A novel exhaustive search algorithm for predicting the conformation of polypeptide segments in proteins

We present a fast ab initio method for the prediction of local conformation s in proteins. The program, PETRA, selects polypeptide fragments front a co mputer-generated database (APD) encoding all possible peptide fragments up to twelve amino acids long. Each fragment is defined by a representative se t of eight phi/psi pairs, obtained iteratively from a trial set by calculat ing how fragments generated from them represent the protein databank (PDB), Ninety-six percent (96%) of length five fragments in crystal structures, w ith a resolution better than 1.5 Angstrom and less than 25% identity, have a conformer in the database with less than 1 root-mean-square deviation (rm sd), In order to select segments from APD, PETRA uses a set of simple rule- based filters, thus reducing the number of potential conformations to a man ageable total. This reduced set is scored and sorted using rmsd fit to the anchor regions and a knowledge-based energy function dependent on the seque nce to be modelled. The best scoring fragments can then be optimized by min imization of contact potentials and rmsd fit to the core model. The quality of the prediction made by PETRA is evaluated by calculating both the diffe rences in rmsd and backbone torsion angles between the final model and the native fragment. The average rmsd ranges from 1.4 Angstrom for three residu e loops to 3.9 Angstrom for eight residue loops. (C) 2000 Wiley-Liss, Inc.