An Autonomous Institute of Dept. of Biotechnology, Ministry of Science and Technology, Govt. of India

Dr. G. Senthil Kumar

Research Interest:

Protein-protein interactions, NMR Spectroscopy, X-ray Crystallography, Antigen-antibody interactions, Epitope/paratope mapping, Structure-function relationship studies, Structural dynamics

Summary of Research:

The laboratory's major focus is to characterize the molecular basis of interactions between viral pathogens and antibodies (critical components of the immune system that help neutralize viral pathogens). Antibodies recognize a unique molecule of the pathogens, called an antigen (Ag), with high affinity and specificity. Hence, characterizing the region of the pathogens (called epitopes) that interacts with antibodies is crucial for vaccine design. Furthermore, the importance of protein dynamics, in addition to structure, for the function of intermolecular interactions is well recognized. To this end, our laboratory is interested in characterizing the roles of structural and dynamic changes induced by antigen-antibody interactions using a combination of biochemical, biophysical, and immunological techniques. Our laboratory is also interested in developing antibody-based therapies for multiple viral infections.

Key Questions:

1. Can solution NMR spectroscopy be used routinely as a fast and reliable method for the characterization of unidentified epitopes that are inaccessible by other methods?

2. What is the molecular basis for the interaction of antigens with high-affinity antibodies through their flexible regions?

3. Does the antigen switch between different conformations, one of which is selected by the antibodies (conformational selection), or do the antigens adopt different conformations upon binding to antibodies to enhance their binding (induced fit)?

4. Do the highly flexible regions of antigens become rigid upon complex formation with antibodies?

5. What are the differences in the thermodynamics and kinetics of the antigen-antibody interaction?

6. What is the mode of interaction between antigens and host proteins?

Group Members:
Senior Technical Officer: Sunder Singh Bisht
Ph.D. Students: Rahul Yadav, Shahil Ansari, Kalyani Singh, Supriya Bhatia, Manisha, Saumya Jaiswal
Post-Doctoral Fellows: Prakhar Agrawal, Anamika Sharma, Ramesh Mariappan, Aathira Gopinath, Sonali Jena

Funding:
Department of Science and Technology (SERB, ANRF), Indian Council of Medical Research (ICMR), Department of Biotechnology (DBT), Department of Health Research (DHR, ICMR), National One Health Mission (NOHM, DHR), BRIC-National Institute of Immunology (BRIC-NII),

Publications:

Agrawal, P., Yadav, R., Madhumalar, A., Kumar, G.S.* (2026) Phosphorylation landscape of Dengue virus proteins and their implications in protein-protein interactions, PLos One, 21(5), e0345872.
Hunashal, Y., Fonvielle, M., Kobayashi, M.T., Choy, M.S., Kumar, G.S., Silva, P.U., Liang, Y., Desbonnet,C., Rice, L.B., Arthur, M., Page, R., Peti, W. (2025) Peptidoclycan recruitment by a penicillin binding protein, Nat. Commun., Dec 17: 16(1), 11244.
Kaur, M., Agrawal, P., Singh, G., Kumar, G.S.*, Barnwal, R.P*. (2024) Deciphering significant interaction between Clp1 (CF IA) and Ssu72 (CPF) in pre-mRNA processing via in silico approaches, Journal of Biomolecular Structure and Dynamics, Dec 11: 1-15.
Kaur, M., Arya, H., Sharma, A., Singh, G., Kumar, G.S.*, Barnwal, R.P*. (2024) Computational insight into crucial interaction between Pcf11 and Ydh1 for pre-mRNA 3’-end processing, Journal of Biomolecular Structure and Dynamics, Nov 10, 1-16.
Agrawal, P., Arya, H., Kumar, G.S*. (2024) Structure-based identification of small-molecule inhibitors that target DENV glycoprotein E pan-serotypically, PLos One, 19(10), e0311548.
Choy, M.S., Nguyen, H.T., Kumar, G.S., Peti, W., Kettenbach, A.N., Page, R. (2024) A protein phosphatase 1 specific phosphatase targeting peptide (PhosTAP) to identify the PP1 interactome, Proc. Natl. Acad. Sci. USA., 121(44), e2415383121.
Kumar, G.S*. (2024) Preparation of Oxidized and Reduced PTP4A1 for Structural and Functional Studies, Methods Mol. Biol. 2743, 211-222.
Hunashal, H., Kumar, G.S., Choy, M.S., D’Andrea, E.D., Santiago, A.D.S., Schoenle, M.V., Desbonnet, C., Arthur, M., Rice, L.B., Page, R., Peti, W. (2023) Molecular basis of β-lactam antibiotic resistance of ESKAPE bacterium E. faecium Pencillin Binding Protein PBP5, Nat. Commun., 14(1), 4268.
Srivastava, G., Bajaj, R., Kumar, G.S., Gaudreau-Lapierre, A., Nicolas, H., Chamousset, D., Kreitler, D., Peti, W., Trinkle-Mulcahy, L., Page, R. (2022) The Ribosomal RNA processing 1B: protein phosphatase 1 holoenzyme reveals non-canonical PP1 interaction motifs, Cell Rep., 41(9), 111726.
Zhang, R.*, Kumar, G.S.*, Hansen, U., Zoccheddu, M., Sacchetti, C., Holmes, Z.J., Lee, M.C., Beckmann, D., Wen, Y., Mikulski, Z., Yang, S., Santelli, E., Page, R., Boin, F., Peti, W., Bottini, N. (2022) Oxidative stress promotes fibrosis in systemic sclerosis through stabilization of kinase-phosphatase complex, JCI Insight, 7(8), e155761. (*Joint First Authors)
Kumar GS*, Page R., Peti W. (2021) ¹H,¹⁵N, and ¹³C sequence-specific backbone assignment of the MAP kinase binding domain of the Dual Specificity Phosphatase 1 and its interaction with the MAPK p38, Biomol NMR Assign. 15(2), 243-348.
Kumar GS*, Page R., Peti W.* (2021) The interaction of p38 with its upstream kinase MKK6, Protein Sci. 30(4), 908-913.