2019 Fiscal Year Research-status Report
Atomistic mechanism of the oligomerization of p53 protein in DNA scanning
| Project/Area Number |
19K23721
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
TRAN PHUOC・DUY 東京工業大学, 生命理工学院, 助教 (50848546)
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Keywords | p53 protein / PaCS-MD / kinetic rate calculation / association simulation / dissociation simulation |
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| Outline of Annual Research Achievements |
We have successfully simulated the association and dissociation process of Transactivation domain of p53 protein to its inhibitor MDM2 protein which is in agreement with experimental data. The results further show the atomistic mechanism of the association, in which is consisted of the induced fitting process to find the correct binding pose, dehydration, helical formation process as the final stage to complete the association. In addition, we successfully built the stable full structure of p53 protein in complex with DNA duplex, and the tetrameric core-domain of p53 protein in complex with DNA duplex. We successfully performed dissociation of DNA out of the tetrameric complex.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The research is currently in smooth process as planned.
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| Strategy for Future Research Activity |
In the future, we will carry out the study of full length p53 protein dissociation out of the p53 protein to yield atomistic mechanism on how the p53 scan the DNA. Moreover, we will carry out the study of p53 hetero-oligomerization with other types of inhibitors affecting the p53 functions.
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