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. C. Pindi, V.R. Chirasani, S. Senapati*, "Identifying crucial E-protein residues responsible for unusual stability of Zika virus envelope",Biophys. J. 120, 1-14. (2021).
2. S. Bardhan, M. H. Rahman, S. Banerjee, A. P. Singh and S. Senapati*, "Extended H-Bonding through Protic Ionic Liquids Facilitates the Growth and Stability of Water Domains in Hydrophobic Environment"Langmuir 36, 15362-15373 (2020).
3. M. Ahsan, C. Pindi and S. Senapati*, "Electrostatics Plays a Crucial Role in HIV-1 Protease Substrate Binding, Drugs Fail to Take the Advantage" Biochemistry.,59, 3316-3331 (2020).
4. D. Ghoshdastidar, S. Senapati*; Dehydrated DNA in B-form: Ionic liquids in rescue "Nucleic Acids Res. 2018, 46, 4344-4353. (2018).
5. V.Chirasani, P.D. Revanasiddappa, S. Senapati*, "Structural plasticity of cholesteryl ester transfer protein assists its lipid transfer activity", J. Biol. Chem. 2016, 291, 19462-19473.,
6. D. Ghoshdastidar, S. Senapati*, "Ion-Water Wires in Imidazolium-Based Ionic Liquid/Water Solutions Induce Unique Trends in Density", Soft Matter 2016, 12, 3032-3045.
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. 2016, 120, 492-501.
8. C. Aneesh, 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. 2012, 134, 20330.
9. C. Aneesh, K. Prakash and S. Senapati*, "Self-assembled Inverted Micelles Stabilize Ionic Liquid Domains in Supercritical CO2", J. Am. Chem. Soc 2010, 132, 12511.
10. V. S. V. Chaitanya and S. Senapati, "Self-assembled Reverse Micelles in Supercritical CO2 Entrap Protein in Native State ", J. Am. Chem. Soc. 2008, 130, 1866.