We focus on understanding the relationship between protein structure, function, and dynamics. Research is focused into two major sub-groups: 1) molecular modeling of enzyme-substrate / enzyme-inhibitor interactions and 2) structure-based drug discovery. Studies are performed using computer simulation methods ranging from molecular dynamics simulations, Monte Carlo simulations, Brownian dynamics simulations, and protein-ligand docking. General properties that we address include change in protein structure and dynamics upon binding inhibitors and with mutations, ligand binding strength and specificity, and bound water structure.
Ionic liquids and super critical CO2 have been identified as promising green solvents for biotransformation, enzyme catalysis and long-term preservation of biomolecules. Our objective is to elucidate molecular level interactions between biomolecules and ionic liquids, modulated kinetics of protein folding and increased solubilization & enhanced extraction of proteins and other hydrophilic substances in ionic liquids and water/oil reverse micelles.
While rationalizing experimental behavior of biomolecules using molecular dynamics simulation remain our forte, we have moved on to use MD as a central engine of experimental research by validating our findings from computational studies using various spectroscopic & calorimetric techniques. With leads from our computational data we perform inhibitor synthesis, enzymatic assays and drug design in our laboratory.
1. M. Ahsan and S. Senapati, "Water Plays a Co-catalytic Role in Epoxide Ring Opening Reaction in Aspartate Proteases: A QM/MM Study" J. Phys. Chem. B, 123, 7955-7964 (2019).
2. D.Ghoshdastidar and S. Senapati, "Dehydrated DNA in B-form: Ionic Liquids in Rescue" Nucleic Acids Res., 46, 4344-4353 (2018).
3. Rajeswari Appadurai and S. Senapati, "How Mutations Can Resist Drug Binding Yet Keep HIV-1 Protease Functional" Biochemistry., 56 , 2907-2920 (2017).
4. V.Chirasani, P.D. Revanasiddappa, and S. Senapati, "Structural plasticity of cholesteryl ester transfer protein assists its lipid transfer activity",J. Biol. Chem.vol. 291 (37) p. 19462-73 (2016).
5. R. Appadurai, S. Senapati, "Dynamical Network of HIV-1 Protease Mutants Reveals the Mechanism of Drug Resistance and Unhindered Activity", Biochemistry, 55 (10), pp 1529-1540 (2016).
6. D. Ghoshdastidar, S. Senapati, "Ion-Water Wires in Imidazolium-Based Ionic Liquid/Water Solutions Induce Unique Trends in Density",Soft Matter, 12,3032-3045 (2016).
7. D. Ghoshdastidar, D. Ghosh, S. Senapati, "High Nucleobase-Solubilizing Ability of Low-Viscous Ionic Liquid/Water Mixtures: Measurements and Mechanism", J. Phys. Chem. B., 120, 492-503 (2016).
8. A. Chandran, D. Ghoshdastidar, S. Senapati, "Groove binding mechanism of Ionic liquids: A key factor in long-term stability of DNA in hydrated Ionic liquids?" J. Am. Chem. Soc., 134, 20330-39, (2012).
9. A. Chandran, K. Prakash and S. Senapati, "Self-assembled Inverted Micelles Stabilize Ionic Liquid Domains in Supercritical CO2", J. Am. Chem. Soc. 132, 12511, (2010).
10. V. S. V. Chaitanya and S. Senapati, ""Self-assembled Reverse Micelles in Supercritical CO2 Entrap Protein in Native State ", J. Am. Chem. Soc. 130, 1866 (2008).