Action! Modelling DNA nano-machines for deciphering their molecular mechanisms

这个计算性博士项目旨在为基本的病毒DNA纳米机器的实验高分辨率结构快照建模，包括解旋酶和DNA包装马达，以解开它们的工作原理。这项研究将解决几个选定的蛋白质-核酸机器的分子机制方面的知识空白，对于这些机器，安森实验室(YSBL，化学系)已经获得了准确的X射线结构。其中一台机器是乳头瘤病毒E1解旋酶，它在病毒复制过程中解开dsDNA。另一台机器，这个项目的目标，是存在于尾部噬菌体和进化相关的疱疹病毒(如巨细胞病毒)中的DNA包装发动机。该机器将在宿主细胞内复制的病毒DNA转移到一个空的预先形成的病毒衣壳中。尽管有详细的结构信息，但这些机器到底是如何工作的仍然是未知的。分子马达将使用AMBER(Assisted Model Building With Energy Refinement)软件进行模拟，这是一个分子动力学软件包，通过使用Amber力场来模拟生物分子。因此，它可以显示分子是如何运动和弯曲的，大大增加了我们对马达的理解，因为目前只获得了它的静态图像。

This computational PhD project aims to model experimental high-resolution structural snapshots of essential viral DNA nanomachines, including helicases and DNA packaging motors for unravelling how they work. The research will address the knowledge gap in the molecular mechanisms of several selected protein-nucleic acid machines, for which accurate X-ray structures have already been obtained in Antson lab (YSBL, Chemistry Department). One such machine is the papillomavirus E1 helicase, which unwinds dsDNA during viral replication. Another machine, targeted in this project, is the DNA packaging motor present in tailed bacteriophages and evolutionarily related herpes viruses (such as Cytomegalovirus). The machine translocates viral DNA, replicated within the host cell, into an empty pre-formed viral capsid. In spite of detailed structural information, it is still unknown how exactly these machines work.The molecular motors will be simulated using the AMBER (Assisted Model Building with Energy Refinement) software, a molecular dynamics software package that simulates biomolecules through the use of the AMBER force fields. It therefore can show how the molecules move and flex, greatly increasing our understanding of the motor as currently only static pictures of it have been obtained.