title: Drugging specific conformational states of GPCRs: challenges and opportunities for computational chemistry.
abstract: 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.
authors.affiliation: Research Programme on Biomedical Informatics, Department of Experimental and Health Sciences, Pompeu Fabra University, Hospital del Mar Medical Research Institute, Dr Aiguader 88, Barcelona 08003, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Martí-Solano
authors.affiliation: Department of Pharmaceutical Chemistry, Philipps-University, Marbacher Weg 6, Marburg 35032, Germany.
authors.forename: Denis
authors.initials: D
authors.lastname: Schmidt
authors.affiliation: Department of Pharmaceutical Chemistry, Philipps-University, Marbacher Weg 6, Marburg 35032, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kolb
authors.affiliation: Research Programme on Biomedical Informatics, Department of Experimental and Health Sciences, Pompeu Fabra University, Hospital del Mar Medical Research Institute, Dr Aiguader 88, Barcelona 08003, Spain. Electronic address: jana.selent@upf.edu.
authors.forename: Jana
authors.initials: J
authors.lastname: Selent
mesh_terms: D015195:Drug Design; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*
chemical_list: D043562:Receptors, G-Protein-Coupled