Quantum theory of the structure and bonding in proteins: Part 12. Conformational analysis of side chains and the ethyl group as a model side chain

Abstract

The conformational effects of the side chains of proteins have been examined at the ab initio molecular orbital level of approximation using the ethyl group as a model side chain. The conformational energy map of the C α ethyl glycine dipeptide (with the side chain away from the backbone) is computed first and the energetic consequences of rotating the ethyl group about its bond to the backbone are computed subsequently. The results may be analysed in terms of torsion barriers about the single bond and non-bonded repulsions. The conformational energy map is very like that of alanine. Rotation of the ethyl group shows the familiar staggering about a single bond (χ 1 = + 60, 180, −60°); this effect is sometimes obscured, however, by large non-bonded repulsions between the side chain and the backbone. When the side chain points away from the backbone (χ 1 = 180, −60°), there is little or no interaction between the two parts but when it is folded towards the backbone (χ 1 = + 60°) there are extensive interactions. Comparisons with experiment show that the ethyl group is an accurate model for such side chains as leucine and an approximate model for many others. One major simplification of protein structural theory implied by these results is that side-chain conformations are local effects which are generally unaffected by the secondary and tertiary structure of the protein.