W. F. van Gunsteren

MOLECULAR-DYNAMICS WITH COUPLING TO AN EXTERNAL BATH

In molecular dynamics (MD) simulations the need often arises to maintain such parameters as temperature or pressure rather than energy and volume, or to impose gradients for studying transport properties in nonequilibrium MD. A method is described to realize coupling to an external bath with constant temperature or pressure with adjustable time constants for the coupling. The method is easily extendable to other variables and to gradients, and can be applied also to polyatomic molecules involving internal constraints. The influence of coupling time constants on dynamical variables is evaluated. A leap‐frog algorithm is presented for the general case involving constraints with coupling to both a constant temperature and a constant pressure bath.

Interaction Models for Water in Relation to Protein Hydration

For molecular dynamics simulations of hydrated proteins a simple yet reliable model for the intermolecular potential for water is required. Such a model must be an effective pair potential valid for liquid densities that takes average many-body interactions into account. We have developed a three-point charge model (on hydrogen and oxygen positions) with a Lennard-Jones 6–12 potential on the oxygen positions only. Parameters for the model were determined from 12 molecular dynamics runs covering the two-dimensional parameter space of charge and oxygen repulsion. Both potential energy and pressure were required to coincide with experimental values. The model has very satisfactory properties, is easily incorporated into protein-water potentials, and requires only 0.25 sec computertime per dynamics step (for 216 molecules) on a CRAY-1 computer.

ALGORITHMS FOR MACROMOLECULAR DYNAMICS AND CONSTRAINT DYNAMICS

The application of the computer simulation method of molecular dynamics to macromolecules is investigated. The protein trypsin inhibitor (BPTI), consisting of 454 united atoms, is used as an example. Different algorithms for integrating the equations of motion are compared, both theoretically and in practice. It is examined to what extent the chain structure of a macromolecule allows a reduction of the computational effort by the introduction of constraints in the dynamics of the chain. A calculational scheme is proposed, by which constraints can be incorporated in predictor-corrector algorithms. The optimum choice of an algorithm depends on the desired accuracy of the solution and on the character of the forces acting on the molecule, viz. whether these are noisy or not. For nonconstraint dynamics a Gear predictor-corrector algorithm yields the best results, whereas for constraint dynamics the Gear and Verlet algorithms produce comparable results. The application of bond-length constraints reduces the re...

A LEAP-FROG ALGORITHM FOR STOCHASTIC DYNAMICS

A third-order algorithm for stochastic dynamics (SD) simulations is proposed, identical to the powerful molecular dynamics leap-frog algorithm in the limit of infinitely small friction coefficient ...

A protein structure from nuclear magnetic resonance data. lac repressor headpiece.

A procedure is described to determine the three-dimensional structure of biomolecules from nuclear magnetic resonance data. This procedure combines model building with a restrained molecular dynamics algorithm, in which distance information from nuclear Overhauser effects is incorporated in the form of pseudo potentials. The method has been applied to the N-terminal DNA-binding domain or headpiece (amino acid residues 1 to 51) of the lac repressor from Escherichia coli, for which no crystal structure is available. The relative orientation of the three helices of the headpiece is similar to that of the three homologous helices found in the cI repressor of bacteriophage lambda.

Molecular Dynamics Simulation of the Transport of Small Molecules Across a Polymer Membrane

The transport of small molecules through a polymer membrane is modeled using the computer simulation technique of molecular dynamics (MD). The transport coefficient is derived from a combination of the excess free energy and the diffusion constant. Both properties are derived from MD simulations, applied to helium and methane in polydimethylsiloxane (PDMS). The diffusional process appears to have the character of a jump diffusion for methane and less so for helium. Jumps are allowed by fluctuations of the size and shape of holes. Experimental diffusion constants are well reproduced. The excess free energies, determined by a particle insertion method, are lower by 5–7 kJ/mol than experimental values. It is shown that, as a result of a higher solubility, methane has a higher permeability constant than helium, despite its lower diffusion constant.

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 α‐D‐glucose and α‐D‐galactose the ratios for the three different conformations of the hydroxymethylene group and the average 3JH,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.

GROMOS++ Software for the Analysis of Biomolecular Simulation Trajectories

GROMOS++ is a set of C++ programs for pre- and postprocessing of molecular dynamics simulation trajectories and as such is part of the GROningen MOlecular Simulation software for (bio)molecular simulation. It contains more than 70 programs that can be used to prepare data for the production of molecular simulation trajectories and to analyze these. These programs are reviewed and the various structural, dynamic, and thermodynamic quantities that can be analyzed using time series, correlation functions, and distributions are described together with technical aspects of their implementation in GROMOS. A few examples of the use of GROMOS++ for the analysis of MD trajectories are given. A full list of all GROMOS++ programs, together with an indication of their capabilities, is given in the Appendix .

A MOLECULAR-DYNAMICS SIMULATION OF CRYSTALLINE ALPHA-CYCLODEXTRIN HEXAHYDRATE

The structure of crystalline α-cyclodextrin (α-CD) hexahydrate, form I (C36H60O30·6H2O, space group P212121) is experimentally so well determined by X-ray and by neutron diffraction analyses that the positions of all the hydrogen atoms are available. This provides an opportunity for testing an empirical force field that is currently used in simulations of protein and nucleic acid structures by performing molecular dynamics studies employing the GROMOS program package on a system of 4 unit cells containing 16 α-CD molecules and 96 water molecules.A detailed comparison of the simulated and experimentally determined crystal structures shows that the experimental positions of the α-CD atoms are reproduced within 0.025 nm, well within the overall experimental accuracy of 0.036 nm; that the water molecules are on average within 0.072 nm from their experimental sites, with two thirds reproduced within experimental accuracy by the calculations; that high correlation is produced, between the occurrence of simulated and experimentally observed hydrogen bonds.The good agreement between simulated and experimental results suggests that the tested force field is reliable.

A molecular dynamics study of the nematic phase of 4-n-pentyl-4'-cyanobiphenyl

Abstract Preliminary molecular dynamics simulations of the nematic phase of 4-n-pentyl-4′-cyanobiphenyl are described. The simulations include all molecular degrees of freedom. The influence of the molecular dipole moment is investigated by comparing simulations with and without a charge distribution on the molecules. Inclusion of the charge distribution is found to lead to a slight broadening of the orientational distribution function, in qualitative agreement with Raman measurements of the orientational order parameters.