Selent, JanaSanz, FerranPastor Maeso, ManuelDe Fabritiis, Gianni2015-04-172015-04-172010Selent J, Sanz F, Pastor M, de Fabritiis G. Induced effects of sodium ions on dopaminergic G-protein coupled receptors. PLoS Computational Biology. 2010;6(8):e1000884. DOI: 10.1371/journal.pcbi.10008841553-734Xhttp://hdl.handle.net/10230/23430G-protein coupled receptors, the largest family of proteins in the human genome, are involved in many complex signal transduction pathways, typically activated by orthosteric ligand binding and subject to allosteric modulation. Dopaminergic receptors, belonging to the class A family of G-protein coupled receptors, are known to be modulated by sodium ions from an allosteric binding site, although the details of sodium effects on the receptor have not yet been described. In an effort to understand these effects, we performed microsecond scale all-atom molecular dynamics simulations on the dopaminergic D2 receptor, finding that sodium ions enter the receptor from the extracellular side and bind at a deep allosteric site (Asp2.50). Remarkably, the presence of a sodium ion at this allosteric site induces a conformational change of the rotamer toggle switch Trp6.48 which locks in a conformation identical to the one found in the partially inactive state of the crystallized human β2 adrenergic receptor. This study provides detailed quantitative information about binding of sodium ions in the D2 receptor and reports a possibly important sodium-induced conformational change for modulation of D2 receptor function.application/pdfeng© 2010 Selent et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedProteïnesGenoma humàinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1371/journal.pcbi.1000884info:eu-repo/semantics/openAccess