Accurate and efficient description of protein vibrational dynamics: comparing molecular dynamics and Gaussian models

摘要

Current all-atom potential based molecular dynamics (MD) allow theidentification of a protein's functional motions on a wide-range oftime-scales, up to few tens of ns. However, functional large scale motions ofproteins may occur on a time-scale currently not accessible by all-atompotential based molecular dynamics. To avoid the massive computational effortrequired by this approach several simplified schemes have been introduced. Oneof the most satisfactory is the Gaussian Network approach based on the energyexpansion in terms of the deviation of the protein backbone from its nativeconfiguration. Here we consider an extension of this model which captures in amore realistic way the distribution of native interactions due to theintroduction of effective sidechain centroids. Since their location is entirelydetermined by the protein backbone, the model is amenable to the same exact andcomputationally efficient treatment as previous simpler models. The ability ofthe model to describe the correlated motion of protein residues inthermodynamic equilibrium is established through a series of successfulcomparisons with an extensive (14 ns) MD simulation based on the AMBERpotential of HIV-1 protease in complex with a peptide substrate. Thus, themodel presented here emerges as a powerful tool to provide preliminary, fastyet accurate characterizations of proteins near-native motion.