HYDRATION OF AN ALPHA-HELICAL PEPTIDE - COMPARISON OF THEORY AND MOLECULAR-DYNAMICS SIMULATION

We present a statistical mechanical description of biomolecular hydrat ion that accurately describes the hydrophobic and hydrophilic hydratio n of a model alpha-helical peptide, The local density of water molecul es around a biomolecule is obtained by means of a potential-of-mean-fo rce (PMF) expansion in terms of pair- and triplet-correlation function s of bulk water and dilute solutions of nonpolar atoms. The accuracy o f the method is verified by comparing PMF results with the local densi ty and site-site correlation functions obtained by molecular dynamics simulations of a model alpha-helix in solution. The PMF approach quant itatively reproduces all features of the peptide hydration determined from the molecular dynamics simulation. Regions of hydrophobic hydrati on near the C-alpha and C-beta atoms along the helix are well reproduc ed. The hydration of exposed polar groups at the N and C-termini of th e helix are also well described by the theory. A detailed comparison o f the local hydration by means of site-site radial distribution functi ons evaluated with the PMF theory shows agreement with the molecular d ynamics simulations. The formulation of this theory is general and can be applied to any biomolecular system. The accuracy, speed of computa tion, and local character of this theory make it especially suitable f or studying large biomolecular systems. (C) 1997 Wiley-Liss, Inc.