Conformation of amino acid side-chains in proteins

We have analysed the side-chain dihedral angles in 2536 residues from 19 protein structures. The distributions of x1 and x2 are compared with predictions made on the basis of simple energy calculations. The x1 distribution is trimodal; the g− position of the side-chain (trans to Hα), which is rare except in serine, the t position (trans to the amino group), and the g+ position (trans to the carbonyl group), which is preferred in all residues. Characteristic x2 distributions are observed for residues with a tetrahedral γ-carbon, for aromatic residues, and for aspartic acid/asparagine. The number of configurations actually observed is small for all types of side-chains, with 60% or more of them in only one or two configurations. We give estimates of the experimental errors on x1 and x2 (3 ° to 16 °, depending on the type of the residue), and show that the dihedral angles remain within 15 ° to 18 ° (standard deviation) from the configurations with the lowest calculated energies. The distribution of the side-chains among the permitted configurations varies slightly with the conformation of the main chain, and with the position of the residue relative to the protein surface. Configurations that are rare for exposed residues are even rarer for buried residues, suggesting that, while the folded structure puts little strain on side-chain conformations, the side-chain positions with the lowest energy in the unfolded structure are chosen preferentially during folding.