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W F Van Gunsteren

Publications and source records attributed to W F Van Gunsteren.

9 recordsLinked to original sources
PubMed2002

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.

Carbohydrate Conformation↗
PubMed1996

An efficient mean solvation force model for use in molecular dynamics simulations of proteins in aqueous solution.

An empirical solvation model that allows for the elimination of solvent degrees of freedom in molecular dynamics (MD) simulations of biomolecules is proposed. The potential of mean force due to the first solvation shell is approximated by means of a simple, easily derivable analytic function of the solvent-accessible surface area of the molecule. The solvent contribution to the free energy is evaluated by means of only two atomic solvation parameters. This approach requires about 30% more computational effort than an in vacuo simulation, but a factor of 10 to 50 less than a MD simulation involving solvation by explicit water molecules. The implicit solvation model is assessed by application to proteins of different size. Average structural properties are calculated and compared to values obtained from X-ray structures and from MD simulations using explicit water molecules. The complementarity of the implicit solvation force and the intra-solute force field has been checked. The artefacts induced by the use of a vacuum boundary condition without solvation force in a MD simulation are considerably reduced.

Models, Chemical↗
PubMed1995

Investigation of protein unfolding and stability by computer simulation.

Structural, dynamic and energetic properties of proteins in solution can be studied in atomic detail by molecular dynamics computer simulation. Protein unfolding can be caused by a variety of driving forces induced in different ways: increased temperature or pressure, change of solvent composition, or protein amino acid mutation. The stability and unfolding of four different proteins (bovine pancreatic trypsin inhibitor, hen egg white lysozyme, the surfactant protein C and the DNA-binding domain of the 434 repressor) have been studied by applying the afore-mentioned driving forces and also to some artificial forces. The results give a picture of protein (in)stability and possible unfolding pathways, and are compared to experimental data where possible.

Amino Acid Sequence↗
PubMed1989

Calculating three-dimensional molecular structure from atom-atom distance information: cyclosporin A.

In recent years methods for deriving spatial molecular structure from atom-atom distance information have gained in importance due to the emergence of two-dimensional nuclear magnetic resonance (n.m.r) techniques, which make it possible to obtain such distance information for polypeptides, small proteins, sugars, and DNA fragments in solution. Distance geometry (DG) and restrained molecular dynamics (MD) refinement are applied to a cyclic polypeptide, the immunosuppressive drug cyclosporin A, and the results are compared. Two different procedures, DG followed by restrained MD, and straightforward restrained MD starting from the X-ray structure, both lead to a unique conformation that satisfies the 58 experimentally determined distance constraints. The results nicely show the relative merits of DG and restrained MD techniques for determining spatial molecular structure from distance information.

Cyclosporins↗
PubMed1986

Simulations of proteins in water.

Molecular dynamics simulations of hydrated protein crystals have been carried out in only three cases: two simulations of pancreatic trypsin inhibitor (PTI) and one of avian pancreatic polypeptide (aPP). The purpose of such simulations is to evaluate the accuracy and reliability of molecular dynamics simulations of hydrated proteins. A 40-psec simulation on crystalline PTI, involving 4 protein molecules (of 58 amino acids each), 552 water molecules, and 24 Cl- ions is described. Considerations are energetic and structural stability, division of interaction energy among water and protein, and precision of average structure and structural fluctuations compared to X-ray data from a new 0.94-A resolution study of Wlodawer et al. Water and ion dynamics are considered by analysis of diffusional motions and of residence times of water molecules in specific sites.

Computer Simulation↗
PubMed1986

A molecular dynamics computer simulation of an eight-base-pair DNA fragment in aqueous solution: comparison with experimental two-dimensional NMR data.

The structure and dynamics of an 8-base-pair DNA fragment (dCGCAACGC/dGCGTTGCG) in aqueous solution (14 Na+ ions, 1231 water molecules) have been simulated by using the molecular-dynamics method. Interproton distances have been calculated for various structures and are compared with a set of 174 distances which have been derived from 2D NOE experiments. The averaged MD structures are compared with ideal A-DNA and B-DNA structures in terms of helix parameters, dihedral angles, and so forth. The hydration of various atoms of the DNA fragment and of the Na+ ions is analyzed by calculating coordination numbers and first-neighbor shell residence times.

Base Composition↗