ArticleScientific reports2016
Conformational Selection and Induced Fit Mechanisms in the Binding of an Anticancer Drug to the c-Src Kinase.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 71 citations in OpenAlex.
- Beyond the flat screen: evaluating virtual reality as a complementary tool for molecular docking in drug discovery.Journal of computer-aided molecular design · 2026Review
- Flexible protein-ligand docking with diffusion-based side-chain packing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Protein-Ligand Interactions: Recent Advances in Biophysics, Biochemistry, and Bioinformatics.International journal of molecular sciences · 2025Article
- Conformational modulation of intrinsically disordered transactivation domains for cancer therapy.PNAS nexus · 2025Review
- Molecular Modelling in Bioactive Peptide Discovery and Characterisation.Biomolecules · 2025Review
- Prospective Evaluation of Structure-Based Simulations Reveal Their Ability to Predict the Impact of Kinase Mutations on Inhibitor Binding.The journal of physical chemistry. B · 2025Article
- Prospective evaluation of structure-based simulations reveal their ability to predict the impact of kinase mutations on inhibitor binding.bioRxiv : the preprint server for biology · 2025Article
- Structure optimization and molecular dynamics studies of new tumor-selectiveJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Utilizing Molecular Dynamics Simulations, Machine Learning, Cryo-EM, and NMR Spectroscopy to Predict and Validate Protein Dynamics.International journal of molecular sciences · 2024Review
- Molecular basis for differential recognition of an allosteric inhibitor by receptor tyrosine kinases.Proteins · 2024Article
- Classifying protein kinase conformations with machine learning.Protein science : a publication of the Protein Society · 2024Article
- Structural mechanism of a drug-binding process involving a large conformational change of the protein target.Nature communications · 2023Article
- Molecularly Imprinted Polymeric Particles Created Using Droplet-Based Microfluidics: Preparation and Applications.Micromachines · 2023Review
- Integrating Protein Interaction Surface Prediction with a Fragment-Based Drug Design: Automatic Design of New Leads with Fragments on Energy Surfaces.Journal of chemical information and modeling · 2023Article
- A Guide to In Silico Drug Design.Pharmaceutics · 2022Review
- Atomic resolution protein allostery from the multi-state structure of a PDZ domain.Nature communications · 2022Article
- Using azobenzene photocontrol to set proteins in motion.Nature reviews. Chemistry · 2022Review
- Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective.Frontiers in molecular biosciences · 2022Review
- Practical Protocols for Efficient Sampling of Kinase-Inhibitor Binding Pathways Using Two-Dimensional Replica-Exchange Molecular Dynamics.Frontiers in molecular biosciences · 2022Article
- TYROSINE KINASES: COMPLEX MOLECULAR SYSTEMS CHALLENGING COMPUTATIONAL METHODOLOGIES.The European physical journal. B · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Understanding the conformational changes associated with the binding of small ligands to their biological targets is a fascinating and meaningful question in chemistry, biology and drug discovery. One of the most studied and important is the so-called "DFG-flip" of tyrosine kinases. The conserved three amino-acid DFG motif undergoes an "in to out" movement resulting in a particular inactive conformation to which "type II" kinase inhibitors, such as the anti-cancer drug Imatinib, bind. Despite many studies, the details of this prototypical conformational change are still debated. Here we combine various NMR experiments and surface plasmon resonance with enhanced sampling molecular dynamics simulations to shed light into the conformational dynamics associated with the binding of Imatinib to the proto-oncogene c-Src. We find that both conformational selection and induced fit play a role in the binding mechanism, reconciling opposing views held in the literature. Moreover, an external binding pose and local unfolding (cracking) of the aG helix are observed.
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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.