A model for hydration of peptides and its application to the conformational analysis of terminally blocked amino acids and dipeptides.

A theoretical model for peptide structure, which takes into account the effects of hydration in conformational energy calculations, is described. The free energy of hydration is composed of a term for "specific hydration," representing solute-water hydrogen bonding, and a term for "non-specific hydration," describing the interaction of the solute with water molecules in a first-neighbor shell. Minimum-energy conformations were computed for the hydrated N-acetyl-N'-methylamides of the 20 naturally occurring amino acids, and the results were compared with those computed in the absence of hydration. The relative energies of many conformations and the width of some low-energy regions of the (ø, Psi) conformational maps are altered when the free energy of nonspecific hydration is included. The term for specific hydration causes large charges of the energy, but only in some regions of the maps. Observed vicinal coupling constants are approximated better by the computation when hydration is included. Conformational preferences of the individual residues in hydrated dipeptides are similar to those computed for the hydrated single residues, showing that intraresidue interactions predominate in dipeptides. This supports the concept of the importance of short-range interactions in proteins. Bend probabilities were computed and compared with observed frequencies of occurrence of bends in proteins of known structure. Computed values improve only for some of the dipeptides containing polar residues or glycine when hydration is included. For bends involving two nonpolar residues, computations omitting hydration give better results.