan@berkeley.edu; Tong, Qi

2015-04-21

In this work, we have derived a multiscale micromorphic molecular dynamics (MMMD) from first principle to extend the (Andersen)-Parrinello-Rahman molecular dynamics to mesoscale and continuum scale. The multiscale micromorphic molecular dynamics is a con-current three-scale dynamics that couples a fine scale molecular dynamics, a mesoscale micromorphic dynamics, and a macroscale nonlocal particle dynamics together. By choosing proper statistical closure conditions, we have shown that the original Andersen-Parrinello-Rahman molecular dynamics is the homogeneous and equilibrium case of the proposed multiscale micromorphic molecular dynamics. In specific, we have shown that the Andersen-Parrinello-Rahman molecular dynamics can be rigorously formulated and justified from firstmore » principle, and its general inhomogeneous case, i.e., the three scale con-current multiscale micromorphic molecular dynamics can take into account of macroscale continuum mechanics boundary condition without the limitation of atomistic boundary condition or periodic boundary conditions. The discovered multiscale scale structure and the corresponding multiscale dynamics reveal a seamless transition from atomistic scale to continuum scale and the intrinsic coupling mechanism among them based on first principle formulation.« less

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.

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.

Construction of the Free Energy Landscape of Peptide Aggregation from Molecular Dynamics Simulations.

PubMed

Riccardi, Laura; Nguyen, Phuong H; Stock, Gerhard

2012-04-10

To describe the structure and dynamics of oligomers during peptide aggregation, a method is proposed that considers both the intramolecular and intermolecular structures of the multimolecule system and correctly accounts for its degeneracy. The approach is based on the "by-parts" strategy, which partitions a complex molecular system into parts, determines the metastable conformational states of each part, and describes the overall conformational state of the system in terms of a product basis of the states of the parts. Starting from a molecular dynamics simulation of n molecules, the method consists of three steps: (i) characterization of the intramolecular structure, that is, of the conformational states of a single molecule in the presence of the other molecules (e.g., β-strand or random coil); (ii) characterization of the intermolecular structure through the identification of all occurring aggregate states of the peptides (dimers, trimers, etc.); and (iii) construction of the overall conformational states of the system in terms of a product basis of the n "single-molecule" states and the aggregate states. Considering the Alzheimer β-amyloid peptide fragment Aβ16-22 as a first application, about 700 overall conformational states of the trimer (Aβ16-22)3 were constructed from all-atom molecular dynamics simulation in explicit water. Based on these states, a transition network reflecting the free energy landscape of the aggregation process can be constructed that facilitates the identification of the aggregation pathways.

System and method for chromatography and electrophoresis using circular optical scanning

DOEpatents

Balch, Joseph W.; Brewer, Laurence R.; Davidson, James C.; Kimbrough, Joseph R.

2001-01-01

A system and method is disclosed for chromatography and electrophoresis using circular optical scanning. One or more rectangular microchannel plates or radial microchannel plates has a set of analysis channels for insertion of molecular samples. One or more scanning devices repeatedly pass over the analysis channels in one direction at a predetermined rotational velocity and with a predetermined rotational radius. The rotational radius may be dynamically varied so as to monitor the molecular sample at various positions along a analysis channel. Sample loading robots may also be used to input molecular samples into the analysis channels. Radial microchannel plates are built from a substrate whose analysis channels are disposed at a non-parallel angle with respect to each other. A first step in the method accesses either a rectangular or radial microchannel plate, having a set of analysis channels, and second step passes a scanning device repeatedly in one direction over the analysis channels. As a third step, the scanning device is passed over the analysis channels at dynamically varying distances from a centerpoint of the scanning device. As a fourth step, molecular samples are loaded into the analysis channels with a robot.

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

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.

Towards Efficient and Accurate Description of Many-Electron Problems: Developments of Static and Time-Dependent Electronic Structure Methods

NASA Astrophysics Data System (ADS)

Ding, Feizhi

Understanding electronic behavior in molecular and nano-scale systems is fundamental to the development and design of novel technologies and materials for application in a variety of scientific contexts from fundamental research to energy conversion. This dissertation aims to provide insights into this goal by developing novel methods and applications of first-principle electronic structure theory. Specifically, we will present new methods and applications of excited state multi-electron dynamics based on the real-time (RT) time-dependent Hartree-Fock (TDHF) and time-dependent density functional theory (TDDFT) formalism, and new development of the multi-configuration self-consist field theory (MCSCF) for modeling ground-state electronic structure. The RT-TDHF/TDDFT based developments and applications can be categorized into three broad and coherently integrated research areas: (1) modeling of the interaction between moleculars and external electromagnetic perturbations. In this part we will first prove both analytically and numerically the gauge invariance of the TDHF/TDDFT formalisms, then we will present a novel, efficient method for calculating molecular nonlinear optical properties, and last we will study quantum coherent plasmon in metal namowires using RT-TDDFT; (2) modeling of excited-state charge transfer in molecules. In this part, we will investigate the mechanisms of bridge-mediated electron transfer, and then we will introduce a newly developed non-equilibrium quantum/continuum embedding method for studying charge transfer dynamics in solution; (3) developments of first-principles spin-dependent many-electron dynamics. In this part, we will present an ab initio non-relativistic spin dynamics method based on the two-component generalized Hartree-Fock approach, and then we will generalized it to the two-component TDDFT framework and combine it with the Ehrenfest molecular dynamics approach for modeling the interaction between electron spins and nuclear motion. All these developments and applications will open up new computational and theoretical tools to be applied to the development and understanding of chemical reactions, nonlinear optics, electromagnetism, and spintronics. Lastly, we present a new algorithm for large-scale MCSCF calculations that can utilize massively parallel machines while still maintaining optimal performance for each single processor. This will great improve the efficiency in the MCSCF calculations for studying chemical dissociation and high-accuracy quantum-mechanical simulations.

The application of HIV molecular epidemiology to public health.

PubMed

Paraskevis, D; Nikolopoulos, G K; Magiorkinis, G; Hodges-Mameletzis, I; Hatzakis, A

2016-12-01

HIV is responsible for one of the largest viral pandemics in human history. Despite a concerted global response for prevention and treatment, the virus persists. Thus, urgent public health action, utilizing novel interventions, is needed to prevent future transmission events, critical to eliminating HIV. For public health planning to prove effective and successful, we need to understand the dynamics of regional epidemics and to intervene appropriately. HIV molecular epidemiology tools as implemented in phylogenetic, phylodynamic and phylogeographic analyses have proven to be powerful tools in public health planning across many studies. Numerous applications with HIV suggest that molecular methods alone or in combination with mathematical modelling can provide inferences about the transmission dynamics, critical epidemiological parameters (prevalence, incidence, effective number of infections, Re, generation times, time between infection and diagnosis), or the spatiotemporal characteristics of epidemics. Molecular tools have been used to assess the impact of an intervention and outbreak investigation which are of great public health relevance. In some settings, molecular sequence data may be more readily available than HIV surveillance data, and can therefore allow for molecular analyses to be conducted more easily. Nonetheless, classic methods have an integral role in monitoring and evaluation of public health programmes, and should supplement emerging techniques from the field of molecular epidemiology. Importantly, molecular epidemiology remains a promising approach in responding to viral diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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.

Ligand diffusion in proteins via enhanced sampling in molecular dynamics.

PubMed

Rydzewski, J; Nowak, W

2017-12-01

Computational simulations in biophysics describe the dynamics and functions of biological macromolecules at the atomic level. Among motions particularly important for life are the transport processes in heterogeneous media. The process of ligand diffusion inside proteins is an example of a complex rare event that can be modeled using molecular dynamics simulations. The study of physical interactions between a ligand and its biological target is of paramount importance for the design of novel drugs and enzymes. Unfortunately, the process of ligand diffusion is difficult to study experimentally. The need for identifying the ligand egress pathways and understanding how ligands migrate through protein tunnels has spurred the development of several methodological approaches to this problem. The complex topology of protein channels and the transient nature of the ligand passage pose difficulties in the modeling of the ligand entry/escape pathways by canonical molecular dynamics simulations. In this review, we report a methodology involving a reconstruction of the ligand diffusion reaction coordinates and the free-energy profiles along these reaction coordinates using enhanced sampling of conformational space. We illustrate the above methods on several ligand-protein systems, including cytochromes and G-protein-coupled receptors. The methods are general and may be adopted to other transport processes in living matter. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Molecular dynamics approach to water structure of HII mesophase of monoolein

NASA Astrophysics Data System (ADS)

Kolev, Vesselin; Ivanova, Anela; Madjarova, Galia; Aserin, Abraham; Garti, Nissim

2012-02-01

The goal of the present work is to study theoretically the structure of water inside the water cylinder of the inverse hexagonal mesophase (HII) of glyceryl monooleate (monoolein, GMO), using the method of molecular dynamics. To simplify the computational model, a fixed structure of the GMO tube is maintained. The non-standard cylindrical geometry of the system required the development and application of a novel method for obtaining the starting distribution of water molecules. A predictor-corrector schema is employed for generation of the initial density of water. Molecular dynamics calculations are performed at constant volume and temperature (NVT ensemble) with 1D periodic boundary conditions applied. During the simulations the lipid structure is kept fixed, while the dynamics of water is unrestrained. Distribution of hydrogen bonds and density as well as radial distribution of water molecules across the water cylinder show the presence of water structure deep in the cylinder (about 6 Å below the GMO heads). The obtained results may help understanding the role of water structure in the processes of insertion of external molecules inside the GMO/water system. The present work has a semi-quantitative character and it should be considered as the initial stage of more comprehensive future theoretical studies.

Recursive Factorization of the Inverse Overlap Matrix in Linear Scaling Quantum Molecular Dynamics Simulations

DOE PAGES

Negre, Christian F. A; Mniszewski, Susan M.; Cawkwell, Marc Jon; ...

2016-06-06

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 re nement of an initial guess Z of the inverse overlap matrix S. The initial guess of Z is obtained beforehand either by using an approximate divide and conquer technique or dynamically, propagated within an extended Lagrangian dynamics from previous MD time steps. With this formulation, we achieve long-term stability and energy conservation even under incomplete approximate iterative re nement of Z. Linear scaling performance ismore » obtained using numerically thresholded sparse matrix algebra based on the ELLPACK-R sparse matrix data format, which also enables e cient shared memory parallelization. As we show in this article using selfconsistent density functional based tight-binding MD, our approach is faster than conventional methods based on the direct diagonalization of the 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 4,158 atom water-solvated polyalanine system we nd an average speedup factor of 122 for the computation of Z in each MD step.« less

Integrating atomistic molecular dynamics simulations, experiments, and network analysis to study protein dynamics: strength in unity.

PubMed

Papaleo, Elena

2015-01-01

In the last years, we have been observing remarkable improvements in the field of protein dynamics. Indeed, we can now study protein dynamics in atomistic details over several timescales with a rich portfolio of experimental and computational techniques. On one side, this provides us with the possibility to validate simulation methods and physical models against a broad range of experimental observables. On the other side, it also allows a complementary and comprehensive view on protein structure and dynamics. What is needed now is a better understanding of the link between the dynamic properties that we observe and the functional properties of these important cellular machines. To make progresses in this direction, we need to improve the physical models used to describe proteins and solvent in molecular dynamics, as well as to strengthen the integration of experiments and simulations to overcome their own limitations. Moreover, now that we have the means to study protein dynamics in great details, we need new tools to understand the information embedded in the protein ensembles and in their dynamic signature. With this aim in mind, we should enrich the current tools for analysis of biomolecular simulations with attention to the effects that can be propagated over long distances and are often associated to important biological functions. In this context, approaches inspired by network analysis can make an important contribution to the analysis of molecular dynamics simulations.

Young's moduli of carbon materials investigated by various classical molecular dynamics schemes

NASA Astrophysics Data System (ADS)

Gayk, Florian; Ehrens, Julian; Heitmann, Tjark; Vorndamme, Patrick; Mrugalla, Andreas; Schnack, Jürgen

2018-05-01

For many applications classical carbon potentials together with classical molecular dynamics are employed to calculate structures and physical properties of such carbon-based materials where quantum mechanical methods fail either due to the excessive size, irregular structure or long-time dynamics. Although such potentials, as for instance implemented in LAMMPS, yield reasonably accurate bond lengths and angles for several carbon materials such as graphene, it is not clear how accurate they are in terms of mechanical properties such as for instance Young's moduli. We performed large-scale classical molecular dynamics investigations of three carbon-based materials using the various potentials implemented in LAMMPS as well as the EDIP potential of Marks. We show how the Young's moduli vary with classical potentials and compare to experimental results. Since classical descriptions of carbon are bound to be approximations it is not astonishing that different realizations yield differing results. One should therefore carefully check for which observables a certain potential is suited. Our aim is to contribute to such a clarification.

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.

Modeling light-induced charge transfer dynamics across a metal-molecule-metal junction: Bridging classical electrodynamics and quantum dynamics

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

Hu, Zixuan; Ratner, Mark A.; Seideman, Tamar, E-mail: t-seideman@northwestern.edu

2014-12-14

We develop a numerical approach for simulating light-induced charge transport dynamics across a metal-molecule-metal conductance junction. The finite-difference time-domain method is used to simulate the plasmonic response of the metal structures. The Huygens subgridding technique, as adapted to Lorentz media, is used to bridge the vastly disparate length scales of the plasmonic metal electrodes and the molecular system, maintaining accuracy. The charge and current densities calculated with classical electrodynamics are transformed to an electronic wavefunction, which is then propagated through the molecular linker via the Heisenberg equations of motion. We focus mainly on development of the theory and exemplify ourmore » approach by a numerical illustration of a simple system consisting of two silver cylinders bridged by a three-site molecular linker. The electronic subsystem exhibits fascinating light driven dynamics, wherein the charge density oscillates at the driving optical frequency, exhibiting also the natural system timescales, and a resonance phenomenon leads to strong conductance enhancement.« less

Chemical Reaction Rates from Ring Polymer Molecular Dynamics: Zero Point Energy Conservation in Mu + H2 → MuH + H.

PubMed

Pérez de Tudela, Ricardo; Aoiz, F J; Suleimanov, Yury V; Manolopoulos, David E

2012-02-16

A fundamental issue in the field of reaction dynamics is the inclusion of the quantum mechanical (QM) effects such as zero point energy (ZPE) and tunneling in molecular dynamics simulations, and in particular in the calculation of chemical reaction rates. In this work we study the chemical reaction between a muonium atom and a hydrogen molecule. The recently developed ring polymer molecular dynamics (RPMD) technique is used, and the results are compared with those of other methods. For this reaction, the thermal rate coefficients calculated with RPMD are found to be in excellent agreement with the results of an accurate QM calculation. The very minor discrepancies are within the convergence error even at very low temperatures. This exceptionally good agreement can be attributed to the dominant role of ZPE in the reaction, which is accounted for extremely well by RPMD. Tunneling only plays a minor role in the reaction.

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.

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.

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

All-atomic Molecular Dynamic Studies of Human CDK8: Insight into the A-loop, Point Mutations and Binding with Its Partner CycC

PubMed Central

Xu, Wu; Amire-Brahimi, Benjamin; Xie, Xiao-Jun; Huang, Liying; Ji, Jun-Yuan

2014-01-01

The Mediator, a conserved multisubunit protein complex in eukaryotic organisms, regulates gene expression by bridging sequence-specific DNA-binding transcription factors to the general RNA polymerase II machinery. In yeast, Mediator complex is organized in three core modules (head, middle and tail) and a separable ‘CDK8 submodule’ consisting of four subunits including Cyclin-dependent kinase CDK8 (CDK8), Cyclin C (CycC), MED12, and MED13. The 3-D structure of human CDK8-CycC complex has been recently experimentally determined. To take advantage of this structure and the improved theoretical calculation methods, we have performed molecular dynamic simulations to study dynamics of CDK8 and two CDK8 point mutations (D173A and D189N), which have been identified in human cancers, with and without full length of the A-loop as well as the binding between CDK8 and CycC. We found that CDK8 structure gradually loses two helical structures during the 50-ns molecular dynamic simulation, likely due to the presence of the full-length A-loop. In addition, our studies showed the hydrogen bond occupation of the CDK8 A-loop increases during the first 20-ns MD simulation and stays stable during the later 30-ns MD simulation. Four residues in the A-loop of CDK8 have high hydrogen bond occupation, while the rest residues have low or no hydrogen bond occupation. The hydrogen bond dynamic study of the A-loop residues exhibits three types of changes: increasing, decreasing, and stable. Furthermore, the 3-D structures of CDK8 point mutations D173A, D189N, T196A and T196D have been built by molecular modeling and further investigated by 50-ns molecular dynamic simulations. D173A has the highest average potential energy, while T196D has the lowest average potential energy, indicating that T196D is the most stable structure. Finally, we calculated theoretical binding energy of CDK8 and CycC by MM/PBSA and MM/GBSA methods, and the negative values obtained from both methods demonstrate stability of CDK8-CycC complex. Taken together, these analyses will improve our understanding of the exact functions of CDK8 and the interaction with its partner CycC. PMID:24754906

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/.

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

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.

Estimating Arrhenius parameters using temperature programmed molecular dynamics.

PubMed

Imandi, Venkataramana; Chatterjee, Abhijit

2016-07-21

Kinetic rates at different temperatures and the associated Arrhenius parameters, whenever Arrhenius law is obeyed, are efficiently estimated by applying maximum likelihood analysis to waiting times collected using the temperature programmed molecular dynamics method. When transitions involving many activated pathways are available in the dataset, their rates may be calculated using the same collection of waiting times. Arrhenius behaviour is ascertained by comparing rates at the sampled temperatures with ones from the Arrhenius expression. Three prototype systems with corrugated energy landscapes, namely, solvated alanine dipeptide, diffusion at the metal-solvent interphase, and lithium diffusion in silicon, are studied to highlight various aspects of the method. The method becomes particularly appealing when the Arrhenius parameters can be used to find rates at low temperatures where transitions are rare. Systematic coarse-graining of states can further extend the time scales accessible to the method. Good estimates for the rate parameters are obtained with 500-1000 waiting times.

Full-direct method for imaging pharmacokinetic parameters in dynamic fluorescence molecular tomography

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

Zhang, Guanglei, E-mail: guangleizhang@bjtu.edu.cn; Department of Biomedical Engineering, School of Computer and Information Technology, Beijing Jiaotong University, Beijing 100044; Pu, Huangsheng

2015-02-23

Images of pharmacokinetic parameters (also known as parametric images) in dynamic fluorescence molecular tomography (FMT) can provide three-dimensional metabolic information for biological studies and drug development. However, the ill-posed nature of FMT and the high temporal variation of fluorophore concentration together make it difficult to obtain accurate parametric images in small animals in vivo. In this letter, we present a method to directly reconstruct the parametric images from the boundary measurements based on hybrid FMT/X-ray computed tomography (XCT) system. This method can not only utilize structural priors obtained from the XCT system to mitigate the ill-posedness of FMT but alsomore » make full use of the temporal correlations of boundary measurements to model the high temporal variation of fluorophore concentration. The results of numerical simulation and mouse experiment demonstrate that the proposed method leads to significant improvements in the reconstruction quality of parametric images.« less

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.

Deep Potential Molecular Dynamics: A Scalable Model with the Accuracy of Quantum Mechanics

NASA Astrophysics Data System (ADS)

Zhang, Linfeng; Han, Jiequn; Wang, Han; Car, Roberto; E, Weinan

2018-04-01

We introduce a scheme for molecular simulations, the deep potential molecular dynamics (DPMD) method, based on a many-body potential and interatomic forces generated by a carefully crafted deep neural network trained with ab initio data. The neural network model preserves all the natural symmetries in the problem. It is first-principles based in the sense that there are no ad hoc components aside from the network model. We show that the proposed scheme provides an efficient and accurate protocol in a variety of systems, including bulk materials and molecules. In all these cases, DPMD gives results that are essentially indistinguishable from the original data, at a cost that scales linearly with system size.

Molecular dynamics of oligofluorenes: A dielectric spectroscopy investigation

NASA Astrophysics Data System (ADS)

Papadopoulos, P.; Floudas, G.; Chi, C.; Wegner, G.

2004-02-01

The molecular dynamics were investigated in a series of "defect-free" oligofluorenes up to the polymer by dielectric spectroscopy (DS). The method is very sensitive to the presence of keto "defects" that when incorporated on the backbone give rise to poor optical and electronic properties. Two dielectrically active processes were found (β and α process). The latter process (α) displays strongly temperature dependent relaxation times and temperature- and molecular weight-dependent spectral broadening associated with intramolecular correlations. The glass temperature (Tg) obeys the Fox-Flory equation and the polymer Tg is obtained by DS at 332 K. The effective dipole moment associated with the α process is 0.27±0.03 D.

Ultrafast dynamics induced by the interaction of molecules with electromagnetic fields: Several quantum, semiclassical, and classical approaches.

PubMed

Antipov, Sergey V; Bhattacharyya, Swarnendu; El Hage, Krystel; Xu, Zhen-Hao; Meuwly, Markus; Rothlisberger, Ursula; Vaníček, Jiří

2017-11-01

Several strategies for simulating the ultrafast dynamics of molecules induced by interactions with electromagnetic fields are presented. After a brief overview of the theory of molecule-field interaction, we present several representative examples of quantum, semiclassical, and classical approaches to describe the ultrafast molecular dynamics, including the multiconfiguration time-dependent Hartree method, Bohmian dynamics, local control theory, semiclassical thawed Gaussian approximation, phase averaging, dephasing representation, molecular mechanics with proton transfer, and multipolar force fields. In addition to the general overview, some focus is given to the description of nuclear quantum effects and to the direct dynamics, in which the ab initio energies and forces acting on the nuclei are evaluated on the fly. Several practical applications, performed within the framework of the Swiss National Center of Competence in Research "Molecular Ultrafast Science and Technology," are presented: These include Bohmian dynamics description of the collision of H with H 2 , local control theory applied to the photoinduced ultrafast intramolecular proton transfer, semiclassical evaluation of vibrationally resolved electronic absorption, emission, photoelectron, and time-resolved stimulated emission spectra, infrared spectroscopy of H-bonding systems, and multipolar force fields applications in the condensed phase.

Ultrafast dynamics induced by the interaction of molecules with electromagnetic fields: Several quantum, semiclassical, and classical approaches

PubMed Central

Antipov, Sergey V.; Bhattacharyya, Swarnendu; El Hage, Krystel; Xu, Zhen-Hao; Meuwly, Markus; Rothlisberger, Ursula; Vaníček, Jiří

2018-01-01

Several strategies for simulating the ultrafast dynamics of molecules induced by interactions with electromagnetic fields are presented. After a brief overview of the theory of molecule-field interaction, we present several representative examples of quantum, semiclassical, and classical approaches to describe the ultrafast molecular dynamics, including the multiconfiguration time-dependent Hartree method, Bohmian dynamics, local control theory, semiclassical thawed Gaussian approximation, phase averaging, dephasing representation, molecular mechanics with proton transfer, and multipolar force fields. In addition to the general overview, some focus is given to the description of nuclear quantum effects and to the direct dynamics, in which the ab initio energies and forces acting on the nuclei are evaluated on the fly. Several practical applications, performed within the framework of the Swiss National Center of Competence in Research “Molecular Ultrafast Science and Technology,” are presented: These include Bohmian dynamics description of the collision of H with H2, local control theory applied to the photoinduced ultrafast intramolecular proton transfer, semiclassical evaluation of vibrationally resolved electronic absorption, emission, photoelectron, and time-resolved stimulated emission spectra, infrared spectroscopy of H-bonding systems, and multipolar force fields applications in the condensed phase. PMID:29376107

Semiclassical modelling of finite-pulse effects on non-adiabatic photodynamics via initial condition filtering: The predissociation of NaI as a test case

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

Martínez-Mesa, Aliezer; Institut für Chemie, Universität Potsdam, Karl-Liebknecht-Strasse 24-25, D-14476 Potsdam-Golm; Saalfrank, Peter

2015-05-21

Femtosecond-laser pulse driven non-adiabatic spectroscopy and dynamics in molecular and condensed phase systems continue to be a challenge for theoretical modelling. One of the main obstacles is the “curse of dimensionality” encountered in non-adiabatic, exact wavepacket propagation. A possible route towards treating complex molecular systems is via semiclassical surface-hopping schemes, in particular if they account not only for non-adiabatic post-excitation dynamics but also for the initial optical excitation. One such approach, based on initial condition filtering, will be put forward in what follows. As a simple test case which can be compared with exact wavepacket dynamics, we investigate the influencemore » of the different parameters determining the shape of a laser pulse (e.g., its finite width and a possible chirp) on the predissociation dynamics of a NaI molecule, upon photoexcitation of the A(0{sup +}) state. The finite-pulse effects are mapped into the initial conditions for semiclassical surface-hopping simulations. The simulated surface-hopping diabatic populations are in qualitative agreement with the quantum mechanical results, especially concerning the subpicosend photoinduced dynamics, the main deviations being the relative delay of the non-adiabatic transitions in the semiclassical picture. Likewise, these differences in the time-dependent electronic populations calculated via the semiclassical and the quantum methods are found to have a mild influence on the overall probability density distribution. As a result, the branching ratios between the bound and the dissociative reaction channels and the time-evolution of the molecular wavepacket predicted by the semiclassical method agree with those computed using quantum wavepacket propagation. Implications for more challenging molecular systems are given.« less

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

Calculation of the Maxwell stress tensor and the Poisson-Boltzmann force on a solvated molecular surface using hypersingular boundary integrals

NASA Astrophysics Data System (ADS)

Lu, Benzhuo; Cheng, Xiaolin; Hou, Tingjun; McCammon, J. Andrew

2005-08-01

The electrostatic interaction among molecules solvated in ionic solution is governed by the Poisson-Boltzmann equation (PBE). Here the hypersingular integral technique is used in a boundary element method (BEM) for the three-dimensional (3D) linear PBE to calculate the Maxwell stress tensor on the solvated molecular surface, and then the PB forces and torques can be obtained from the stress tensor. Compared with the variational method (also in a BEM frame) that we proposed recently, this method provides an even more efficient way to calculate the full intermolecular electrostatic interaction force, especially for macromolecular systems. Thus, it may be more suitable for the application of Brownian dynamics methods to study the dynamics of protein/protein docking as well as the assembly of large 3D architectures involving many diffusing subunits. The method has been tested on two simple cases to demonstrate its reliability and efficiency, and also compared with our previous variational method used in BEM.

Molecular Mechanics of the α-Actinin Rod Domain: Bending, Torsional, and Extensional Behavior

PubMed Central

Golji, Javad; Collins, Robert; Mofrad, Mohammad R. K.

2009-01-01

α-Actinin is an actin crosslinking molecule that can serve as a scaffold and maintain dynamic actin filament networks. As a crosslinker in the stressed cytoskeleton, α-actinin can retain conformation, function, and strength. α-Actinin has an actin binding domain and a calmodulin homology domain separated by a long rod domain. Using molecular dynamics and normal mode analysis, we suggest that the α-actinin rod domain has flexible terminal regions which can twist and extend under mechanical stress, yet has a highly rigid interior region stabilized by aromatic packing within each spectrin repeat, by electrostatic interactions between the spectrin repeats, and by strong salt bridges between its two anti-parallel monomers. By exploring the natural vibrations of the α-actinin rod domain and by conducting bending molecular dynamics simulations we also predict that bending of the rod domain is possible with minimal force. We introduce computational methods for analyzing the torsional strain of molecules using rotating constraints. Molecular dynamics extension of the α-actinin rod is also performed, demonstrating transduction of the unfolding forces across salt bridges to the associated monomer of the α-actinin rod domain. PMID:19436721

Learning Kinetic Monte Carlo Models of Condensed Phase High Temperature Chemistry from Molecular Dynamics

NASA Astrophysics Data System (ADS)

Yang, Qian; Sing-Long, Carlos; Chen, Enze; Reed, Evan

2017-06-01

Complex chemical processes, such as the decomposition of energetic materials and the chemistry of planetary interiors, are typically studied using large-scale molecular dynamics simulations that run for weeks on high performance parallel machines. These computations may involve thousands of atoms forming hundreds of molecular species and undergoing thousands of reactions. It is natural to wonder whether this wealth of data can be utilized to build more efficient, interpretable, and predictive models. In this talk, we will use techniques from statistical learning to develop a framework for constructing Kinetic Monte Carlo (KMC) models from molecular dynamics data. We will show that our KMC models can not only extrapolate the behavior of the chemical system by as much as an order of magnitude in time, but can also be used to study the dynamics of entirely different chemical trajectories with a high degree of fidelity. Then, we will discuss three different methods for reducing our learned KMC models, including a new and efficient data-driven algorithm using L1-regularization. We demonstrate our framework throughout on a system of high-temperature high-pressure liquid methane, thought to be a major component of gas giant planetary interiors.

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

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)

System and methods for predicting transmembrane domains in membrane proteins and mining the genome for recognizing G-protein coupled receptors

DOEpatents

Trabanino, Rene J; Vaidehi, Nagarajan; Hall, Spencer E; Goddard, William A; Floriano, Wely

2013-02-05

The invention provides computer-implemented methods and apparatus implementing a hierarchical protocol using multiscale molecular dynamics and molecular modeling methods to predict the presence of transmembrane regions in proteins, such as G-Protein Coupled Receptors (GPCR), and protein structural models generated according to the protocol. The protocol features a coarse grain sampling method, such as hydrophobicity analysis, to provide a fast and accurate procedure for predicting transmembrane regions. Methods and apparatus of the invention are useful to screen protein or polynucleotide databases for encoded proteins with transmembrane regions, such as GPCRs.

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.

Transfer coefficients in ultracold strongly coupled plasma

NASA Astrophysics Data System (ADS)

Bobrov, A. A.; Vorob'ev, V. S.; Zelener, B. V.

2018-03-01

We use both analytical and molecular dynamic methods for electron transfer coefficients in an ultracold plasma when its temperature is small and the coupling parameter characterizing the interaction of electrons and ions exceeds unity. For these conditions, we use the approach of nearest neighbor to determine the average electron (ion) diffusion coefficient and to calculate other electron transfer coefficients (viscosity and electrical and thermal conductivities). Molecular dynamics simulations produce electronic and ionic diffusion coefficients, confirming the reliability of these results. The results compare favorably with experimental and numerical data from earlier studies.

Parametrizing linear generalized Langevin dynamics from explicit molecular dynamics simulations

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

Gottwald, Fabian; Karsten, Sven; Ivanov, Sergei D., E-mail: sergei.ivanov@uni-rostock.de

2015-06-28

Fundamental understanding of complex dynamics in many-particle systems on the atomistic level is of utmost importance. Often the systems of interest are of macroscopic size but can be partitioned into a few important degrees of freedom which are treated most accurately and others which constitute a thermal bath. Particular attention in this respect attracts the linear generalized Langevin equation, which can be rigorously derived by means of a linear projection technique. Within this framework, a complicated interaction with the bath can be reduced to a single memory kernel. This memory kernel in turn is parametrized for a particular system studied,more » usually by means of time-domain methods based on explicit molecular dynamics data. Here, we discuss that this task is more naturally achieved in frequency domain and develop a Fourier-based parametrization method that outperforms its time-domain analogues. Very surprisingly, the widely used rigid bond method turns out to be inappropriate in general. Importantly, we show that the rigid bond approach leads to a systematic overestimation of relaxation times, unless the system under study consists of a harmonic bath bi-linearly coupled to the relevant degrees of freedom.« less

Quantum Dynamics and a Semiclassical Description of the Photon.

ERIC Educational Resources Information Center

Henderson, Giles

1980-01-01

Uses computer graphics and nonstationary, superposition wave functions to reveal the dynamic quantum trajectories of several molecular and electronic transitions. These methods are then coupled with classical electromagnetic theory to provide a conceptually clear picture of the emission process and emitted radiation localized in time and space.…

Ultrafast High Harmonic, Soft X-Ray Probing of Molecular Dynamics

DTIC Science & Technology

2013-04-30

590 L/s scroll pump and a titanium sublimation pump . A TOF-PES has been designed and constructed to analyze the energy of the photoelectrons...are studied using the quasi-continuous vacuum ultraviolet light of the Advanced Light Source at Lawrence Berkeley National Laboratory. The molecular...34), the method of high order harmonic generation of ultrashort vacuum ultraviolet pulses was used to investigate molecular photodissociation, ultrafast

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.

Hybrid Steered Molecular Dynamics-Docking: An Efficient Solution to the Problem of Ranking Inhibitor Affinities Against a Flexible Drug Target.

PubMed

Whalen, Katie L; Chang, Kevin M; Spies, M Ashley

2011-05-16

Existing techniques which attempt to predict the affinity of protein-ligand interactions have demonstrated a direct relationship between computational cost and prediction accuracy. We present here the first application of a hybrid ensemble docking and steered molecular dynamics scheme (with a minimized computational cost), which achieves a binding affinity rank-ordering of ligands with a Spearman correlation coefficient of 0.79 and an RMS error of 0.7 kcal/mol. The scheme, termed Flexible Enzyme Receptor Method by Steered Molecular Dynamics (FERM-SMD), is applied to an in-house collection of 17 validated ligands of glutamate racemase. The resulting improved accuracy in affinity prediction allows elucidation of the key structural components of a heretofore unreported glutamate racemase inhibitor (K(i) = 9 µM), a promising new lead in the development of antibacterial therapeutics.

Quantum molecular dynamics simulation of shock-wave experiments in aluminum

NASA Astrophysics Data System (ADS)

Minakov, D. V.; Levashov, P. R.; Khishchenko, K. V.; Fortov, V. E.

2014-06-01

We present quantum molecular dynamics calculations of principal, porous, and double shock Hugoniots, release isentropes, and sound velocity behind the shock front for aluminum. A comprehensive analysis of available shock-wave data is performed; the agreement and discrepancies of simulation results with measurements are discussed. Special attention is paid to the melting region of aluminum along the principal Hugoniot; the boundaries of the melting zone are estimated using the self-diffusion coefficient. Also, we make a comparison with a high-quality multiphase equation of state for aluminum. Independent semiempirical and first-principle models are very close to each other in caloric variables (pressure, density, particle velocity, etc.) but the equation of state gives higher temperature on the principal Hugoniot and release isentropes than ab initio calculations. Thus, the quantum molecular dynamics method can be used for calibration of semiempirical equations of state in case of lack of experimental data.

Transport properties and efficiency of elastically coupled particles in asymmetric periodic potentials

NASA Astrophysics Data System (ADS)

Igarashi, Akito; Tsukamoto, Shinji

2000-02-01

Biological molecular motors drive unidirectional transport and transduce chemical energy to mechanical work. In order to identify this energy conversion which is a common feature of molecular motors, many workers have studied various physical models, which consist of Brownian particles in spatially periodic potentials. Most of the models are, however, based on "single-particle" dynamics and too simple as models for biological motors, especially for actin-myosin motors, which cause muscle contraction. In this paper, particles coupled by elastic strings in an asymmetric periodic potential are considered as a model for the motors. We investigate the dynamics of the model and calculate the efficiency of energy conversion with the use of molecular dynamical method. In particular, we find that the velocity and efficiency of the elastically coupled particles where the natural length of the springs is incommensurable with the period of the periodic potential are larger than those of the corresponding single particle model.

Quantum molecular dynamics simulation of shock-wave experiments in aluminum

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

Minakov, D. V.; Khishchenko, K. V.; Fortov, V. E.

2014-06-14

We present quantum molecular dynamics calculations of principal, porous, and double shock Hugoniots, release isentropes, and sound velocity behind the shock front for aluminum. A comprehensive analysis of available shock-wave data is performed; the agreement and discrepancies of simulation results with measurements are discussed. Special attention is paid to the melting region of aluminum along the principal Hugoniot; the boundaries of the melting zone are estimated using the self-diffusion coefficient. Also, we make a comparison with a high-quality multiphase equation of state for aluminum. Independent semiempirical and first-principle models are very close to each other in caloric variables (pressure, density,more » particle velocity, etc.) but the equation of state gives higher temperature on the principal Hugoniot and release isentropes than ab initio calculations. Thus, the quantum molecular dynamics method can be used for calibration of semiempirical equations of state in case of lack of experimental data.« less

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

Molecular dynamic simulation of mGluR5 amino terminal domain: essential dynamics analysis captures the agonist or antagonist behaviour of ligands.

PubMed

Casoni, Alessandro; Clerici, Francesca; Contini, Alessandro

2013-04-01

We describe the application of molecular dynamics followed by principal component analysis to study the inter-domain movements of the ligand binding domain (LBD) of mGluR5 in response to the binding of selected agonists or antagonists. Our results suggest that the method is an attractive alternative to current approaches to predict the agonist-induced or antagonist-blocked LBD responses. The ratio between the eigenvalues of the first and second eigenvectors (R1,2) is also proposed as a numerical descriptor for discriminating the ligand behavior as a mGluR5 agonist or antagonist. Copyright © 2013 Elsevier Inc. All rights reserved.

Polarizable Force Fields and Polarizable Continuum Model: A Fluctuating Charges/PCM Approach. 1. Theory and Implementation.

PubMed

Lipparini, Filippo; Barone, Vincenzo

2011-11-08

We present a combined fluctuating charges-polarizable continuum model approach to describe molecules in solution. Both static and dynamic approaches are discussed: analytical first and second derivatives are shown as well as an extended lagrangian for molecular dynamics simluations. In particular, we use the polarizable continuum model to provide nonperiodic boundary conditions for molecular dynamics simulations of aqueous solutions. The extended lagrangian method is extensively discussed, with specific reference to the fluctuating charge model, from a numerical point of view by means of several examples, and a rationalization of the behavior found is presented. Several prototypical applications are shown, especially regarding solvation of ions and polar molecules in water.

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

Neural Network and Nearest Neighbor Algorithms for Enhancing Sampling of Molecular Dynamics.

PubMed

Galvelis, Raimondas; Sugita, Yuji

2017-06-13

The free energy calculations of complex chemical and biological systems with molecular dynamics (MD) are inefficient due to multiple local minima separated by high-energy barriers. The minima can be escaped using an enhanced sampling method such as metadynamics, which apply bias (i.e., importance sampling) along a set of collective variables (CV), but the maximum number of CVs (or dimensions) is severely limited. We propose a high-dimensional bias potential method (NN2B) based on two machine learning algorithms: the nearest neighbor density estimator (NNDE) and the artificial neural network (ANN) for the bias potential approximation. The bias potential is constructed iteratively from short biased MD simulations accounting for correlation among CVs. Our method is capable of achieving ergodic sampling and calculating free energy of polypeptides with up to 8-dimensional bias potential.

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.

Two-step relaxation mode analysis with multiple evolution times applied to all-atom molecular dynamics protein simulation.

PubMed

Karasawa, N; Mitsutake, A; Takano, H

2017-12-01

Proteins implement their functionalities when folded into specific three-dimensional structures, and their functions are related to the protein structures and dynamics. Previously, we applied a relaxation mode analysis (RMA) method to protein systems; this method approximately estimates the slow relaxation modes and times via simulation and enables investigation of the dynamic properties underlying the protein structural fluctuations. Recently, two-step RMA with multiple evolution times has been proposed and applied to a slightly complex homopolymer system, i.e., a single [n]polycatenane. This method can be applied to more complex heteropolymer systems, i.e., protein systems, to estimate the relaxation modes and times more accurately. In two-step RMA, we first perform RMA and obtain rough estimates of the relaxation modes and times. Then, we apply RMA with multiple evolution times to a small number of the slowest relaxation modes obtained in the previous calculation. Herein, we apply this method to the results of principal component analysis (PCA). First, PCA is applied to a 2-μs molecular dynamics simulation of hen egg-white lysozyme in aqueous solution. Then, the two-step RMA method with multiple evolution times is applied to the obtained principal components. The slow relaxation modes and corresponding relaxation times for the principal components are much improved by the second RMA.

Two-step relaxation mode analysis with multiple evolution times applied to all-atom molecular dynamics protein simulation

NASA Astrophysics Data System (ADS)

Karasawa, N.; Mitsutake, A.; Takano, H.

2017-12-01

Proteins implement their functionalities when folded into specific three-dimensional structures, and their functions are related to the protein structures and dynamics. Previously, we applied a relaxation mode analysis (RMA) method to protein systems; this method approximately estimates the slow relaxation modes and times via simulation and enables investigation of the dynamic properties underlying the protein structural fluctuations. Recently, two-step RMA with multiple evolution times has been proposed and applied to a slightly complex homopolymer system, i.e., a single [n ] polycatenane. This method can be applied to more complex heteropolymer systems, i.e., protein systems, to estimate the relaxation modes and times more accurately. In two-step RMA, we first perform RMA and obtain rough estimates of the relaxation modes and times. Then, we apply RMA with multiple evolution times to a small number of the slowest relaxation modes obtained in the previous calculation. Herein, we apply this method to the results of principal component analysis (PCA). First, PCA is applied to a 2-μ s molecular dynamics simulation of hen egg-white lysozyme in aqueous solution. Then, the two-step RMA method with multiple evolution times is applied to the obtained principal components. The slow relaxation modes and corresponding relaxation times for the principal components are much improved by the second RMA.

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.

The Global Optimization of Pt13 Cluster Using the First-Principle Molecular Dynamics with the Quenching Technique

NASA Astrophysics Data System (ADS)

Chen, Xiangping; Duan, Haiming; Cao, Biaobing; Long, Mengqiu

2018-03-01

The high-temperature first-principle molecular dynamics method used to obtain the low energy configurations of clusters [L. L. Wang and D. D. Johnson, PRB 75, 235405 (2007)] is extended to a considerably large temperature range by combination with the quenching technique. Our results show that there are strong correlations between the possibilities for obtaining the ground-state structure and the temperatures. Larger possibilities can be obtained at relatively low temperatures (as corresponds to the pre-melting temperature range). Details of the structural correlation with the temperature are investigated by taking the Pt13 cluster as an example, which suggests a quite efficient method to obtain the lowest-energy geometries of metal clusters.

Efficient "on-the-fly" calculation of Raman spectra from ab-initio molecular dynamics: Application to hydrophobic/hydrophilic solutes in bulk water.

PubMed

Partovi-Azar, Pouya; Kühne, Thomas D

2015-11-05

We present a novel computational method to accurately calculate Raman spectra from first principles. Together with an extension of the second-generation Car-Parrinello method of Kühne et al. (Phys. Rev. Lett. 2007, 98, 066401) to propagate maximally localized Wannier functions together with the nuclei, a speed-up of one order of magnitude can be observed. This scheme thus allows to routinely calculate finite-temperature Raman spectra "on-the-fly" by means of ab-initio molecular dynamics simulations. To demonstrate the predictive power of this approach we investigate the effect of hydrophobic and hydrophilic solutes in water solution on the infrared and Raman spectra. © 2015 Wiley Periodicals, Inc.

Assessing Electrolyte Transport Properties with Molecular Dynamics

DOE PAGES

Jones, R. E.; Ward, D. K.; Gittleson, F. S.; ...

2017-04-15

Here in this work we use estimates of ionic transport properties obtained from molecular dynamics to rank lithium electrolytes of different compositions. We develop linear response methods to obtain the Onsager diffusivity matrix for all chemical species, its Fickian counterpart, and the mobilities of the ionic species. We apply these methods to the well-studied propylene carbonate/ethylene carbonate solvent with dissolved LiBF 4 and O 2. The results show that, over a range of lithium concentrations and carbonate mixtures, trends in the transport coefficients can be identified and optimal electrolytes can be selected for experimental focus; however, refinement of these estimationmore » techniques is necessary for a reliable ranking of a large set of electrolytes.« less

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

Interferometric Scattering Microscopy for the Study of Molecular Motors

PubMed Central

Andrecka, J.; Takagi, Y.; Mickolajczyk, K.J.; Lippert, L.G.; Sellers, J.R.; Hancock, W.O.; Goldman, Y.E.; Kukura, P.

2016-01-01

Our understanding of molecular motor function has been greatly improved by the development of imaging modalities, which enable real-time observation of their motion at the single-molecule level. Here, we describe the use of a new method, interferometric scattering microscopy, for the investigation of motor protein dynamics by attaching and tracking the motion of metallic nanoparticle labels as small as 20 nm diameter. Using myosin-5, kinesin-1, and dynein as examples, we describe the basic assays, labeling strategies, and principles of data analysis. Our approach is relevant not only for motor protein dynamics but also provides a general tool for single-particle tracking with high spatiotemporal precision, which overcomes the limitations of single-molecule fluorescence methods. PMID:27793291

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.

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

Wave function continuity and the diagonal Born-Oppenheimer correction at conical intersections

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

Meek, Garrett A.; Levine, Benjamin G., E-mail: levine@chemistry.msu.edu

2016-05-14

We demonstrate that though exact in principle, the expansion of the total molecular wave function as a sum over adiabatic Born-Oppenheimer (BO) vibronic states makes inclusion of the second-derivative nonadiabatic energy term near conical intersections practically problematic. In order to construct a well-behaved molecular wave function that has density at a conical intersection, the individual BO vibronic states in the summation must be discontinuous. When the second-derivative nonadiabatic terms are added to the Hamiltonian, singularities in the diagonal BO corrections (DBOCs) of the individual BO states arise from these discontinuities. In contrast to the well-known singularities in the first-derivative couplingsmore » at conical intersections, these singularities are non-integrable, resulting in undefined DBOC matrix elements. Though these singularities suggest that the exact molecular wave function may not have density at the conical intersection point, there is no physical basis for this constraint. Instead, the singularities are artifacts of the chosen basis of discontinuous functions. We also demonstrate that continuity of the total molecular wave function does not require continuity of the individual adiabatic nuclear wave functions. We classify nonadiabatic molecular dynamics methods according to the constraints placed on wave function continuity and analyze their formal properties. Based on our analysis, it is recommended that the DBOC be neglected when employing mixed quantum-classical methods and certain approximate quantum dynamical methods in the adiabatic representation.« less

Wave function continuity and the diagonal Born-Oppenheimer correction at conical intersections

NASA Astrophysics Data System (ADS)

Meek, Garrett A.; Levine, Benjamin G.

2016-05-01

We demonstrate that though exact in principle, the expansion of the total molecular wave function as a sum over adiabatic Born-Oppenheimer (BO) vibronic states makes inclusion of the second-derivative nonadiabatic energy term near conical intersections practically problematic. In order to construct a well-behaved molecular wave function that has density at a conical intersection, the individual BO vibronic states in the summation must be discontinuous. When the second-derivative nonadiabatic terms are added to the Hamiltonian, singularities in the diagonal BO corrections (DBOCs) of the individual BO states arise from these discontinuities. In contrast to the well-known singularities in the first-derivative couplings at conical intersections, these singularities are non-integrable, resulting in undefined DBOC matrix elements. Though these singularities suggest that the exact molecular wave function may not have density at the conical intersection point, there is no physical basis for this constraint. Instead, the singularities are artifacts of the chosen basis of discontinuous functions. We also demonstrate that continuity of the total molecular wave function does not require continuity of the individual adiabatic nuclear wave functions. We classify nonadiabatic molecular dynamics methods according to the constraints placed on wave function continuity and analyze their formal properties. Based on our analysis, it is recommended that the DBOC be neglected when employing mixed quantum-classical methods and certain approximate quantum dynamical methods in the adiabatic representation.

Wave function continuity and the diagonal Born-Oppenheimer correction at conical intersections.

PubMed

Meek, Garrett A; Levine, Benjamin G

2016-05-14

We demonstrate that though exact in principle, the expansion of the total molecular wave function as a sum over adiabatic Born-Oppenheimer (BO) vibronic states makes inclusion of the second-derivative nonadiabatic energy term near conical intersections practically problematic. In order to construct a well-behaved molecular wave function that has density at a conical intersection, the individual BO vibronic states in the summation must be discontinuous. When the second-derivative nonadiabatic terms are added to the Hamiltonian, singularities in the diagonal BO corrections (DBOCs) of the individual BO states arise from these discontinuities. In contrast to the well-known singularities in the first-derivative couplings at conical intersections, these singularities are non-integrable, resulting in undefined DBOC matrix elements. Though these singularities suggest that the exact molecular wave function may not have density at the conical intersection point, there is no physical basis for this constraint. Instead, the singularities are artifacts of the chosen basis of discontinuous functions. We also demonstrate that continuity of the total molecular wave function does not require continuity of the individual adiabatic nuclear wave functions. We classify nonadiabatic molecular dynamics methods according to the constraints placed on wave function continuity and analyze their formal properties. Based on our analysis, it is recommended that the DBOC be neglected when employing mixed quantum-classical methods and certain approximate quantum dynamical methods in the adiabatic representation.

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.

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

Molecular Dynamics, Monte Carlo Simulations, and Langevin Dynamics: A Computational Review

PubMed Central

Paquet, Eric; Viktor, Herna L.

2015-01-01

Macromolecular structures, such as neuraminidases, hemagglutinins, and monoclonal antibodies, are not rigid entities. Rather, they are characterised by their flexibility, which is the result of the interaction and collective motion of their constituent atoms. This conformational diversity has a significant impact on their physicochemical and biological properties. Among these are their structural stability, the transport of ions through the M2 channel, drug resistance, macromolecular docking, binding energy, and rational epitope design. To assess these properties and to calculate the associated thermodynamical observables, the conformational space must be efficiently sampled and the dynamic of the constituent atoms must be simulated. This paper presents algorithms and techniques that address the abovementioned issues. To this end, a computational review of molecular dynamics, Monte Carlo simulations, Langevin dynamics, and free energy calculation is presented. The exposition is made from first principles to promote a better understanding of the potentialities, limitations, applications, and interrelations of these computational methods. PMID:25785262

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.

Probing amyloid protein aggregation with optical superresolution methods: from the test tube to models of disease

PubMed Central

Kaminski, Clemens F.; Kaminski Schierle, Gabriele S.

2016-01-01

Abstract. The misfolding and self-assembly of intrinsically disordered proteins into insoluble amyloid structures are central to many neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Optical imaging of this self-assembly process in vitro and in cells is revolutionizing our understanding of the molecular mechanisms behind these devastating conditions. In contrast to conventional biophysical methods, optical imaging and, in particular, optical superresolution imaging, permits the dynamic investigation of the molecular self-assembly process in vitro and in cells, at molecular-level resolution. In this article, current state-of-the-art imaging methods are reviewed and discussed in the context of research into neurodegeneration. PMID:27413767

Two-dimensional fourier transform spectrometer

DOEpatents

DeFlores, Lauren; Tokmakoff, Andrei

2016-10-25

The present invention relates to a system and methods for acquiring two-dimensional Fourier transform (2D FT) spectra. Overlap of a collinear pulse pair and probe induce a molecular response which is collected by spectral dispersion of the signal modulated probe beam. Simultaneous collection of the molecular response, pulse timing and characteristics permit real time phasing and rapid acquisition of spectra. Full spectra are acquired as a function of pulse pair timings and numerically transformed to achieve the full frequency-frequency spectrum. This method demonstrates the ability to acquire information on molecular dynamics, couplings and structure in a simple apparatus. Multi-dimensional methods can be used for diagnostic and analytical measurements in the biological, biomedical, and chemical fields.

Two-dimensional fourier transform spectrometer

DOEpatents

DeFlores, Lauren; Tokmakoff, Andrei

2013-09-03

The present invention relates to a system and methods for acquiring two-dimensional Fourier transform (2D FT) spectra. Overlap of a collinear pulse pair and probe induce a molecular response which is collected by spectral dispersion of the signal modulated probe beam. Simultaneous collection of the molecular response, pulse timing and characteristics permit real time phasing and rapid acquisition of spectra. Full spectra are acquired as a function of pulse pair timings and numerically transformed to achieve the full frequency-frequency spectrum. This method demonstrates the ability to acquire information on molecular dynamics, couplings and structure in a simple apparatus. Multi-dimensional methods can be used for diagnostic and analytical measurements in the biological, biomedical, and chemical fields.

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.

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.

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.

Molecular dynamic approach to the study of the intense heat and mass transfer processes on the vapor-liquid interface

NASA Astrophysics Data System (ADS)

Levashov, V. Yu; Kamenov, P. K.

2017-10-01

The paper is devoted to research of the heat and mass transfer processes on the vapor-liquid interface. These processes can be realized for example at metal tempering, accidents at nuclear power stations, followed by the release of the corium into the heat carrier, getting hot magma into the water during volcanic eruptions and other. In all these examples the vapor film can arise on the heated body surface. In this paper the vapor film formation process will be considered with help of molecular dynamics simulation methods. The main attention during this process modeling will be focused on the subject of the fluid and vapor interactions with the heater surface. Another direction of this work is to study of the processes inside the droplet that may take place as result of impact of the high-power laser radiation. Such impact can lead to intensive evaporation and explosive destruction of the droplet. At that the duration of heat and mass transfer processes in droplet substance is tens of femtoseconds. Thus, the methods of molecular dynamics simulation can give the possibilities describe the heat and mass transfer processes in the droplet and the vapor phase formation.

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.

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.

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.

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.

Nonequilibrium flows with smooth particle applied mechanics

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

Kum, Oyeon

1995-07-01

Smooth particle methods are relatively new methods for simulating solid and fluid flows through they have a 20-year history of solving complex hydrodynamic problems in astrophysics, such as colliding planets and stars, for which correct answers are unknown. The results presented in this thesis evaluate the adaptability or fitness of the method for typical hydrocode production problems. For finite hydrodynamic systems, boundary conditions are important. A reflective boundary condition with image particles is a good way to prevent a density anomaly at the boundary and to keep the fluxes continuous there. Boundary values of temperature and velocity can be separatelymore » controlled. The gradient algorithm, based on differentiating the smooth particle expression for (uρ) and (Tρ), does not show numerical instabilities for the stress tensor and heat flux vector quantities which require second derivatives in space when Fourier`s heat-flow law and Newton`s viscous force law are used. Smooth particle methods show an interesting parallel linking to them to molecular dynamics. For the inviscid Euler equation, with an isentropic ideal gas equation of state, the smooth particle algorithm generates trajectories isomorphic to those generated by molecular dynamics. The shear moduli were evaluated based on molecular dynamics calculations for the three weighting functions, B spline, Lucy, and Cusp functions. The accuracy and applicability of the methods were estimated by comparing a set of smooth particle Rayleigh-Benard problems, all in the laminar regime, to corresponding highly-accurate grid-based numerical solutions of continuum equations. Both transient and stationary smooth particle solutions reproduce the grid-based data with velocity errors on the order of 5%. The smooth particle method still provides robust solutions at high Rayleigh number where grid-based methods fails.« less

Quantum structural fluctuation in para-hydrogen clusters revealed by the variational path integral method

NASA Astrophysics Data System (ADS)

Miura, Shinichi

2018-03-01

In this paper, the ground state of para-hydrogen clusters for size regime N ≤ 40 has been studied by our variational path integral molecular dynamics method. Long molecular dynamics calculations have been performed to accurately evaluate ground state properties. The chemical potential of the hydrogen molecule is found to have a zigzag size dependence, indicating the magic number stability for the clusters of the size N = 13, 26, 29, 34, and 39. One-body density of the hydrogen molecule is demonstrated to have a structured profile, not a melted one. The observed magic number stability is examined using the inherent structure analysis. We also have developed a novel method combining our variational path integral hybrid Monte Carlo method with the replica exchange technique. We introduce replicas of the original system bridging from the structured to the melted cluster, which is realized by scaling the potential energy of the system. Using the enhanced sampling method, the clusters are demonstrated to have the structured density profile in the ground state.

Quantum structural fluctuation in para-hydrogen clusters revealed by the variational path integral method.

PubMed

Miura, Shinichi

2018-03-14

In this paper, the ground state of para-hydrogen clusters for size regime N ≤ 40 has been studied by our variational path integral molecular dynamics method. Long molecular dynamics calculations have been performed to accurately evaluate ground state properties. The chemical potential of the hydrogen molecule is found to have a zigzag size dependence, indicating the magic number stability for the clusters of the size N = 13, 26, 29, 34, and 39. One-body density of the hydrogen molecule is demonstrated to have a structured profile, not a melted one. The observed magic number stability is examined using the inherent structure analysis. We also have developed a novel method combining our variational path integral hybrid Monte Carlo method with the replica exchange technique. We introduce replicas of the original system bridging from the structured to the melted cluster, which is realized by scaling the potential energy of the system. Using the enhanced sampling method, the clusters are demonstrated to have the structured density profile in the ground state.

Angle-dependent strong-field molecular ionization rates with tuned range-separated time-dependent density functional theory.

PubMed

Sissay, Adonay; Abanador, Paul; Mauger, François; Gaarde, Mette; Schafer, Kenneth J; Lopata, Kenneth

2016-09-07

Strong-field ionization and the resulting electronic dynamics are important for a range of processes such as high harmonic generation, photodamage, charge resonance enhanced ionization, and ionization-triggered charge migration. Modeling ionization dynamics in molecular systems from first-principles can be challenging due to the large spatial extent of the wavefunction which stresses the accuracy of basis sets, and the intense fields which require non-perturbative time-dependent electronic structure methods. In this paper, we develop a time-dependent density functional theory approach which uses a Gaussian-type orbital (GTO) basis set to capture strong-field ionization rates and dynamics in atoms and small molecules. This involves propagating the electronic density matrix in time with a time-dependent laser potential and a spatial non-Hermitian complex absorbing potential which is projected onto an atom-centered basis set to remove ionized charge from the simulation. For the density functional theory (DFT) functional we use a tuned range-separated functional LC-PBE*, which has the correct asymptotic 1/r form of the potential and a reduced delocalization error compared to traditional DFT functionals. Ionization rates are computed for hydrogen, molecular nitrogen, and iodoacetylene under various field frequencies, intensities, and polarizations (angle-dependent ionization), and the results are shown to quantitatively agree with time-dependent Schrödinger equation and strong-field approximation calculations. This tuned DFT with GTO method opens the door to predictive all-electron time-dependent density functional theory simulations of ionization and ionization-triggered dynamics in molecular systems using tuned range-separated hybrid functionals.

Angle-dependent strong-field molecular ionization rates with tuned range-separated time-dependent density functional theory

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

Sissay, Adonay; Abanador, Paul; Mauger, François

2016-09-07

Strong-field ionization and the resulting electronic dynamics are important for a range of processes such as high harmonic generation, photodamage, charge resonance enhanced ionization, and ionization-triggered charge migration. Modeling ionization dynamics in molecular systems from first-principles can be challenging due to the large spatial extent of the wavefunction which stresses the accuracy of basis sets, and the intense fields which require non-perturbative time-dependent electronic structure methods. In this paper, we develop a time-dependent density functional theory approach which uses a Gaussian-type orbital (GTO) basis set to capture strong-field ionization rates and dynamics in atoms and small molecules. This involves propagatingmore » the electronic density matrix in time with a time-dependent laser potential and a spatial non-Hermitian complex absorbing potential which is projected onto an atom-centered basis set to remove ionized charge from the simulation. For the density functional theory (DFT) functional we use a tuned range-separated functional LC-PBE*, which has the correct asymptotic 1/r form of the potential and a reduced delocalization error compared to traditional DFT functionals. Ionization rates are computed for hydrogen, molecular nitrogen, and iodoacetylene under various field frequencies, intensities, and polarizations (angle-dependent ionization), and the results are shown to quantitatively agree with time-dependent Schrödinger equation and strong-field approximation calculations. This tuned DFT with GTO method opens the door to predictive all-electron time-dependent density functional theory simulations of ionization and ionization-triggered dynamics in molecular systems using tuned range-separated hybrid functionals.« less

On the room-temperature phase diagram of high pressure hydrogen: an ab initio molecular dynamics perspective and a diffusion Monte Carlo study.

PubMed

Chen, Ji; Ren, Xinguo; Li, Xin-Zheng; Alfè, Dario; Wang, Enge

2014-07-14

The finite-temperature phase diagram of hydrogen in the region of phase IV and its neighborhood was studied using the ab initio molecular dynamics (MD) and the ab initio path-integral molecular dynamics (PIMD). The electronic structures were analyzed using the density-functional theory (DFT), the random-phase approximation, and the diffusion Monte Carlo (DMC) methods. Taking the state-of-the-art DMC results as benchmark, comparisons of the energy differences between structures generated from the MD and PIMD simulations, with molecular and dissociated hydrogens, respectively, in the weak molecular layers of phase IV, indicate that standard functionals in DFT tend to underestimate the dissociation barrier of the weak molecular layers in this mixed phase. Because of this underestimation, inclusion of the quantum nuclear effects (QNEs) in PIMD using electronic structures generated with these functionals leads to artificially dissociated hydrogen layers in phase IV and an error compensation between the neglect of QNEs and the deficiencies of these functionals in standard ab initio MD simulations exists. This analysis partly rationalizes why earlier ab initio MD simulations complement so well the experimental observations. The temperature and pressure dependencies for the stability of phase IV were also studied in the end and compared with earlier results.

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.

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.

Scalable Molecular Dynamics with NAMD

PubMed Central

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

2008-01-01

NAMD is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD scales to hundreds of processors on high-end parallel platforms, as well as tens of processors on low-cost commodity clusters, and also runs on individual desktop and laptop computers. NAMD works with AMBER and CHARMM potential functions, parameters, and file formats. This paper, directed to novices as well as experts, first introduces concepts and methods used in the NAMD program, describing the classical molecular dynamics force field, equations of motion, and integration methods along with the efficient electrostatics evaluation algorithms employed and temperature and pressure controls used. Features for steering the simulation across barriers and for calculating both alchemical and conformational free energy differences are presented. The motivations for and a roadmap to the internal design of NAMD, implemented in C++ and based on Charm++ parallel objects, are outlined. The factors affecting the serial and parallel performance of a simulation are discussed. Next, typical NAMD use is illustrated with representative applications to a small, a medium, and a large biomolecular system, highlighting particular features of NAMD, e.g., the Tcl scripting language. Finally, the paper provides a list of the key features of NAMD and discusses the benefits of combining NAMD with the molecular graphics/sequence analysis software VMD and the grid computing/collaboratory software BioCoRE. NAMD is distributed free of charge with source code at www.ks.uiuc.edu. PMID:16222654

Collective Langevin dynamics of conformational motions in proteins

NASA Astrophysics Data System (ADS)

Lange, Oliver F.; Grubmüller, Helmut

2006-06-01

Functionally relevant slow conformational motions of proteins are, at present, in most cases inaccessible to molecular dynamics (MD) simulations. The main reason is that the major part of the computational effort is spend for the accurate description of a huge number of high frequency motions of the protein and the surrounding solvent. The accumulated influence of these fluctuations is crucial for a correct treatment of the conformational dynamics; however, their details can be considered irrelevant for most purposes. To accurately describe long time protein dynamics we here propose a reduced dimension approach, collective Langevin dynamics (CLD), which evolves the dynamics of the system within a small subspace of relevant collective degrees of freedom. The dynamics within the low-dimensional conformational subspace is evolved via a generalized Langevin equation which accounts for memory effects via memory kernels also extracted from short explicit MD simulations. To determine the memory kernel with differing levels of regularization, we propose and evaluate two methods. As a first test, CLD is applied to describe the conformational motion of the peptide neurotensin. A drastic dimension reduction is achieved by considering one single curved conformational coordinate. CLD yielded accurate thermodynamical and dynamical behaviors. In particular, the rate of transitions between two conformational states agreed well with a rate obtained from a 150ns reference molecular dynamics simulation, despite the fact that the time scale of the transition (˜50ns) was much longer than the 1ns molecular dynamics simulation from which the memory kernel was extracted.

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.

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

Adaptive Detection and ISI Mitigation for Mobile Molecular Communication.

PubMed

Chang, Ge; Lin, Lin; Yan, Hao

2018-03-01

Current studies on modulation and detection schemes in molecular communication mainly focus on the scenarios with static transmitters and receivers. However, mobile molecular communication is needed in many envisioned applications, such as target tracking and drug delivery. Until now, investigations about mobile molecular communication have been limited. In this paper, a static transmitter and a mobile bacterium-based receiver performing random walk are considered. In this mobile scenario, the channel impulse response changes due to the dynamic change of the distance between the transmitter and the receiver. Detection schemes based on fixed distance fail in signal detection in such a scenario. Furthermore, the intersymbol interference (ISI) effect becomes more complex due to the dynamic character of the signal which makes the estimation and mitigation of the ISI even more difficult. In this paper, an adaptive ISI mitigation method and two adaptive detection schemes are proposed for this mobile scenario. In the proposed scheme, adaptive ISI mitigation, estimation of dynamic distance, and the corresponding impulse response reconstruction are performed in each symbol interval. Based on the dynamic channel impulse response in each interval, two adaptive detection schemes, concentration-based adaptive threshold detection and peak-time-based adaptive detection, are proposed for signal detection. Simulations demonstrate that the ISI effect is significantly reduced and the adaptive detection schemes are reliable and robust for mobile molecular communication.

40 CFR 75.22 - Reference test methods.

Code of Federal Regulations, 2011 CFR

2011-07-01

... recertification of continuous emission monitoring Systems; NOX emission tests of low mass emission units under... continuous moisture monitoring systems are conducted. For the purpose of determining the stack gas molecular... traverse requirement of the method; (iv) Section 8.6 of the method allowing for the use of “Dynamic Spiking...

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.

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.

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

Simulation of ablation and plume dynamics under femtosecond double-pulse laser irradiation of aluminum: Comparison of atomistic and continual approaches

NASA Astrophysics Data System (ADS)

Fokin, Vladimir B.; Povarnitsyn, Mikhail E.; Levashov, Pavel R.

2017-02-01

We elaborated two numerical methods, two-temperature hydrodynamics and hybrid two-temperature molecular dynamics, which take into account basic mechanisms of a metal target response to ultrashort laser irradiation. The model used for the description of the electronic subsystem is identical for both approaches, while the ionic part is defined by an equation of state in hydrodynamics and by an interatomic potential in molecular dynamics. Since the phase diagram of the equation of state and corresponding potential match reasonably well, the dynamics of laser ablation obtained by both methods is quite similar. This correspondence can be considered as a first step towards the development of a self-consistent combined model. Two important processes are highlighted in simulations of double-pulse ablation: (1) the crater depth decrease as a result of recoil flux formation in the nascent plume when the delay between the pulses increases; (2) the plume reheating by the second pulse that gives rise to two- three-fold growth of the electron temperature with the delay varying from 0 to 200 ps.

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.