A new pairwise folding potential based on improved decoy generation and side‐chain packing

A new force field for pairwise residue interactions as a function of C α to C α distances is presented. The force field was developed through the solution of a linear programming formulation with large sets of constraints. The constraints are based on the construction of >80,000 low‐energy decoys for a set of proteins and requiring the decoy energies for each protein system to be higher than the native conformation of that particular protein. The generation of a robust force field was facilitated by the use of a novel decoy generation process, which involved the rational selection of proteins to add to the training set and included a significant energy minimization of the decoys. The force field was tested on a large set of decoys for various proteins not included in the training set and shown to perform well compared with a leading force field in identifying the native conformation for these proteins. Proteins 2003. © 2003 Wiley‐Liss, Inc.