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GPCRsignal (https://gpcrsignal.biomodellab.eu/) is a webserver devoted to signaling complexes of G-protein-coupled receptors (GPCRs). The recent improvement in cryo-electron microscopy resulted in the determination of a large number of high-resolution structures of GPCRs bound to their effector proteins: G proteins or arrestins. Analyzing the interfaces between receptor and an effector protein is of high importance since a selection of proper G protein or specific conformation of arrestin leads to changes of signaling that can significantly affect action of drugs. GPCRsignal provides a possibility of running molecular dynamics simulations of all currently available GPCR-effector protein complexes for curated structures: wild-type, with crystal/cryo-EM mutations, or with mutations introduced by the user. The simulations are performed in an implicit water-membrane environment, so they are rather fast. User can run several simulations to obtain statistically valid results. The simulations can be analyzed separately using dynamic FlarePlots for particular types of interactions. One can also compare groups of simulations in Interaction frequency analysis as HeatMaps and also in interaction frequency difference analysis as sticks, linking the interacting residues, of different color and size proportional to differences in contact frequencies.

GPCRsignal: webserver for analysis of the interface between G-protein–coupled receptors and their effector proteins by dynamics and mutations