The overall goal of our research is to unravel the structural basis of functioning of macromolecules and there by identify potential drug targets. We have been applying multidisciplinary approach of molecular biology, biochemistry, cell biology, cheminformatics, bioinformatics and structural biology to understand the structure and function of proteins and to find efficient inhibitors in combating diseases. We use protein crystallography to determine the atomic structure of these proteins, as well as biochemical and biophysical approaches to understand how they work. We utilize computer-aided drug design methods to model new compounds and these virtually-designed compounds are then synthesized in collaboration with Medicinal Chemistry labs for testing in biochemical and cellular assays. Research activities focus on modelling protein-ligand interactions, structure-based drug design, homology modelling and QSAR. Because our laboratory combines bioinformatics(dry lab) with structural biology (wet lab), we are uniquely equipped to explore and develop new therapeutic strategies involving novel targets.In this respect, we are applying structure-based strategies to design several classes of bioactive compounds targeted to specific diseases, with particular reference to infectious diseases, diabetes and cancer.

Following are the ongoing research projects.

1. Insights into inhibition of Peptidoglycan Pentaglycine cross bridge forming Fem proteins of Methicillin Resistance Staphylococcus aureus

Over the last few decades, Multidrug Resistance Staphylococcusaureus has become a global concern and a major challenge to treat with regularly available antibiotics. The fem family members are known to be novel therapeutic targets due to their role in peptidoglycan synthesis. By understanding the role of fem proteins and their interactions with effective inhibitors at the molecular level, it would contribute to the interpretation of the cellwall biosynthesis aspects that are good stand-alone points to control the growth and multidrug resistance in pathogenic bacteria.The present study focuses on the S. aureus species specific marker genes (fem genes) cloning, expression, purification and their biochemical characteristics which will induce the expression of Penicillin binding proteins (PBP2a) that confer methicillin resistance to the organism.

2. Transient over-expression of human CD-200 gene in Nicotiana model plant and biochemical characterization of purified protein for immunotherapy

A large number of drugs currently in development are recombinant antibodies and most of these are produced in cultured ExpiCHO and SF9 cells which are expensive, difficult to scale-up and may contain human pathogens. Plants represent a cost-effective, convenient and safe alternative production system and are slowly gaining acceptance. Expression of antibody in transformed plants might be a solution to successfully scale up therapeutic antibodies, as it results in high yield and lower the production costs. CD200, also known as OX-2, is a 45kDa transmembrane immunoregulatory protein that belongs to the immunoglobulin (Ig) super family. The CD200/CD200R homeostatic mechanism is of major interest as a target for immunomodulation both to reduce myeloid activity in inflammatory conditions and to block inhibitory signals provided by cancer cells. In this study, we would amplify the truncated CD200, clone in the plant transformation vector. We would further carry out biochemical and biophysical characterization of plant derived antibody, drug molecule conjugate and finally, comparison of production cost mammalian versus plant derived antibody.