G-Protein coupled receptors: answers from simulations
نویسنده
چکیده
Molecular-dynamics (MD) simulations are playing an increasingly important role in research into the modes of action of G-protein coupled receptors (GPCRs). In this field, MD simulations are unusually important as, because of the difficult experimental situation, they often offer the only opportunity to determine structural and mechanistic features in atomistic detail. Modern combinations of soft- and hardware have made MD simulations a powerful tool in GPCR research. This is important because GPCRs are targeted by approximately half of the drugs on the market, so that computer-aided drug design plays a major role in GPCR research.
منابع مشابه
G-protein Coupled Receptor Dimerization
A growing body of evidence suggests that GPCRs exist and function as dimers or higher oligomers. The evidence for GPCR dimerization comes from biochemical, biophysical and functional studies. In addition, researchers have shown the occurrence of heterodimerization between different members of the GPCR family. Two receptors can interact with each other to make a dimer through their extracellular...
متن کاملHigh glucose condition down-regulates the inhibitory G-protein subunit, Gαi, in pheochromocytoma PC12 cells
Introduction: G-proteins have an important role in the cell signaling of numerous receptors. The situation of G-proteins in health and disease and their critical role in the development of diabetic side effects is an interested scientific field. Here, the changes in the expression of G-protein subunits (Gαi, Gαs and Gβ) were evaluated in hyperglycemic situation of PC12 cells as...
متن کاملRecent progress in the study of G protein-coupled receptors with molecular dynamics computer simulations.
G protein-coupled receptors (GPCRs) are a large, biomedically important family of proteins, and the recent explosion of new high-resolution structural information about them has provided an enormous opportunity for computational modeling to make major contributions. In particular, molecular dynamics simulations have become a driving factor in many areas of GPCR biophysics, improving our underst...
متن کاملPathway and mechanism of drug binding to G-protein-coupled receptors.
How drugs bind to their receptors--from initial association, through drug entry into the binding pocket, to adoption of the final bound conformation, or "pose"--has remained unknown, even for G-protein-coupled receptor modulators, which constitute one-third of all marketed drugs. We captured this pharmaceutically critical process in atomic detail using the first unbiased molecular dynamics simu...
متن کاملDetection of Side Chain Rearrangements Mediating the Motions of Transmembrane Helices in Molecular Dynamics Simulations of G Protein-Coupled Receptors
Structure and dynamics are essential elements of protein function. Protein structure is constantly fluctuating and undergoing conformational changes, which are captured by molecular dynamics (MD) simulations. We introduce a computational framework that provides a compact representation of the dynamic conformational space of biomolecular simulations. This method presents a systematic approach de...
متن کامل