An empirical energy potential with a reference state for protein fold and sequence recognition

We consider modifications of an empirical energy potential for fold and seq uence recognition to represent approximately the stabilities of proteins in various environments. A potential used here includes a secondary structure potential representing short-range interactions for secondary structures o f proteins, and a tertiary structure potential consisting of a long-range, pairwise contact potential and a repulsive packing potential. This potentia l is devised to evaluate together the total conformational energy of a prot ein at the coarse grained residue level. It was previously estimated from t he observed frequencies of secondary structures, from contact frequencies b etween residues, and from the distributions of the number of residues in co ntact in known protein structures by regarding those distributions as the e quilibrium distributions with the Boltzmann factor of these interaction ene rgies. The stability of native structures is assumed as a primary requireme nt for proteins to fold into their native structures. A collapse energy is subtracted from the contact energies to remove the protein size dependence and to represent protein stabilities for monomeric and multimeric states. T he free energy of the whole ensemble of protein conformations that is subtr acted from the conformational energy to represent protein stability is appr oximated as the average energy expected for a typical native structure with the same amino acid composition. This term may be constant in fold recogni tion but essentially varies in sequence recognition. A simple test of threa ding sequences into structures without gaps is employed to demonstrate the importance of the present modifications that permit the same potential to b e utilized for both fold and sequence recognition. Published 1999 Wiley-Lis s, Inc.