ArticleProteins2010
GPCR 3D homology models for ligand screening: lessons learned from blind predictions of adenosine A2a receptor complex.
Article in Proteins, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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67 citing papers in PubMed, 139 citations in OpenAlex.
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- Improving AlphaFold2 Performance in Virtual Screens Targeting GPCRs by Enhancing Binding-Site Conformational Sampling.Journal of chemical information and modeling · 2026Article
- Multi-target computational pipeline for discovery of pan-influenza neuraminidase inhibitors.Frontiers in pharmacology · 2026Article
- Protein Structural Model Selection Informed by Comparison of Predicted Ligand Binding Poses.Journal of chemical information and modeling · 2025Article
- AI meets physics in computational structure-based drug discovery for GPCRs.npj drug discovery · 2025Review
- AlphaFold accelerated discovery of psychotropic agonists targeting the trace amine-associated receptor 1.Science advances · 2024Article
- Molecular determinants of antagonist interactions with chemokine receptors CCR2 and CCR5.bioRxiv : the preprint server for biology · 2024Article
- Evolutionary Couplings and Molecular Dynamic Simulations Highlight Details of GPCRs Heterodimers' Interfaces.Molecules (Basel, Switzerland) · 2023Article
- Irreversible Antagonists for the Adenosine AMolecules (Basel, Switzerland) · 2022Article
- A practical guide to large-scale docking.Nature protocols · 2021Review
- Discovery and Validation of Lmj_04_BRCT Domain, a Novel Therapeutic Target: Identification of Candidate Drugs for Leishmaniasis.International journal of molecular sciences · 2021Article
- Can molecular dynamics simulations improve the structural accuracy and virtual screening performance of GPCR models?PLoS computational biology · 2021Article
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- β-Adrenergic receptor, an essential target in cardiovascular diseases.Heart failure reviews · 2020Review
- Dual binding mode of "bitter sugars" to their human bitter taste receptor target.Scientific reports · 2019Article
- Integrated computational and Drosophila cancer model platform captures previously unappreciated chemicals perturbing a kinase network.PLoS computational biology · 2019Article
- Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1.Scientific reports · 2018Article
- Improving virtual screening of G protein-coupled receptors via ligand-directed modeling.PLoS computational biology · 2017Article
- Structural features embedded in G protein-coupled receptor co-crystal structures are key to their success in virtual screening.PloS one · 2017Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Proteins of the G-protein coupled receptor (GPCR) family present numerous attractive targets for rational drug design, but also a formidable challenge for identification and conformational modeling of their 3D structure. A recently performed assessment of blind predictions of adenosine A2a receptor (AA2AR) structure in complex with ZM241385 (ZMA) antagonist provided a first example of unbiased evaluation of the current modeling algorithms on a GPCR target with approximately 30% sequence identity to the closest structural template. Several of the 29 groups participating in this assessment exercise (Michino et al., doi: 10.1038/nrd2877) successfully predicted the overall position of the ligand ZMA in the AA2AR ligand binding pocket, however models from only three groups captured more than 40% the ligand-receptor contacts. Here we describe two of these top performing approaches, in which all-atom models of the AA2AR were generated by homology modeling followed by ligand guided backbone ensemble receptor optimization (LiBERO). The resulting AA2AR-ZMA models, along with the best models from other groups are assessed here for their vitual ligand screening (VLS) performance on a large set of GPCR ligands. We show that ligand guided optimization was critical for improvement of both ligand-receptor contacts and VLS performance as compared to the initial raw homology models. The best blindly predicted models performed on par with the crystal structure of AA2AR in selecting known antagonists from decoys, as well as from antagonists for other adenosine subtypes and AA2AR agonists. These results suggest that despite certain inaccuracies, the optimized homology models can be useful in the drug discovery process.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.