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

α-Helical peptides of the form For-AAAAAAXAAAAAA-NH 2 , 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 3 10 -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 ( r c )) 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 ( r c ) at HBCPs and an α-helix propensity scale, however, the ∑ ρ ( r c ) 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.