Profile
I am a principal Scientist II in the Computational and Mathematical Biology Centre (CMBC) of THSTI. I did my PhD from University of Cagliari, Italy, in Computational Biophysics and Structural Bioinformatics, followed by two Post-docs specializing in protein-dynamics based Computer-assisted drug discovery. My lab is broadly concerned with the development and applications using state-of-the-art computational and theoretical techniques to investigate the structure, function, and dynamics of complex biological systems to apply the extracted insights towards translational outcomes such as small molecule modulators, antibodies activity enhancement and designing vaccine candidates by targeting disease specific key targets and their interactomes. We have an arsenal of advanced tools at the interface of computational-chemistry, -biology, -physics, and pharmacology, as our research integrates both applied and basic science components, with goals to bridge the basic and translational research. Fundamentals of protein structural understanding and drug discovery studies are tightly coupled to correlated well with experiments that allow us to engage in dynamic and exciting collaborations with various experimental labs at national and international level.
Current Focus Areas
Exploring molecular recognition process to map biological events at atomic level to underpin the structural determinants for therapeutics intervention. Why are proteins being so flexible and predicting their flexibility in protein-protein interactions to design small molecule modulators.
Autophagy inducers are reported as a broad spectrum therapeutics application however it is paramount challenging to discover inducers. We are exploring structural organisation such as ordered and disordered regions localized at regulators (+ve/-ve) of certain key proteins like beclin-1 and IRGM to discover inducers via protein-protein interaction interfaces (PoC established).
Antibodies re-engineering is a promising approach to enhance the potency of existing biotherapeutics. The antibodies arrest the biological function via conformational lock of the target proteins. We characterize the conformational determinants and pockets (cryptic) to design small molecule which can mimic the inhibitory activity of antibodies.
Developing computational tool/pipeline by Integrating state-of-the-art computational and theoretical biophysics techniques with computational chemistry and AI for target specific-understanding to explore molecular mechanism at atomic level and implement identified critical insights towards therapeutic intervention.
Selected Publications
M Singh, D C. Indurthi, L Mittal, A Auerbach, S Asthana*, Conformational dynamics of a nicotinic receptor neurotransmitter binding site, elife, 2024.
M. Srivastava, L. Mittal, A. Kumari, M. Singh, AK Agrahari, R. Mathur, S. Asthana*, Characterizing (un)binding mechanism of USP7 inhibitors to unravel the cause of enhanced binding potencies at allosteric checkpoint, Protein Science, 2022
L Mittal, R Tonk, A Awasthi, S Asthana*, Traversing through the Dynamic Protein–Protein Interaction Landscape and Conformational Plasticity of PD-1 for Small-Molecule Discovery, Journal of Medicinal Chemistry 65 (8), 5941-5953
C. Suri, A. Awasthi, S. Asthana*, Crystallographic Landscape Illustrate the Molecular Insights of Diverse ROR-γt Modulators, Drug Discovery Today, 2021.
AK Agrahari, M. Dikshit, S. Asthana*, Crystallographic mining of ASK1 regulators to unravel the intricate PPI interfaces for the discovery of small molecule, Computational and Structural Biology Journal, 2022.