Classification of the environment of protein residues

Abstract

We have studied the classification of the environment of residues within protein structures. Eisenberg's original idea created environmental categories to discriminate between similar residues [Bowie et al., Science (1991), 253, 164-170]. These environments grouped residues based upon their buried surface area, polarity of the surrounding environment, and secondary structure element in which the residue is found. However, Eisenberg's original categories led to incomplete discrimination between residues that only partially substitute for each other. We have expanded on Eisenberg's original idea of environmental categories, by both considering additional contacts in the calculation of the solvent-accessible molecular surface area and by subdividing the environmental plot into regions based upon its theoretical features. Our alternative surface area calculations were used in conjunction with the polarity of the environment of the residue to define a new set of environmental categories. These new categories were able to discriminate between residues such as threonine, valine, and aspartic acid while reflecting the propensity of these residues to substitute for each other.