ReviewCurrent pharmaceutical design2013
The role of protonation states in ligand-receptor recognition and binding.
Review in Current pharmaceutical design, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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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
44 citing papers in PubMed.
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- From Single Ligand-Receptor Bond Strength to Collective Avidity: Mechanics-Guided Superselective Nanoparticle Adhesion to Biological Membranes.Langmuir : the ACS journal of surfaces and colloids · 2025Article
- 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
- Improved Structure-Based Histidine pJournal of chemical information and modeling · 2025Article
- A dual experimental-theoretical perspective on ESPT photoacids and their challenges ahead.Chemical science · 2025Review
- How to Personalize General Anesthesia-A Prospective Theoretical Approach to Conformational Changes of Halogenated Anesthetics in Fire Smoke Poisoning.International journal of molecular sciences · 2024Article
- Pregnenolone sulfate analogues differentially modulate GABABritish journal of pharmacology · 2023Article
- PKAD-2: New entries and expansion of functionalities of the database of experimentally measured pKa's of proteins.Journal of computational biophysics and chemistry · 2023Article
- Activity Models of Key GPCR Families in the Central Nervous System: A Tool for Many Purposes.Journal of chemical information and modeling · 2023Article
- Biologically relevant small variations of intra-cellular pH can have significant effect on stability of protein-DNA complexes, including the nucleosome.Frontiers in molecular biosciences · 2023Article
- Cysteine Oxidation in Proteins: Structure, Biophysics, and Simulation.Biochemistry · 2022Review
- Structural Design and Synthesis of Novel Cyclic Peptide Inhibitors TargetingLife (Basel, Switzerland) · 2022Article
- Acid-Base Equilibrium and Self-Association in Relation to High Antitumor Activity of Selected Unsymmetrical Bisacridines Established by Extensive Chemometric Analysis.Molecules (Basel, Switzerland) · 2022Article
- Identification of potent inhibitors against transmembrane serine protease 2 for developing therapeutics against SARS-CoV-2.Journal of biomolecular structure & dynamics · 2022Article
- A comprehensive review of integrative pharmacology-based investigation: A paradigm shift in traditional Chinese medicine.Acta pharmaceutica Sinica. B · 2021Review
- Endothelial Glycocalyx-Mediated Intercellular Interactions: Mechanisms and Implications for Atherosclerosis and Cancer Metastasis.Cardiovascular engineering and technology · 2021Review
- Effect of pH on the Ability of N-Terminal Domain of Human NPC1 to Recognize, Bind, and Transfer Cholesterol.ACS omega · 2020Article
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Authors and funding
3 authors.
Funding
Abstract
In this review we discuss the role of protonation states in receptor-ligand interactions, providing experimental evidences and computational predictions that complex formation may involve titratable groups with unusual pKa's and that protonation states frequently change from unbound to bound states. These protonation changes result in proton uptake/release, which in turn causes the pH-dependence of the binding. Indeed, experimental data strongly suggest that almost any binding is pH-dependent and to be correctly modeled, the protonation states must be properly assigned prior to and after the binding. One may accurately predict the protonation states when provided with the structures of the unbound proteins and their complex; however, the modeling becomes much more complicated if the bound state has to be predicted in a docking protocol or if the structures of either bound or unbound receptor-ligand are not available. The major challenges that arise in these situations are the coupling between binding and protonation states, and the conformational changes induced by the binding and ionization states of titratable groups. In addition, any assessment of the protonation state, either before or after binding, must refer to the pH of binding, which is frequently unknown. Thus, even if the pKa's of ionizable groups can be correctly assigned for both unbound and bound state, without knowing the experimental pH one cannot assign the corresponding protonation states, and consequently one cannot calculate the resulting proton uptake/release. It is pointed out, that while experimental pH may not be the physiological pH and binding may involve proton uptake/release, there is a tendency that the native receptor-ligand complexes have evolved toward specific either subcellular or tissue characteristic pH at which the proton uptake/release is either minimal or absent.
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