ArticleJournal of chemical theory and computation2018
A Streamlined, General Approach for Computing Ligand Binding Free Energies and Its Application to GPCR-Bound Cholesterol.
Article in Journal of chemical theory and computation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed.
- Dual-LAO for calculating fast and robust relative binding free energies of simple and complex transformations.Communications chemistry · 2026Article
- Effects of Membrane Cholesterol on the Structure and Function of Selected Class A GPCRs─Challenges and Future Perspectives.Biochemistry · 2025Review
- Targeting RNA with small molecules using state-of-the-art methods provides highly predictive affinities of riboswitch inhibitors.Communications biology · 2025Article
- The cryo-EM structure and physical basis for anesthetic inhibition of the THIK1 K2P channel.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Expanded Functionality and Portability for the Colvars Library.The journal of physical chemistry. B · 2024Article
- Propofol binds and inhibits skeletal muscle ryanodine receptor 1.British journal of anaesthesia · 2024Article
- Improved Highly Mobile Membrane Mimetic Model for Investigating Protein-Cholesterol Interactions.Journal of chemical information and modeling · 2024Article
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- alchemlyb: the simple alchemistry library.Journal of open source software · 2024Article
- Structural and thermodynamic framework for PIEZO1 modulation by small molecules.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Alchemical Free Energy Calculations on Membrane-Associated Proteins.Journal of chemical theory and computation · 2023Review
- The energetics and ion coupling of cholesterol transport through Patched1.Science advances · 2023Article
- Binding site plasticity regulation of the FimH catch-bond mechanism.Biophysical journal · 2023Article
- Comparison of Receptor-Ligand Restraint Schemes for Alchemical Absolute Binding Free Energy Calculations.Journal of chemical theory and computation · 2023Article
- The Energetics and Ion Coupling of Cholesterol Transport Through Patched1.bioRxiv : the preprint server for biology · 2023Article
- Regulation of membrane protein structure and function by their lipid nano-environment.Nature reviews. Molecular cell biology · 2023Review
- Importance of molecular dynamics equilibrium protocol on protein-lipid interaction near channel pore.Biophysical reports · 2022Article
- Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation.Nature communications · 2022Article
- PyLipID: A Python Package for Analysis of Protein-Lipid Interactions from Molecular Dynamics Simulations.Journal of chemical theory and computation · 2022Article
- Concentration-dependent thermodynamic analysis of the partition process of small ligands into proteins.Computational and structural biotechnology journal · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
The theory of receptor-ligand binding equilibria has long been well-established in biochemistry, and was primarily constructed to describe dilute aqueous solutions. Accordingly, few computational approaches have been developed for making quantitative predictions of binding probabilities in environments other than dilute isotropic solution. Existing techniques, ranging from simple automated docking procedures to sophisticated thermodynamics-based methods, have been developed with soluble proteins in mind. Biologically and pharmacologically relevant protein-ligand interactions often occur in complex environments, including lamellar phases like membranes and crowded, nondilute solutions. Here, we revisit the theoretical bases of ligand binding equilibria, avoiding overly specific assumptions that are nearly always made when describing receptor-ligand binding. Building on this formalism, we extend the asymptotically exact Alchemical Free Energy Perturbation technique to quantifying occupancies of sites on proteins in a complex bulk, including phase-separated, anisotropic, or nondilute solutions, using a thermodynamically consistent and easily generalized approach that resolves several ambiguities of current frameworks. To incorporate the complex bulk without overcomplicating the overall thermodynamic cycle, we simplify the common approach for ligand restraints by using a single distance-from-bound-configuration (DBC) ligand restraint during AFEP decoupling from protein. DBC restraints should be generalizable to binding modes of most small molecules, even those with strong orientational dependence. We apply this approach to compute the likelihood that membrane cholesterol binds to known crystallographic sites on three GPCRs (β
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.