Characterization of hydrogen bonding in a continuum solvent model

A simple approach for calculating hydrogen bonding (H-bonding) effects in m olecular mechanics simulations of peptides and proteins is presented for us e in the framework of the continuum solvent model described in the previous paper. In this approach, the solvated macromolecule is treated as a three- component dielectric system consisting of the solvent, bulk protein, and pr oton acceptor media. The hydrogen bond (H-bond) interaction is identified f rom the interpenetration of the van der Waals spheres of the polar hydrogen and the proton acceptor. The H-bond geometry is characterized by the ideal orientation of the electron lone pairs in the acceptor atom and the direct ionality of the proton donor bond, as observed in experimental and ab initi o studies, and classified according to the hybridization state of the accep tor atom. The algorithm was implemented into CHARMM using the PAR22 force f ield. By introducing the concept of a Born radius of a polar hydrogen immer sed in an acceptor environment, the stabilization of H-bond energies can be introduced by means of a simple fitting procedure. This H-bonding descript ion is easily implemented in standard force fields, with virtually no addit ional computing time requirements. Monte Carlo simulations were carried out on two peptides with this H-bonding treatment and the continuum solvent mo del. The results clearly demonstrate the need for an explicit treatment of H-bonding with the proposed continuum model, and its reliability to predict peptide structures from the primary sequence that are in agreement with ex perimental results.