Mattedi, G;
Deflorian, F;
Mason, JS;
de Graaf, C;
Gervasio, FL;
(2019)
Understanding ligand binding selectivity in a prototypical GPCR family.
Journal of Chemical Information and Modeling
10.1021/acs.jcim.9b00298.
(In press).
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Abstract
Adenosine receptors are involved in many pathological conditions and are thus promising drug targets. However, developing drugs that target this GPCR subfamily is a challenging task. A number of drug candidates fail due to lack of selectivity which results in unwanted side effects. The extensive structural similarity of adenosine receptors complicates the design of selective ligands. The problem of selective targeting is a general concern in GPCRs and in this respect adenosine receptors are a prototypical example. Here we use enhanced sampling simulations to decipher the determinants of selectivity of ligands in A2a and A1 adenosine receptors. Our model shows how small differences in the binding pocket and in the water network around the ligand can be leveraged to achieve selectivity.
| Type: | Article |
|---|---|
| Title: | Understanding ligand binding selectivity in a prototypical GPCR family |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.jcim.9b00298 |
| Publisher version: | https://doi.org/10.1021/acs.jcim.9b00298 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10075766 |
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