{"title":"自由和堆积 DNA 系统内的氧化缺陷检测:量子力学/分子力学(QM/MM)方法","authors":"Sophia K. Johnson, Ursula Rothlisberger","doi":"10.2533/chimia.2024.243","DOIUrl":null,"url":null,"abstract":"Base excision repair enzymes (BERs) detect and repair oxidative DNA damage with efficacy despite the small size of the defects and their often only minor structural impact. A charge transfer (CT) model for rapid scanning of DNA stretches has been evoked to explain the high detection rate in the face of numerous, small lesions. The viability of CT DNA defect detection is explored via hybrid QM/MM computational studies that leverage the accuracy of quantum mechanics (QM) for a region of interest and the descriptive power of molecularmechanics (MM) for the remainder of the system. We find that the presence of an oxidative lesion lowers theredox free energy of oxidation by approximately 1.0 eV regardless of DNA compaction (free DNA versus packed DNA in nucleosome core particles) and damage location indicating the high feasibility of a CT-based process for defect detection in DNA.","PeriodicalId":9957,"journal":{"name":"Chimia","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Oxidative Defect Detection Within Free and Packed DNA Systems: A Quantum Mechanical/Molecular Mechanics (QM/ MM) Approach\",\"authors\":\"Sophia K. Johnson, Ursula Rothlisberger\",\"doi\":\"10.2533/chimia.2024.243\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Base excision repair enzymes (BERs) detect and repair oxidative DNA damage with efficacy despite the small size of the defects and their often only minor structural impact. A charge transfer (CT) model for rapid scanning of DNA stretches has been evoked to explain the high detection rate in the face of numerous, small lesions. The viability of CT DNA defect detection is explored via hybrid QM/MM computational studies that leverage the accuracy of quantum mechanics (QM) for a region of interest and the descriptive power of molecularmechanics (MM) for the remainder of the system. We find that the presence of an oxidative lesion lowers theredox free energy of oxidation by approximately 1.0 eV regardless of DNA compaction (free DNA versus packed DNA in nucleosome core particles) and damage location indicating the high feasibility of a CT-based process for defect detection in DNA.\",\"PeriodicalId\":9957,\"journal\":{\"name\":\"Chimia\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2024-04-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chimia\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.2533/chimia.2024.243\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chimia","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.2533/chimia.2024.243","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
碱基切除修复酶(BER)能有效地检测和修复氧化 DNA 损伤,尽管缺陷很小,对结构的影响也很小。一种用于快速扫描 DNA 片段的电荷转移(CT)模型被用来解释在面对大量小缺陷时的高检测率。CT DNA 缺陷检测的可行性通过 QM/MM 混合计算研究进行了探讨,该研究利用量子力学(QM)对感兴趣区域的准确性和分子力学(MM)对系统其余部分的描述能力。我们发现,无论 DNA 的压实度(游离 DNA 与核糖体核心颗粒中的包装 DNA)和损伤位置如何,氧化性病变的存在都会使氧化还原自由能降低约 1.0 eV,这表明基于 CT 的 DNA 缺陷检测过程具有很高的可行性。
Oxidative Defect Detection Within Free and Packed DNA Systems: A Quantum Mechanical/Molecular Mechanics (QM/ MM) Approach
Base excision repair enzymes (BERs) detect and repair oxidative DNA damage with efficacy despite the small size of the defects and their often only minor structural impact. A charge transfer (CT) model for rapid scanning of DNA stretches has been evoked to explain the high detection rate in the face of numerous, small lesions. The viability of CT DNA defect detection is explored via hybrid QM/MM computational studies that leverage the accuracy of quantum mechanics (QM) for a region of interest and the descriptive power of molecularmechanics (MM) for the remainder of the system. We find that the presence of an oxidative lesion lowers theredox free energy of oxidation by approximately 1.0 eV regardless of DNA compaction (free DNA versus packed DNA in nucleosome core particles) and damage location indicating the high feasibility of a CT-based process for defect detection in DNA.
期刊介绍:
CHIMIA, a scientific journal for chemistry in the broadest sense covers the interests of a wide and diverse readership. Contributions from all fields of chemistry and related areas are considered for publication in the form of Review Articles and Notes. A characteristic feature of CHIMIA are the thematic issues, each devoted to an area of great current significance.