ArticleNature communications2021
Reduced efficacy of a Src kinase inhibitor in crowded protein solution.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Phosphorylation Modification Characteristics of Liver Injury-Related Proteins inPathogens (Basel, Switzerland) · 2026Article
- Selective antitumor and apoptosis‑inducing effects of the Src inhibitor PP1 in human tongue squamous cell carcinoma cells.International journal of oncology · 2026Article
- Allosteric regulation of enzymatic catalysis by molecular crowding.Communications chemistry · 2026Article
- Underestimated role of macromolecular crowding in bioengineeredMaterials today. Bio · 2025Article
- PEG-mCherry interactions beyond classical macromolecular crowding.Protein science : a publication of the Protein Society · 2025Article
- Recent Progress in Modeling and Simulation of Biomolecular Crowding and Condensation Inside Cells.Journal of chemical information and modeling · 2024Review
- BEMM-GEN: A Toolkit for Generating a Biomolecular Environment-Mimicking Model for Molecular Dynamics Simulation.Journal of chemical information and modeling · 2024Article
- Computational Approaches to Predict Protein-Protein Interactions in Crowded Cellular Environments.Chemical reviews · 2024Review
- In-Cell Dynamics: The Next Focus of All-Atom Simulations.The journal of physical chemistry. B · 2023Review
- Real-time monitoring of the reaction of KRAS G12C mutant specific covalent inhibitor by in vitro and in-cell NMR spectroscopy.Scientific reports · 2023Article
- The c-Src/LIST Positive Feedback Loop Sustains Tumor Progression and Chemoresistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Varying molecular interactions explain aspects of crowder-dependent enzyme function of a viral protease.PLoS computational biology · 2023Article
- Characterizing Transient Protein-Protein Interactions by Trp-Cys Quenching and Computer Simulations.The journal of physical chemistry letters · 2022Article
- Impact of the Cellular Environment on Adenosine Triphosphate Conformations.The journal of physical chemistry letters · 2022Article
- Diffusion of small molecule drugs is affected by surface interactions and crowder proteins.iScience · 2022Article
- Modified Protein-Water Interactions in CHARMM36m for Thermodynamics and Kinetics of Proteins in Dilute and Crowded Solutions.Molecules (Basel, Switzerland) · 2022Article
- Protein assembly and crowding simulations.Current opinion in structural biology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The inside of a cell is highly crowded with proteins and other biomolecules. How proteins express their specific functions together with many off-target proteins in crowded cellular environments is largely unknown. Here, we investigate an inhibitor binding with c-Src kinase using atomistic molecular dynamics (MD) simulations in dilute as well as crowded protein solution. The populations of the inhibitor, 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1), in bulk solution and on the surface of c-Src kinase are reduced as the concentration of crowder bovine serum albumins (BSAs) increases. This observation is consistent with the reduced PP1 inhibitor efficacy in experimental c-Src kinase assays in addition with BSAs. The crowded environment changes the major binding pathway of PP1 toward c-Src kinase compared to that in dilute solution. This change is explained based on the population shift mechanism of local conformations near the inhibitor binding site in c-Src kinase.
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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.