Evaluation of short-range interactions as secondary structure energies forprotein fold and sequence recognition

Short-range interactions for secondary structures of proteins are evaluated as potentials of mean force from the observed frequencies of secondary str uctures in known protein structures which are assumed to have an equilibriu m distribution with the Boltzmann factor of secondary structure energies. A secondary conformation at each residue position in a protein is described by a tripeptide, including one nearest neighbor on each side. The secondary structure potentials are approximated as additive contributions from neigh boring residues along the sequence. These are part of an empirical potentia l to provide a crude estimate of protein conformational energy at a residue level. Unlike previous works, interactions are decoupled into intrinsic po tentials of residues, potentials of backbone-backbone interactions, and of side chain-backbone interactions. Also interactions are decoupled into one- body, two-body, and higher order interactions between peptide backbone and side chain and between backbones. These decouplings are essential to correc tly evaluate the total secondary structure energy of a protein structure wi thout over-counting interactions. Each interaction potential is evaluated s eparately by taking account of the correlation in the amino acid order of p rotein sequences, Interactions among side chains are neglected, because of the relatively limited number of protein structures. Published 1999 Wiley-L iss, Inc.