Simulation of phase separation in alcohol/water mixtures using two-body force field and standard molecular dynamics

Standard molecular dynamics simulations have been carried out on pure alcohols and alcohol/water mixtures. A simple atom-atom force field consisting of Lennard-Jones potentials plus coulombic terms over atomic point charges, but without explicit polarization terms, has been specifically fitted to reproduce several experimental properties of the pure alcohols, and has been used for mixtures by developing combination rules with the TIP3P water model. Densities, enthalpies of vaporization, radial distribution functions, self-diffusion coefficients, and rotational correlation functions of the pure alcohols are well reproduced and compare favorably with those from more sophisticated force fields. Some key aspects of the phase behaviour are correctly reproduced by the molecular dynamics simulation, showing a distinct demixing process for the n-butanol/water mixture as opposed to the stability of the t-butanol/water mixtures. The results demonstrate the ability of a molecular dynamics simulation, even in its standard form and with easily accessible time ranges, but with a carefully optimized force field, to simulate and, to a certain extent, predict the properties of binary mixtures.     

Computer simulation of trifluoromethane properties with ab initio force field

Intermolecular interaction potentials of the trifluoromethane dimer in 15 orientations have been calculated using the Hartree‐Fock (HF) self‐consistent theory and the second‐order Møller‐Plesset (MP2) perturbation theory. Single point energies at important geometries were also calibrated by the coupled cluster with single and double and perturbative triple excitation [CCSD(T)] calculations. We have employed Pople's medium size basis sets [up to 6‐311++G(3df,3pd)] and Dunning's correlation consistent basis sets (up to aug‐cc‐pVQZ). Basis set limit potential values were obtained through well‐studied extrapolation methods. The calculated MP2 potential data were employed to parameterize a 5‐site force field for molecular simulations. We performed molecular dynamics simulations using the constructed ab initio force field and compared the simulation results with experiments. Quantitative agreements for the atom‐wise radial distribution functions and the self‐diffusion coefficients over a wide range of experimental conditions can be obtained, thus validating the ab initio force field without using experimental data a priori. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

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.     

锂-,钠-,钾水化蒙脱石层间结构的分子动力学模拟

运用分子动力学(molecular dynamics, MD)方法分别研究了含有32, 64和96个水分子的Li-, Na-, K-蒙脱石层间阳离子与水分子的位置和结构. 计算结果表明蒙脱石层间阳离子位置与四面体和八面体电荷位置及离子的大小有关. 一层水合物中可以观察到三种阳离子都能和四面体电荷与八面体电荷位置分别形成内、外配位作用. 二层水合物中, 仍然可以观察到Li^＋和Na^＋与电荷位置的配位作用, 但是已经开始向层中其他方向扩散, 而K^＋仍然在粘土的表面附近. 三层水合物中, Li^＋, Na^＋开始从电荷位置和表面分离, K^＋也开始向层间其他方向扩散. 水分子在所有三种水合物中都分散于层间各个方向. 径向分布函数的分析结果表明层间三种阳离子组织水分子的能力不同, 水化作用随着阳离子半径的增大而减弱; 此外层中水分子的聚合程度随着水分子的增加而加强, 水分子的结构也不同于模拟的液体水分子的结构; 说明蒙脱石层间阳离子的溶剂化作用对水分子的组织起着重要的作用.     

Molecular dynamics simulation for studying the stability of structure H clathrate-hydrates of argon and large guest molecules

The aim of present paper is to study the stability of (argon + large guest molecules) structure H clathrate-hydrates by using molecular dynamics simulations and with employing the COMPASS force field to consider the molecular interactions. The simulations are performed by embedding the structure H clathrate-hydrates in a simulation cell under isobaric-isothermal (NPT) conditions. The obtained equilibrium lattice parameters are compared with the experimental data, where a good consistency is observed. The results show that the size and dipole moment of the guest molecules enclosed in the hydrate cages play the main role in the interactions between the guest molecules and the water molecules, which constitute the surrounding walls of the hydrate cage and these interactions would stabilize the hydrate structure. The characteristics of the clathrate-hydrate structure are analyzed by evaluating the radial distribution function, where the agreement between the results obtained in this work and other similar theoretical and experimental investigations validates the simulation procedure and related interpretations.     

Liquid properties of dimethyl ether from molecular dynamics simulations using Ab Initio force fields

We have used molecular dynamic simulations to study the structural and dynamical properties of liquid dimethyl ether (DME) with a newly constructed ab initio force field in this article. The ab initio potential energy data were calculated at the second order Møller‐Plesset (MP2) perturbation theory with Dunning's correlation consistent basis sets (up to aug‐cc‐pVQZ). We considered 17 configurations of the DME dime for the orientation sampling. The calculated MP2 potential data were used to construct a 3‐site united atom force field model. The simulation results are compared with those using the empirical force field of Jorgensen and Ibrahim (Jorgensen and Ibrahim, J Am Chem Soc 1981, 103, 3976) and with available experimental measurements. We obtain quantitative agreements for the atom‐wise radial distribution functions, the self‐diffusion coefficients, and the shear viscosities over a wide range of experimental conditions. This force field thus provides a suitable starting point to predict liquid properties of DME from first principles intermolecular interactions with no empirical data input a priori. © 2012 Wiley Periodicals, Inc.     

A coarse‐grained MARTINI‐like force field for DNA unzipping in nanopores

In nanopore force spectroscopy (NFS) a charged polymer is threaded through a channel of molecular dimensions. When an electric field is applied across the insulating membrane, the ionic current through the nanopore reports on polymer translocation, unzipping, dissociation, and so forth. We present a new model that can be applied in molecular dynamics simulations of NFS. Although simplified, it does reproduce experimental trends and all‐atom simulations. The scaled conductivities in bulk solution are consistent with experimental results for NaCl for a wide range of electrolyte concentrations and temperatures. The dependence of the ionic current through a nanopore on the applied voltage is symmetric and, in the voltage range used in experiments (up to 2 V), linear and in good agreement with experimental data. The thermal stability and geometry of DNA is well represented. The model was applied to simulations of DNA hairpin unzipping in nanopores. The results are in good agreement with all‐atom simulations: the scaled translocation times and unzipping sequence are similar. © 2015 Wiley Periodicals, Inc.     

Additive empirical force field for hexopyranose monosaccharides

We present an all-atom additive empirical force field for the hexopyranose monosaccharide form of glucose and its diastereomers allose, altrose, galactose, gulose, idose, mannose, and talose. The model is developed to be consistent with the CHARMM all-atom biomolecular force fields, and the same parameters are used for all diastereomers, including both the alpha- and beta-anomers of each monosaccharide. The force field is developed in a hierarchical manner and reproduces the gas-phase and condensed-phase properties of small-molecule model compounds corresponding to fragments of pyranose monosaccharides. The resultant parameters are transferred to the full pyranose monosaccharides, and additional parameter development is done to achieve a complete hexopyranose monosaccharide force field. Parametrization target data include vibrational frequencies, crystal geometries, solute-water interaction energies, molecular volumes, heats of vaporization, and conformational energies, including those for over 1800 monosaccharide conformations at the MP2/cc-pVTZ//MP2/6-31G(d) level of theory. Although not targeted during parametrization, free energies of aqueous solvation for the model compounds compare favorably with experimental values. Also well-reproduced are monosaccharide crystal unit cell dimensions and ring pucker, densities of concentrated aqueous glucose systems, and the thermodynamic and dynamic properties of the exocyclic torsion in dilute aqueous systems. The new parameter set expands the CHARMM additive force field to allow for simulation of heterogeneous systems that include hexopyranose monosaccharides in addition to proteins, nucleic acids, and lipids.     

New energy terms for reduced protein models implemented in an off‐lattice force field

Parameterization and test calculations of a reduced protein model with new energy terms are presented. The new energy terms retain the steric properties and the most significant degrees of freedom of protein side chains in an efficient way using only one to three virtual atoms per amino acid residue. The energy terms are implemented in a force field containing predefined secondary structure elements as constraints, electrostatic interaction terms, and a solvent‐accessible surface area term to include the effect of solvation. In the force field the main‐chain peptide units are modeled as electric dipoles, which have constant directions in α‐helices and β‐sheets and variable conformation‐dependent directions in loops. Protein secondary structures can be readily modeled using these dipole terms. Parameters of the force field were derived using a large set of experimental protein structures and refined by minimizing RMS errors between the experimental structures and structures generated using molecular dynamics simulations. The final average RMS error was 3.7 Å for the main‐chain virtual atoms (C_α atoms) and 4.2 Å for all virtual atoms for a test set of 10 proteins with 58–294 amino acid residues. The force field was further tested with a substantially larger test set of 608 proteins yielding somewhat lower accuracy. The fold recognition capabilities of the force field were also evaluated using a set of 27,814 misfolded decoy structures. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1229–1242, 2001     

Modification of the CHARMM force field for DMPC lipid bilayer

The CHARMM force field for DMPC lipids was modified in order to improve agreement with experiment for a number of important properties of hydrated lipid bilayer. The modification consists in introduction of a scaling factor 0.83 for 1-4 electrostatic interactions (between atoms separated by three covalent bonds), which provides correct transgauche ratio in the alkane tails, and recalculation of the headgroup charges on the basis of HF/6-311(d,p) ab-initio computations. Both rigid TIP3P and flexible SPC water models were used with the new lipid model, showing similar results. The new model in a 75 ns simulation has shown a correct value of the area per lipid at zero surface tension, as well as good agreement with the experiment for the electron density, structure factor, and order parameters, including those in the headgroup part of lipids.     

A new GROMOS force field for hexopyranose-based carbohydrates

A new parameter set (referred to as 45A4) is developed for the explicit-solvent simulation of hexopyranose-based carbohydrates. This set is compatible with the most recent version of the GROMOS force field for proteins, nucleic acids, and lipids, and the SPC water model. The parametrization procedure relies on: (1) reassigning the atomic partial charges based on a fit to the quantum-mechanical electrostatic potential around a trisaccharide; (2) refining the torsional potential parameters associated with the rotations of the hydroxymethyl, hydroxyl, and anomeric alkoxy groups by fitting to corresponding quantum-mechanical profiles for hexopyranosides; (3) adapting the torsional potential parameters determining the ring conformation so as to stabilize the (experimentally predominant) (4)C(1) chair conformation. The other (van der Waals and nontorsional covalent) parameters and the rules for third and excluded neighbors are taken directly from the most recent version of the GROMOS force field (except for one additional exclusion). The new set is general enough to define parameters for any (unbranched) hexopyranose-based mono-, di-, oligo- or polysaccharide. In the present article, this force field is validated for a limited set of monosaccharides (alpha- and beta-D-glucose, alpha- and beta-D-galactose) and disaccharides (trehalose, maltose, and cellobiose) in solution, by comparing the results of simulations to available experimental data. More extensive validation will be the scope of a forthcoming article. (c) 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1400-1412, 2005.     

Development of the force field parameters for phosphoimidazole and phosphohistidine

Phosphorylation of histidine-containing proteins is a key step in the mechanism of many phosphate transfer enzymes (kinases, phosphatases) and is the first stage in a wide variety of signal transduction cascades in bacteria, yeast, higher plants, and mammals. Studies of structural and dynamical aspects of such enzymes in the phosphorylated intermediate states are important for understanding the intimate molecular mechanisms of their functioning. Such information may be obtained via molecular dynamics and/or docking simulations, but in this case appropriate force field parameters for phosphohistidine should be explicitly defined. In the present article we describe development of the GROMOS96 force field parameters for phosphoimidazole molecule--a realistic model of the phosphohistidine side chain. The parameterization is based on the results of ab initio quantum chemical calculations with subsequent refinement and testing using molecular mechanics and molecular dynamics simulations. The set of force constants and equilibrium geometry is employed to derive force field for the phosphohistidine moiety. Resulting parameters and topology are incorporated into the molecular modeling package GROMACS and used in molecular dynamics simulations of a phosphohistidine-containing protein in explicit solvent.     

An improved OPLS-AA force field for carbohydrates

This work describes an improved version of the original OPLS-all atom (OPLS-AA) force field for carbohydrates (Damm et al., J Comp Chem 1997, 18, 1955). The improvement is achieved by applying additional scaling factors for the electrostatic interactions between 1,5- and 1,6-interactions. This new model is tested first for improving the conformational energetics of 1,2-ethanediol, the smallest polyol. With a 1,5-scaling factor of 1.25 the force field calculated relative energies are in excellent agreement with the ab initio-derived data. Applying the new 1,5-scaling makes it also necessary to use a 1,6-scaling factor for the interactions between the C4 and C6 atoms in hexopyranoses. After torsional parameter fitting, this improves the conformational energetics in comparison to the OPLS-AA force field. The set of hexopyranoses included in the torsional parameter derivation consists of the two anomers of D-glucose, D-mannose, and D-galactose, as well as of the methyl-pyranosides of D-glucose, D-mannose. Rotational profiles for the rotation of the exocyclic group and of different hydroxyl groups are also compared for the two force fields and at the ab initio level of theory. The new force field reduces the overly high barriers calculated using the OPLS-AA force field. This leads to better sampling, which was shown to produce more realistic conformational behavior for hexopyranoses in liquid simulation. From 10-ns molecular dynamics (MD) simulations of alpha-D-glucose and alpha-D-galactose the ratios for the three different conformations of the hydroxymethylene group and the average (3)J(H,H) coupling constants are derived and compared to experimental values. The results obtained for OPLS-AA-SEI force field are in good agreement with experiment whereas the properties derived for the OPLS-AA force field suffer from sampling problems. The undertaken investigations show that the newly derived OPLS-AA-SEI force field will allow simulating larger carbohydrates or polysaccharides with improved sampling of the hydroxyl groups.     

Ramachandran-type plots for glycosidic linkages: Examples from molecular dynamic simulations using the Glycam06 force field

The goals of this article are to (1) provide further validation of the Glycam06 force field, specifically for its use in implicit solvent molecular dynamic (MD) simulations, and (2) to present the extension of G.N. Ramachandran's idea of plotting amino acid phi and psi angles to the glycosidic phi, psi, and omega angles formed between carbohydrates. As in traditional Ramachandran plots, these carbohydrate Ramachandran-type (carb-Rama) plots reveal the coupling between the glycosidic angles by displaying the allowed and disallowed conformational space. Considering two-bond glycosidic linkages, there are 18 possible conformational regions that can be defined by (alpha, phi, psi) and (beta, phi, psi), whereas for three-bond linkages, there are 54 possible regions that can be defined by (alpha, phi, psi, omega) and (beta, phi, psi, omega). Illustrating these ideas are molecular dynamic simulations on an implicitly hydrated oligosaccharide (700 ns) and its eight constituent disaccharides (50 ns/disaccharide). For each linkage, we compare and contrast the oligosaccharide and respective disaccharide carb-Rama plots, validate the simulations and the Glycam06 force field through comparison to experimental data, and discuss the general trends observed in the plots.     

CHARMM general force field: A force field for drug‐like molecules compatible with the CHARMM all‐atom additive biological force fields

The widely used CHARMM additive all‐atom force field includes parameters for proteins, nucleic acids, lipids, and carbohydrates. In the present article, an extension of the CHARMM force field to drug‐like molecules is presented. The resulting CHARMM General Force Field (CGenFF) covers a wide range of chemical groups present in biomolecules and drug‐like molecules, including a large number of heterocyclic scaffolds. The parametrization philosophy behind the force field focuses on quality at the expense of transferability, with the implementation concentrating on an extensible force field. Statistics related to the quality of the parametrization with a focus on experimental validation are presented. Additionally, the parametrization procedure, described fully in the present article in the context of the model systems, pyrrolidine, and 3‐phenoxymethylpyrrolidine will allow users to readily extend the force field to chemical groups that are not explicitly covered in the force field as well as add functional groups to and link together molecules already available in the force field. CGenFF thus makes it possible to perform “all‐CHARMM” simulations on drug‐target interactions thereby extending the utility of CHARMM force fields to medicinally relevant systems. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010     

水化锂蒙脱石层间结构和动力特征的分子模拟

利用分子力场和分子动力学(MD)的方法研究了Li-蒙脱石的结构构型, 层间阳离子的水化行为、水分子的结构特征以及它们的扩散性质. 分子力场构型优化结果表明: Li-蒙脱石的层间距、体积和密度与层间水含量有关; MD模拟的动画轨迹显示Li-蒙脱石层间Li^＋的位置与层间电荷位置有关. 均方根位移和自扩散系数的计算结果表明: 层间阳离子、水分子在Li-蒙脱石一、二层水合物中的扩散受到上下粘土片表面的限制, 在三层水合物中开始离开粘土层面向其它方向快速扩散. 径向分布函数及其结构因子的分析结果表明Li^＋在一、二、三层水合物中有不同的水合层; 层间水分子的结构特征说明其在蒙脱石层间有水合水分子和自由水分子之分, 且它们的比值在一、二和三层水合物中有所不同.     

Additive CHARMM force field for naturally occurring modified ribonucleotides

More than 100 naturally occurring modified nucleotides have been found in RNA molecules, in particular in tRNAs. We have determined molecular mechanics force field parameters compatible with the CHARMM36 all‐atom additive force field for all these modifications using the CHARMM force field parametrization strategy. Emphasis was placed on fine tuning of the partial atomic charges and torsion angle parameters. Quantum mechanics calculations on model compounds provided the initial set of target data, and extensive molecular dynamics simulations of nucleotides and oligonucleotides in aqueous solutions were used for further refinement against experimental data. The presented parameters will allow for computational studies of a wide range of RNAs containing modified nucleotides, including the ribosome and transfer RNAs. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.     

Paramfit: Automated optimization of force field parameters for molecular dynamics simulations

The generation of bond, angle, and torsion parameters for classical molecular dynamics force fields typically requires fitting parameters such that classical properties such as energies and gradients match precalculated quantum data for structures that scan the value of interest. We present a program, Paramfit, distributed as part of the AmberTools software package that automates and extends this fitting process, allowing for simplified parameter generation for applications ranging from single molecules to entire force fields. Paramfit implements a novel combination of a genetic and simplex algorithm to find the optimal set of parameters that replicate either quantum energy or force data. The program allows for the derivation of multiple parameters simultaneously using significantly fewer quantum calculations than previous methods, and can also fit parameters across multiple molecules with applications to force field development. Paramfit has been applied successfully to systems with a sparse number of structures, and has already proven crucial in the development of the Assisted Model Building with Energy Refinement Lipid14 force field. © 2014 Wiley Periodicals, Inc.