Browsing by Author "Singh, Sangeeta"

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    A candidate triple-negative breast cancer vaccine design by targeting clinically relevant cell surface markers: an integrated immuno and bio-informatics approach
    (Springer Science and Business Media Deutschland GmbH, 2022-02-20T00:00:00) Kumar, Shashank; Shuaib, Mohd; Prajapati, Kumari Sunita; Singh, Atul Kumar; Choudhary, Princy; Singh, Sangeeta; Gupta, Sanjay
    Triple-negative breast cancer (TNBC) is an aggressive, metastatic/invasive sub-class of breast cancer (BCa). Cell surface protein-derived multi-epitope vaccine-mediated targeting of TNBC cells could be a better strategy against the disease. Literature-based identified potential cell surface markers for TNBC cells were subjected to expression pattern and survival analysis in BCa patient sample using TCGA database. The cytotoxic and helper T-lymphocytes antigenic epitopes in the test proteins were identified, selected and fused together with the appropriate linkers and an adjuvant, to construct the multi-epitope vaccine (MEV). The immune profile, physiochemical property (PP) and world population coverage of the MEV was studied. Immune simulation, cloning in a suitable vector, molecular docking (against Toll-like receptors, MHC (I/II) molecules), and molecular dynamics simulations of the MEV was performed. Cell surface markers were differentially expressed in TNBC samples and showed poor survival in TNBC patients. Satisfactory PP and WPC (up to 89 and 99%) was observed. MEV significant stable binding with the immune molecules and induced the immune cells in silico. The designed vaccine has capability to elicit immune response which could be utilized to target TNBC alone/combination with other therapy. The experimental studies are required to check the efficacy of the vaccine. � 2022, King Abdulaziz City for Science and Technology.
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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.