Role of Metastable Conformational States in Proteins: From Function to Drug Discovery
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Event Date:
November 27 - November 27, 2024
Application Area: Drug Discovery, Material Design
About the Speaker:- Dr. Suman Chakrabarty has a broad research interest in the area of computational (bio)physical chemistry. He obtained B.Sc. in Chemistry from Presidency College, Kolkata (2002) and MS (2005)/PhD (2010) from Indian Institute of Science (IISc), Bangalore. After a postdoctoral research stint at the University of Southern California, USA (2009-2012), he joined CSIR-NCL, Pune as a Ramanujan Fellow. He is presently an Associate Professor at the S. N. Bose National Centre for Basic Sciences, Kolkata. His group studies the structure, function and dynamics of complex molecular systems, including large-scale biomolecular machinery, using theoretical and computational techniques. His group has made significant contributions towards understanding the molecular mechanism of allosteric regulation, biomolecular recognition/signalling, development of enhanced sampling methods for navigating the conformational free energy landscape in proteins.
Abstract:- Structural biology of proteins is dominated by a native structure-centric view. However, biomolecular functions are intimately connected to protein motion/dynamics, and often low-lying metastable or “excited” conformational states play an important role. 1,2 For example, recent examples of “dynamic allostery” have established that a static structural view is not enough. 3,4 In this talk, we shall discuss several such examples based on large-scale classical molecular dynamics (MD) simulations. We shall demonstrate how conformational plasticity and dynamics can be crucial to the function. Finally, we shall discuss our new ideas on identifying allosteric hotspots on protein surfaces to modulate therapeutically important protein-protein interactions (PPI) as a promising alternative strategy in computer-aided discovery of allosteric inhibitors. 5 References:
- B. Pandey, K. Sinha, A. Dev, H. K. Ganguly, S. Polley, S. Chakrabarty* and G. Basu*, Biochemistry 62, 989 (2023).
- S. Mitra, A. Sil, R. Biswas* and S. Chakrabarty*, J. Phys. Chem. Lett. 14, 1892 (2023).
- A. Kumawat and S. Chakrabarty, Proc. Natl. Acad. Sci. USA 114, E5825 (2017).
- A. Kumawat and S. Chakrabarty, J. Phys. Chem. Lett. 11, 9026 (2020).
- I. Basu, K. Sinha, Z. Shah, S. Shah and S. Chakrabarty, J. Chem. Inf. Model. 64, 3923 (2024).