Peptide backbone reconstruction using dead‐end elimination and a knowledge‐based forcefield

A novel, yet simple and automated, protocol for reconstruction of complete peptide backbones from Cα coordinates only is described, validated, and benchmarked. The described method collates a set of possible backbone conformations for each set of residue triads from a structural library derived from the PDB. The optimal permutation of these three residue segments of backbone conformations is determined using the dead-end elimination (DEE) algorithm. Putative conformations are evaluated using a pairwise-additive knowledge-based forcefield term and a fragment overlap term. The protocol described in this report is able to restore the full backbone coordinates to within 0.2–0.6 A of the actual crystal structure from Cα coordinates only. In addition, it is insensitive to errors in the input Cα coordinates with RMSDs of 3.0 A, and this is illustrated through application to deliberately distorted Cα traces. The entire process, as described, is rapid, requiring of the order of a few minutes for a typical protein on a typical desktop PC. Approximations enable this to be reduced to a few seconds, although this is at the expense of prediction accuracy. This compares very favorably to previously published methods, being sufficiently fast for general use and being one of the most accurate methods. Because the method is not restricted to the reconstruction from only Cα coordinates, reconstruction based on Cβ coordinates is also demonstrated. © 2003 Wiley Periodicals, Inc. J Comput Chem 25: 16–27, 2004