由于DNA的碱基互补特性和可精确编程性，它可以作为反应基元用于分子机器构建及组装，并广泛应用于DNA分子计算、疾病诊治和生物传感等研究领域。DNA toehold链替换反应是DNA恒温纳米技术的基础。目前，人们对DNA toehold链替换反应的微观物理图像和速率调控机制缺乏深刻的了解。本项目将采用分子动力学模拟和自由能计算，结合实验方法，(1)系统研究DNA toehold链替换反应的链替换机制; (2)建立高浓度条件下链替换反应速率的理论计算模型; (3)考察有机小分子溶剂调控链替换反应速率的机制; (4)探讨链替换反应中焓和熵的竞争机制。本项目研究将加深我们对DNA toehold链替换反应的理解，为其反应速率的精确调控提供理论基础，为DNA恒温纳米技术在分子计算、化学反应网络调控细胞生理过程等领域的应用打下基础。

With its programmable behaviors and the property of base pairing in building molecular machine and realization of self-assembly, DNA molecule has found broad applications in the areas of DNA molecular computation, diagnosis of diseases and biosensors. DNA toehold-mediated strand displacement reactions are the bases of isothermal dynamic DNA nanotechnology, and have been systematically used to design complex autonomous behaviors. Currently, a complete understanding about the DNA toehold-mediated strand displacement reaction and its kinetics modulation is still missing. In the present proposal, using molecular dynamics simulations combined with free energy calculations and experiments, we suggest to: (1) investigate the detailed biophysical process of DNA toehold-mediated strand displacement reaction; (2) build a model for the rate constant of the strand displacement reactions at high concentration; (3) investigate the mechanism of reaction rate modulation using organic solvents; (4) study the competition behaviors between the enthalpy and entropy during the reaction. The expected results and conclusions will deepen our understanding of DNA toehold-mediated strand displacement reaction, and would contribute to its potential applications in DNA molecular computation, cellular process modulation through chemical reaction network, and so on.