INFLUENCE OF HYDRATION ON THE CONFORMATIONAL STABILITY AND FORMATION OF BENDS IN TERMINALLY BLOCKED DIPEPTIDES

The conformations of 23 terminally blocked dipeptide sequences were examined by conformational energy calculations that included the effects of the aqueous solvent. Starting structures were derived from combinations of minimum‐energy conformations of hydrated single residues. Their conformational energies were then minimized using the ECEPP potential (Empirical Conformational Energy Program for Peptides) with hydration included. Short‐range interactions dominate in stabilizing the conformations of the hydrated dipeptides. Differences between conformational stabilities of hydrated and unhydrated dipeptides in many cases are due to the competition of solute–water and intramolecular hydrogen bonds. In other cases, perturbation of the hydration shell of the solute by close approach of solute atoms alters conformational preferences. Probabilities of formation of bends were calculated and compared to the corresponding quantities for unhydrated dipeptides and to those calculated from x‐ray structures. For bends in dipeptides containing two nonpolar amino acids, computations omitting hydration yield better results. However, better agreement with experimental (x‐ray) bend probabilities for dipeptides containing glycine or polar amino acids is obtained only in some sequences when hydration is included. The results are rationalized by the observation that, in proteins, bends containing nonpolar sequences occur on the inside, shielded from the solvent. Bends containing glycine or polar amino acids occur frequently on the surface of the protein, but they are not completely hydrated. Copyright © 1979 John Wiley & Sons, Inc.