ArticleJournal of chemical theory and computation2018
The Role of Interfacial Water in Protein-Ligand Binding: Insights from the Indirect Solvent Mediated Potential of Mean Force.
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 17 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
17 citing papers in PubMed, 35 citations in OpenAlex.
- Predicting water at the protein interface in cryo-EM structures from MD-excess chemical potential.Biophysical journal · 2026Article
- A novel approach for enhancing the potency of kinase inhibitors using topological water networks.Journal of cheminformatics · 2026Article
- Thermodynamics of Water Displacement from Binding Sites and its Contributions to Supramolecular and Biomolecular Affinity.Angewandte Chemie (International ed. in English) · 2025Article
- De Novo Hydration of Cryo-EM Reconstructions through Molecular Dynamics Simulations of the Excess Chemical Potential.bioRxiv : the preprint server for biology · 2025Article
- Free Energy Density of a Fluid and Its Role in Solvation and Binding.Journal of chemical theory and computation · 2024Article
- Article
- Elucidating the molecular determinants for binding modes of a third-generation HIV-1 integrase strand transfer inhibitor: Importance of side chain and solvent reorganization.bioRxiv : the preprint server for biology · 2023Article
- TWN-FS method: A novel fragment screening method for drug discovery.Computational and structural biotechnology journal · 2023Article
- Understanding the role of water on temperature-dependent structural modifications of SARS CoV-2 main protease binding sites.Journal of molecular liquids · 2022Article
- Outliers in SAR and QSAR: 3. Importance of considering the role of water molecules in protein-ligand interactions and quantitative structure-activity relationship studies.Journal of computer-aided molecular design · 2021Article
- Solvation Thermodynamics from the Perspective of Endpoints DFT.The journal of physical chemistry. B · 2020Review
- Cavity Particle in Aqueous Solution with a Hydrophobic Solute: Structure, Energetics, and Functionals.The journal of physical chemistry. B · 2020Article
- Distribution and Function of Glycosaminoglycans and Proteoglycans in the Development, Homeostasis and Pathology of the Ocular Surface.Frontiers in cell and developmental biology · 2020Review
- Spatially-Decomposed Free Energy of Solvation Based on the Endpoint Density-Functional Method.Journal of chemical theory and computation · 2019Article
- Comparing alchemical and physical pathway methods for computing the absolute binding free energy of charged ligands.Physical chemistry chemical physics : PCCP · 2018Article
- The Excess Chemical Potential of Water at the Interface with a Protein from End Point Simulations.The journal of physical chemistry. B · 2018Article
- Adaptive Membrane Fluidity Modulation: A Feedback Regulated Homeostatic System and Target for Pharmacological Intervention.In vivo (Athens, Greece)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Classical density functional theory (DFT) can be used to relate the thermodynamic properties of solutions to the indirect solvent mediated part of the solute-solvent potential of mean force (PMF). Standard, but powerful numerical methods can be used to estimate the solute-solvent PMF from which the indirect part can be extracted. In this work we show how knowledge of the direct and indirect parts of the solute-solvent PMF for water at the interface of a protein receptor can be used to gain insights about how to design tighter binding ligands. As we show, the indirect part of the solute-solvent PMF is equal to the sum of the 1-body (energy + entropy) terms in the inhomogeneous solvation theory (IST) expansion of the solvation free energy. To illustrate the effect of displacing interfacial water molecules with particular direct/indirect PMF signatures on the binding of ligands, we carry out simulations of protein binding with several pairs of congeneric ligands. We show that interfacial water locations that contribute favorably or unfavorably at the 1-body level (energy + entropy) to the solvation free energy of the solute can be targeted as part of the ligand design process. Water locations where the indirect PMF is larger in magnitude provide better targets for displacement when adding a functional group to a ligand core.
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.