Conformational behaviour of the architectural units of peptides and proteins. Assessment of current understanding by ab initio quantum mechanical methods and refinement of the dipeptide energy surface

Abstract

The conformational energy surfaces of analogues of the dipeptide unit of polypeptides and proteins are calculated by ab initio methods using extended basis sets. The calculations are not particularly sensitive to the choice of (extended) basis set. The calculations are shown to support a particular empirical method parameterized with respect to crystal data. Non-hydrogen bonded conformations agree to within 3 kcal mol −1, even for conformations in which quite considerable degrees of atomic overlap occur. Hydrogen bonded conformations, are, however, in less satisfactory agreement and it is the ab initio calculations which appear to be at fault. A simple correction is applied to the ab initio energy for hydrogen bonded conformations, and with the use of the empirical energy surface a full quantum mechanical conformational energy map is interpolated for the alanyl dipeptide. The effect of flexibility in the peptide backbone is taken into account, and supports recent empirical findings that distortions in valence angles must be considered in calculations of the conformational behaviour of peptides.