Solvent effects on the φ– ψ potential surfaces of glycine and alanine dipeptides studied by PCM and I-PCM methods

Abstract

Two-dimensional φ– ψ potential surfaces of representative amino acid models, For-Gly-NH 2 ( 1) and For-Ala-NH 2 ( 2), were calculated at the HF/6-311++G(2d,2p)//HF/6-31G(d) level of theory in various solvents by applying the polarizable continuum model (PCM) and isodensity polarizable continuum model (I-PCM) methods. Three dielectric constants of medium (i.e. 4.335, 32.63, and 78.39) were selected corresponding to ether, methanol, and water, respectively. The PCM potential surfaces in the solvents were found to be significantly different from the corresponding I-PCM potential surfaces due presumably to the lower approximation level. However, the both methods commonly resulted in local energy minima at the α region for 1 and the α and β regions for 2. Thus, intrinsic conformational propensities of glycine and alanine residues to adopt folded secondary structures were suggested in the solvents. Comparison of the more reliable I-PCM potentials with the Ramachandran plots extracted from protein databank (PDB_SELECT) revealed that glycine and alanine residues in folded proteins roughly adopt random statistical structures in high energy ranges (Δ E>3 and 5 kcal/mol for 1 and 2, respectively). It was also proposed that the conformational space of a polypeptide molecule is significantly restricted in water compared with that in the gas phase.