{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:20:30Z","timestamp":1760232030381,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research (MIUR)"},{"name":"\u2018Consorzio Interuniversitario del Nord-Est per il Calcolo Automatico\u2019 (CINECA) to the University of Milano-Bicocca"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurofibromin, the main RasGAP in the nervous system, is a 2818 aa protein with several poorly characterized functional domains. Mutations in the NF1-encoding gene lead to an autosomal dominant syndrome, neurofibromatosis, with an incidence of 1 out of 3000 newborns. Missense mutations spread in the Sec14-PH-encoding sequences as well. Structural data could not highlight the defect in mutant Sec14-PH functionality. By performing molecular dynamics simulations at different temperatures, we found that the lid-lock is fundamental for the structural interdependence of the NF1 bipartite Sec14-PH domain. In fact, increased flexibility in the lid-lock loop, observed for the K1750\u0394 mutant, leads to disconnection of the two subdomains and can affect the stability of the Sec14 subdomain.<\/jats:p>","DOI":"10.3390\/ijms23105707","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T04:27:22Z","timestamp":1653020842000},"page":"5707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Dynamics Simulations Reveal Structural Interconnections within Sec14-PH Bipartite Domain from Human Neurofibromin"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1615-3178","authenticated-orcid":false,"given":"Fabio","family":"Rizza","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacopo","family":"Vertemara","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0869-3345","authenticated-orcid":false,"given":"Renata","family":"Tisi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy"},{"name":"Milan Center for Neuroscience (NeuroMI), University of Milano-Bicocca, 20126 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/s41416-020-0903-x","article-title":"Translating Current Basic Research into Future Therapies for Neurofibromatosis Type 1","volume":"123","author":"Brosseau","year":"2020","journal-title":"Br. 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