A STATISTICAL-ANALYSIS OF SIDE-CHAIN CONFORMATIONS IN PROTEINS - COMPARISON WITH ECEPP PREDICTIONS

A comparison of the statistical distributions of side-chain conformations of 17 amino acids (Gly, Ala, and Pro excluded), observed in 63 nonhomologous globular proteins (covering 10,832 residues), is made with similar distributions calculated from the low-energy conformational states for the same amino acids (blocked with acetyl and N-methylamide groups at the N- and C-termini, respectively) obtained by Vasquez et al. [(1983), Macromolecules 16, 1043-1049] using the ECEPP/2 force field. Those residues (i) with linear side chains (Arg, Lys, Met, Cys, Ser), or those that are unbranched through the gamma-carbon atom (Glu, Gin) show good agreement, whereas (ii) those with side chains that are branched at CP or CY show poor agreement with ECEPP calculations. A possible explanation for this is shown to be the greater tendency for side-chain atoms in class (ii) to interact with the backbone and/or adjacent side chains. Accordingly, ECEPP/3 calculations, carried out after elongating the backbone chain of the model peptide unit (by adding three Ala residues on each side of the central residue, and then blocking the termini as before), result in distributions that are often closer to the observed side-chain distributions. The implications of these results for the relative importance of short-range versus long-range interactions in determining protein structure are discussed.