新型核酸碱基分子设计及其功能性研究

DNA presents significant advantages as a building block for nanostructured materials, as specific sequences of DNA can be easily manipulated using a large set of biochemical tools and protocols. These can both modify its existing biological functions and design and construct completely novel functionality. In addition to its standard role of encoding genetic information, DNA also possesses unique physical properties that make it amenable for use as a template or material for nanostructures. These include its mechanical stiffness and its ability to self-assemble driven by the specific recognition of complementary bases. Therefore，the design of new DNA motifs is a very interesting topic at present. To pursue suitable building blocks for functional DNA, this project tries to establish an effective base modification program. The relevant modified base structures and electronic properties are investigated by means of density functional calculations. Then, modified bases form base pairs specifically with their natural counterparts and assemble duplex helices which have comparable stability to native ones using molecular dynamics simulations. The corresponding base-pairing capabilities, charge transfer mechanism and fluorescent properties are discussed under the different ways of modification and environmental factors. We try to build modified structure-activity relationship between the structure and functional properties. The research of this project is of great significance that can reveal the difference of the natural and modified DNA, as well as it can provide important information about the synthesis of DNA molecular wire and molecular devices.

DNA具有独特的纳米尺度、分子线性结构、物理化学稳定性、自组装和严格自我复制等优良性质，正逐步被应用于分子生物学和电子学领域。为了激发和调控DNA在构建纳米器件中的潜在应用价值，DNA修饰研究一直是人们关注的热点课题。项目围绕修饰功能化碱基的相干问题，构建有效的碱基修饰方案。运用密度泛函理论方法表征出修饰碱基的结构参数、电子性质和光谱特性等。明确不同修饰碱基的独特性质，并在此基础上运用分子动力学方法建立以修饰碱基为构筑单元的修饰DNA螺旋链，深入探讨修饰方案对修饰DNA的结构稳定性、电子光谱性质和电荷沿链传递机制等功能特性的影响，建立修饰结构与功能特性之间的构效关系。以期从分子层次上探索人工修饰和外部环境对天然DNA性质的影响，这对揭示天然及修饰DNA的差异性具有重要意义，同时这种理论设计和基本信息分析对组建新的生物器件和发展新型的分子电子器件也能提供重要理论信息。

DNA具有独特的纳米尺度、分子线性结构、物理化学稳定性、自组装和严格自我复制等优良性质，为了激发和调控DNA在构建纳米器件中的潜在应用价值，DNA分子的相关研究一直是人们关注的热点课题。本项目围绕修饰功能化碱基的相干问题进行了探讨。（1）利用密度泛函方法理论研究了作为空穴迁移载体的蛋白质复合的DNA三聚体（protonated Arginine-GC）的氢键性质。结果表明ArgH+基团在大小沟与GC碱基对形成氢键，空穴转移至此会削弱氢键至亚稳态，使之具有一定的离解势垒和负的离解能。这种势垒抑制的负离解能现象意味着由于空穴俘获，此三体结构单元在它的ArgH+…N7/O6键区有储能现象；（2）基于特定目标设计扩展核酸碱，探讨具有特定目标的苯基环、杂环扩展等方案，完善和寻找了具有优良功能性的x-base和xx-base类似物，从第一性原理出发深入研究扩环碱基的几何特性和电磁性质，明确扩环碱基的配对能力、HOMO-LUMO 能隙以及π-π*跃迁能隙等各类电子性质，并基于电子亲合势和电离势等能量指标研究氧化还原致自由基机制，同时对相应的双氧化碱基对的双自由基性质进行了细致的研究，表征出它们的磁耦合特性，希望能够为设计新型的、以DNA 双螺旋为结构基础的、具有铁磁性或者反铁磁性的纳米级分子线提供一个新的思路；（3）采用“扩环”策略设计得到了一系列新型碱基。采用理论模拟方法对新设计碱基的结构性质、电子性质和激发态性质进行了详细研究，明确了新型碱基的光谱特性，为进一步的应用提供了理论基础。