Model for the conformational analysis of hydrated peptides. Effect of hydration on the conformational stability of the terminally blocked residues of the 20 naturally occurring amino acids

The effects of hydration are included in empirical conformational energy computations on oligopeptides by means of a modified hydration‐shell model. Free energy terms are introduced to account for “specific hydration” due to water–solute hydrogen bonding and for “nonspecific hydration” describing the interaction of the solute with water molecules in a first‐neighbor shell. The dielectric constant has been doubled (over the value used for calculations in the absence of water) to take into account the presence of solvent. Computations were carried out for the N ‐acetyl‐ N ′‐methylamides of the 20 naturally occurring amino acids. Conformational energy maps are compared with similar maps calculated in the absence of hydration. Minimum‐energy conformations are located and compared with the corresponding minima for unhydrated peptides in terms of ordering with respect to potential energy, the dihedral angles at the minima, and the presence of intramolecular hydrogen bonds. The Boltzmann factors for various conformational regions are altered significantly on hydration in some cases. These changes can be explained in terms of differences in the hydration free energy terms for various conformations.