Multi-Scale Computer Modeling of the Structural Impact and Biochemical Reactions of Damaged DNA

这项拟议的研究的最终目标是了解DNA在我们体内是如何受损和修复的。我们DNA中包含的遗传信息可能会因暴露在外部和内部影响(例如紫外线、污染物和激素)而受到破坏。尽管我们细胞中的酶可以修复这种损伤，但一些损伤仍然存在，并对健康产生重大影响(例如，癌症、炎症性疾病和自身免疫性疾病)。这项拟议工作的短期目标是使用计算化学来破译特定DNA损伤和修复途径的细节。高精度的计算机计算可以作为实验结果的强大预测因子，澄清实验假设和结果之间的差异，并提供传统的“湿”实验无法提供的信息。这项拟议的研究独特地基于对一系列计算方法的明智使用，并与领先的实验者进行了密切的磋商。

The ultimate goal of the proposed research is to understand how DNA is damaged and repaired in our bodies. The genetic information contained in our DNA can be damaged by exposure to external and internal influences (e.g., UV light, pollutants and hormones). Although enzymes in our cells can repair this damage, some damage persists and has significant health effects (e.g., cancer, inflammatory diseases and autoimmune disorders). The short-term goal of the proposed work is to use computational chemistry to decipher the details of specific DNA damage and repair pathways. Highly accurate computer calculations can serve as powerful predictors of experimental outcomes, clarify discrepancies between experimental hypotheses and results, and provide information not available from traditional ‘wet’ experiments. The proposed research is uniquely based on the judicious use of a range of computational approaches and close consultations with leading experimentalists.