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

DNA双螺旋通过一个简单的化学密码携带生命所必需的遗传信息。然而，DNA受到细胞自然产生的毒素的持续攻击。如果DNA被化学破坏，那么当遗传信息被读取或复制时就会产生错误，导致严重的疾病，如癌症。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，但这些方法仍然知之甚少。最近，实验学家设计了新的方法，在受控条件下将损伤引入DNA，以便研究这一过程。他们观察到，某些类型的损伤会导致正电荷沿着DNA沿着跳跃，直到它化学地改变一个脆弱的位点。然而，如果DNA的规则分子结构以任何方式被中断，则不会发生电荷传输，因为这阻碍了跳跃过程。这些观察结果对遗传损伤如何以及在何处发生具有深远的影响。在细胞中，DNA要么紧密地包裹在细胞核中，要么经常被DNA加工机器操纵，这些机器足够强大，可以扭曲双螺旋结构。因此，了解DNA常规分子结构的变化如何影响电荷传输和损伤迁移非常重要。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，解释电荷如何沿着DNA跳跃。然后，我们可以使用这个模型来理解为什么跳跃是通过其双螺旋结构的特殊扭曲来阻止的。计算机模拟是理解复杂生物分子的一个非常强大的工具。它们可以在原子水平上提供有关DNA分子结构的信息，从而可以比实验更详细地研究分子。这项研究将使用计算机建模来模拟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，我们可以使用损伤跳跃的数学模型来计算电荷传输是否仍然会通过这些变形的DNA结构发生。该模型将为现有实验提供新的见解，并为未来的研究提供建议，以显示DNA如何在细胞中免受损伤。

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.