↓ Skip to main content

Ensemble-Based Computational Approach Discriminates Functional Activity of p53 Cancer and Rescue Mutants

Overview of attention for article published in PLoS Computational Biology, October 2011
Altmetric Badge

About this Attention Score

  • Average Attention Score compared to outputs of the same age
  • Above-average Attention Score compared to outputs of the same age and source (54th percentile)

Mentioned by

patent
1 patent

Citations

dimensions_citation
35 Dimensions

Readers on

mendeley
69 Mendeley
citeulike
3 CiteULike
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Ensemble-Based Computational Approach Discriminates Functional Activity of p53 Cancer and Rescue Mutants
Published in
PLoS Computational Biology, October 2011
DOI 10.1371/journal.pcbi.1002238
Pubmed ID
Authors

Özlem Demir, Roberta Baronio, Faezeh Salehi, Christopher D. Wassman, Linda Hall, G. Wesley Hatfield, Richard Chamberlin, Peter Kaiser, Richard H. Lathrop, Rommie E. Amaro

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.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 69 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 4 6%
Korea, Republic of 1 1%
Italy 1 1%
France 1 1%
Canada 1 1%
India 1 1%
Japan 1 1%
Argentina 1 1%
Unknown 58 84%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 22%
Researcher 13 19%
Professor > Associate Professor 6 9%
Student > Master 6 9%
Professor 4 6%
Other 12 17%
Unknown 13 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 22%
Agricultural and Biological Sciences 13 19%
Chemistry 12 17%
Engineering 6 9%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Other 7 10%
Unknown 14 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 August 2017.
All research outputs
#8,693,470
of 25,756,911 outputs
Outputs from PLoS Computational Biology
#5,679
of 9,032 outputs
Outputs of similar age
#51,955
of 152,158 outputs
Outputs of similar age from PLoS Computational Biology
#55
of 129 outputs
Altmetric has tracked 25,756,911 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,032 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.2. This one is in the 33rd percentile – i.e., 33% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 152,158 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 129 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.