{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:07:18Z","timestamp":1760238438291,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31660240"],"award-info":[{"award-number":["31660240"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Xijiang Innovation and Entrepreneurship Team of Zhaoqing","award":["N.A."],"award-info":[{"award-number":["N.A."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The recently discovered 340-cavity in influenza neuraminidase (NA) N6 and N7 subtypes has introduced new possibilities for rational structure-based drug design. However, the plasticity of the 340-loop (residues 342\u2013347) and the role of the 340-loop in NA activity and substrate binding have not been deeply exploited. Here, we investigate the mechanism of 340-cavity formation and demonstrate for the first time that seven of nine NA subtypes are able to adopt an open 340-cavity over 1.8 \u03bcs total molecular dynamics simulation time. The finding that the 340-loop plays a role in the sialic acid binding pathway suggests that the 340-cavity can function as a druggable pocket. Comparing the open and closed conformations of the 340-loop, the side chain orientation of residue 344 was found to govern the formation of the 340-cavity. Additionally, the conserved calcium ion was found to substantially influence the stability of the 340-loop. Our study provides dynamical evidence supporting the 340-cavity as a druggable hotspot at the atomic level and offers new structural insight in designing antiviral drugs.<\/jats:p>","DOI":"10.3390\/ijms21165655","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T09:30:54Z","timestamp":1596792654000},"page":"5655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Plasticity of the 340-Loop in Influenza Neuraminidase Offers New Insight for Antiviral Drug Development"],"prefix":"10.3390","volume":"21","author":[{"given":"Nanyu","family":"Han","sequence":"first","affiliation":[{"name":"School of Life Sciences, Yunnan Normal University, Kunming 650500, China"},{"name":"Key Laboratory of Enzyme Engineering, Yunnan Normal University, Kunming 650500, China"},{"name":"Engineering Research Center of Sustainable and Utilization of Biomass Energy, Ministry of Education, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Ng","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 639798, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanpeng","family":"Li","sequence":"additional","affiliation":[{"name":"Zhaoqing Institute of Biotechnology Co., Ltd., Zhaoqing 526238, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2499-026X","authenticated-orcid":false,"given":"Yuguang","family":"Mu","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 639798, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zunxi","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Yunnan Normal University, Kunming 650500, China"},{"name":"Key Laboratory of Enzyme Engineering, Yunnan Normal University, Kunming 650500, China"},{"name":"Engineering Research Center of Sustainable and Utilization of Biomass Energy, Ministry of Education, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3201\/eid1201.050983","article-title":"Pandemic influenza threat and preparedness","volume":"12","author":"Fauci","year":"2006","journal-title":"Emerg. 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