{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:59:02Z","timestamp":1791824342161,"version":"4.3.4"},"reference-count":70,"publisher":"Wiley","issue":"5-6","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Informatics"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p>BRAF is a proto oncogene that functions as a key signal transducer in the MAPK\u2010ERK pathway, which regulates cell growth, division, and survival. Mutations in BRAF, particularly the V600E substitution in its kinase domain, are major drivers in melanoma and several other metastatic cancers, including breast, colorectal, NSCLC, and gastrointestinal cancers. In this study, novel inhibitors targeting the BRAF(V600E) mutant using a structure\u2010based drug design approach are identified. Four chemical libraries ChemDiv Kinase, ChemDiv Anticancer, NCI, and ChEMBL Kinase SARfari are screened. Compounds from the ChemDiv Anticancer database show better Glide scores comparable to the FDA\u2010approved BRAF inhibitor Vemurafenib. The compounds P184\u20101419 and P184\u20101479 score \u221212.688 and \u221212.012 kcal\/mol, respectively, versus \u221214.288 kcal\/mol for Vemurafenib. Top hits are further validated using GOLD docking, X\u2010score ranking, and interaction profiling via LigPlot. Molecular dynamics simulations, principal component analysis, and free energy calculations confirm the stability of protein\u2013ligand complexes. Biolayer interferometry assays reveal P184\u20101419 exhibits stronger binding affinity (KD = 151 \u03bcM) than Vemurafenib (KD = 437 \u03bcM). These findings suggest P184\u20101419 is a promising lead compound against BRAF(V600E), offering potential for future development of more effective cancer therapies.<\/jats:p>","DOI":"10.1002\/minf.202400372","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T06:50:15Z","timestamp":1750143015000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["In Silico Identification of Novel and Potent Inhibitors Against Mutant BRAF (V600E), MD Simulations, Free Energy Calculations, and Experimental Determination of Binding Affinity"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9158-6702","authenticated-orcid":false,"given":"Vikas","family":"Yadav","sequence":"first","affiliation":[{"name":"School of Computational and Integrative Sciences Jawaharlal Nehru University  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Kashif","sequence":"additional","affiliation":[{"name":"School of Computational and Integrative Sciences Jawaharlal Nehru University  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenab","family":"Kamali","sequence":"additional","affiliation":[{"name":"School of Life Sciences Jawaharlal Nehru University  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samudrala","family":"Gourinath","sequence":"additional","affiliation":[{"name":"School of Life Sciences Jawaharlal Nehru University  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1720-2165","authenticated-orcid":false,"given":"Naidu","family":"Subbarao","sequence":"additional","affiliation":[{"name":"School of Computational and Integrative Sciences Jawaharlal Nehru University  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.9790\/0853-0524656"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1484-6"},{"key":"e_1_2_8_7_1","volume-title":"Foundations of Algorithms","author":"Neapolitan R. 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