Theoretical Study on Repair Mechanisms of DNA Damages

DNA损伤修复机制的理论研究

• 批准号: 09440211
• 负责人: AIDA Misako
• 金额: $ 9.34万
• 依托单位: Hiroshima University (1998-1999)National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East (1997)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09440211/
• 关键词: ab initio MO method; density functional method; molecular dynamics method; DNA; biotogical molecutes; pyrimidine; pyrimidine dimer; radical cation; チミン; チミンダイマー; ラジカルアニオン

When DNA is exposed to radiation at wavelengths of about 260 nm, adjacent phyrimidines become covalently linked by the formation of a four-member ring structure resulting from the saturation of their respective C5 . C6 double bonds. The structure formed by this photochemical cycloaddition is referred to as a pyrimidine dimer. In this study, we investigated 1) the structures of the homo- and hetero-pyrimidine dimers by means of HF, CASSCF and dft methods and the process of the dimer splitting by means of CASSCF method, and 2) the conformational change of DNA with pyrimidine dimer by means of molecular dynamics.It is found that the dft structure of pyrimidine dimer is very close to the HF and CASSCF structures. T, he ring fusion at the C5 and C6 atoms leads to the puckered four-member cyclobutane ring. The four bonds and the four angles in the cyclobutane ring are almost equal. The puckering has axial or equatorial directions for the substituent atoms on the cyclobutane ring: corresponding atoms on the two pyrimidine bases differ in directionality. Upon ionization, the C6-C6' bond becomes very long, corresponding to a bond with only one electron. Calculations at the level of CASSCF indicate that the fragmentation reaction of the thymine dimer radical cation is a stepwise process and may proceed easily with low energy barriers once an electron is removed from the thymine dimer. The puckering of the four-member ring in the thymine dimer determines the direction of the electron movement along the fragmentation. Taking account of the molecular environment of pyrimidine dimer (DNA and solvent environments) , the molecular dynamics simulations have been performed.

当DNA暴露于约260nm波长的辐射时，相邻的嘧啶通过由于其各自的C5饱和而形成四元环结构而变得共价连接。 C6双键。通过这种光化学环加成形成的结构被称为嘧啶二聚体。在本研究中，我们研究了 1) 通过 HF、CASSCF 和 dft 方法研究了同源和异源嘧啶二聚体的结构，并通过 CASSCF 方法研究了二聚体分裂的过程，以及 2) DNA 的构象变化通过分子动力学研究发现嘧啶二聚体的dft结构与HF和CASSCF结构非常接近。 T，C5和C6原子处的环稠合产生褶皱的四元环丁烷环。环丁烷环中的四个键和四个角几乎相等。环丁烷环上的取代基原子的褶皱具有轴向或赤道方向：两个嘧啶碱基上的相应原子方向性不同。电离后，C6-C6'键变得很长，相当于只有一个电子的键。 CASSCF水平的计算表明，胸腺嘧啶二聚体自由基阳离子的裂解反应是一个逐步过程，一旦电子从胸腺嘧啶二聚体中移出，就可以在低能垒下轻松进行。胸腺嘧啶二聚体中四元环的褶皱决定了电子沿着碎片运动的方向。考虑嘧啶二聚体的分子环境（DNA和溶剂环境），进行了分子动力学模拟。

项目成果

Misako Aida: "Ab initio MD simulations on the hydrolysis of methyl chioride with explicit consideration of 3 water molecules" Chemical Physics Letters. 292. 474-480 (1998)

Misako Aida：“从头开始 MD 模拟氯甲烷水解，明确考虑 3 个水分子”《化学物理快报》。

M. Aida, M. Kaneko and M. Dupuis: "Radiation-induced DNA damage and repair : an approach from ab initio MO method"Computational Molecular Biology. 211-243 (1999)

M. Aida、M. Kaneko 和 M. Dupuis：“辐射诱导的 DNA 损伤和修复：从头开始 MO 方法的方法”计算分子生物学。

M.Tsuboi: "Raman spectrum of[5'-13C]thymidine:vibration of its 5'-end atomic group"Spectrochimical Acta. A55. 1887-1896 (1999)

M.Tsuboi：“[5-13C]胸苷的拉曼光谱：其5端原子团的振动”光谱化学学报。

H. Yamataka and M. Aida: "An ab initio MO study on the hydrolysis of methyl chloride with explicit consideration of 13 water molecules"Chemical Physics Letters. 289. 105-109 (1998)

H. Yamataka 和 M. Aida：“关于氯甲烷水解的从头开始 MO 研究，明确考虑了 13 个水分子”《化学物理快报》。

M.Aida: "Ab initio MD simulations on the hidrolysis of methyl chloride with explicit consideration of 3 water molecules"Chemical Physics Letters. 292. 474-480 (1998)

M.Aida：“从头开始 MD 模拟氯甲烷水解，明确考虑 3 个水分子”《化学物理快报》。