Relative stability of major types of β-turns as a function of amino acid composition:: A study based on ab initio energetic and natural abundance data

Folding properties of small globular proteins are determined by their amino acid sequence (primary structure). Ibis holds both for local (secondary structure) and for global conformational features of linear polypeptides and proteins composed from natural amino acid derivatives. It thus provides the rational basis of structure prediction algorithms. The shortest secondary structure element, the beta-turn, most typically adopts either a type I or a type 11 form, depending on the amino acid composition. Herein we investigate the sequence-dependent folding stability of both major types of beta-turns, using simple dipeptide models (-Xxx-Yyy-). Gas-phase ab initio properties of 16 carefully selected and suitably protected dipeptide models (for example Val-Ser, Ala-Gly, Ser-Ser) were studied. For each backbone fold most probable side-chain conformers were considered. Fully optimized 3-21G RHF molecular structures were employed in medium level [B3LYP/6-311++G(d,p)//RHF/3-21G] energy calculations to estimate relative populations of the different backbone conformers. Our results show that the preference for beta-turn forms as calculated by quantum mechanics and observed in X-ray determined proteins correlates significantly.