Integral equation model for aqueous solvatlon of polyatomic solutes: Application to the determination of the free energy surface for the internal motion of biomolecules

A model is presented for determining the intramolecular potential of mean force for flexible polyatomic molecules in aqueous solution. This is an essential step in developing a reduced simulation technique for studying solvated biopolymers. The Ornstein-Zernike-like integral equation theory within a superposition formalism is shown to lead to a convenient and efficient method for calculating the solvent-modified intramolecular potential. Solute-solvent distribution functions for the atoms (sites) composing the polyatomic molecule are evaluated individually and introduced into the appropriate integral equations to obtain the site-site potentials of mean force for all distinct atom pairs in the molecule. The superposition approximation plus an empirical energy function for the internal degrees of freedom can then be employed to determine the total solvent-modified potential of mean force surface for the molecular system. An application to the evaluation of the intramolecular free energy surface for the alanine dipeptide (N-methylalanylacetamide) under vacuum and in aqueous solution is given to illustrate the method.