2020 Fiscal Year Research-status Report
Characterizing the mechanism of chromatin remodeling by molecular dynamics simulations
| Project/Area Number |
20K06587
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | MD simulation / nucleosome / chromatin remodeling / all-atom |
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| Outline of Annual Research Achievements |
In the past year we made significant advancements in refining the simulation protocol to investigate nucleosome repositioning, and already started production runs that will be used for the main analysis. More specifically:
- We realized of some shortcoming of the standard all-atom force field originally employed, and applied force field corrections that are well suited for investigating protein-DNA complexes such as the nucleosome, as recommended in the literature.
- We turned our attention to a more ambitious H3/H4 tetrasome system instead of the H3/H4 disome originally used in our preliminary simulations. The new system is more computationally expensive, but still feasible, and it is also more relevant to realistic experimental conditions, so we believe the results will have a stronger impact.
- We refined the methodology for reconstructing the free energy landscape and the dynamics of nucleosome repositioning, opting for a Markov state modeling approach based on relatively short molecular dynamics (MD) trajectories initiated along a set of biased MD repositioning pathways.
Preliminary results have been presented at the Biophysical society meeting in 2020.
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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 project is progressing as originally planned. We made a few changes to the target system and computational approach relative to what used in our preliminary tests, but we are now ready for the production runs and the main analysis of the simulations.
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| Strategy for Future Research Activity |
This year we will run the majority of the production runs of our target system, and we will then analyze the trajectories using Markov state modeling to reconstruct the free energy landscape and kinetics of nucleosome repositioning. We plan to present some of the results at the next Biophysical society meeting.
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| Causes of Carryover |
The incurring amount will be used to buy computational resources from the Kyoto University supercomputer center, and then to present our results at at least one conference within Japan. Using the supercomputer resources allocated, we will run the main production runs used to characterize the nucleosome repositioning process.
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