Department Of Biochemistry And Microbial Sciences

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    In silico identification of potential ?-secretase inhibitor of marine-algal origin: an anticancer intervention
    (Taylor and Francis Ltd., 2022-12-28T00:00:00) Singh, Atul Kumar; Choudhary, Princy; Singh, Sangeeta; Kumar, Shashank
    Gamma secretase (GS) activates notch signalling pathway (NSP) by liberating the truncated notch intracellular domain (NICD). The NSP is associated with the cancer development and progression, which makes GS a potential therapeutic target. Now day�s marine compounds emerged as a major source of bioactive entity. The NSP inhibition potential of marine-algal compounds has not yet been studied. Thus, in the present study, we have used molecular docking, molecular dynamics (MD) simulations, principal component analysis (PCA) and free energy and binding energy calculations to identify the potential GS inhibitors of marine-algal origin. Laminarin showed better docking score (?12.72) compared to the known GS inhibitor DAPT (?9.2). Laminarin formed H-Bond interaction with the Asp257 and Asp385 required for the catalytic cleavage activity of gamma-secretase. It potentially stabilised the structural parameters (RMSD, RMSF, Rg and SASA) of GS catalytic subunit compared to DAPT during the MD simulation. The PCA and free energy calculation revealed conformationally and energetically stable Laminarin�GS complex formation. Laminarin showed lower binding energy (?44.75 kcal/mol) with GS catalytic subunit than DAPT (?20.92 kcal/mol). In conclusion, the present study provides a marine-algal compound as a novel potential GS inhibitor, which requires further validation in experimental model. � 2022 Informa UK Limited, trading as Taylor & Francis Group.
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    Repurposing FDA-approved anti-diabetic drug to target H. pylori peptidyl deformylase using computer-based drug discovery approach
    (Taylor and Francis Ltd., 2022-10-06T00:00:00) Singh, Atul Kumar; Maurya, Santosh; Kumar, Shashank
    Peptide deformylase (PDF), a metalloenzyme is an important and attractive target in antibacterial drug discovery. It removes the N-formyl group from the nascent peptide and generates a mature N-terminal end of the protein molecule. Acarbose is an FDA-approved microbial origin anti-diabetic drug and is known to alter the gut microbiota in clinical studies. The present study first time identifies the binding efficacy of acarbose isolated from a natural source against PDF. We performed molecular docking and molecular dynamics (MD) simulation studies to check the binding efficacy of acarbose with the catalytic site of Helicobacter pylori PDF. Molecular docking results of acarbose complexed with PDF showed a good docking score (?12.55 kcal/mole) in comparison to standard drug bind with PDF (?8.99 kcal/mole). Interaction with the amino acids (Gly95, Glu139, His138, Gly46 and Glu940) and metal ion present at the catalytic site of the test protein was found to be common in PDF during interaction with the acarbose and actinonin. Various parameters such as RMSD, RMSF, Rg, SASA, Hydrogen-bond formation, energy landscape and principal component analysis showed that the acarbose form stable and energetically stable complex with PDF in comparison to actinonin. Taken together, our study concludes that the acarbose possesses significant efficacy in binding at the catalytic site of H. pylori PDF. Acarbose is a FDA-approved anti-diabetic drug thus its antibacterial efficacy may be directly studied in clinical trials. Further, the in vitro and in vivo studies are needed to study the antibacterial mode of action of acarbose in physiological conditions. � 2022 Informa UK Limited, trading as Taylor & Francis Group.