ArticlePLoS computational biology2011
Ensemble-based computational approach discriminates functional activity of p53 cancer and rescue mutants.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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
23 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Discovery of novel covalent stabilizers for p53 Y220C using structure-based drug discovery methods.Molecular diversity · 2025Article
- Computational Prediction and Experimental Validation of the Unique Molecular Mode of Action of Scoulerine.Molecules (Basel, Switzerland) · 2022Article
- GCAT: A network model of mutational influences between amino acid positions in PSD95Frontiers in molecular biosciences · 2022Article
- Mapping Function from Dynamics: Future Challenges for Network-Based Models of Protein Structures.Frontiers in molecular biosciences · 2021Article
- Markov state models and NMR uncover an overlooked allosteric loop in p53.Chemical science · 2020Article
- Tumorigenic p53 mutants undergo common structural disruptions including conversion to α-sheet structure.Protein science : a publication of the Protein Society · 2020Article
- A novel hotspot and rare somatic mutation p.A138V, at TP53 is associated with poor survival of pancreatic ductal and periampullary adenocarcinoma patients.Molecular medicine (Cambridge, Mass.) · 2020Article
- Combining Ramachandran plot and molecular dynamics simulation for structural-based variant classification: UsingComputational and structural biotechnology journal · 2020Article
- Experimental Protein Molecular Dynamics: Broadband Dielectric Spectroscopy coupled with nanoconfinement.Scientific reports · 2019Article
- Improving the Efficiency of Ligand-Binding Protein Design with Molecular Dynamics Simulations.Journal of chemical theory and computation · 2019Article
- Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting.Journal of molecular cell biology · 2019Review
- Computational Approaches to Prioritize Cancer Driver Missense Mutations.International journal of molecular sciences · 2018Review
- Insights into the Effect of the G245S Single Point Mutation on the Structure of p53 and the Binding of the Protein to DNA.Molecules (Basel, Switzerland) · 2017Article
- An optimal distance cutoff for contact-based Protein Structure Networks using side-chain centers of mass.Scientific reports · 2017Article
- Structural Evolution and Dynamics of the p53 Proteins.Cold Spring Harbor perspectives in medicine · 2017Review
- Model of the Ankyrin and SOCS Box Protein, ASB9, E3 Ligase Reveals a Mechanism for Dynamic Ubiquitin Transfer.Structure (London, England : 1993) · 2016Article
- The p53 tetramer shows an induced-fit interaction of the C-terminal domain with the DNA-binding domain.Oncogene · 2016Article
- Article
- Investigating DNA Binding and Conformational Variation in Temperature Sensitive p53 Cancer Mutants Using QM-MM Simulations.PloS one · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
The tumor suppressor protein p53 can lose its function upon single-point missense mutations in the core DNA-binding domain ("cancer mutants"). Activity can be restored by second-site suppressor mutations ("rescue mutants"). This paper relates the functional activity of p53 cancer and rescue mutants to their overall molecular dynamics (MD), without focusing on local structural details. A novel global measure of protein flexibility for the p53 core DNA-binding domain, the number of clusters at a certain RMSD cutoff, was computed by clustering over 0.7 µs of explicitly solvated all-atom MD simulations. For wild-type p53 and a sample of p53 cancer or rescue mutants, the number of clusters was a good predictor of in vivo p53 functional activity in cell-based assays. This number-of-clusters (NOC) metric was strongly correlated (r(2) = 0.77) with reported values of experimentally measured ΔΔG protein thermodynamic stability. Interpreting the number of clusters as a measure of protein flexibility: (i) p53 cancer mutants were more flexible than wild-type protein, (ii) second-site rescue mutations decreased the flexibility of cancer mutants, and (iii) negative controls of non-rescue second-site mutants did not. This new method reflects the overall stability of the p53 core domain and can discriminate which second-site mutations restore activity to p53 cancer mutants.
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.