  Environment 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.
