2026-07-072026-07-07http://salesiana.dossiersoluciones.com/handle/123456789/140049Environment specific substitution tables have been used effectively for distinguishing structural and functional constraints on proteins and thereby identify their active sites (Chelliah et al. (2004)). This work explores whether a similar approach can be used to identify specificity determining residues (SDRs) responsible for cofactor dependence, substrate specificity or subtle catalytic variations. We combine structure-sequence information and functional annotation from various data sources to create structural alignments for homologous enzymes and functional partitions therein. We develop a scoring procedure to predict SDRs and assess their accuracy using information from bound specific ligands and published literature.Quantitative Methodstext