A multi-scale model of charge transport through melted, stretched and in vacuo DNA structures

DNA双螺旋通过一种简单的化学密码携带生命所需的遗传信息。然而，DNA不断受到细胞自然产生的毒素的攻击。如果DNA受到化学损伤，那么在阅读或复制遗传信息时可能会出错，从而导致癌症等严重疾病。生物学有许多聪明的方法来保护DNA，并在损伤发生时检测和修复损伤，但这些方法仍然缺乏了解。最近，实验者设计了新的方法，在受控条件下将损伤引入DNA，以便他们能够研究这一过程。他们观察到，某些类型的损伤会导致正电荷沿着DNA跳跃，直到它在化学上改变了脆弱的部位。然而，如果DNA的规则分子结构以任何方式中断，电荷传输就不会发生，因为这阻碍了跳跃过程。这些观察结果对基因损伤发生的方式和地点具有深远的影响。在细胞中，DNA要么被紧密包装在细胞核中，要么经常被DNA处理机操纵，这些处理机的强度足以扭曲双螺旋结构。因此，了解DNA的规则分子结构的变化如何影响电荷传输和损伤迁移是很重要的。这项理论研究将使用物理学和计算机模拟相结合的方法来产生一个数学模型，解释电荷是如何沿着DNA跳跃的。然后我们可以使用这个模型来理解为什么跳跃是通过对其双螺旋结构的特殊扭曲来防止的。计算机模拟是理解复杂生物分子的一个极其强大的工具。它们可以在原子水平上提供有关DNA分子结构的信息，以便对分子进行比实验可能更详细的研究。这项研究将使用计算机模型来模拟DNA的结构在以各种方式受到压力时是如何扭曲的。利用这些信息，我们可以使用我们的损伤跳跃数学模型来计算是否仍然会通过这些变形的DNA结构进行电荷传输。这个模型将为现有的实验提供新的见解，并建议进行未来的研究，以显示DNA是如何在细胞中受到保护的。

The DNA double helix carries the genetic information necessary for life using a simple chemical code. However, DNA is under continuous attack from toxins generated naturally by the cell. If the DNA is chemically damaged, then errors can be made when the genetic message is read or copied leading to serious diseases such as cancer. Biology has a number of clever methods both for protecting DNA and for detecting and repairing damage when it occurs, but these remain poorly understood.Recently, experimentalists have devised new ways to introduce damage into DNA under controlled conditions so that they can study the process. They have observed that certain types of damage can cause a positive charge to hop along the DNA until it chemically changes a vulnerable site. However, charge transport does not occur if the regular molecular structure of the DNA is interrupted in any way since this impedes the hopping process. These observations have far reaching implications for how and where genetic damage occurs. In the cell, the DNA is either tightly packaged in the nucleus, or is frequently being manipulated by DNA processing machines which are strong enough to distort the double helical structure. Consequently, it is important to understand how charge transport and damage migration are affected by changes to the regular molecular structure of DNA. This theoretical study will use a combination of physics and computer simulation to produce a mathematical model explaining how charge hops along DNA. We can then use this model to understand why hopping is prevented by particular distortions to its double helical structure. Computer simulations are an extremely powerful tool for understanding complex biological molecules. They can provide information about the molecular structure of the DNA at an atomic level so that the molecule can be investigated in far more detail than would be possible experimentally. This study will use computer modelling to simulate how the structure of the DNA is distorted when it is placed under stress in a variety of ways. Using this information, we can use our mathematical model of damage hopping to calculate whether charge transport will still occur through these deformed DNA structures. This model will provide new insight into existing experiments and suggest future studies to show how the DNA is protected from damage in the cell.