ArticlePloS one2012
The impact of small molecule binding on the energy landscape of the intrinsically disordered protein C-myc.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 77 citations in OpenAlex.
- Targeting the intrinsically disordered AR-NTD through a machine learning-based enhanced sampling workflow.Nature communications · 2026Article
- Molecular driving force of a small molecule-induced protein disorder-order transition.Communications chemistry · 2026Article
- New Approach for Targeting Small-Molecule Candidates for Intrinsically Disordered Proteins.Methods and protocols · 2025Article
- Ensemble Docking for Intrinsically Disordered Proteins.Journal of chemical information and modeling · 2025Article
- Discovery of a Pyrazolopyridinone-Based MYC Inhibitor That Selectively Engages Intracellular c-MYC and Disrupts MYC-MAX Heterodimerization.Journal of medicinal chemistry · 2025Article
- Comparison of Methodologies for Absolute Binding Free Energy Calculations of Ligands to Intrinsically Disordered Proteins.Journal of chemical theory and computation · 2024Article
- High-throughput structure determination of an intrinsically disordered protein using cell-free protein crystallization.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeting MYC at the intersection between cancer metabolism and oncoimmunology.Frontiers in immunology · 2024Review
- Modes of Action of a Novel c-MYC Inhibiting 1,2,4-Oxadiazole Derivative in Leukemia and Breast Cancer Cells.Molecules (Basel, Switzerland) · 2023Article
- The Novel Artemisinin Dimer Isoniazide ELI-XXIII-98-2 Induces c-MYC Inhibition, DNA Damage, and Autophagy in Leukemia Cells.Pharmaceutics · 2023Article
- Review
- Energetics of a protein disorder-order transition in small molecule recognition.Chemical science · 2022Article
- Molecular Basis of Small-Molecule Binding to α-Synuclein.Journal of the American Chemical Society · 2022Article
- Synthetic fluorescent MYC probe: Inhibitor binding site elucidation and development of a high-throughput screening assay.Bioorganic & medicinal chemistry · 2021Article
- Intrinsically disordered proteins and biomolecular condensates as drug targets.Current opinion in chemical biology · 2021Review
- Turning Up the Heat on MYC: Progress in Small-Molecule Inhibitors.Cancer research · 2021Review
- Computational strategy for intrinsically disordered protein ligand design leads to the discovery of p53 transactivation domain I binding compounds that activate the p53 pathway.Chemical science · 2020Article
- Drug Discovery Targeting the Disorder-To-Order Transition Regions through the Conformational Diversity Mimicking and Statistical Analysis.International journal of molecular sciences · 2020Article
- Targeting Intrinsically Disordered Proteins through Dynamic Interactions.Biomolecules · 2020Review
- Structural and Biophysical Insights into the Function of the Intrinsically Disordered Myc Oncoprotein.Cells · 2020Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intrinsically disordered proteins are attractive therapeutic targets owing to their prevalence in several diseases. Yet their lack of well-defined structure renders ligand discovery a challenging task. An intriguing example is provided by the oncoprotein c-Myc, a transcription factor that is over expressed in a broad range of cancers. Transcriptional activity of c-Myc is dependent on heterodimerization with partner protein Max. This protein-protein interaction is disrupted by the small molecule 10058-F4 (1), that binds to monomeric and disordered c-Myc. To rationalize the mechanism of inhibition, structural ensembles for the segment of the c-Myc domain that binds to 1 were computed in the absence and presence of the ligand using classical force fields and explicit solvent metadynamics molecular simulations. The accuracy of the computed structural ensembles was assessed by comparison of predicted and measured NMR chemical shifts. The small molecule 1 was found to perturb the composition of the apo equilibrium ensemble and to bind weakly to multiple distinct c-Myc conformations. Comparison of the apo and holo equilibrium ensembles reveals that the c-Myc conformations binding 1 are already partially formed in the apo ensemble, suggesting that 1 binds to c-Myc through an extended conformational selection mechanism. The present results have important implications for rational ligand design efforts targeting intrinsically disordered proteins.
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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.