THE ROLE PLAYED BY ENVIRONMENTAL RESIDUES ON SIDE-CHAIN TORSIONAL ANGLES WITHIN HOMOLOGOUS FAMILIES OF PROTEINS - A NEW METHOD OF SIDE-CHAIN MODELING

We investigated the conservation of sidechain conformation for each re sidue within a homologous family of proteins in the Protein Data Bank (PDB) and performed sidechain modeling using this information. The inf ormation was represented by the probability of conserved sidechain tor sional angles obtained from many families of proteins, and these were calculated for a pair of residues at topologically equivalent position s as a result of structural alignment. Probabilities were obtained for a pair of same amino acids and for a pair of different amino acids. T he correlation between environmental residues and the fluctuation of p robability was examined for the pair of same amino acid residues, and the simple probability was calculated for the pair of different amino acids. From the results on the same amino acid pairs, 17 amino acids, except for Ala, Gly, and Pro, were divided into two types: those that were influenced and those that were not influenced by the environmenta l residues. From results on different amino acid pairs, a replacement between large residues, such as Trp, Phe, and Tyr, was performed assum ing conservation of their torsional angles within a homologous family of proteins. We performed sidechain modeling for 11 known proteins fro m their native and modeled backbones, respectively. With the native ba ckbones, the percentage of the chi(1) angle correct within 30 degrees was found to be 67% and 80% for all and core residues, respectively. W ith the modeled backbones, the percentage of the correct chi(1) angle was found to be 60% and 72% for all and core residues, respectively. T o estimate an upper limit on the accuracy for predicting sidechain con formations, we investigated the probability of conserved sidechain tor sional angles for highly similar proteins having > 90% sequence identi ty and < 2.5-Angstrom X-ray resolution. In those proteins, 83% of the sidechain conformations were conserved for the chi(1) angle. (C) 1998 Wiley-Liss, Inc.