Department of Chemical Sciences
School of Natural Sciences

Sri Rama Koti Ainavarapu

A. Sri Rama Koti
Associate Professor
Department of Chemical Sciences
Department of Chemical Sciences,
Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba,
Mumbai 400 005, INDIA
91 22 2278 2790
91 22 2280 4610/4611
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Academic Profile
Doctoral Degree
2002, T.I.F.R, Mumbai, Maharashtra, India.
Postdoctoral Experience
2003-2008, Columbia University, NY, USA.
  • Current Research
  • Selected Publications

Mechanical forces play a central role in ubiquitous phenomena such as cell-adhesion, tissue organization, and muscle function in multi-cellular organisms. Cell-adhesion is also essential in wound healing, protecting us from microorganisms, and maintaining immunity. Unraveling the molecular mechanism of these important biophysical and mechanochemical (chemistry of single-molecules under a stretching forces) processes is an exciting question in modern cell biology. The key players in cell-adhesion are protein molecules on the cell-surface, which act as mechanosensors and communicate the surrounding dynamic microenvironment with the cell. Hence, studying the mechanical response of these biomolecules would provide a wealth of information about their structure, function, and chemistry. We use state-of-the-aft atomic force microscope (AFM) to probe single molecules. By using this novel technique, we can apply stretching force to a single protein molecule, measure its mechanical response and study protein mechanics.

The following are the research interests:
  • Mechanochemistry (chemistry upon mechanical activation of bonds) and kinetic characterization of chemical and biochemical reactions.
  • Investigation of mechanical behaviour and functional role of different classes of cell-adhesion biomolecules.
  • Engineering novel proteins with diverse mechanical functions based on cell-adhesionproteins. Elucidation of mechanical unfolding/unfolding pathways of proteins and their relation with biochemical pathways.
  • Development of novel single-molecule assays for protein-protein, protein-DNA, and protein-RNA interactions.

  • Small peptide binding stiffens the ubiquitin-like protein SUMO1
    Hema Chandra Kotamarthi, Anju Yadav, and Sri Rama Koti Ainavarapu*
    Biophysical Journal, Vol 108, No 2 (2015) p360-367.
  • Mechanical Unfolding of Ribose Binding Protein (RBP) and Its Comparison with Other
    Periplasmic Binding Proteins (PBPs)
    Hema Chandra Kotamarthi, Satya Narayan, and Sri Rama Koti Ainavarapu*
    Journal of Physical Chemistry B, Vol 118 (2014), No 39, p11449-11454.
  • Ca2+ binding enhanced mechanical stability of an archaeal crystallin
    Venkatraman Ramanujam, Hema Chandra Kotamarthi, Sri Rama Koti Ainavarapu*
    PLOS ONE Vol 9, (2014), e94513
  • Preventing Disulphide Bond Formation Weakens Non-covalent Forces Among Lysozyme Aggregates
    Vijay Kumar Ravi, Mohit Goel, Hema Chandra Kotamarthi, Sri Rama Koti Ainavarapu, and Rajaram Swaminathan*
    PLOS ONE, Vol 9 (2014), e87012
  • Multiple unfolding pathways of leucine binding protein (LBP) probed by single-molecule force spectroscopy (SMFS)
    Hema Chandra Kotamarthi, Riddhi Sharma, Satya Narayan, Sayoni Ray, and Sri Rama Koti Ainavarapu*
    J. Am. Chem. Soc. Vol 135 (2013) p14768-14774
    This paper is highlighted in ‘Spotlights on Recent JACS Publications’ of JACS,
    2013, 135 (41), pp 15269, : Pulling on a Protein To Map Its Unfolding Pathways
  • Single-molecule studies on polySUMO proteins reveal their mechanical flexibility, Hema Chandra Kotamarthi, Riddhi Sharma, and Sri Rama Koti Ainavarapu* Biophysical Journal Vol. 104, No. 10 (2013) p 2273-2281.
  • Iterative cloning, overexpression, purification and isotopic labeling of an engineered dimer of a Ca2+-binding protein of the bg-crystallin superfamily from Methanosarcina acetivorans
    Venkatraman Ramanujam, Kandala V.R. Chary, and Sri Rama Koti Ainavarapu*
    Protein Expression and Purification Vol 84 (2012) p 116-122.
  • Ligand modulated parallel mechanical unfolding pathways of Maltose Binding Proteins (MBPs),
    Vasudha Aggarwal, S. Rajendra Kulothungan, M.M. Balamurali, S.R. Saranya, Raghavan Varadarajan, and Sri Rama Koti Ainavarapu,
    J. Biol.Chem. Vol 286, No. 32 (2011) p28056-28065.
  • Single-molecule force-clamp spectroscopy: Probing transition states of mechanically activated chemical reactions,
    Sri Rama Koti Ainavarapu,
    ISRAPS Bulletin Vol. 21 (2009) p32-39.
  • A Single-Molecule Perspective on the Role of Solvent Hydrogen Bonds in Protein Folding and Chemical Reactions,
    Lorna Dougan, Sri Rama Koti Ainavarapu, Georgi Genchev, Hui Lu and Julio M. Fernandez,
    Chem Phys Chem Vol. 9 (2008) p2836-2847.
  • Single-Molecule Force Spectroscopy Measurements of Bond Elongation during a Bimolecular Reaction,
    Sri Rama Koti Ainavarapu, Arun P. Wiita, Lorna Dougan, Einar Uggerud, and Julio M. Fernandez,
    Journal of American Chemical Society Vol. 130 (2008) p6479-6487. (Our mechanochemistry JACS paper has been mentioned in Research Highlights section of Nature (2008), 453, p261: “Disulphide dichotimies”.)
  • A Single-Molecule Assay to Directly Identify Solvent Accessible Disulfide Bonds and Probe Their Effect on Protein Folding
    Sri Rama Koti Ainavarapu*, Arun P. Wiita, Hector H. Huang, and Julio M. Fernandez
    Journal of American Chemical Society Vol. 130 (2008) p436-437.
  • Contour Length and Refolding Rate of a Small Protein Controlled by Engineered Disulfide Bonds
    Sri Rama Koti Ainavarapu, Jasna Brujic, Hector H. Huang, Arun P. Wiita, Hui Lu, Lewyn Li, Kirstin A. Walther, Mariano Carrion-Vazquez, Hongbin Li, and J.M. Fernandez
    Biophysical Journal Vol. 92, No. 1 (2007) p225-233.
  • Mechanical Unfolding Pathways of the Enhanced yellow Fluorescent Protein Revealed by Single Molecule Force Spectroscopy
    Raul Perez-Jimenez, Sergi Garcia-Manyes, Sri Rama Koti Ainavarapu, and J.M. Fernandez
    J. Biol.Chem. Vol. 281, No. 52 (2006) p40010-40014.
  • Force-dependent chemical kinetics of disulfide bond reduction observed with single-molecule techniques
    Arun P. Wiita, Sri Rama Koti Ainavarapu, Hector H. Huang, and J.M. Fernandez
    Proc. Natl. Acad. Sci. (USA) Vol. 103, No. 19 (2006) p7222-7227. (Commentary on this article is reported in PNAS (2006), 103, p7533: “Covalent chemistry on distended proteins”)
  • Ligand binding modulates the mechanical stability of dihydrofolate reductase (DHFR),
    Sri Rama Koti Ainavarapu, Lewyn Li, Carmen L. Badilla, and J.M. Fernandez,
    Biophysical Journal Vol. 89, No. 5 (2005) p3337-3344.