Signaling of neurotransmitters, hormones and many other biological molecules across the cellular membrane is regulated by a superfamily of membrane proteins known as G protein-coupled receptors (GPCRs). This makes them a key player in biological signaling and explains the deep interest understanding the molecular basis of their pharmacology. Within this scenario, the GPCR-ModSim web-based service was created to facilitate and enhance the current strategies for the computational modeling and simulation of GPCRs.
GPCR-ModSim was launched in 2011 by Hugo Gutiérrez de Terán and his team at the Genomic Medicine unit at the Santiago de Compostela University Hospital, with funding from the Health Department of the Autonomous Government of Galicia (2009-2011) and the Spanish Ministry of Science and Technology (2012-2013). In 2013 Hugo moved to Uppsala University (Sweden) where he is coordinating the research projects in membrane receptors and channels. Consequently, the GPCR-Modsim server migrated recently to our computational infrastructure at the Computational and Systems Biology program, at the Department of Cell and Molecular Biology, thanks to the current funding from the Carl-Trygger Foundation
The project objective is to facilitate the comprehensive and systematic study of G-protein coupled receptors (GPCRs) from the structural point of view. A growing number of GPCR experimental structures is becoming available, as a consequence of recent breakthroughs in membrane protein crystallography. However, only a few (aprox. 1%) of the human GPCR structures have been determined, whereas for the remaining receptors the structural characterization is restricted to the use of computational models and biophysical techniques. In the GPCR-ModSim framework, we are progressively implementing and optimizing different computational protocols that combine an extensive automation of the process, ease of use and flexibility of adaptation to the needs of each project:
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).