Stabilizing effect of solvent and guest residue amino acids on a model alpha-helix peptide

Abstract

α-Helical peptides of the form For-AAAAAAXAAAAAA-NH2, where X is one of 21 amino acids, have been optimized by use of density-functional theory with the inclusion of solvent by a polarizable continuum model and analyzed by use of the quantum theory of atoms in molecules. Inclusion of solvent results in the transition from a partial 310-helix geometry that was previously observed in gas-phase optimized structures to a fully α-helical geometry, resulting in a substantial loss of NH⋯O i+3 contacts and concurrent formation of NH⋯O i+4 contacts. An increase in the number of N⋯O i+3 contacts was also observed. The total electron density (∑ρ(rc)) at the hydrogen bond critical points (HBCPs) within the peptide backbone increased by up to 160% in the solvated structure. No correlation was found between the ∑ρ(rc) at HBCPs and an α-helix propensity scale, however, the ∑ρ(rc) at HBCPs for the substituted amino acids yields a helix-stabilizing order for the amino acids: Thr>Asn>Ser>Glu>Trp>Arg>Asp>Leu>Cys>His+>Gln>Lys>Met>Ile>Val>Phe>His>Ala>Tyr>Pro>Gly.