An extensible interface for QM/MM molecular dynamics simulations with AMBER

We present an extensible interface between the AMBER molecular dynamics (MD) software package and electronic structure software packages for quantum mechanical (QM) and mixed QM and classical molecular mechanical (MM) MD simulations within both mechanical and electronic embedding schemes. With this interface, ab initio wave function theory and density functional theory methods, as available in the supported electronic structure software packages, become available for QM/MM MD simulations with AMBER. The interface has been written in a modular fashion that allows straight forward extensions to support additional QM software packages and can easily be ported to other MD software. Data exchange between the MD and QM software is implemented by means of files and system calls or the message passing interface standard. Based on extensive tests, default settings for the supported QM packages are provided such that energy is conserved for typical QM/MM MD simulations in the microcanonical ensemble. Results for the free energy of binding of calcium ions to aspartate in aqueous solution comparing semiempirical and density functional Hamiltonians are shown to demonstrate features of this interface. © 2013 Wiley Periodicals, Inc.     

An efficient hybrid explicit/implicit solvent method for biomolecular simulations

We present a new hybrid explicit/implicit solvent method for dynamics simulations of macromolecular systems. The method models explicitly the hydration of the solute by either a layer or sphere of water molecules, and the generalized Born (GB) theory is used to treat the bulk continuum solvent outside the explicit simulation volume. To reduce the computational cost, we implemented a multigrid method for evaluating the pairwise electrostatic and GB terms. It is shown that for typical ion and protein simulations our method achieves similar equilibrium and dynamical observables as the conventional particle mesh Ewald (PME) method. Simulation timings are reported, which indicate that the hybrid method is much faster than PME, primarily due to a significant reduction in the number of explicit water molecules required to model hydration effects.     

Density functional theory for efficient ab initio molecular dynamics simulations in solution

We present a density functional for first-principles molecular dynamics simulations that includes the electrostatic effects of a continuous dielectric medium. It allows for numerical simulations of molecules in solution in a model polar solvent. We propose a smooth dielectric model function to model solvation into water and demonstrate its good numerical properties for total energy calculations and constant energy molecular dynamics.     

The dynamo library for molecular simulations using hybrid quantum mechanical and molecular mechanical potentials

The Dynamo module library has been developed for the simulation of molecular systems using hybrid quantum mechanical (QM) and molecular mechanical (MM) potentials. Dynamo is not a program package but is a library of Fortran 90 modules that can be employed by those interested in writing their own programs for performing molecular simulations. The library supports a range of different types of molecular calculation including geometry optimizations, reaction‐path determinations and molecular dynamics and Monte Carlo simulations. This article outlines the general structure and capabilities of the library and describes in detail Dynamo's semiempirical QM/MM hybrid potential. Results are presented to indicate three particular aspects of this implementation—the handling of long‐range nonbonding interactions, the nature of the boundary between the quantum mechanical and molecular mechanical atoms and how to perform path‐integral hybrid‐potential molecular dynamics simulations. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1088–1100, 2000     

Using molecular dynamics simulations to identify the key factors responsible for chiral recognition by an amino acid-based molecular micelle

Molecular dynamics (MD) simulations were used to investigate the binding of six chiral compounds to the amino acid-based molecular micelle (MM) poly-(sodium undecyl-(L)-leucine-leucine) or poly(SULL). The MM investigated is used as a chiral selector in capillary electrophoresis. The project goal was to characterize the chiral recognition mechanism in these separations and to move toward predictive models to identify the best amino acid-based MM for a given separation. Poly(SULL) was found to contain six binding sites into which chiral compounds could insert. Four sites had similar sizes, shapes, and electrostatic properties. Enantiomers of alprenolol, propranolol, 1,1′-bi-2-naphthyl-2,2′-diyl hydrogen phosphate, 1,1′-bi-2-naphthol, chlorthalidone, or lorazepam were separately docked into each binding pocket and MD simulations with the resulting intermolecular complexes were performed. Solvent-accessible surface area calculations showed the compounds preferentially associated with binding sites where they penetrated into the MM core and shielded their non-polar atoms from solvent. Furthermore, with five of the six compounds the enantiomer with the most favorable free energy of MM association also experienced the most favorable intermolecular hydrogen bonding interactions with the MM. This result suggests that stereoselective intermolecular hydrogen bonds play an important role in chiral discrimination in separations using amino acid-based MMs.GRAPHICAL ABSTRACT     

LINCS: A linear constraint solver for molecular simulations

In this article, we present a new LINear Constraint Solver (LINCS) for molecular simulations with bond constraints. The algorithm is inherently stable, as the constraints themselves are reset instead of derivatives of the constraints, thereby eliminating drift. Although the derivation of the algorithm is presented in terms of matrices, no matrix matrix multiplications are needed and only the nonzero matrix elements have to be stored, making the method useful for very large molecules. At the same accuracy, the LINCS algorithm is three to four times faster than the SHAKE algorithm. Parallelization of the algorithm is straightforward. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1463–1472, 1997     

Organolithium complex as a gas sensing material for oxides from ab initio calculations and molecular dynamics simulations

Gas sensing study of C₂H₄Li complex toward oxides viz. CO, CO₂, NO, NO₂, SO, and SO₂ gas molecules has been carried out using ab initio method. Different possible configurations of gas molecule adsorption on C₂H₄Li complex are considered. The structural parameters of most stable configuration of gas molecule adsorbed complexes are thoroughly analysed. Electronic properties are studied using total density of states (DOS) plot. Charge transferred between the gas molecule and the substrate is studied using NBO charge analysis. Gas sensing of all the six gas molecules is possible at ambient conditions. Atom centred density matrix propagation (ADMP) molecular dynamics simulations confirmed that all the gas molecules remain adsorbed on C₂H₄Li complex at room temperature during the simulation. This study suggests that the C₂H₄Li complex acts as a novel gas sensing material for CO, CO₂, NO, NO₂, SO, and SO₂ gas molecules at ambient conditions, below room temperature as well as at high pressure.     

A detailed reaction mechanism for hexamethyldisiloxane combustion via experiments and ReaxFF molecular dynamics simulations

Hexamethyldisiloxane (HMDSO) is one of the main impurities in the syngas produced from sewage and landfill plants. In order to utilize this syngas or control the characteristics of the generated silica particles, it is crucial to understand the chemical kinetics of HMDSO combustion. This study investigated the process of HMDSO combustion using synchrotron radiation mass spectrometry (SRMS), gas chromatography (GC), and ReaxFF molecular dynamics simulations. First, the force field used for ReaxFF simulation was validated by comparing the energies of different bond lengths, bond angles, and dihedral angles with the ones from DFT calculations. Good agreements were found. Then, ReaxFF simulations of HMDSO combustion with this force field were conducted under various conditions, which include different equivalence ratios (0.67, 1.0, and 1.5) and temperatures ranging from 2000 to 3500 K. The oxidation characteristics of HMDSO were analyzed, including the evolution of gas products and particle formation. Finally, based on the results from experiments and ReaxFF simulations, the reaction pathways, reaction lists, and reaction kinetics data during HMDSO combustion were obtained. A detailed reaction mechanism was proposed and validated by applying it in modeling the H₂/HMDSO/O₂ combustion systems. The temperature and part of the gas products such as CO and CO₂ as well as SiO could be well predicted.     

Steered molecular dynamics simulations of protein-ligand interactions

Molecular recognition and specific protein-ligandinteractions are central to many biochemical processes,such as enzyme catalysis, assembly of organelles, en-ergy transduction, signaling, diverse control functions,and replication, expression and storage of the geneticmaterial[1]. Moreover, protein-ligand interactions pro-vide the mechanism of many drug therapies and un-derstanding of such interactions is thus significant forrational drug design[1,2]. For the experimental studiesof protein-ligan…     

FAMUSAMM: An algorithm for rapid evaluation of electrostatic interactions in molecular dynamics simulations

Within molecular dynamics simulations of protein–solvent systems the exact evaluation of long-range Coulomb interactions is computationally demanding and becomes prohibitive for large systems. Conventional truncation methods circumvent that computational problem, but are hampered by serious artifacts concerning structure and dynamics of the simulated systems. To avoid these artifacts we have developed an efficient and yet sufficiently accurate approximation scheme which combines the structure-adapted multipole method (SAMM) [C. Niedermeier and P. Tavan, J. Chem. Phys., 101 , 734 (1994)] with a multiple-time-step method. The computational effort for MD simulations required within our fast multiple-time-step structure-adapted multipole method (FAMUSAMM) scales linearly with the number of particles. For a system with 36,000 atoms we achieve a computational speed-up by a factor of 60 as compared with the exact evaluation of the Coulomb forces. Extended test simulations show that the applied approximations do not seriously affect structural or dynamical properties of the simulated systems. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1729–1749, 1997     

Charge distributions for molecular dynamics simulations from self-consistent polarization method

Partial atomic charges are important force field parameters. They are usually computed by applying quantum-chemical calculations and the assumed population scheme. In this study polarization consistent scheme of deriving a charge distribution inside solute molecule is proposed. The environment effect is explicitly taken into account by distributing solvent molecules around the solute target. The performed analysis includes a few computational schemes (HF, MP2, B3LYP, and M026X), basis sets (cc-pvnz, n = 2, 3, …, 6), and electrostatically derived charge distributions (KS, CHELP, CHELPG, and HLY). It is demonstrated that the environment effect is very important and cannot be disregarded. The second solvation shell should be included to achieve the charge convergence. Huge corrections to charge distribution are due to induction and dispersion. The B3LYP/cc-pvqz level of theory is recommended for deriving the charges within self-consistent polarization scheme.     

Improving efficiency of large time-scale molecular dynamics simulations of hydrogen-rich systems

A systematic analysis is performed on the effectiveness of removing degrees of freedom from hydrogen atoms and/or increasing hydrogen masses to increase the efficiency of molecular dynamics simulations of hydrogen-rich systems such as proteins in water. In proteins, high-frequency bond-angle vibrations involving hydrogen atoms limit the time step to 3 fs, which is already a factor of 1.5 beyond the commonly used time step of 2 fs. Removing these degrees of freedom from the system by constructing hydrogen atoms as dummy atoms, allows the time step to be increased to 7 fs, a factor of 3.5 compared with 2 fs. Additionally, a gain in simulation stability can be achieved by increasing the masses of hydrogen atoms with remaining degrees of freedom from 1 to 4 u. Increasing hydrogen mass without removing the high-frequency degrees of freedom allows the time step to be increased only to 4 fs, a factor of two, compared with 2 fs. The net gain in efficiency of sampling configurational space may be up to 15% lower than expected from the increase in time step due to the increase in viscosity and decrease in diffusion constant. In principle, introducing dummy atoms and increasing hydrogen mass do not influence thermodynamical properties of the system and dynamical properties are shown to be influenced only to a moderate degree. Comparing the maximum time step attainable with these methods (7 fs) to the time step of 2 fs that is routinely used in simulation, and taking into account the increase in viscosity and decrease in diffusion constant, we can say that a net gain in simulation efficiency of a factor of 3 to 3.5 can be achieved. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 786–798, 1999     

基于分子模拟技术煤焦分子模型构建

煤、焦是过程工业的重要原料。因此,有必要深入了解煤、焦分子结构以揭示其反应性。采用Materials Studio 7.0软件,从分子层次研究煤、焦的分子结构。根据已报道的文献,构建煤、焦的初始结构;基于分子力学原理对这些结构进行优化,使得模型物性与煤、焦物性相符;基于退火模拟算法对模型进行优化,从而使得模型密度、元素分析数据与真实值吻合;基于能量最小化原理,对煤、焦模型再次优化,从而获得其稳定、真实的分子构型。由计算结果发现,模型的估算密度、元素组成与已报道一致,说明构建的模型是有效、合理的;在模型优化过程中,相对于其他能量而言,库伦能和范德华能起着重要的作用。因此可以推断在煤、焦热加工过程中,弱键占据主要地位。另外,本文采用分子模拟技术构建煤、焦模型的方法对于构建其他复杂大分子结构有着重要的借鉴作用。     

An efficient parallelization scheme for molecular dynamics simulations with many-body, flexible, polarizable empirical potentials: application to water

An efficient parallelization scheme for classical molecular dynamics simulations with flexible, polarizable empirical potentials is presented. It is based on the standard Ewald summation technique to handle the long-range electrostatic and induction interactions. The algorithm for this parallelization scheme is designed for systems containing several thousands of polarizable sites in the simulation box. Its performance is evaluated during molecular dynamics simulations under periodic boundary conditions with unit cell sizes ranging from 128 to 512 molecules employing two flexible polarizable water models [DC(F) and TTM2.1-F] containing 1 and 3 polarizable sites, respectively. The time-to-solution for these two polarizable models is compared with the one for a flexible, pairwise-additive water model (TIP4F). The benchmarks were performed on both shared and distributed memory platforms. As a result of the efficient calculation of the induced dipole moments, a superlinear scaling as a function of the number of the processors is observed. To the best of our knowledge, this is the first reported results of parallel scaling and performance for simulations of liquid water with a polarizable potential under periodic boundary conditions.     

A method for predicting protein conformational pathways by using molecular dynamics simulations guided by difference distance matrices

Here, an efficient method that predicts natural transition pathways between two endpoint states of an allosteric protein has been proposed. This method helps create structures that bridge these endpoints through multiple iterative and unbiased molecular dynamics simulations with explicit water. Difference distance matrices provide an approach for identifying states involving concerted slow motion. A series of structures are readily generated along the transition pathways of adenylate kinase. Predicted structures may be useful for an initial pathway to evaluate free energy landscapes via umbrella sampling and chain‐of‐states methods. © 2016 Wiley Periodicals, Inc.     

Etomica: An object‐oriented framework for molecular simulation

We describe the design of an object‐oriented library of software components that are suitable for constructing simulations of systems of interacting particles. The emphasis of the discussion is on the general design of the components and how they interact, and less on details of the programming interface or its implementation. Example code is provided as an aid to understanding object‐oriented programming structures and to demonstrate how the framework is applied. © 2015 Wiley Periodicals, Inc.     

Libra: An open‐Source “methodology discovery” library for quantum and classical dynamics simulations

The “methodology discovery” library for quantum and classical dynamics simulations is presented. One of the major foci of the code is on nonadiabatic molecular dynamics simulations with model and atomistic Hamiltonians treated on the same footing. The essential aspects of the methodology, design philosophy, and implementation are discussed. The code capabilities are demonstrated on a number of model and atomistic test cases. It is demonstrated how the library can be used to study methodologies for quantum and classical dynamics, as well as a tool for performing detailed atomistic studies of nonadiabatic processes in molecular systems. The source code and additional information are available on the Web at http://www.acsu.buffalo.edu/~alexeyak/libra/index.html . © 2016 Wiley Periodicals, Inc.