Pathway and mechanism of drug binding to G-protein-coupled receptors

By Ron O. Dror, Albert C. Pan, Daniel H Arlow, David W. Borhani, Paul Maragakis, Yibing Shan, Huafeng Xu, David E. Shaw. 2011

717 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

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Citations in the corpus

Protein 3D Structure Computed from Evolutionary Sequence Variation (2011, neutral): “such as BPTI and WW domains [29,30].”
3D structures of membrane proteins from genomic sequencing (2012, neutral): “To improve the quality of the predicted contacts and resulting atomic structures, four areas of focus hold particular promise: (1) improved information handling in sequence space, such as improvements in weighting schemes for sequences, evaluation of alignment diversity, inclusion of higher-order te”
Cloud-based simulations on Google Exacycle reveal ligand-modulation of GPCR activation pathways (2013, background): “The gaps on either side of this bridge have been shown to permit the ligand carazolol to enter the binding pocket, and exhibits rates of 109 s-1 and 108 s-1 for bond formation and breakage, respectively(27).”
Ligand–receptor interaction platforms and their applications for drug discovery (2012, background): “GPCRs are known to adopt multiple conformations, some of which are dominant for the binding of distinct classes of ligands [14,15].”
Multiensemble Markov models of molecular thermodynamics and kinetics (2016, background): “The TRAM likelihood combines the MSM likelihood [ 6 ] and local equilibrium likelihood [8].”
Bridging Molecular Docking to Molecular Dynamics in Exploring Ligand-Protein Recognition Process: An Overview (2018, methodology): “Moreover, with unbiased simulations in the order of ten microseconds, Shaw’s group could simulate the complete binding process of beta blockers and agonists to the β 2 -adrenergic receptor (Dror et al., 2011) and kinase inhibitors to Src kinase (Shan et al., 2011).”
The future of molecular dynamics simulations in drug discovery (2011, background): “The unbiased binding of kinase inhibitors [41] and G protein–coupled receptor (GPCR) agonists [42] and antagonists [43] has also been demonstrated.”