2023 Fiscal Year Annual Research 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 process / quantum chemistry / reaction dynamics / reaction mechanisms |
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| Outline of Annual Research Achievements |
In order to elucidate the mineralization mechanism of phospholipids, we assumed that their hydrolysis reactions are the first step in the process. The reaction dynamics of hydrolysis was analyzed via quantum chemical calculations conducted using Gaussian16 at the B3LYP/6-31G(d,p) level. Phospholipids containing 6 carbon atoms in the hydrophobic tail, and choline (PC6) or serine (PS6) as the hydrophilic head were considered in the simulations. In the 2023 academic year, complexes composed of two phospholipid molecules surrounding a Ca ion (2PC6Ca or 2PS6Ca) were taken as the reactants. The elementary steps involved in the hydrolysis of these complexes were identified, and the free energies of reactants, transition states and products were determined after re-evaluation of the energy of the stationary points at the APFD/6-311+G(2d,p) level. From the values of activation energy and heat release, the sequence through which the elementary steps proceed was determined, and important aspects of the hydrolysis mechanism were identified. Significant differences between the hydrolysis of 2PC6Ca and 2PS6Ca were found, and we conclude that these differences are related to the differences in the mineralization rates of phosphatidylcholine and phosphatidylserine that have been observed experimentally.
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