Overall my research is interdisciplinary spanning diverse domains and techniques like illustrated above. A short overview of my current research can be found in the Brief outline section. Below here some of my current and past projects are listed down. Most of the projects (specially Past ones) produced multiple publications including journal, proceedings or talks/posters. The following descriptions are taken from those to help describe the work quickly. For more details please consult the original publications that can be found in Publication section or feel free to drop me a note or email.

Current Projects

  • Accelerating simulations using high-performance computing and machine/deep learning learning techniques
    Lead Principal Investigator

  • Generative biochemistry
    Lead Principal Investigator
    Applications with deep learning (DL) offer important capabilities to assist in identifying new, potential therapeutics through the use of advanced computing. Specifically we are developing upon generative chemistry leveraging within a drug pipeline to create an enhanced search space for docking, screening, and synthesizing new drug-like compounds, while also specifically driving the design of these molecules based on directed metrics.

Past Projects

  • Comprehensive novel AI based approach to fight against COVID-19
    Lead Principal Investigator
    Successful, efficient and faster drug discovery efforts to fight against COVID-19 pandemic requires effective collaboration among computational scientists, clinical chemists and biologists. Traditional wet-lab experiments are resource (time, economical, energy, human-hour) demanding and draining. With advent of AI, generating new drug molecules and finding drug or therapeutic targets are now efficient, faster and accurate. Deep clustering and AI driven steered simulation are prominent tool to achieve this.

  • Data-driven CRISPR design
    Lead Principal Investigator

  • Characterising the structure, dynamics and function of intrinsically disordered proteins (IDPs)
    Lead Principal Investigator

  • RAS proteins in membranes - DOE/NCI Pilot
    Technical Lead (ORNL)

  • Studying flexible biomolecular systems by data-driven integration of cryo-EM, scattering and MD simulations
    Co-Principal Investigator
    We developed an integrated experimental and computational pipeline utilizing multi-scale molecular simulations and scalable statistical inference techniques to meaningfully fuse partial information from multi-modal experimental observations. We demonstrate our AI-driven approach enables dintinguishable shift in characterizing conformational events that underlie complex biological phenomena. The framework also facilitate broader targeting of synthetic and systems biology for directed self-assembly of complex materials systems and probe disordered/soft materials by establishing a virtual facility that integrates strengths across national laboratories.

  • Influence of molecular shape on self-diffusion under severe confinement: A molecular dynamics study
    Lead Investigator
    We have investigated the effect of molecular shape and charge asymmetry on the translation dynamics of confined hydrocarbon molecules having different shapes but similar kinetic diameters, inside ZSM-5 pores using molecular dynamics simulations. Overall the difference in shape and asymmetry in charge imposes severe restriction inside the ZSM-5 channels for all the molecules to different extents. Further, the behavior of molecules confined in ZSM-5, quantified wherever possible, is compared to their behavior in bulk or in other porous media reported in literature.

  • Collective Excitations in Protein as a Measure of Balance Between its Softness and Rigidity
    We elucidate the protein activity from the perspective of protein softness and flexibility by studying the collective phonon like excitations in a globular protein, human serum albumin (HSA), and taking advantage of the state-of-the-art inelastic X-ray scattering (IXS) technique. Such excitations demonstrate that the protein becomes softer upon thermal denaturation due to disruption of weak noncovalent bonds. On the other hand, no significant change in the local excitations is detected in ligand- (drugs) bound HSA compared to the ligand-free HSA. Our results clearly suggest that the protein conformational flexibility and rigidity are balanced by the native protein structure for biological activity.

  • Quasi-elastic Neutron Scattering Reveals Ligand-Induced Protein Dynamics of a G‑Protein-Coupled Receptor
    Light activation of the visual G-protein-coupled receptor (GPCR) rhodopsin leads to significant structural fluctuations of the protein embedded within the membrane yielding the activation of cognate G-protein (transducin), which initiates biological signaling. Here, we report a quasi-elastic neutron scattering study of the activation of rhodopsin as a GPCR prototype. Our results reveal a broadly distributed relaxation of hydrogen atom dynamics of rhodopsin on picosecond−nanosecond time scale, crucial for protein function, as only observed for globular proteins previously. Interestingly, the results suggest significant differences in the intrinsic protein dynamics of the dark-state rhodopsin versus the ligand-free apoprotein, opsin. These differences can be attributed to the influence of the covalently bound retinal ligand. Furthermore, an idea of the generic free-energy landscape is used to explain the GPCR dynamics of ligand-binding and ligand-free protein conformations, which can be further applied to other GPCR systems.

  • Effects of pressure on the dynamics of an oligomeric protein from deep-sea hyperthermophile
    Inorganic pyrophosphatase (IPPase) from Thermococcus thioredu- cens is a large oligomeric protein derived from a hyperthermophilic microorganism that is found near hydrothermal vents deep under the sea, where the pressure is up to 100 MPa (1 kbar). It has attracted great interest in biophysical research because of its high activity under extreme conditions in the seabed. In this study, we use the quasielastic neutron scattering (QENS) technique to investigate the effects of pressure on the conformational flexibility and relaxation dynamics of IPPase over a wide temperature range. The β-relaxation dynamics of proteins was studied in the time ranges from 2 to 25 ps, and from 100 ps to 2 ns, using two spectrometers. Our results indicate that, under a pressure of 100 MPa, close to that of the native environment deep under the sea, IPPase displays much faster relaxation dynamics than a mesophilic model protein, hen egg white lysozyme (HEWL), at all measured temperatures, opposite to what we observed previously under ambient pressure. This contradictory observation provides evidence that the protein energy landscape is distorted by high pressure, which is significantly different for hyperthermophilic (IPPase) and mesophilic (HEWL) proteins. We further derive from our observations a schematic denaturation phase diagram together with energy landscapes for the two very different proteins, which can be used as a general picture to understand the dynamical properties of thermophilic proteins under pressure.

  • Effect of Nanodiamond Surfaces on tRNA Dynamics Studied by Neutron Scattering and MD Simulations
    Lead Investigator
    Nanodiamond (ND) inherits most of the superior properties of bulk diamond and delivers them at the nanoscale. ND is non-toxic and possesses excellent mechanical and optical properties with large surface area and surface functionality. ND mixed with biomolecules can be a good platform for drug delivery. Here we demonstrate the adsorption of tRNA on the ND surface and investigate the change in the tRNA dynamics using neutron scattering technique and molecular dynamics (MD) Simulations. We compare the dynamics of hydrated tRNA on ND surfaces with that of freestanding hydrated tRNA molecules and dry tRNA on ND surfaces. Both experiments and simulations show that the relaxational dynamics of tRNA on ND surface is faster than that of the freestanding tRNA molecules and dry tRNA on ND surfaces. Our results suggest that the tRNA on the ND surfaces has fewer hydration water molecules on it due to the water adsorption on the ND hydrophilic surface. Therefore fewer hydrogen bonds formed on its surface results in the tRNA faster motion. The MD simulations also show a ‘caged’ dynamics of the water molecules adsorbed on the ND surfaces.

  • Quasielastic neutron scattering (QENS) insight into the molecular dynamics of all-polymer nano-composites
    Lead Investigator
    QENS has selectively revealed the component dynamics in isotopically labelled nano-composites (NCs) where single-chain nano-particles (SCNPs) based on PMMA, poly(methyl methacrylate)] are mixed with PEO, poly(ethylene oxide). Effects on the α-methyl group dynamics of SCNPs have been characterized. PEO dynamics shows deviations from Gaussian behavior which become more pronounced with increasing concentration of SC-NPs.

  • Study of microscopic dynamics of complex fluids containing charged hydrophobic species by neutron scattering coupled with molecular dynamics simulations
    Lead Investigator
    Symmetric tetraalkylammonium (TAA) cations are model systems to study the behaviour of hydrophobic ions. In this work, concentrated aqueous solutions of TAA bromides are investigated to obtain information on micro- scopic structure and dynamics of both the ions and solvent, by a combination of Neutron Scattering and Molecular Dynamics (MD) simulations. It is shown that TAA cations do not aggregate in aqueous solution even at high concentrations, they are penetrable for both the Br anions and solvent water molecules. The average water orientation is tangential around the cation surface, which contrasts with the simple alkali cations, such as Na+. Using quasi-elastic neutron scattering (Neutron Spin Echo and Time of Flight techniques) and with the aid of MD simulations, the dynamics in the coherent and incoherent neutron scattering signal is decoupled. The former is identified with the center-of-mass (CoM) motion of a single TAA cation, while the latter, based on the signal of individual H atoms of the TAA cation, is a complex combination of the CoM motion and H movements internal to the cation. MD helps to identify the timescale of the global cation rotation. The slowing down of water dynamics in these solutions relative to bulk water is also made evident, though the effect is lower than might be expected.

  • Characterization of polyethylene terephthalate (PET) detector to search for rare events in cosmic rays
    Search for exotic particles (e.g. strangelets) in cosmic rays is an active field of research. An ideal choice of detectors to look for rare events in cosmic rays at very high mountain altitudes are solid state nuclear track detectors (SSNTDs). In our work we are using a commercially available polymer, polyethylene terephthalate (PET), as a SSNTD. It was found to have a higher detection threshold compared to many other widely used SSNTDs and hence is particularly suited for rare event search in cosmic rays as it eliminates the huge low Z background. A SSNTD has to be properly characterized before it can be used as charged particle detector. So systematic studies were carried out on PET to determine the ideal etching condition for it. Also the charge response of PET was studied using various ion beams from accelerators. The results of such studies and also the calibration curve obtained for PET is presented.