- 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 (ARSs)
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 duynamics and local fluctutations modulate substrate recognition, catalysis, and allosteric communication in these multi-domain enzymes.
Chacterization 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.
Grants and Fellowships
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
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, in press.
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. Molecular Modeling, 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.