This program involves development and application of molecular and stochastic dynamics computer simulation methods to biopolymers (proteins, carbohydrates and DNA) and lipid assemblies (membranes and micelles). Systems of present interest include: interaction of peptides with cell membranes and micelles; and solution conformation of polysaccharide vaccines. A straightforward method that accounts for the long-range Lennard-Jones terms in constant pressure molecular dynamics (MD) simulations was developed. This long-range correction consists of an additional applied pressure tensor which is periodically calculated from the difference of instantaneous pressures at the selected cutoff and a very long cutoff. It provides results that are nearly independent of the LJ cutoff distance at negligible additional calculation costs, and is particularly suited for anisotropic systems such as liquid/liquid interfaces or heterogeneous macromolecules where approximations based on spherically symmetric radial distribution functions are expected to fail. A paper describing the work was accepted for publication in the Journal of Physical Chemistry. A series of molecular dynamics simulations of the fusion peptide of HIV were carried out in micelles and a lipid bilayer. The calculations indicated that experimental results for the peptide in micelles are not necessarily applicable to cell membranes, the system of primary interest. The results of these studies will shortly be submitted for publication. Extensive MD simulations of peptides expected to be alpha helical yielded pi-helices when using the CHARMM parameter set C22. This result motivated the development of a new parameter set C22/CMAP by Feig, MacKerell and Brooks. Follow-up simulations on the same peptides confirmed the validity of C22/CMAP (i.e., alpha-helices were stable; pi-helices reverted to alpha). The results of these simulations and related experimental studies will shortly be submitted for publication.
