Statistical and energetic analysis of side‐chain conformations in oligopeptides

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Abstract
The distributions of side-chain conformations in 258 crystal structures of oligopeptides have been analyzed. The sample contains 321 residues having side chains that extend beyond the Cβ atom. Statistically observed preferences of side-chain dihedral angles are summarized and correlated with stereochemical and energetic constraints. The distributions are compared with observed distributions in proteins of known X-ray structures and with computed minimum-energy conformations of amino acid derivatives. The distributions are similar in all three sets of data, and they appear to be governed primarily by intraresidue interactions. In side chains with no β-branching, the most important interactions that determine χ1 are those between the CγH2 group and atoms of the neighboring peptide groups. As a result, the g- conformation (χ1 ⋍ -60°) occurs most frequently for rotation around the Cα-Cβ bond in oligopeptides, followed by the t conformation (χ1 ⋍ 180°), while the g + conformation (χ1 ⋍ 60°) is least favored. In residues with β-branching, steric repulsions between the CγH2 or CγH3 groups and backbone atoms govern the distribution of χ1. The extended (t) conformation is highly favored for rotation around the Cβ-Cγ Cγ-Cδ bonds in unbranched side chains, because the t conformer has a lower energy than the g + g - conformers in hydrocarbon chains. This study of the observed side-chain conformations has led to a refinement of one of the energy parameters used in empirical conformational energy computations.