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Evaluation of the conformational free energies of loops in proteins
Author(s) -
Smith Kenneth C.,
Honig Barry
Publication year - 1994
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/prot.340180205
Subject(s) - solvation , chemistry , implicit solvation , chemical physics , phase (matter) , crystal structure , protein crystallization , energy minimization , electrostatics , phase problem , computational chemistry , rnase p , static electricity , accessible surface area , crystallography , thermodynamics , physics , solvent , crystallization , quantum mechanics , organic chemistry , rna , biochemistry , diffraction , gene
Abstract In this paper we discuss the problem of including solvation free energies in evaluating the relative stabilities of loops in proteins. A conformational search based on a gas‐phase potential function is used to generate a large number of trial conformations. As has been found previously, the energy minimization step in this process tends to pack charged and polar side chains against the protein surface, resulting in conformations which are unstable in the aqueous phase. Various solvation models can easily identify such structures. In order to provide a more severe test of solvation models, gas phase conformations were generated in which side chains were kept extended so as to maximize their interaction with the solvent. The free energies of these conformations were compared to that calculated for the crystal structure in three loops of the protein E. coli RNase H, with lengths of 7, 8, and 9 residues. Free energies were evaluated with a finite difference Poisson‐Boltzmann (FDPB) calculation for electrostatics and a surface area‐based term for nonpolar contributions. These were added to a gas‐phase potential function. A free energy function based on atomic solvation parameters was also tested. Both functions were quite successful in selecting, based on a free energy criterion, conformations quite close to the crystal structure for two of the three loops. For one loop, which is involved in crystal contacts, conformations that are quite different from the crystal structure were also selected. A method to avoid precision problems associated with using the FDPB method to evaluate conformational free energies in proteins is described. © 1994 John Wiley & Sons, Inc.