Refereed Journals

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  • Bhendle M, Srivastava A and Singh JK “Insights into the thermodynamics and morphology of different phases of pluronic L64 from molecular simulations using derived coarse-grained model,” The Journal of Physical Chemistry B

    Abstract: We investigate the concentration-dependent phase diagram of pluronic L64 in aqueous media at 300 and 320 K using coarse-grained (CG) molecular dynamics (MD) simulations. The CG model is derived by adapting the Martini model for nonbonded interactions along with the Boltzmann inversion (BI) of bonded interactions from all-atom (AA) simulations. Our derived CG model successfully captures the experimentally observed micellar-, hexagonal-, lamellar-, and polymer-rich solution phase. The end-to-end distance reveals the conformational change from an open-chain structure in the micellar phase to a folded-chain structure in the lamellar phase, increasing the orientational order. An increase in temperature leads to expulsion of water molecules from the L64 moiety, suggesting an increase in L64 hydrophobicity. Thermodynamic analysis using the two-phase thermodynamics (2PT) method suggests the entropy of the system decreases with increasing L64 concentration and the decrease in free energy (F) with temperature is mainly driven by the entropic factor (−TS). Further, the increase in aggregation number at lower concentrations and self-assembly at very high concentrations is energetically driven, whereas the change from the micellar phase to the lamellar phase with increasing L64 concentration is entropically driven. Our model provides molecular insights into L64 phases which can be further explored to design functionality-based suprastructures for drug delivery and tissue engineering applications.


  • Namsani S, Praminik D, Khan MA, Roy S and Singh JK “Metadynamics-based enhanced sampling protocol for virtual screening: case study for 3CLpro protein for SARS-CoV-2” Journal of Biomolecular Structure and Dynamics 40,7002-7017

    Abstract: In recent times, computational methods played an important role in the down selection of chemical compounds, which could be a potential drug candidate with a high affinity to target proteins. However, the screening methodologies, including docking, often fails to identify the most effective compound, which could be a ligand for the target protein. To solve that, here we have integrated meta-dynamics, an enhanced sampling molecular simulation method, with all-atom molecular dynamics to determine a specific compound that could target the main protease of novel severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). This combined computational approach uses the enhanced sampling to explore the free energy surface associated with the protein's binding site (including the ligand) in an explicit solvent. We have implemented this method to find new chemical entities that exhibit high specificity of binding to the 3-chymotrypsin-like cysteine protease (3CLpro) present in the SARS-CoV-2 and segregated to the most strongly bound ligands based on free energy and scoring functions (defined and implemented) from a set of 17 ligands which were prescreened for synthesizability and druggability. Additionally, we have compared these 17 ligands' affinities against controls, N3 and 13b α-ketoamide inhibitors, for which experimental crystal structures are available. Based on our results and analysis from the combined molecular simulation approach, we could identify the best compound which could be further taken as a potential candidate for experimental validation.