The project objective is to achieve a comprehensive and systematic study of G-protein coupled receptors (GPCRs) and generating structural information on the overall receptorome. The recent availability of new crystallographic structures puts us in a key strategic point for this challenge with guarantees. In this way, we want to create a reference platform for the computational study of these receptors. We propose to develop this line of work employing techniques in which the applicant team has proven experience: homology modeling, virtual screening, computational prediction of affinities and molecular dynamics.

The meta-analysis of the receptorome will allow a systematic but detailed study of delicate phenomena like the specificity of binding between high homologous receptors (selectivity); the effect of mutations, like those present in non-synonymous SNPs (nsSNP, pharmacogenetic studies), specificity among species (translation of data from preclinical to clinical research) or site directed mutagenesis experiments (molecular biology studies). The range of receptors under study will be as broad as possible, encompassing not only GPCRs involved in pathophysiological phenomena but also those commonly implicated in side effects of drugs (antitargets). The specific issues addressed include: i) structural and dynamic information on GPCRs and their conformations, ii) to support the design of chemical ligands, within a chemical biology approach; iii) to address complex phenomena in molecular association of GPCRs (ligand binding or structural study of dimers). The project complements existing partnerships with other groups (see letters of support) so it can be defined as part of a multidisciplinary approach.

More information on the official web site of the server: http://gpcr-modsim.org