Title:Applying Knowledge of Enzyme Biochemistry to the Prediction of Functional Sites for Aiding Drug Discovery
Volume: 17
Issue: 21
Author(s): Priyadarshini P. Pai and Sukanta Mondal*
Affiliation:
- ABC group, Department of Biological Sciences, Birla Institute of Technology and Science-Pilani, K. K. Birla Goa Campus, Near NH17 Bypass Road, Zuarinagar, Goa-403726,India
Keywords:
Catalytic residues, Protein-ligand interaction, Post-translational modifications, Allostery, De novo prediction, Template-
based prediction, Enzyme engineering, Rational drug design.
Abstract: Enzymes are biological catalysts that play an important role in determining the patterns of
chemical transformations pertaining to life. Many milestones have been achieved in unraveling the
mechanisms in which the enzymes orchestrate various cellular processes using experimental and
computational approaches. Experimental studies generating nearly all possible mutations of target enzymes
have been aided by rapid computational approaches aiming at enzyme functional classification,
understanding domain organization, functional site identification. The functional architecture,
essentially, is involved in binding or interaction with ligands including substrates, products, cofactors,
inhibitors, providing for their function, such as in catalysis, ligand mediated cell signaling, allosteric
regulation and post-translational modifications. With the increasing availability of enzyme information
and advances in algorithm development, computational approaches have now become more capable
of providing precise inputs for enzyme engineering, and in the process also making it more efficient.
This has led to interesting findings, especially in aberrant enzyme interactions, such as hostpathogen
interactions in infection, neurodegenerative diseases, cancer and diabetes. This review aims
to summarize in retrospection – the mined knowledge, vivid perspectives and challenging strides in
using available experimentally validated enzyme information for characterization. An analytical outlook
is presented on the scope of exploring future directions.
