Computer Modeling of the Properties, Interactions and Reactions of Natural and Modified DNA

脱氧核糖核酸（DNA）的独特结构包含生物体的遗传组成，为设计和构建具有重要科学应用的创新分子提供了有用的模板。事实上，修饰的DNA片段已经被设计用于医学（与DNA中负责疾病的区域结合的药物），生物技术（用于研究酶的结构和功能的生物探针）和纳米技术（DNA介导的纳米级材料和设备的合成）。尽管有这些有用的应用，但修饰的DNA在细胞内形成时是有害的，其中DNA损伤可以由于外力（X射线，UV光）或内部过程（复制错误，脂质过氧化）而形成，并且与疾病如癌症有关。 拟议的研究使用计算化学来研究在生物学，生物化学和医学中具有重要作用的天然和修饰的DNA组分的性质和反应性。计算化学使用计算机计算来获得有关化学系统的信息。计算化学是研究修饰DNA的有用工具，因为计算可以很容易地对正常、稳定的分子和反应性物质进行，而后者的实验是困难或不可能的。因此，计算可以用来补充和/或指导实验。 我们的研究将研究受损DNA的化学去除，这是由我们体内的酶促进的。我们还将研究损伤形成的途径。通过了解大自然如何修复损伤以及损伤如何发生，科学家们可能能够开发出更有效的技术来修复或预防DNA损伤。我们还将研究广泛的化学修饰的DNA片段，这些片段可用作药物或生物技术工具，以确定在传统实验室中制造和测试的新分子。

The unique structure of deoxyribonucleic acid (DNA), which contains the genetic makeup of living organisms, provides a useful template from which to design and build innovative molecules with important applications in science. Indeed, modified DNA pieces have been designed for, and are used in, medicine (drugs that bind to regions in DNA responsible for disease), biotechnology (bioprobes used to study the structure and function of enzymes) and nanotechnology (DNA mediated synthesis of materials and devices on the nanoscale). Despite these useful applications, modified DNA is detrimental when formed within cells, where DNA damage can be formed due to external forces (X-rays, UV light) or internal processes (replication errors, lipid peroxidation) and has been linked to diseases such as cancer. The proposed research uses computational chemistry to study the properties and reactivity of natural and modified DNA components with important roles in biology, biochemistry and medicine. Computational chemistry uses computer calculations to obtain information about chemical systems. Computational chemistry is a useful tool to study modified DNA since calculations can be readily carried out for both normal, stable molecules and reactive species, where experiments on the latter are difficult or impossible. Therefore, calculations can be used to complement and/or guide experiment. Our research will study the chemical removal of damaged DNA that is facilitated by enzymes in our bodies. We will also study the pathways through which the damage forms. By understanding both how nature repairs the damage and how the damage occurs, scientists may be able to develop more effective techniques to repair or prevent DNA damage. We will also study a wide range of chemically modified DNA pieces that have applications as drugs or tools for biotechnology in anticipation to identify new molecules to be made and tested in a traditional experimental laboratory.