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dc.contributor.author Cong, Xiaojing ko
dc.contributor.author Golebiowski, Jerome ko
dc.date.accessioned 2018-10-30T05:59:49Z -
dc.date.available 2018-10-30T05:59:49Z -
dc.date.created 2018-10-22 -
dc.date.issued 2018-09 -
dc.identifier.citation Physical Chemistry Chemical Physics, v.20, no.38, pp.24915 - 24920 -
dc.identifier.issn 1463-9076 -
dc.identifier.uri http://hdl.handle.net/20.500.11750/9384 -
dc.description.abstract G protein-coupled receptors (GPCRs) control most cellular communications with the environment and are the largest protein family of drug targets. As strictly regulated molecular machines, profound comprehension of their activation mechanism is expected to significantly facilitate structure-based drug design. This study provides atomistic-level description of the activation dynamics of the C-X-C chemokine receptor type 4 (CXCR4), a class A GPCR and important drug target. Using molecular dynamics and enhanced sampling, we demonstrate how mutations and protonation of conserved residues trigger activation through microswitches at the receptor core, while sodium ion-a known allosteric modulator-inhibits it. The findings point to a conserved mechanism of activation and the allosteric modulation by sodium in the chemokine receptor family. From the technical aspect, the enhanced sampling protocol effectively samples receptor conformational changes toward activation, and differentiates three variants of the receptor by their basal activity. This work provides structural basis and a powerful in silico tool for CXCR4 agonist design. © 2018 the Owner Societies. -
dc.language English -
dc.publisher Royal Society of Chemistry -
dc.subject PROTEIN-COUPLED RECEPTORS -
dc.subject MU-OPIOID RECEPTOR -
dc.subject SODIUM-ION BINDING -
dc.subject ODORANT RECEPTORS -
dc.subject CRYSTAL-STRUCTURE -
dc.subject FORCE-FIELD -
dc.subject CHEMOKINE -
dc.subject INSIGHTS -
dc.subject GPCR -
dc.subject SIMULATIONS -
dc.title Allosteric Na+-binding site modulates CXCR4 activation -
dc.type Article -
dc.identifier.doi 10.1039/c8cp04134b -
dc.identifier.wosid 000449171800044 -
dc.identifier.scopusid 2-s2.0-85054395145 -
dc.type.local Article(Overseas) -
dc.type.rims ART -
dc.description.journalClass 1 -
dc.contributor.nonIdAuthor Cong, Xiaojing -
dc.identifier.citationVolume 20 -
dc.identifier.citationNumber 38 -
dc.identifier.citationStartPage 24915 -
dc.identifier.citationEndPage 24920 -
dc.identifier.citationTitle Physical Chemistry Chemical Physics -
dc.type.journalArticle Article -
dc.description.isOpenAccess N -
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