ArticleProceedings of the National Academy of Sciences of the United States of America2011
Successful prediction of the intra- and extracellular loops of four G-protein-coupled receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Orphan G protein-coupled receptors: the ongoing search for a home.Frontiers in pharmacology · 2024Review
- GPCR Intracellular Loop Regulation of Beta-Arrestin-Mediated Endosomal Signaling Dynamics.Journal of molecular neuroscience : MN · 2022Article
- The Molecular Control of Calcitonin Receptor Signaling.ACS pharmacology & translational science · 2019Article
- Using Dimensionality Reduction to Analyze Protein Trajectories.Frontiers in molecular biosciences · 2019Article
- Cryo-EM structure of the active, GNature · 2018Article
- Molecular mechanism of activation of human musk receptors OR5AN1 and OR1A1 by (Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers asActa pharmaceutica Sinica. B · 2017Article
- Methods for the Development of In Silico GPCR Models.Methods in enzymology · 2017Article
- SL2: an interactive webtool for modeling of missing segments in proteins.Nucleic acids research · 2016Article
- Isoquinoline-1,3-diones as Selective Inhibitors of Tyrosyl DNA Phosphodiesterase II (TDP2).Journal of medicinal chemistry · 2016Article
- X-ray Crystallography, DFT Calculations and Molecular Docking of Indole-Arylpiperazine Derivatives as α1A-Adrenoceptor Antagonists.Molecules (Basel, Switzerland) · 2015Article
- Transmembrane domains of attraction on the TSH receptor.Endocrinology · 2015Article
- Monte Carlo loop refinement and virtual screening of the thyroid-stimulating hormone receptor transmembrane domain.Journal of biomolecular structure & dynamics · 2015Article
- Cellular signalling of non-synonymous single-nucleotide polymorphisms of the human μ-opioid receptor (OPRM1).British journal of pharmacology · 2015Review
- Advancements in therapeutically targeting orphan GPCRs.Frontiers in pharmacology · 2015Review
- Antibody structure determination using a combination of homology modeling, energy-based refinement, and loop prediction.Proteins · 2014Article
- Structure prediction of the second extracellular loop in G-protein-coupled receptors.Biophysical journal · 2014Article
- Fast protein loop sampling and structure prediction using distance-guided sequential chain-growth Monte Carlo method.PLoS computational biology · 2014Article
- Do plants contain g protein-coupled receptors?Plant physiology · 2014Article
- The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach.Journal of the Royal Society, Interface · 2013Article
Corrections and comments
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- Erratum issued
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We present results of the restoration of all crystallographically available intra- and extracellular loops of four G-protein-coupled receptors (GPCRs): bovine rhodopsin (bRh), the turkey β-1 adrenergic receptor (β1Ar), and the human β-2 adrenergic (β2Ar) and A2A adenosine (A2Ar) receptors. We use our Protein Local Optimization Program (PLOP), which samples conformational space from first principles to build sets of loop candidates and then discriminates between them using our physics-based, all-atom energy function with implicit solvent. We also discuss a new kind of explicit membrane calculation developed for GPCR loops that interact, either in the native structure or in low-energy false-positive structures, with the membrane, and thus exist in a multiphase environment not previously incorporated in PLOP. Our results demonstrate a significant advance over previous work reported in the literature, and of particular note we are able to accurately restore the extremely long second extracellular loop (ECL2), which is also key for GPCR ligand binding. In the case of β2Ar, accurate ECL2 restoration required seeding a small helix into the loop in the appropriate region, based on alignment with the β1Ar ECL2 loop, and then running loop reconstruction simulations with and without the seeded helix present; simulations containing the helix attain significantly lower total energies than those without the helix, and have rmsds close to the native structure. For β1Ar, the same protocol was used, except the alignment was done to β2Ar. These results represent an encouraging start for the more difficult problem of accurate loop refinement for GPCR homology modeling.
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