ArticleNature communications2014
Activation pathway of Src kinase reveals intermediate states as targets for drug design.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 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
168 citing papers in PubMed, 352 citations in OpenAlex.
- Conformational Sampling of CPT1A Enables Dynamic Structure-Based Ligand Screening.International journal of molecular sciences · 2026Article
- An Expanded Markov State Model-Transition Path Theory Framework for Ion Conduction Reactive Pathways through Membrane Channels.The journal of physical chemistry letters · 2026Article
- Membrane Curvature Activates Src kinase and Promotes Metastatic Cancer Cell Survival.bioRxiv : the preprint server for biology · 2026Article
- Nucleosome condensate and linker DNA alter chromatin folding pathways and rates.Biophysical journal · 2026Article
- Building multiscale Markov state models by systematic mapping of temporal communities.Bioinformatics (Oxford, England) · 2026Article
- Markovian state models uncover casein kinase 1 dynamics that govern circadian period.Biophysical journal · 2025Article
- Water-Based Pharmacophore Modeling in Kinase Inhibitor Design: A Case Study on Fyn and Lyn Protein Kinases.Journal of chemical information and modeling · 2025Article
- Advances and challenges in drug repurposing in precision therapeutics of colorectal cancer.World journal of gastrointestinal oncology · 2025Review
- Allosteric Coupling in Full-Length Lyn Kinase Revealed by Molecular Dynamics and Network Analysis.International journal of molecular sciences · 2025Article
- Unveiling the Conformational Dynamics of the Histone Tails Using Markov State Modeling.Journal of chemical theory and computation · 2025Article
- Energetics of substrate transport in proton-dependent oligopeptide transporters.Communications chemistry · 2024Article
- Halloysite Nanotube-Based Delivery of Pyrazolo[3,4-Pharmaceutics · 2024Article
- MEF-AlloSite: an accurate and robust Multimodel Ensemble Feature selection for the Allosteric Site identification model.Journal of cheminformatics · 2024Article
- Exploring the conformational landscape of protein kinases.Current opinion in structural biology · 2024Review
- Delineating the stepwise millisecond allosteric activation mechanism of the class C GPCR dimer mGlu5.Nature communications · 2024Article
- Molecular basis for differential recognition of an allosteric inhibitor by receptor tyrosine kinases.Proteins · 2024Article
- Article
- The Arabidopsis AtSWEET13 transporter discriminates sugars by selective facial and positional substrate recognition.Communications biology · 2024Article
- CDK2 and CDK4: Cell Cycle Functions Evolve Distinct, Catalysis-Competent Conformations, Offering Drug Targets.JACS Au · 2024Article
- Computational Investigation of the Covalent Inhibition Mechanism of Bruton's Tyrosine Kinase by Ibrutinib.Journal of chemical information and modeling · 2024Article
108 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
Unregulated activation of Src kinases leads to aberrant signalling, uncontrolled growth and differentiation of cancerous cells. Reaching a complete mechanistic understanding of large-scale conformational transformations underlying the activation of kinases could greatly help in the development of therapeutic drugs for the treatment of these pathologies. In principle, the nature of conformational transition could be modelled in silico via atomistic molecular dynamics simulations, although this is very challenging because of the long activation timescales. Here we employ a computational paradigm that couples transition pathway techniques and Markov state model-based massively distributed simulations for mapping the conformational landscape of c-src tyrosine kinase. The computations provide the thermodynamics and kinetics of kinase activation for the first time, and help identify key structural intermediates. Furthermore, the presence of a novel allosteric site in an intermediate state of c-src that could be potentially used for drug design is predicted.
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.