ArticleNature communications2023
Structural mechanism of a drug-binding process involving a large conformational change of the protein target.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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Who cites it
53 citing papers in PubMed, 103 citations in OpenAlex.
- Uncovering hidden druggable sites: computational approaches to allosteric and cryptic pocket discovery-from molecular dynamics to AI.Journal of computer-aided molecular design · 2026Review
- From Enhanced Sampling to Human-Readable Representations of Protein Dynamics.Journal of chemical theory and computation · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Intrinsic cellular resistance to BCR::ABL1 inhibitors.Haematologica · 2026Review
- Results of a Large-Scale Study of the Binding of 50 Type II Inhibitors to 348 Kinases: The Role of Protein Reorganization.Journal of medicinal chemistry · 2026Article
- Altered residence time as a cause of drug resistance.Current opinion in structural biology · 2026Review
- Fast sampling of protein conformational dynamics.Science advances · 2026Article
- Results of a large scale study of the binding of 50 type II inhibitors to 348 kinases: The role of protein reorganization.bioRxiv : the preprint server for biology · 2026Article
- Contact Cluster Modeling of Allosteric Communication in PDZ Domains.The journal of physical chemistry. B · 2026Review
- Rational Design, Synthesis, and Molecular Docking of Novel Terpene Analogues of Imatinib, and Their Inhibition on Downstream BCR-ABL Signaling.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Molecular dynamics simulations elucidate the role of the F-F' loop in substrate entry into CYP3A4.Communications chemistry · 2026Article
- DRESIS 2.0: the comprehensive landscape of drug resistance information.Nucleic acids research · 2026Article
- Measuring and locating the changes in protein structure using MELO.Nature communications · 2026Article
- Alexidine is a TAZ-specific small-molecule inhibitor that suppresses breast cancer invasion and metastasis.iScience · 2025Article
- Weighted Ensemble Simulations Reveal Novel Conformations and Modulator Effects in Hepatitis B Virus Capsid Assembly.Journal of chemical theory and computation · 2025Article
- Suppressing protein damage response to overcome multidrug resistance in cancer therapy.Cell discovery · 2025Article
- Recent Advances in Elucidating the Mechanism of the NADPH-Cytochrome P450 Reductase-Mediated Electron Transfer Cycle: Experimental and Computational Perspectives.Molecules (Basel, Switzerland) · 2025Review
- Path-Based Nonequilibrium Binding Free Energy Estimation, from Protein-Ligand to RNA-Ligand Binding.Journal of chemical information and modeling · 2025Article
- Integrating Hydrogen Exchange with Molecular Dynamics for Improved Ligand Binding Predictions.Journal of chemical information and modeling · 2025Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Proteins often undergo large conformational changes when binding small molecules, but atomic-level descriptions of such events have been elusive. Here, we report unguided molecular dynamics simulations of Abl kinase binding to the cancer drug imatinib. In the simulations, imatinib first selectively engages Abl kinase in its autoinhibitory conformation. Consistent with inferences drawn from previous experimental studies, imatinib then induces a large conformational change of the protein to reach a bound complex that closely resembles published crystal structures. Moreover, the simulations reveal a surprising local structural instability in the C-terminal lobe of Abl kinase during binding. The unstable region includes a number of residues that, when mutated, confer imatinib resistance by an unknown mechanism. Based on the simulations, NMR spectra, hydrogen-deuterium exchange measurements, and thermostability measurements and estimates, we suggest that these mutations confer imatinib resistance by exacerbating structural instability in the C-terminal lobe, rendering the imatinib-bound state energetically unfavorable.
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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.