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Large and flexible NNRTIs, such as JLJ636, offer potential advantages in retaining efficacy against drug-resistant mutations in HIV reverse transcriptase. However, the dissociation pathways of such inhibitors from the enzyme\u2019s hydrophobic binding pocket remain unclear. In this study, we use atomistic simulations to investigate the unbinding dynamics of JLJ636. A combination of random acceleration molecular dynamics and Milestoning simulations is adopted to identify dissociation pathways, estimate mean residence time, and compute free energy profiles. Among the three candidate exit routes (termed the \u201centrance\u201d, \u201ctunnel\u201d, and \u201cgroove\u201d channels), the \u201ctunnel\u201d channel is most favorable, followed by the \u201cgroove\u201d channel, while the \u201centrance\u201d channel is rarely visited. This unbinding behavior differs significantly from that of smaller NNRTIs, such as JLJ135 and its analogues, which predominantly dissociate through the \u201centrance\u201d channel.<\/jats:p>","DOI":"10.1021\/acs.jpcb.5c04843","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T18:11:10Z","timestamp":1763403070000},"page":"12076-12086","source":"Crossref","is-referenced-by-count":0,"title":["Unbinding Dynamics of Large HIV Non-Nucleoside Reverse\nTranscriptase Inhibitors Revealed by Atomistic Milestoning Simulations"],"prefix":"10.1021","volume":"129","author":[{"given":"Ying","family":"Liu","sequence":"first","affiliation":[{"name":"Shandong University , , , ,","place":["Qingdao, Shandong, P. R. China, 266237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Qingdao, Shandong, P. R. China, 266237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0431-0826","authenticated-orcid":true,"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Qingdao, Shandong, P. R. China, 266237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1630-3466","authenticated-orcid":true,"given":"Wenjian","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Qingdao, Shandong, P. R. 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Phys."},{"key":"2026081810470381300_cit52","doi-asserted-by":"publisher","first-page":"4177","DOI":"10.1063\/1.467468","article-title":"Constant pressure molecular dynamics\nalgorithms","volume":"101","author":"Martyna","year":"1994","journal-title":"J. Chem. Phys."},{"key":"2026081810470381300_cit53","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1002\/jcc.540130805","article-title":"Settle: An analytical\nversion of the SHAKE and RATTLE\nalgorithm for rigid water models","volume":"13","author":"Miyamoto","year":"1992","journal-title":"J. Comput.\nChem."},{"key":"2026081810470381300_cit54","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the cartesian\nequations of motion of a system with constraints: molecular dynamics\nof n-alkanes","volume":"23","author":"Ryckaert","year":"1977","journal-title":"J. Comput. Phys."},{"key":"2026081810470381300_cit55","doi-asserted-by":"publisher","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle\nmesh Ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"J. Chem. Phys."},{"key":"2026081810470381300_cit56","doi-asserted-by":"publisher","DOI":"10.1063\/5.0014475","article-title":"Scalable\nmolecular dynamics on CPU and GPU architectures\nwith NAMD","volume":"153","author":"Phillips","year":"2020","journal-title":"J. Chem. Phys."},{"key":"2026081810470381300_cit57","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: An improved force field for folded and intrinsically\ndisordered proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat. 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