{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:19Z","timestamp":1787028559986,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Research (France)","award":["ANR-18-IDEX-0001"],"award-info":[{"award-number":["ANR-18-IDEX-0001"]}]},{"name":"Universit\u00e9 Paris Cit\u00e9 (formerly University Paris Diderot, Sorbonne Paris Cit\u00e9, France and formerly Universit\u00e9 de Paris)","award":["ANR-18-IDEX-0001"],"award-info":[{"award-number":["ANR-18-IDEX-0001"]}]},{"name":"Universit\u00e9 de la R\u00e9union, National Institute for Health and Medical Research (INSERM, France)","award":["ANR-18-IDEX-0001"],"award-info":[{"award-number":["ANR-18-IDEX-0001"]}]},{"name":"France 2030 program through the Idex Universit\u00e9 Paris Cit\u00e9","award":["ANR-18-IDEX-0001"],"award-info":[{"award-number":["ANR-18-IDEX-0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Janus kinase 2 (JAK2) is an important intracellular mediator of cytokine signaling. Mutations in the JAK2 gene are associated with myeloproliferative neoplasms (MPNs) such as polycythemia vera (PV) and essential thrombocythemia (ET), while aberrant JAK2 activity is also associated with a number of immune diseases. The acquired somatic mutation JAK2 V617F (95% of cases of PV and in 55\u201360% of cases of ET), which constitutively activates the JAK2, is the most common molecular event in MPN. The development of specific JAK2 inhibitors is therefore of considerable clinical importance. Ruxolitinib is a JAK inhibitor recently approved by the FDA\/EMA and effective in relieving symptoms in patients with MPN. Ruxolitinib binds to the JAK2 last domain, namely JH1; its action on the dynamics of the domain is still only partially known. Using Molecular Dynamics simulations, we have analyzed the JH1 domain in four different states as follows: (i) alone, (ii) with one phosphorylation, (iii) adding Ruxolitinib, and (iv) with five phosphorylations and Ruxolitinib. The ligand induces a dynamic behavior similar to the inactive form of JH1, with a less flexible state than the phosphorylated active form of JH1. This study highlights the inhibitory effect of Ruxolitinib on the JH1 domain, demonstrating the importance of dynamics in regulating JH1 activation.<\/jats:p>","DOI":"10.3390\/ijms26083727","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T06:50:27Z","timestamp":1744699827000},"page":"3727","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of Ruxolitinib Interactions on JAK2 JH1 Domain Dynamics"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7669-5725","authenticated-orcid":false,"given":"Hong Nhung","family":"Vu","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 de la R\u00e9union, INSERM, EFS, BIGR U1134, DSIMB Bioinformatics Team, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragousandirane","family":"Radjasandirane","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 de la R\u00e9union, INSERM, EFS, BIGR U1134, DSIMB Bioinformatics Team, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6400-927X","authenticated-orcid":false,"given":"Julien","family":"Diharce","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 de la R\u00e9union, INSERM, EFS, BIGR U1134, DSIMB Bioinformatics Team, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7112-5626","authenticated-orcid":false,"given":"Alexandre G.","family":"de Brevern","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 de la R\u00e9union, INSERM, EFS, BIGR U1134, DSIMB Bioinformatics Team, F-75015 Paris, France"},{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 de la R\u00e9union, INSERM, EFS, BIGR U1134, DSIMB Bioinformatics Team, F-97715 Saint Denis Messag, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pbiomolbio.2009.12.009","article-title":"Evolution of domain combinations in protein kinases and its implications for functional diversity","volume":"102","author":"Deshmukh","year":"2010","journal-title":"Prog. 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