{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:17:42Z","timestamp":1772173062286,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010113","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000}}],"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SURFSARA","award":["2020.015"],"award-info":[{"award-number":["2020.015"]}]},{"name":"CONACYT","award":["327780 \/ 382262"],"award-info":[{"award-number":["327780 \/ 382262"]}]},{"DOI":"10.13039\/501100001827","name":"Universiteit van Amsterdam","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001827","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Hoogsteen (HG) base pairing is characterized by a 180\u00b0 rotation of the purine base with respect to the Watson-Crick-Franklin (WCF) motif. Recently, it has been found that both conformations coexist in a dynamical equilibrium and that several biological functions require HG pairs. This relevance has motivated experimental and computational investigations of the base-pairing transition. However, a systematic simulation of sequence variations has remained out of reach. Here, we employ advanced path-based methods to perform unprecedented free-energy calculations. Our methodology enables us to study the different mechanisms of purine rotation, either remaining inside or after flipping outside of the double helix. We study seven different sequences, which are neighbor variations of a well-studied A\u22c5T pair in A\n                    <jats:sub>6<\/jats:sub>\n                    -DNA. We observe the known effect of A\u22c5T steps favoring HG stability, and find evidence of triple-hydrogen-bonded neighbors hindering the inside transition. More importantly, we identify a dominant factor: the direction of the A rotation, with the 6-ring pointing either towards the longer or shorter segment of the chain, respectively relating to a lower or higher barrier. This highlights the role of DNA\u2019s relative flexibility as a modulator of the WCF\/HG dynamic equilibrium. Additionally, we provide a robust methodology for future HG proclivity studies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1010113","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T13:54:18Z","timestamp":1653573258000},"page":"e1010113","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Sequence dependence of transient Hoogsteen base pairing in DNA"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4776-5521","authenticated-orcid":true,"given":"Alberto","family":"P\u00e9rez de Alba 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