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The extracellular deposition of A\u03b2 peptides in human AD brain causes neuronal death. Therefore, it has been found that A\u03b2 peptide degradation is a possible therapeutic target for AD. CathD has been known to breakdown amyloid beta peptides. However, the structural role of CathD is not yet clear. Hence, for the purpose of gaining a deeper comprehension of the structure of CathD, the present computational investigation was performed using virtual screening technique to predict CathD's active site residues and substrate binding mode. Ligand-based virtual screening was implemented on small molecules from ZINC database against crystal structure of CathD. Further, molecular docking was utilised to investigate the binding mechanism of CathD with substrates and virtually screened inhibitors. Localised compounds obtained through screening performed by PyRx and AutoDock 4.2 with CathD receptor and the compounds having highest binding affinities were picked as; ZINC00601317, ZINC04214975 and ZINCC12500925 as our top choices. The hydrophobic residues Viz<jats:italic>.<\/jats:italic> Gly35, Val31, Thr34, Gly128, Ile124 and Ala13 help stabilising the CathD-ligand complexes, which in turn emphasises substrate and inhibitor selectivity. Further, MM-GBSA approach has been used to calculate binding free energy between CathD and selected compounds. Therefore, it would be beneficial to understand the active site pocket of CathD with the assistance of these discoveries. Thus, the present study would be helpful to identify active site pocket of CathD, which could be beneficial to develop novel therapeutic strategies for the AD.<\/jats:p>","DOI":"10.1007\/s00726-023-03367-1","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T20:29:32Z","timestamp":1713817772000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Structural insights into the potential binding sites of Cathepsin D using molecular modelling techniques"],"prefix":"10.1007","volume":"56","author":[{"given":"Subodh A.","family":"Kamble","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagar S.","family":"Barale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Abdulmawjood","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha B.","family":"Paymal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitin M.","family":"Naik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailas D.","family":"Sonawane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"issue":"3","key":"3367_CR1","volume":"242","author":"AM Ali","year":"2023","unstructured":"Ali AM, Barale SS, Kamble SA, Paymal SB, Sonawane KD (2023) Molecular insights into the inhibition of early stages of A\u03b2 peptide aggregation and destabilization of Alzheimer\u2019s A\u03b2 protofibril by dipeptide D-Trp-Aib: a molecular modelling approach. 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