Molecular dynamics of cryptophane and its complexes with tetramethylammonium and neopentane using a continuum solvent model

Time scales currently obtainable in explicit-solvent molecular dynamics sim ulations are inadequate for the study of many biologically important proces ses. This has led to increased interest in the use of continuum solvent mod els. For such models to be used effectively, it is important that their beh avior relative to explicit simulation be clearly understood. Accordingly, 5 ns stochastic dynamics simulations of a derivative of cryptophane-E alone, and complexed with tetramethylammonium and neopentane were carried out. So lvation electrostatics were accounted for;ia solutions to the Poisson equat ion. Nonelectrostatic aspects of solvation were incorporated using a surfac e area-dependent energy term. Comparison of the trajectories to those from previously reported 25 ns explicit-solvent simulations shows that use of a continuum solvent model results in enhanced sampling. Use of the continuum solvent model also results in a considerable increase in computational effi ciency. The continuum solvent model is found to predict qualitative structu ral characteristics that are similar to those observed in explicit solvent. However, some differences are significant, and optimization of the continu um parameterization will be required for this method to become a efficient alternative to explicit-solvent simulation. (C) 1999 John Wiley & Sons, Inc .