Applications of Empirical Amino Acid Potential Functions

Abstract

Many characteristics of protein folds can be described at less than atomic detail. We have been pursuing a reductionist approach to represent proteins in which residues, rather than atoms, are considered as single points. Direct averages of protein crystal structures provide empirical potential functions that describe residue-residue interactions. These functions have averaged away many details but include essential features with attractive and repulsive terms, that are overall akin to a pair-wise hydrophobicity. Most computational evaluations of protein structures are deficient in not considering a broad enough range of possible conformations; this less detailed approach makes possible a more thorough consideration of conformations. We are developing a new lattice approach to generalize and improve the efficient generation of folded protein conformations, and these empirical potentials are an important part of this approach. Applications of these potential functions presented here include the location of binding sites for peptides on proteins based on geometry and hydrophobicity, specification of similarities of sequence substitutions, and investigations on the variability of the hydrophobicity of a given type residue averaged over occurrences in individual proteins. Recent progress in these areas will be described. This new approach is leading us to the ability to consider more complete sets of protein conformations.