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In principle, extended timescale atomic-resolution simulations may be used to characterize the dynamics of such peptides. However, the resultant accuracy is critically dependent upon both the underlying force field and sufficient conformational sampling. In the present study, we report a comprehensive comparison of three simulation methods and four force fields comprising a total of more than 40\u2009\u03bcs of sampling. Additionally, we describe the conformational landscape of the FP fold across all flavivirus family members. All investigated methods sampled conformations close to available X-ray structures, but exhibited differently populated ensembles. The best force field \/ sampling combination was sufficiently accurate to predict that the solvated peptide fold is less ordered than in the crystallographic state, which was subsequently confirmed via circular dichroism and spectrofluorometric measurements. Finally, the conformational landscape of a mutant incapable of membrane fusion was significantly shallower than wild-type variants, suggesting that dynamics should be considered when therapeutically targeting FP epitopes.<\/jats:p>","DOI":"10.1038\/srep19160","type":"journal-article","created":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T14:55:12Z","timestamp":1453301712000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Characterizing the Conformational Landscape of Flavivirus Fusion Peptides via Simulation and Experiment"],"prefix":"10.1038","volume":"6","author":[{"given":"Jan K.","family":"Marzinek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajamani","family":"Lakshminarayanan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eunice","family":"Goh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland G.","family":"Huber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadhana","family":"Panzade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandra","family":"Verma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Bond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,1,20]]},"reference":[{"key":"BFsrep19160_CR1","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1056\/NEJMra1201534","volume":"369","author":"CJL Murray","year":"2013","unstructured":"Murray, C. 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