2021 Fiscal Year Research-status Report
Designing of novel bone-inducing molecules by an experimental-computational approach
| Project/Area Number |
21K09963
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| Research Institution | Waseda University |
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Principal Investigator |
国吉 ニルソン 早稲田大学, 理工学術院, 教授 (30254577)
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| Co-Investigator(Kenkyū-buntansha) |
ハラ エミリオ・サトシ 岡山大学, 医歯薬学域, 研究准教授 (40779443)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | mineralization / phospholipids / quantum chemistry / activation energies / reaction dynamics / reaction mechanism |
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| Outline of Annual Research Achievements |
Phospholipids have been shown to be the nucleation site for bone and tooth formation. However, the exact process of phospholipid mineralization remains unclear. Here, the mineralization process from phospholipid molecules was investigated through experimental and theoretical approaches. Phospholipids are composed of a phosphate group linked to a hydrophilic group and a hydrophobic tail. Different kinds of kinds of phospholipids have different hydrophilic groups.
Experimentally, it was found that each kind of phospholipid has a different mineralization efficiency. In addition, the mineralization efficiency was seen to depend also on the length of the hydrophobic tail.
In order to clarify the mineralization mechanism, we analyzed hydrolysis reactions of phopspholipids, assuming that hydrolysis is the first step in the mineralization process and a potential step controling the rate of the whole process. The analysis of the reactions was conducted through quantum chemical methods, using Gaussian16. The B3LYP/6-31G(d,p) level was employed in the structure optimizations and the activation energies were determined under APFD/6-311+G(2d,p) level, with SMD correction. The calculation results did show some differences among the different phospholipids but these results alone could not explain completely the experimental results.
We plan to revise the reactions to be analyzed. Only single phospholipid molecules linked to a single calcium ion were taken into account; next we will analyze hydrolysis reactions of two phospholipid molecules of the same kind linked to a single calcium ion.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
The calculation results were not able to explain the experimental results as well as we expected. The reactions to be analyzed need to be revised and measurements of the intermediate products are needed to confirm the calculation results obtained so far.
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| Strategy for Future Research Activity |
In the actual aqueous solution, multiple phospholipid molecules may be linked to a single calcium ion, and this large molecular system then reacts with water molecules. The calculation of these large systems is challenging but they are expected to be closer to the real reaction systems and the calculation results are expected to better match the experimental results.
In addition, in order to clarify the reaction mechanisms, measurements of the intermediate products (hydrolysis products at this stage) are needed. The results of these measurements may then give insights into what reactions to analyze further.
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Research Products
(2 results)
