SOLVATION STRUCTURE AND STABILITY OF PEPTIDES IN AQUEOUS-SOLUTIONS ANALYZED BY THE REFERENCE INTERACTION SITE MODEL-THEORY

We report results of numerical analyses on solvation structure and con formational stability of a dipeptide and Met-enkephalin in the extende d simple point charge (SPC/E) model water. The reference interaction s ite model (RISM) theory is fully solved using our robust, highly effic ient algorithm, It is shown that water structure near the peptides and the hydration free energy are greatly dependent on the peptide confor mations. Stability of Met-enkephalin is examined in terms of the total energy defined as the sum of the conformational energy and the hydrat ion free energy of the peptide. We test several different conformation s including that with the minimum energy in gas phase, which tal;es ra ther compact form due to an intramolecular hydrogen bond. It is shown that a fully extended conformation has the highest stability in water. Our results are in qualitative accord with the recent nuclear magneti c resonance (NMR) experiments which suggest fully extended conformatio ns with large fluctuations for the solution structure of the peptide. A conformation which is similar to that obtained from the NMR experime nts in miceller solutions, is much less stable when it is put in water . Thus, the peptide conformations are greatly sensitive to microscopic solvent environment, and any native treatment of the solvent such as the continuum model will end in failure. (C) 1997 American Institute o f Physics.