Determinants of protein function revealed by combinatorial entropy optimization
Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Genome Biology 2007, 8:R232 doi:10.1186/gb-2007-8-11-r232Published: 1 November 2007
We use a new algorithm (combinatorial entropy optimization [CEO]) to identify specificity residues and functional subfamilies in sets of proteins related by evolution. Specificity residues are conserved within a subfamily but differ between subfamilies, and they typically encode functional diversity. We obtain good agreement between predicted specificity residues and experimentally known functional residues in protein interfaces. Such predicted functional determinants are useful for interpreting the functional consequences of mutations in natural evolution and disease.