On the design and analysis of protein folding potentials

Pairwise interaction models to recognize native folds are designed and anal yzed. Different sets of parameters are considered but the focus was on 20 x 20 contact matrices. Simultaneous solution of inequalities and minimizatio n of the variance of the energy find matrices that recognize exactly the na tive folds of 572 sequences and structures from the protein data bank (PDB) , The set includes many homologous pairs, which present a difficult recogni tion problem. Significant recognition ability is recovered with a small num ber of parameters (e.g., the H/P model). However, full recognition requires a complete set of amino acids. In addition to structures from the PDB, a f olding program (MONSSTER) was used to generate decoy structures for 75 prot eins. It is impossible to recognize all the native structures of the extend ed set by contact potentials. We therefore searched for a new functional fo rm. An energy function U, which is based on a sum of general pairwise inter actions limited to a resolution of 1 angstrom, is considered. This set was infeasible too. We therefore conjecture that it is not possible to find a f olding potential, resolved to 1 angstrom, which is a sum of pair interactio ns. (C) 2000 Wiley-Liss, Inc.