Conservation and relative importance of residues across protein-protein interfaces

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Abstract
A core region surrounded by a rim characterizes biological interfaces. We ascertain the importance of the core by showing the sequence entropies of the residues comprising the core to be smaller than those in the rim. Such a distinction is not seen in the 2-fold-related, nonphysiological interfaces formed in crystal lattices of monomeric proteins, thereby providing a procedure for characterizing the oligomeric state from crystal structures of protein molecules. This method is better than those that rely on the comparison of the sequence entropies in the interface and the rest of the protein surface, especially in cases where the surface harbors additional binding sites. To a good approximation there is a correlation between the accessible surface area lost because of complexation and ΔΔ G values obtained through alanine-scanning mutagenesis (26-38 cal per Å 2 of the surface buried) for residues located in the core, a relationship that is not discernable for rim residues. If, however, a residue participates in hydrogen bonding across the interface, the extent of stabilization is 52 cal/mol per 1 Å 2 of the nonpolar surface area buried by the residue. As opposed to an amino acid classification used earlier, an environment-based grouping of residues yields a better discrimination in the sequence entropy between the core and the rim.