ReviewQuarterly reviews of biophysics2013
Protonation and pK changes in protein-ligand binding.
Review in Quarterly reviews of biophysics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Insights into the Pharmacological Effects of Flavonoids: The Systematic Review of Computer Modeling.International journal of molecular sciences · 2022Pooled it
- From proton microdomains to protein migration: hypothesis for ΔpH-controlled PSII relocation.Photosynthesis research · 2026Article
- Kinase inhibitors can change protonation or tautomeric state upon binding.bioRxiv : the preprint server for biology · 2026Article
- RiboScreenBiomedicines · 2026Review
- AI in Drug Discovery: Clinical Failures, Regulatory Reality, and the Validation Crisis Behind the Hype.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Constant-pH Molecular Dynamics of Cationic Peptide Dendrimers Binding to siRNA.Journal of chemical information and modeling · 2026Article
- AmberTorchPB: A Unified Framework for Poisson-Boltzmann-Based Reaction Field Energy Calculation via Tensor Computation.Journal of chemical theory and computation · 2026Article
- Quantifying the Acidification-Induced Shift of the Dimerization Equilibrium of PsbS.The journal of physical chemistry letters · 2026Article
- Characterization of the interaction between tartrazine andCurrent research in food science · 2026Article
- GPU-Accelerated Implementation of Constant-pH Molecular Dynamics in NAMD.Journal of chemical information and modeling · 2025Article
- PKAD-R: curated, redesigned and expanded database of experimental pKa values in proteins.Journal of computational biophysics and chemistry · 2025Article
- Sensing within: Mitochondrial inside-out signal transduction.Cell chemical biology · 2025Review
- End-to-End Modeling of Reaction Field Energy Using Data-Driven Geometric Graph Neural Networks.Journal of chemical theory and computation · 2025Article
- Comparative Analysis of Biochemical and Cellular Assay Conditions and the Need for a Buffer That Mimics Cytoplasmic Environments.Molecules (Basel, Switzerland) · 2025Review
- Computing the pH-Dependent Thermodynamics of the Allostery between Dimerization and Palmitate Binding in β-Lactoglobulin.The journal of physical chemistry. B · 2025Article
- A role for pH dynamics regulating transcription factor DNA-binding selectivity.Nucleic acids research · 2025Article
- Computational Strategies for Broad Spectrum Venom Phospholipase AJournal of chemical information and modeling · 2025Article
- Review
- Article
- Stabilization of the retromer complex: Analysis of novel binding sites of bis-1,3-phenyl guanylhydrazone 2a to the VPS29/VPS35 interface.Computational and structural biotechnology journal · 2024Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Formation of protein-ligand complexes causes various changes in both the receptor and the ligand. This review focuses on changes in pK and protonation states of ionizable groups that accompany protein-ligand binding. Physical origins of these effects are outlined, followed by a brief overview of the computational methods to predict them and the associated corrections to receptor-ligand binding affinities. Statistical prevalence, magnitude and spatial distribution of the pK and protonation state changes in protein-ligand binding are discussed in detail, based on both experimental and theoretical studies. While there is no doubt that these changes occur, they do not occur all the time; the estimated prevalence varies, both between individual complexes and by method. The changes occur not only in the immediate vicinity of the interface but also sometimes far away. When receptor-ligand binding is associated with protonation state change at particular pH, the binding becomes pH dependent: we review the interplay between sub-cellular characteristic pH and optimum pH of receptor-ligand binding. It is pointed out that there is a tendency for protonation state changes upon binding to be minimal at physiologically relevant pH for each complex (no net proton uptake/release), suggesting that native receptor-ligand interactions have evolved to reduce the energy cost associated with ionization changes. As a result, previously reported statistical prevalence of these changes - typically computed at the same pH for all complexes - may be higher than what may be expected at optimum pH specific to each complex. We also discuss whether proper account of protonation state changes appears to improve practical docking and scoring outcomes relevant to structure-based drug design. An overview of some of the existing challenges in the field is provided in conclusion.
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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.