项目名称： 过度拉伸的DNA的微观结构与稳定性的动力学研究

项目编号： No.11504204

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 屈媛媛

作者单位： 山东大学

项目金额： 21万元

中文摘要： DNA作为遗传信息的载体，是生命能够繁衍不息的基石。在生物机械力作用下构象丰富多变的DNA构型不仅是执行具体生物功能的重要结构基础，也是构建核酸纳米器件的理想材料。因此，对各种DNA 构型的微观结构与稳定性的探索一直以来是生物物理学领域的一项重要工作。本项目主要围绕机械力下过度拉伸的DNA的微观结构,稳定性及其动力学特性开展研究工作。我们将运用动力学蒙特卡洛模拟并结合高精度单分子磁镊技术，试图为DNA过度拉伸相变中的三种转变方式建立动力学模型，探讨过度拉伸的DNA构型的转变条件和转变机理，研究其在不同环境条件下的力学稳定性。另外，我们将运用受控全原子分子动力学模拟的手段，试图探明新型未知结构的S-DNA在原子尺度上的微观结构特点，以及其微观结构对DNA序列的依赖性。另一方面，通过深入研究S-DNA与多种嵌入式配体的结合方式，探究其与嵌入型抗癌药物反应的可能性及其可能的相关生物功能。

中文关键词： DNA；微观力学；DNA；结构；DNA；过度拉伸相变；动力学蒙特卡洛模拟；分子动力学模拟

英文摘要： Deoxyribonucleic acid (DNA), the most fundamental building block of life, stores the genetic codes for all living organism. Mediated by mechanical forces, various reorganizations of DNA comformations are not only the structural basis for it to perform multiple biological functions, but also ideal building units for biological nano-devices. Therefore, to explore the microscopic structures and the stabilities of various DNA conformations has always been an important task in the field of Biophysics. Therefore, this project focuses on the microscopic structures and the stabilities of three overstretched DNAs induced by mechanical forces. Combined with kinetic Monte Carlo simulation and high-resolution single molecule technique, this project intends to build kinetic models for three different DNA overstretching transition types, investigate respective transition conditions and mechanisms, and probe the mechanical stability under different environmental conditions. Besides, by the means of steered all-atom molecular dynamics simulation, this project also intends to reveal the microscopic structural characteristic of the newly discovered unknown structure S-DNA and its dependence on DNA sequence. Furthermore, in order to probe the possible biological functions of S-DNA and the possibility of the reaction between S-DNA and anti-cancer drugs, the binding modes between S-DNA and various intercalators will be investigated thoroughly.

英文关键词： DNA micromechanics;DNA structures;DNA overstretching transition;kinetic Monte Carlo simulation;molecular dynamics simulation