Department of Chemistry & Biochemistry, University of North Carolina Greensboro, Greensboro, NC 27402, United States.
Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, United States.
Curr Top Med Chem. 2020;20(10):901-909. doi: 10.2174/1568026620666200226110019.
Human DNA is a very sensitive macromolecule and slight changes in the structure of DNA can have disastrous effects on the organism. When nucleotides are modified, or changed, the resulting DNA sequence can lose its information, if it is part of a gene, or it can become a problem for replication and repair. Human cells can regulate themselves by using a process known as DNA methylation. This methylation is vitally important in cell differentiation and expression of genes. When the methylation is uncontrolled, however, or does not occur in the right place, serious pathophysiological consequences may result. Excess methylation causes changes in the conformation of the DNA double helix. The secondary structure of DNA is highly dependent upon the sequence. Therefore, if the sequence changes slightly the secondary structure can change as well. These slight changes will then cause the doublestranded DNA to be more open and available in some places where large adductions can come in and react with the DNA base pairs. Computer models have been used to simulate a variety of biological processes including protein function and binding, and there is a growing body of evidence that in silico methods can shed light on DNA methylation. Understanding the anomeric effect that contributes to the structural and conformational flexibility of furanose rings through a combination of quantum mechanical and experimental studies is critical for successful molecular dynamic simulations.
人类 DNA 是一种非常敏感的大分子，其结构的微小变化都会对生物体产生灾难性的影响。当核苷酸被修饰或改变时，其产生的 DNA 序列可能会丢失信息（如果它是基因的一部分），或者会成为复制和修复的问题。人类细胞可以通过一种称为 DNA 甲基化的过程来自我调节。这种甲基化对于细胞分化和基因表达至关重要。然而，当甲基化失控或未发生在正确的位置时，可能会导致严重的病理生理后果。过度甲基化会导致 DNA 双螺旋构象的改变。DNA 的二级结构高度依赖于序列。因此，如果序列稍有变化，二级结构也会发生变化。这些微小的变化会导致双链 DNA 在某些地方变得更加开放和可用，在这些地方，大量的加合物可以进入并与 DNA 碱基对反应。计算机模型已被用于模拟各种生物过程，包括蛋白质功能和结合，越来越多的证据表明，计算方法可以揭示 DNA 甲基化的作用。通过量子力学和实验研究的结合，理解呋喃糖环的端基效应，有助于其结构和构象的灵活性，这对于成功的分子动力学模拟至关重要。
