Functional Sites of Proteins

Ligand-based approach At least two reasons for an alternative strategy to predicting functional site can be contemplated. First, proteins with different folds may share 

Similarity search conducts systematic search of functional site databases for chemical groups able to make ion pairs/hydrogen bonds and/or hydrophobic interactions with ligands from which representative sites as surfaces with electrostatic and hydrophobic characteristics are generated (Schmitt et al, 2002). 

It is important to recognize similarities in functional sites. However, differences are also important as they are often related to specificity. Many protein families share details of molecular function but vary in finer details such as their substrate specificity. Therefore those residues that are involved in discerning subclasses are likewise important in defining functional sites (Hannenhalli and Russell, 2000). For examples, the nicotinamide nucleotide binding core, (a2p3)2 are common to dehydrogenases but the key residue, Asp/Glu for NAD is replaced by Arg for NADP dependent enzymes. Similarly, key catalytic residues are common to all protein kinases but two regions of the sequence differ and are known to confer the specificity for either Ser/Thr or Tyr specific enzymes. 

---