My research addresses diverse and challenging biochemical and biophysical processes that are highly relevant to drug discovery and biotechnology. These include enzymatic reactions, conformational dynamics, molecular recognition, molecular transport, solvation phenomena, and nanopore sequencing. To tackle these problems, I employ multiscale computational modeling and simulation approaches, ranging from coarse-grained to atomistic and hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations. These techniques are further combined with state-of-the-art enhanced sampling methods, including metadynamics and umbrella sampling, to probe rare events and map complex free-energy landscapes. Some of my major research achievements are briefly described below:
Nanopore sequencing & nanofluidic iontronics
Nanopore sequencing holds great promise as an efficient, cost-effective, and chemical-free approach for sequencing biomolecules such as DNA, proteins, and glycans. However, several challenges remain associated with nanopore sequencing. To address these challenges, all-atom molecular dynamics (MD) simulations under a transmembrane electric field have been employed to assess the feasibility and improve the performance of the nanopore-based sequencing approach. Similarly, nanofluidic iontronics has garnered significant attention due to its broad implications for neuromorphic computing and has been explored using MD simulations to better understand ion transport phenomena and device functionality.
Small, 2025, 21, 2407647 DOI:10.1002/smll.202407647
ACS Nano, 2026, 20 (1), 814-822, DOI: 10.1021/acsnano.5c15792
Solving antibiotic resistance
Escalating antibiotic resistance due to beta-lactamase is a matter of great concern. Therefore, the development of new antibiotics and inhibitors to combat this issue is urgently needed. Efforts are ongoing to obtain the atomistic details of the hydrolysis mechanism in order to develop novel antibiotics and inhibitors against beta-lactamase. Extensive hybrid QM/MM enhanced sampling MD simulations have been employed to explore the mechanisms of acylation and various routes of hydrolysis, thereby providing molecular-level insights into the beta-lactamase-mediated antibiotic hydrolysis mechanism. The mechanistic understanding elicited from computations holds great promise for the future development of antibiotics and inhibitors. Watch how New Delhi metallo-beta-lactamase (NDM-1) initiates antibiotic hydrolysis - the beta-lactam ring opening step (QM/MM-Metadynamics simulation)
Phys. Chem. Chem. Phys., 2017, 19, 13111-13121 DOI: 10.1039/C6CP08769H
Phys. Chem. Chem. Phys., 2018, 20, 14482-14490 DOI:10.1039/C8CP01670D
Chem. Eur. J., 2020, 26, 9639 DOI:10.1002/chem.202001261
ACS Catal., 2022, 12, 10338-10352 DOI:10.1021/acscatal.2c02693
Designing oxygen-tolerant [FeFe]-hydrogenase
The increasing interest in hydrogen as a clean alternative to fossil fuels has driven the exploration of [FeFe]-hydrogenases as efficient biocatalysts for hydrogen production. This reaction occurs at the active-site H-cluster of [FeFe]-hydrogenases. However, this promising biocatalyst is highly sensitive to oxygen, which limits its use under aerobic conditions. Therefore, identifying the molecular determinants of oxygen sensitivity in [FeFe]-hydrogenases is crucial, as it provides an essential foundation for the development of oxygen-tolerant variants of these enzymes.
Biochemistry, 2026, 65, 5, 527–531 DOI: 10.1021/acs.biochem.6c00006
J. Am. Chem. Soc., 2025, 147 (18), 15170-15180, DOI: 10.1021/jacs.4c18483
ACS Catal., 2023, 13, 856-865 DOI:10.1021/acscatal.2c04031
ChemSusChem., 2024, 17, e202301365 DOI:10.1002/cssc.202301365
Dynamics of protein-water network
The dynamics of water molecules buried in protein active site often govern structure and dynamics of the protein. Our all-atom MD simulations visualize how the active site pocket is shaped by open/close conformational‐exchange dynamics of the active site loop and associated active site water molecules. We also compute the absolute entropy of the individual water molecules confined in the active site.
J. Am. Chem. Soc., 2019, 141 (49), 19276-19288 DOI:10.1021/jacs.9b05311
Angew. Chem. Int. Ed., 2020, 59, 22916–22921 DOI:10.1002/anie.202009348
J. Chem. Theory Comput., 2021, 17 (8), 5409-5418 DOI:10.1021/acs.jctc.1c00554
Nucleic acids research - from DNA polymerization to epigenetic CpG recognition
Nucleic acid polymerization catalyzed by nucleic acid polymerases lies at the core of genetic inheritance and is highly relevant to anticancer therapeutic research. A detailed QM/MM metadynamics simulation has been conducted to explore the DNA polymerization mechanism of telomerase. Similarly, epigenetic CpG recognition is of great interest in molecular biology. Using extensive classical MD simulations, key molecular features of the reader protein required for the recognition of CpG duplex marks have been investigated.
Phys. Chem. Chem. Phys., 2023, 25, 14147-14157 DOI: 10.1039/D3CP00521F
Nucleic Acids Res., 2023 DOI:10.1093/nar/gkad134
Mol. Cell, 2021, 81 (19), 3992-4007 DOI:10.1016/j.molcel.2021.09.004
Inorganic molecular machines
All-atom MD simulations have been used to reveal the rotary motion of the rotor in a molecular machine within a nanocontainer, as well as to study the translocation of molecules across biological membranes through synthetic channels.
Chem., 2022, 8 (2), 543-556 DOI:10.1016/j.chempr.2021.12.008
Angew. Chem. Int. Ed., 2023, 135, e202214236 DOI:10.1002/ange.202214326
Copyright: Dr. Chandan Kumar Das | Updated on April, 2026