- Biophysical Chemistry
- General Chemistry
To Investigate the Interplay between Protein Dynamics and Function
To Classify and Characterize Proteins based on their Intrinsic Dynamics
Investigation of roles of local and global motions on the enzymatic function of aminoacyl-tRNA synthetases (AARSs)
My research is focused on the simple question - how protein motions influence substrate binding and catalysis. The relationship between protein dynamics and its key functions (such as allosterism and catalysis) is an evolving perspective in enzymology. The more complex is the architecture of a multi-domain protein, the fuzzier is the picture at the molecular-level. For the past several years, my research group has been investigating the interplay of protein dynamics and enzymatic processes in the multi-domain enzyme systems - aminoacyl-tRNA synthetases (AARSs). Using computations and experiments, my research group is exploring how the global dynamics and local fluctuations modulate substrate recognition, catalysis, and allosteric communication in these multi-domain enzymes.
Characterization of proteins based on their intrinsic dynamics
It is increasingly recognized that protein dynamics play an important role in molecular recognition and catalytic activity. As the mobility of a protein is an intrinsic property that is encrypted in its primary structure, my research students and students of biophysical chemistry course are involved in i) classifying proteins based on their intrinsic dynamics and ii) examining if it is possible to characterize the function of a new protein based on its intrinsic mobility pattern.
Investigation of the impact of macromolecular crowding on the conformational ensembles of AARSs
Macromolecular crowding in the cytosolic environment influence substrate binding affinity and enzymatic activity of proteins. However, the mechanism of dynamic changes that occur during substrate binding and catalysis in the presence of macromolecules has remained under-explored for modular enzymes. Currently, we are investigating the impact of macromolecular crowding on the conformational dynamics of an AARS. We are using synthetic crowding agents to mimic cytosolic crowding conditions and have employed a hybrid compuational-experiemental approach (molecular simulations, intrinsic tryptophan fluorescence measurements, and enzyme kinetics) to probe the conformational-shift in the presence of crowding agents.
Grants and Fellowships
NIH Academic Research Enhancement Award, 2015
NIH Recovery Act Administrative Supplement Award, 2010
NIH Academic Research Enhancement Award, 2008
Research Corporation Cottrell College Science Award, 2006
Graduate Research Fellowship, Indian Association for the Cultivation of Science, India, 1991
Lectureship and Research Fellowship Award in Chemistry, University Grant Commission, India, 1991
34. Insight into the Kinetics and Thermodynamics of the Hydride Transfer Reactions between Quinones and Lumiflavin: A Density Functional Theory Study .C. R. Reinhardt,T. C. Jaglinski, A. M. Kastenschmidt, E. H.Song, A. K. Gross, A. J. Krause, J. M. Gollmar, K. J. Meise, Z. S. Stenerson, T. J. Weibel, A. Dison,‡ M. R. Finnegan, D. S. Griesi, M. D. Heltne, T. G. Hughes, C. D. Hunt, K. A. Jansen, A. H. Xiong, S. Hati, and S. Bhattacharyya (2016) J.Mol. Model.,22, 199.
33. Incorporating modeling and simulations in undergraduate biophysical chemistry course to promote understanding of structure-dynamics-function relationships in proteins.S. Hati and S. Bhattacharyya (2016) Biochemistry and Molecular Biology Education, in press.
32. Comparison of intrinsic dynamics of cytochrome P450 proteins using normal mode analysis. M. Dorner, R. McMunn, Students of Biophysical course, Fall 2013, and S. Hati (2015) Protein Science, 1495-1507.
31. Probing the global and local dynamics of aminoacyl-tRNA synthetases using all-atom and coarse-grained simulations. A. M. Strom, S. C. Fehling, S. Bhattacharyya, and S. Hati (2014) J. Mol. Model., 20,2235.
30. Comparison of the intrinsic dynamics of aminoacyl-tRNA synthetases. N. Warren, A. Strom, B. Nicolet, K. Albin, J. Albrecht, B. Bausch, M. Dobbe, M. Dudek, S. Firgens, C. Fritsche, A. Gunderson, J. Heimann, C. Her, J. Hurt, D. Konorev, M. Lively, S. Meacham, V.Rodriguez, S.Tadayon, D. Trcka, Y. Yang, S. Bhattacharyya, and S. Hati (2014) The Protein Journal, 184-198.
29. Strictly conserved lysine of prolyl-tRNA synthetase editing domain facilitates binding and positioning of misacylated tRNAPro. T. G. Bartholow, B. L. Sanford, B. Cao, H. L. Schmit, J. M. Johnson, J. Meitzner, S. Bhattacharyya, K. Musier-Forsyth, and S. Hati (2014) Biochemistry, 53,1059-1068.
28. Multiple pathways promote dynamical coupling between catalytic domains in Escherichia coli prolyl-tRNA synthetase. J. M. Johnson, B. L. Sanford, A. M. Strom, S. N. Tadayon, B. P. Lehman, A. M. Zirbes, S. Bhattacharyya, K. Musier-Forsyth, and S. Hati (2013) Biochemistry, 52, 4399-4412.
27. Role of coupled motions in the catalytic activity of prokaryotic-like prolyl-tRNA synthetases. B. L. Sanford, B. V. Cao, J. M. Johnson, K. Zimmerman, A. M. Storm, R. M. Mueller, S. Bhattacharyya, K. Musier-Forsyth, and S. Hati (2012) Biochemistry, 51, 2146-2156.
26. Interplay of flavin's redox states and protein dynamics: an insight from QM/MM simulations of dihydronicotinamide riboside quinone oxidoreductase 2. R. M. Mueller, M. A. North, C. Yang, S. Hati, and S. Bhattacharyya (2011) J. Phys. Chem. B, 115, 3632-3641.
25. Evolutionary basis for the coupled-domain motions in Thermus thermophilus leucyl-tRNA synthetase. K. M. Weimer, B. L. Shane, M. Brunetto, S. Bhattacharyya, and S. Hati (2009) J. Biol. Chem., 284, 10088-99.
24. Restoring species-specific posttransfer editing activity to a synthetase with a defunct editing domain. J. SternJohn, S. Hati, P. G. Siliciano, and K. Musier-Forsyth (2007) Proc. Natl. Acad. Sci. USA, 104, 2127-32.
23. Pre-transfer editing by class II prolyl-tRNA synthetase: role of aminoacylation active site in “selective release” of noncognate amino acids. S. Hati, B. Ziervogel, J. SternJohn, F. C. Wong, M. C. Nagan, A. R. Rosen, P. G. Siliciano, J. Chihade, and K. Musier-Forsyth (2006) J. Biol. Chem., 281, 27862-27872.