ArticleNucleic acids research2019
Simulations of mutant p53 DNA binding domains reveal a novel druggable pocket.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Determinants of CBiomolecules · 2026Article
- Multi-Site Aggregation of p53: Insights from Self- and Co-Aggregation of Multiple Aggregation-Prone Regions.ACS omega · 2026Article
- The Allosteric Regulation of the DNA-Binding Domain of p53 by the Intrinsically Disordered C-Terminal Domain.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Integrated molecular dynamics elucidation of TP53 H179 zinc-binding variants: genomic and structural characterization across NSCLC subtypes.Frontiers in bioinformatics · 2026Article
- Network Theory Analysis of Allosteric Drug-Rescue Mechanisms in the Tumor Suppressor Protein p53 Y220C Mutant.International journal of molecular sciences · 2025Article
- Profiling of Protein-Coding Missense Mutations in Mendelian Rare Diseases: Clues from Structural Bioinformatics.International journal of molecular sciences · 2025Article
- Exploring the Genetic Orchestra of Cancer: The Interplay Between Oncogenes and Tumor-Suppressor Genes.Cancers · 2025Review
- Deciphering the safeguarding role of cysteine residues in p53 against HCommunications chemistry · 2025Article
- Thermal stress, p53 structures and learning from elephants.Cell death discovery · 2024Review
- Targeting tumor suppressor p53 for organ fibrosis therapy.Cell death & disease · 2024Review
- GOF Mutant p53 in Cancers: A Therapeutic Challenge.Cancers · 2022Review
- Insights into Allosteric Mechanisms of the Lung-Enriched p53 Mutants V157F and R158L.International journal of molecular sciences · 2022Article
- Whole genome duplication in oral squamous cell carcinoma in patients younger than 50 years: implications for prognosis and adverse clinicopathological factors.Genes, chromosomes & cancer · 2022Article
- Structural Basis of Mutation-Dependent p53 Tetramerization Deficiency.International journal of molecular sciences · 2022Article
- Deciphering the mechanisms of HPV E6 mutations in the destabilization of E6/E6AP/p53 complex.Biophysical journal · 2022Article
- Most Probable Druggable Pockets in Mutant p53-Arg175His Clusters Extracted from Gaussian Accelerated Molecular Dynamics Simulations.The protein journal · 2022Article
- Role of Position K+4 in the Phosphorylation and Dephosphorylation Reaction Kinetics of the CheY Response Regulator.Biochemistry · 2021Article
- Structural and Drug Targeting Insights on Mutant p53.Cancers · 2021Review
- An integrated view of p53 dynamics, function, and reactivation.Current opinion in structural biology · 2021Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The DNA binding domain (DBD) of the tumor suppressor p53 is the site of several oncogenic mutations. A subset of these mutations lowers the unfolding temperature of the DBD. Unfolding leads to the exposure of a hydrophobic β-strand and nucleates aggregation which results in pathologies through loss of function and dominant negative/gain of function effects. Inspired by the hypothesis that structural changes that are associated with events initiating unfolding in DBD are likely to present opportunities for inhibition, we investigate the dynamics of the wild type (WT) and some aggregating mutants through extensive all atom explicit solvent MD simulations. Simulations reveal differential conformational sampling between the WT and the mutants of a turn region (S6-S7) that is contiguous to a known aggregation-prone region (APR). The conformational properties of the S6-S7 turn appear to be modulated by a network of interacting residues. We speculate that changes that take place in this network as a result of the mutational stress result in the events that destabilize the DBD and initiate unfolding. These perturbations also result in the emergence of a novel pocket that appears to have druggable characteristics. FDA approved drugs are computationally screened against this pocket.
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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.