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An empirical energy potential with a reference state for protein fold and sequence recognition
Author(s) -
Miyazawa Sanzo,
Jernigan Robert L.
Publication year - 1999
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19990815)36:3<357::aid-prot10>3.0.co;2-u
Subject(s) - threading (protein sequence) , statistical potential , protein secondary structure , protein design , protein structure , chemistry , native state , contact order , protein structure prediction , potential of mean force , protein folding , protein tertiary structure , pairwise comparison , molecular dynamics , crystallography , chemical physics , computational chemistry , mathematics , biochemistry , statistics
We consider modifications of an empirical energy potential for fold and sequence 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 of proteins, and a tertiary structure potential consisting of a long‐range, pairwise contact potential and a repulsive packing potential. This potential is devised to evaluate together the total conformational energy of a protein at the coarse grained residue level. It was previously estimated from the observed frequencies of secondary structures, from contact frequencies between residues, and from the distributions of the number of residues in contact in known protein structures by regarding those distributions as the equilibrium distributions with the Boltzmann factor of these interaction energies. The stability of native structures is assumed as a primary requirement 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. The free energy of the whole ensemble of protein conformations that is subtracted from the conformational energy to represent protein stability is approximated as the average energy expected for a typical native structure with the same amino acid composition. This term may be constant in fold recognition but essentially varies in sequence recognition. A simple test of threading sequences into structures without gaps is employed to demonstrate the importance of the present modifications that permit the same potential to be utilized for both fold and sequence recognition. Proteins 1999;36:357–369. Published 1999 Wiley‐Liss, Inc.