ArticlePLoS computational biology2014
Computational prediction of alanine scanning and ligand binding energetics in G-protein coupled receptors.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 67 citations in OpenAlex.
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- Ligand and Residue Free Energy Perturbations Solve the Dual Binding Mode Proposal for an AThe journal of physical chemistry. B · 2025Article
- Alchemical Free Energy Workflows for the Computation of Protein-Ligand Binding Affinities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Principles of Cold Adaptation of Fish Lactate Dehydrogenases Revealed by Computer Simulations of the Catalytic Reaction.Molecular biology and evolution · 2023Article
- Atomic-level thermodynamics analysis of the binding free energy of SARS-CoV-2 neutralizing antibodies.Proteins · 2023Article
- Deciphering conformational selectivity in the A2A adenosine G protein-coupled receptor by free energy simulations.PLoS computational biology · 2021Article
- Subtype-selective mechanisms of negative allosteric modulators binding to group I metabotropic glutamate receptors.Acta pharmacologica Sinica · 2021Article
- Biomolecular Modeling and Simulation: A Prospering Multidisciplinary Field.Annual review of biophysics · 2021Article
- Can molecular dynamics simulations improve the structural accuracy and virtual screening performance of GPCR models?PLoS computational biology · 2021Article
- SARS-CoV-2 nucleocapsid and Nsp3 binding: an in silico study.Archives of microbiology · 2021Article
- Structural Basis of Inhibition of Human Insulin-Regulated Aminopeptidase (IRAP) by Benzopyran-Based Inhibitors.Frontiers in molecular biosciences · 2021Article
- Free Energy Calculations for Protein-Ligand Binding Prediction.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Hit-to-lead and lead optimization binding free energy calculations for G protein-coupled receptors.Interface focus · 2020Article
- X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of AAngewandte Chemie (International ed. in English) · 2020Article
- Advances in Molecular Dynamics Simulations and Enhanced Sampling Methods for the Study of Protein Systems.International journal of molecular sciences · 2020Review
- Evolution of Angiotensin Peptides and Peptidomimetics as Angiotensin II Receptor Type 2 (AT2) Receptor Agonists.Biomolecules · 2020Article
- Macrocyclic peptidomimetics as inhibitors of insulin-regulated aminopeptidase (IRAP).RSC medicinal chemistry · 2020Article
- Predicting and Experimentally Validating Hot-Spot Residues at Protein-Protein Interfaces.ACS chemical biology · 2019Article
- QligFEP: an automated workflow for small molecule free energy calculations in Q.Journal of cheminformatics · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Site-directed mutagenesis combined with binding affinity measurements is widely used to probe the nature of ligand interactions with GPCRs. Such experiments, as well as structure-activity relationships for series of ligands, are usually interpreted with computationally derived models of ligand binding modes. However, systematic approaches for accurate calculations of the corresponding binding free energies are still lacking. Here, we report a computational strategy to quantitatively predict the effects of alanine scanning and ligand modifications based on molecular dynamics free energy simulations. A smooth stepwise scheme for free energy perturbation calculations is derived and applied to a series of thirteen alanine mutations of the human neuropeptide Y1 receptor and series of eight analogous antagonists. The robustness and accuracy of the method enables univocal interpretation of existing mutagenesis and binding data. We show how these calculations can be used to validate structural models and demonstrate their ability to discriminate against suboptimal ones.
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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.