A multibody, whole‐residue potential for protein structures, with testing by Monte Carlo simulated annealing

A new multibody, whole‐residue potential for protein tertiary structure is described. The potential is based on the local environment surrounding each main‐chain α carbon (CA), defined as the set of all residues whose CA coordinates lie within a spherical volume of set radius in 3‐dimensional (3D) space surrounding that position. It is shown that the relative positions of the CAs in these local environments belong to a set of preferred templates. The templates are derived by cluster analysis of the presently available database of over 3000 protein chains (750,000 residues) having not more than 30% sequence similarity. For each template is derived also a set of residue propensities for each topological position in the template. Using lookup tables of these derived templates, it is then possible to calculate an energy for any conformation of a given protein sequence. The application of the potential to ab initio protein tertiary structure prediction is evaluated by performing Monte Carlo simulated annealing on test protein sequences. Proteins 2005. © 2005 Wiley‐Liss, Inc.