Using Molecular Dynamics Simulations of Crambin to Evaluate the Suitability of Different Continuum Dielectric Models for Protein Simulations.

摘要

Molecular mechanics and dynamics computations of charge-charge interactions for proteins usually involve either a microscopic description of solvent or a continuum dielectric model. In theory the former are superior, but continuum models are thought to incorporate the essence of the underlying physics and are much more computationally practical for proteins. The choice of continuum models is, however, often arrived at largely by intuition rather than by objective empirical criteria. Others have suggested that simple continuum models often overestimate interactions at the protein surface, while underestimating interactions at the interior. The present calculations were performed with a variety of continuum models and neutral partial charges on the ionic residues, which tend to be solvated on the surface of proteins. Because of its small size and well resolved x-ray crystal structure, crambin has been the focus of previous attempts to explore the role of dielectric and other model parameters on its computed structure and stability. We now perform a series of 100 picosecond molecular dynamics simulations on crambin in order to examine how well computed structures, obtained using different simple continuum models, agree with the x-ray structure. A constant dielectric of 1.0 and a linear dielectric model of 1r yield low energy structures that agree with the crystal structure to within an RMS deviation of 1.67A, for the backbone atoms, throughout the 100 picosecond simulations at 300K. Several other dielectric models were found to yield significantly poorer fits. The above trend does not semi-quantitatively converge until about 50 picoseconds into the simulations; these results suggest that similar studies based on energy minimizations or shorter simulations should be viewed with caution. 34 refs., 2 figs., 1 tab.