DIELECTRIC CONTINUUM MODELS FOR HYDRATION EFFECTS ON PEPTIDE CONFORMATIONAL TRANSITIONS

Models for hydration effects that treat the solute and solvent as diel ectric continua with different dielectric constants have achieved cons iderable popularity in recent years. Here we compare such models with microscopic molecular dynamics simulations for a variety of conformati onal transitions in peptides. The conformational changes studied inclu de changing backbone torsion angles in the alanine dipeptide; formatio n of hydrogen bonds of the sort seen in antiparallel B-sheets in forma mide and alanine dipeptide dimers; transitions from type I to type II beta-turns; and propagation of an alpha-helix from the N- and C-termin al ends. In each case, the peptide solute is described with the CHARMM -19 force field, and continuum solvent models (determined from finite- difference solutions to the Poisson equation and a surface-area term) are compared to free energy simulations using explicit TIP3P water as a solvent. In general, the agreement between the two theoretical metho ds is good, but ''solvation'' of a CHARMM-19 solute with TIP3P water t ends to modify the gas-phase conformational energy differences to a gr eater extent than ''solvation'' with the continuum dielectric model. T he need for consistency between the force-field charges and the contin uum-model charges in calculations of this kind is demonstrated.