666 research outputs found
The effect of force-field parameters on properties of liquids:Parametrization of a simple three-site model for methanol
A simple rigid three-site model for methanol compatible with the simple point charge (SPC) water and the GROMOS96 force field is parametrized and tested. The influence of different force-field parameters, such as the methanol geometry and the charge distribution on several properties calculated by molecular dynamics is investigated. In particular an attempt was made to obtain good agreement with experimental data for the static dielectric constant and the mixing enthalpy with water. The model is compared to other methanol models from the literature in terms of the ability to reproduce a range of experimental properties.<br/
Estimating entropies from molecular dynamics simulations
The methods to compute the excess entropy and the entropy of solvation using liquid water as a test system were studied. The accuracy and convergence behavior of five methods based on thermodynamic integration and perturbation techniques was evaluated. Through the thermodynamic integration accurate entropy differences were obtained in which many copies of a solute were desolvated. Only two methods yield useful results, the calculation of solute-solvent entropy through thermodynamic integration and the calculation of solvation entropy through the temperature derivative of the corresponding free-energy difference, when one solute molecule is involved
Protein dynamics with off-lattice Monte Carlo moves
A Monte Carlo method for dynamics simulation of all-atom protein models is
introduced, to reach long times not accessible to conventional molecular
dynamics. The considered degrees of freedom are the dihedrals at
C-atoms. Two Monte Carlo moves are used: single rotations about
torsion axes, and cooperative rotations in windows of amide planes, changing
the conformation globally and locally, respectively. For local moves Jacobians
are used to obtain an unbiased distribution of dihedrals. A molecular dynamics
energy function adapted to the protein model is employed. A polypeptide is
folded into native-like structures by local but not by global moves.Comment: 10 pages, 4 Postscript figures, uses epsf.sty and a4.sty; scheduled
tentatively for Phys.Rev.E issue of 1 March 199
Recurrence quantification analysis as a tool for the characterization of molecular dynamics simulations
A molecular dynamics simulation of a Lennard-Jones fluid, and a trajectory of
the B1 immunoglobulin G-binding domain of streptococcal protein G (B1-IgG)
simulated in water are analyzed by recurrence quantification, which is
noteworthy for its independence from stationarity constraints, as well as its
ability to detect transients, and both linear and nonlinear state changes. The
results demonstrate the sensitivity of the technique for the discrimination of
phase sensitive dynamics. Physical interpretation of the recurrence measures is
also discussed.Comment: 7 pages, 8 figures, revtex; revised for review for Phys. Rev. E
(clarifications and expansion of discussion)-- addition of the 8 postscript
figures previously omitted, but unchanged from version
Effect of the integration method on the accuracy and computational efficiency of free energy calculations using thermodynamic integration
Although calculations of free energy using molecular dynamics simulations have gained significant importance in the chemical and biochemical fields, they still remain quite computationally intensive. Furthermore, when using thermodynamic integration, numerical evaluation of the integral of the Hamiltonian with respect to the coupling parameter may introduce unwanted errors in the free energy. In this paper, we compare the performance of two numerical integration techniques-the trapezoidal and Simpson's rules and propose a new method, based on the analytic integration of physically based fitting functions that are able to accurately describe the behavior of the data. We develop and test our methodology by performing detailed studies on two prototype systems, hydrated methane and hydrated methanol, and treat Lennard-Jones and electrostatic contributions separately. We conclude that the widely used trapezoidal rule may introduce systematic errors in the calculation, but these errors are reduced if Simpson's rule is employed, at least for the electrostatic component. Furthermore, by fitting thermodynamic integration data, we are able to obtain precise free energy estimates using significantly fewer data points (5 intermediate states for the electrostatic component and 11 for the Lennard-Jones term), thus significantly decreasing the associated computational cost. Our method and improved protocol were successfully validated by computing the free energy of more complex systems hydration of 2-methylbutanol and of 4-nitrophenol-thus paving the way for widespread use in solvation free energy calculations of drug molecules
Pressure-energy correlations in liquids. I. Results from computer simulations
We show that a number of model liquids at fixed volume exhibit strong
correlations between equilibrium fluctuations of the configurational parts of
(instantaneous) pressure and energy. We present detailed results for thirteen
systems, showing in which systems these correlations are significant. These
include Lennard-Jones liquids (both single- and two-component) and several
other simple liquids, but not hydrogen-bonding liquids like methanol and water,
nor the Dzugutov liquid which has significant contributions to pressure at the
second nearest neighbor distance. The pressure-energy correlations, which for
the Lennard-Jones case are shown to also be present in the crystal and glass
phases, reflect an effective inverse power-law potential dominating
fluctuations, even at zero and slightly negative pressure. An exception to the
inverse-power law explanation is a liquid with hard-sphere repulsion and a
square-well attractive part, where a strong correlation is observed, but only
after time-averaging. The companion paper [arXiv:0807.0551] gives a thorough
analysis of the correlations, with a focus on the Lennard-Jones liquid, and a
discussion of some experimental and theoretical consequences.Comment: Some changes corresponding to those made in proof of the accepted
articl
CHARMM: The biomolecular simulation program
CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estimators, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numerous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983. © 2009 Wiley Periodicals, Inc.J Comput Chem, 2009.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63074/1/21287_ftp.pd
A Hydrophobic Gate in an Ion Channel: The Closed State of the Nicotinic Acetylcholine Receptor
The nicotinic acetylcholine receptor (nAChR) is the prototypic member of the
`Cys-loop' superfamily of ligand-gated ion channels which mediate synaptic
neurotransmission, and whose other members include receptors for glycine,
gamma-aminobutyric acid, and serotonin. Cryo-electron microscopy has yielded a
three dimensional structure of the nAChR in its closed state. However, the
exact nature and location of the channel gate remains uncertain. Although the
transmembrane pore is constricted close to its center, it is not completely
occluded. Rather, the pore has a central hydrophobic zone of radius about 3 A.
Model calculations suggest that such a constriction may form a hydrophobic
gate, preventing movement of ions through a channel. We present a detailed and
quantitative simulation study of the hydrophobic gating model of the nicotinic
receptor, in order to fully evaluate this hypothesis. We demonstrate that the
hydrophobic constriction of the nAChR pore indeed forms a closed gate.
Potential of mean force (PMF) calculations reveal that the constriction
presents a barrier of height ca. 10 kT to the permeation of sodium ions,
placing an upper bound on the closed channel conductance of 0.3 pS. Thus, a 3 A
radius hydrophobic pore can form a functional barrier to the permeation of a 1
A radius Na+ ion. Using a united atom force field for the protein instead of an
all atom one retains the qualitative features but results in differing
conductances, showing that the PMF is sensitive to the detailed molecular
interactions.Comment: Accepted by Physical Biology; includes a supplement and a
supplementary mpeg movie can be found at
http://sbcb.bioch.ox.ac.uk/oliver/download/Movies/watergate.mp
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