The role played by environmental residues on sidechain torsional angles within homologous families of proteins: a new method of sidechain modeling.
We investigated the conservation of sidechain conformation for each residue within a homologous family of proteins in the Protein Data Bank (PDB) and performed sidechain modeling using this information. The information was represented by the probability of conserved sidechain torsional angles obtained from many families of proteins, and these were calculated for a pair of residues at topologically equivalent positions as a result of structural alignment. Probabilities were obtained for a pair of same amino acids and for a pair of different amino acids. The correlation between environmental residues and the fluctuation of probability 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 environmental residues. From results on different amino acid pairs, a replacement between large residues, such as Trp, Phe, and Tyr, was performed assuming conservation of their torsional angles within a homologous family of proteins. We performed sidechain modeling for 11 known proteins from their native and modeled backbones, respectively. With the native backbones, the percentage of the chi 1 angle correct within 30 degrees was found to be 67% and 80% for all and core residues, respectively. With the modeled backbones, the percentage of the correct chi 1 angle was found to be 60% and 72% for all and core residues, respectively. To estimate an upper limit on the accuracy for predicting sidechain conformations, we investigated the probability of conserved sidechain torsional angles for highly similar proteins having > 90% sequence identity and < 2.5-A X-ray resolution. In those proteins, 83% of the sidechain conformations were conserved for the chi 1 angle.
Ogata
K
K
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. ogatak@platinum.pharm.kitasato-u.ac.jp
Umeyama
H
H
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D008956:Models, Chemical; D005810:Multigene Family; D011336:Probability; D011487:Protein Conformation; D016415:Sequence Alignment