Department of Physics, Wake Forest University, Winston-Salem, NC, USA.
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
J Mol Recognit. 2018 Oct;31(10):e2731. doi: 10.1002/jmr.2731. Epub 2018 Jun 3.
Bent DNA, or DNA that is locally more flexible, is a recognition motif for many DNA binding proteins. These DNA conformational properties can thus influence many cellular processes, such as replication, transcription, and DNA repair. The importance of these DNA conformational properties is juxtaposed to the experimental difficulty to accurately determine small bends, locally more flexible DNA, or a combination of both (bends with increased flexibility). In essence, many current bulk methods use average quantities, such as the average end-to-end distance, to extract DNA conformational properties; they cannot access the additional information that is contained in the end-to-end distance distributions. We developed a method that exploits this additional information to determine DNA conformational parameters. The method is based on matching end-to-end distance distributions obtained experimentally by atomic force microscopy imaging to distributions obtained from simulations. We applied this method to investigate cisplatin GG biadducts. We found that cisplatin induces a bend angle of 36° and softens the DNA locally around the bend.
弯曲 DNA，或局部更灵活的 DNA，是许多 DNA 结合蛋白的识别基序。因此，这些 DNA 构象特性可以影响许多细胞过程，如复制、转录和 DNA 修复。这些 DNA 构象特性的重要性与准确确定小弯曲、局部更灵活的 DNA 或两者（具有增加灵活性的弯曲）的实验难度形成鲜明对比。本质上，许多当前的批量方法使用平均量，如平均末端到末端距离，来提取 DNA 构象特性；它们无法获取端到端距离分布中包含的附加信息。我们开发了一种利用这种附加信息来确定 DNA 构象参数的方法。该方法基于将原子力显微镜成像实验获得的末端到末端距离分布与模拟获得的分布进行匹配。我们将该方法应用于顺铂 GG 双加合物的研究。我们发现，顺铂诱导 36°的弯曲角度，并使弯曲周围的 DNA 局部变软。
