Building proteins fromCαcoordinates using the dihedral probability grid Monte Carlo method

Abstract

Dihedral probability grid Monte Carlo (DPG‐MC) is a general‐purpose method of conformational sampling that can be applied to many problems in peptide and protein modeling. Here we present the DPG‐MC method and apply it to predicting complete protein structures from C_α coordinates. This is useful in such endeavors as homology modeling, protein structure prediction from lattice simulations, or fitting protein structures to X‐ray crystallographic data. It also serves as an example of how DPG‐MC can be applied to systems with geometric constraints. The conformational propensities for individual residues are used to guide conformational searches as the protein is built from the amino‐terminus to the carboxyl‐terminus. Results for a number of proteins show that both the backbone and side chain can be accurately modeled using DPG‐MC. Backbone atoms are generally predicted with RMS errors of about 0.5 Å (compared to X‐ray crystal structure coordinates) and all atoms are predicted to an RMS error of 1.7 Å or better.