{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:25:45Z","timestamp":1780957545263,"version":"3.54.1"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012236","name":"Beijing Institute of Technology Research Fund Program for Young 705 Scholars","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012236","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002805","name":"Carl Trygger Foundation","doi-asserted-by":"crossref","award":["CTS 18:276"],"award-info":[{"award-number":["CTS 18:276"]}],"id":[{"id":"10.13039\/501100002805","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["Contract No. 2018-04411"],"award-info":[{"award-number":["Contract No. 2018-04411"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"COST Action","award":["707 CA17139"],"award-info":[{"award-number":["707 CA17139"]}]},{"name":"Ministry of Science and Higher Education of Russia","award":["0657-2020-0015"],"award-info":[{"award-number":["0657-2020-0015"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Novel topological methods are introduced to protein research. The aim is to identify hot-spot sites where a bifurcation can alter the local topology of the protein backbone. Since the shape of a protein is intimately related to its biological function, a substitution that causes a bifurcation should have an enhanced capacity to change the protein\u2019s function. The methodology applies to any protein but it is developed with the SARS-CoV-2 spike protein as a timely example. First, topological criteria are introduced to identify and classify potential bifurcation hot-spot sites along the protein backbone. Then, the expected outcome of asubstitution, if it occurs, is estimated for a general class of hot-spots, using a comparative analysis of the surrounding backbone segments. The analysis combines the statistics of structurally commensurate amino acid fragments in the Protein Data Bank with general stereochemical considerations. It is observed that the notorious D614G substitution of the spike protein is a good example of a bifurcation hot-spot. A number of topologically similar examples are then analyzed in detail, some of them are even better candidates for a bifurcation hot-spot than D614G. The local topology of the more recently observed N501Y substitution is also inspected, and it is found that this site is proximal to a different kind of local topology changing bifurcation.<\/jats:p>","DOI":"10.1371\/journal.pone.0257886","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T18:37:39Z","timestamp":1633027059000},"page":"e0257886","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Local topology and bifurcation hot-spots in proteins with SARS-CoV-2 spike protein as an example"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6494-9560","authenticated-orcid":true,"given":"Xubiao","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3408-5834","authenticated-orcid":true,"given":"Antti J.","family":"Niemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"issue":"6","key":"pone.0257886.ref001","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/0370-1573(80)90130-1","article-title":"Gravitation, gauge theories and differential geometry","volume":"66","author":"T Eguchi","year":"1980","journal-title":"Physics reports"},{"key":"pone.0257886.ref002","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-642-14700-5","volume-title":"Topology and geometry for physics","author":"H Eschrig","year":"2011"},{"key":"pone.0257886.ref003","volume-title":"Geometry, topology and physics","author":"M Nakahara","year":"2003"},{"key":"pone.0257886.ref004","volume-title":"Nonlinear dynamics and chaos with with applications to physics, biology, chemistry, and engineering","author":"S. 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