酶对核酸进行化学修饰的动力学机理

生命个体的发育主要取决于遗传基因DNA序列，但其复杂性和多样性不能仅由生物学"中心法则"解释。在生命个体的发育过程中生物大分子的化学修饰对决定细胞命运起着关键的调控作用。具有遗传性的生物大分子化学修饰的研究是当前生命科学研究的一个前沿课题。本申请的研究内容是酶对核酸（DNA和RNA）进行化学修饰和去修饰的动力学机理。由于以前研究手段的制约，关于核酸化学修饰动力学机理的研究尚处在初期。我们拟将实验（单分子探测）和理论（分子动力学模拟）结合在一起，采用先进的研究手段深入探究酶对核酸进行化学修饰的动力学过程，以便清楚地了解酶如何和以多快的速率发现被修饰和去修饰的位点，以及酶在发现位点后对其进行化学修饰的分子机制和反应动力学。这些研究将揭示相关生物分子反应的化学本质，有助于更深刻地认识相应的生物过程。

All cells in a living organism share an identical genomic DNA sequence. The status and developing fate of each individual cell cannot be explained by the "central dogma" alone. The chemical modifications on biomacromolecules play key roles in defining cell status and determining cell fate. The study of chemical modification of biomacromolecules has great biological significance. This project is deviced to investigate the reversible chemical modification of nucleic acid (DNA and RNA). Due to previously limited research tools, the study on the dynamic mechanism of chemical modification on nucleic acid is still on a rudimentary stage. We will combine advanced experimental (mainly single molecule detection) with theoretical (mainly molecular dynamics simulation) tools together to explore deeply the dynamic and molecular mechanism of chemical modification on nucleic acid by enzymes: how and how fast do the enzymes find the location they act on? How and how fast do the enzymes carry out the chemical modification? These studies will help us to understand the chemical basis of relevant biomolecular reactions.