Thats a unique idea.You should consider the following idea to enhance your idea so that it would impact uniquely: 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’’).  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 ms 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 DDG protein thermodynamic stability. Interpreting the number of clusters as a measure of protein flexibility: (i) p53 cancer mutants re 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.
['Özlem Demir', 'Roberta Baronio', 'Faezeh Salehi', 'Christopher D. Wassman', 'Linda V. Hall', 'G. Wesley Hatfield', 'Richard Chamberlin', 'Peter Kaiser', 'Richard H. Lathrop', 'Rommie E. Amaro']
I am writing a research paper on a idea Ensemble-based computational approach discriminates functional activity of p53 cancer and rescue mutants.
[{"from": "human", "value": "I am writing a research paper on a idea Ensemble-based computational approach discriminates functional activity of p53 cancer and rescue mutants."}, {"from": "gpt", "value": "Thats a unique idea.You should consider the following idea to enhance your idea so that it would impact uniquely: The tumor suppressor protein p53 can lose its function upon single-point missense mutations in the core DNA-binding domain (\u2018\u2018cancer mutants\u2019\u2019). Activity can be restored by second-site suppressor mutations (\u2018\u2018rescue mutants\u2019\u2019).  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 ms 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 DDG protein thermodynamic stability. Interpreting the number of clusters as a measure of protein flexibility: (i) p53 cancer mutants re 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."}]