ArticleJournal of chemical theory and computation2014
Role of Desolvation in Thermodynamics and Kinetics of Ligand Binding to a Kinase.
Article in Journal of chemical theory and computation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed.
- The network pharmacology prediction and experiment validation of Astragalus membranaceus for alleviating silicosis fibrosis via decreasing MMP9 and EGFR expression.Scientific reports · 2026Article
- Peptide-based ligand antagonists block a Vibrio cholerae adhesin.FEBS letters · 2026Article
- Dissociation kinetics of G proteins from G protein-coupled receptors and effects of allosteric modulation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Thermodynamics and Kinetics of the Deintercalation of a Novel Anthracycline from Double-Stranded Oligonucleotide DNA.The journal of physical chemistry. B · 2025Article
- A quantitative analysis of ligand binding at the protein-lipid bilayer interface.Communications chemistry · 2025Article
- Indazole to 2-Cyanoindole Scaffold Progression for Mycobacterial Lipoamide Dehydrogenase Inhibitors Achieves Extended Target Residence Time and Improved Antibacterial Activity.Angewandte Chemie (International ed. in English) · 2024Article
- Dental biomaterials redefined: molecular docking and dynamics-driven dental resin composite optimization.BMC oral health · 2024Article
- Elucidation of the structural basis for ligand binding and translocation in conserved insect odorant receptor co-receptors.Nature communications · 2023Article
- Computational design of newly engineered DARPins as HER2 receptor inhibitors for breast cancer treatment.Research in pharmaceutical sciences · 2023Article
- Strict Interactions of Fifth Letters, Hydrophobic Unnatural Bases, in XenoAptamers with Target Proteins.Journal of the American Chemical Society · 2023Article
- Designing of potent anti-diabetic molecules by targeting SIK2 using computational approaches.Molecular diversity · 2023Article
- Membrane Lipids Are an Integral Part of Transmembrane Allosteric Sites in GPCRs: A Case Study of Cannabinoid CB1 Receptor Bound to a Negative Allosteric Modulator, ORG27569, and Analogs.Journal of medicinal chemistry · 2022Article
- WaterMap and Molecular Dynamic Simulation-Guided Discovery of Potential PAK1 Inhibitors Using Repurposing Approaches.ACS omega · 2021Article
- Reduced efficacy of a Src kinase inhibitor in crowded protein solution.Nature communications · 2021Article
- Exploring ligand binding pathways on proteins using hypersound-accelerated molecular dynamics.Nature communications · 2021Article
- Thermodynamics and Kinetics of Drug-Target Binding by Molecular Simulation.Chemical reviews · 2020Review
- Improving the Efficiency of Ligand-Binding Protein Design with Molecular Dynamics Simulations.Journal of chemical theory and computation · 2019Article
- Encounter complexes and hidden poses of kinase-inhibitor binding on the free-energy landscape.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Solvents to Fragments to Drugs: MD Applications in Drug Design.Molecules (Basel, Switzerland) · 2018Review
- Role of Molecular Interactions and Protein Rearrangement in the Dissociation Kinetics of p38α MAP Kinase Type-I/II/III Inhibitors.Journal of chemical information and modeling · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Computer simulations are used to determine the free energy landscape for the binding of the anticancer drug Dasatinib to its src kinase receptor and show that before settling into a free energy basin the ligand must surmount a free energy barrier. An analysis based on using both the ligand-pocket separation and the pocket-water occupancy as reaction coordinates shows that the free energy barrier is a result of the free energy cost for almost complete desolvation of the binding pocket. The simulations further show that the barrier is not a result of the reorganization free energy of the binding pocket. Although a continuum solvent model gives the location of free energy minima, it is not able to reproduce the intermediate free energy barrier. Finally, it is shown that a kinetic model for the on rate constant in which the ligand diffuses up to a doorway state and then surmounts the desolvation free energy barrier is consistent with published microsecond time-scale simulations of the ligand binding kinetics for this system [Shaw, D. E. et al. J. Am. Chem. Soc.2011, 133, 9181-9183].
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.