PREDICTION AND EVALUATION OF SIDE-CHAIN CONFORMATIONS FOR PROTEIN BACKBONE STRUCTURES

A common approach to protein modeling is to propose a backbone structu re based on homology or threading and then to attempt to build side ch ains onto this backbone, A fast algorithm using the simple criteria of atomic overlap and overall rotamer probability is proposed for this p urpose, The method was first tested in the context of exhaustive searc hes of side chain configuration space in protein cores and was then ap plied to all side chains in 49 proteins of known structure, using simu lated annealing to sample space, The latter procedure obtains the corr ect rotamer for 57% and the correct chi(1) value for 74% of the 6751 r esidues in the sample, When low-temperature Monte-Carlo simulations ar e initiated from the results of the simulated-annealing processes, con sensus configurations are obtained which exhibit slightly more accurat e predictions, The Monte-Carlo procedure also allows converged side ch ain entropies to be calculated for all residues. These prove to be acc urate indicators of prediction reliability, For example, the correct r otamer is obtained for 79% and the correct chi(1) value is obtained fo r 84% of the half of the sample residues exhibiting the lowest entropi es, Side chain entropy and predictability are nearly completely uncorr elated with solvent-accessible area, Some precedents for and implicati ons of this observation are discussed. (C) 1996 Wiley-Liss, Inc.