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- Sato Ryuma
- Center for Computational Sciences, University of Tsukuba
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- Harada Ryuhei
- Center for Computational Sciences, University of Tsukuba
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- Shigeta Yasuteru
- Center for Computational Sciences, University of Tsukuba
抄録
<p>As for UV-induced DNA damage, which may induce skin cancer in animals and growth inhibition in plants, there are two types of photoproducts, namely cis-sin cyclobutane pyrimidine dimers (CPD) and pyrimidine-pyrimidone (6-4) photoproducts. When they are to be repaired, base-flipping occurs, and they bind to enzymes. However, this process remains relatively unknown at a molecular level. We analyze conformation and interaction energy changes upon base-flipping using classical molecular dynamics (CMD) simulations and ab initio electronic structure calculations. CMD simulations starting with a CPD in the flipped-in and flipped-out states showed that both states were unchanged for 500 ns, indicating the flipped-in and flipped-out processes do not occur spontaneously (without any help of the enzyme) after photo-damage. To deeply understand the reasons, we investigated interaction energy changes among bases upon structure changes during the flipped-in and flipped-out processes using Parallel Cascade Selection-MD (PaCS-MD) simulations at 400 K, followed by a fragment molecular orbital (FMO) method. The total inter-fragment interaction energy (IFIE) between CPD and other bases at the flipped-in state is estimated to be –60.08 kcal/mol. In particular, four bases strongly interact with CPD with interaction energies being –10.96, –13.70, –21.52, and –14.46 kcal/mol each. On the other hand, the total IFIE at the obtained flipped-out state increased to –10.40 kcal/mol by partly losing hydrogen bonds and π-π stacking interactions, respectively. These results clearly indicate that the base-flipping process of DNA lesions occurs with the help of external forces like interactions with appropriate enzymes such as photolyases.</p>
収録刊行物
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- Biophysics and Physicobiology
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Biophysics and Physicobiology 13 (0), 311-319, 2016
一般社団法人 日本生物物理学会
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詳細情報 詳細情報について
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- CRID
- 1390282680740584064
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- NII論文ID
- 130005433879
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- ISSN
- 21894779
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可