Hydration of an alpha-helical peptide: comparison of theory and molecular dynamics simulation

We present a statistical mechanical description of biomolecular hydration that accurately describes the hydrophobic and hydrophilic hydration of a model alpha-helical peptide. The local density of water molecules around a biomolecule is obtained by means of a potential-of-mean-force (PMF) expansion in terms of pair- and triplet-correlation functions of bulk water and dilute solutions of nonpolar atoms. The accuracy of the method is verified by comparing PMF results with the local density and site-site correlation functions obtained by molecular dynamics simulations of a model alpha-helix in solution. The PMF approach quantitatively reproduces all features of the peptide hydration determined from the molecular dynamics simulation. Regions of hydrophobic hydration near the C alpha and C beta atoms along the helix are well reproduced. The hydration of exposed polar groups at the N- and C-termini of the helix are also well described by the theory. A detailed comparison of the local hydration by means of site-site radial distribution functions evaluated with the PMF theory shows agreement with the molecular dynamics simulations. The formulation of this theory is general and can be applied to any biomolecular system. The accuracy, speed of computation, and local character of this theory make it especially suitable for studying large biomolecular systems.