Journal
DRUG DISCOVERY TODAY
Volume 21, Issue 4, Pages 625-631Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2016.01.009
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Funding
- German Research Foundation (DFG) [KO4095/1-1]
- Institute de Salud Carlos III El Fondo Europeo de Desarrollo Regional (FEDER) [CP12/03139, PI15/00460]
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Current advances in structural biology for membrane proteins support the existence of multiple Gprotein-coupled receptor (GPCR) conformations. These conformations can be associated to particular receptor states with definite coupling and signaling capacities. Drugging such receptor states represents an opportunity to discover a new generation of GPCR drugs with unprecedented specificity. However, exploiting recently available structural information to develop these drugs is still challenging. In this context, computational structure-based approaches can inform such drug development. In this review, we examine the potential of these approaches and the challenges they will need to overcome to guide the rational discovery of drugs targeting specific GPCR states.
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