Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea.
LG Chem Ltd, LG Science Park, Seoul 07796, Republic of Korea.
Nanoscale. 2021 Dec 13;13(47):20186-20196. doi: 10.1039/d1nr04672a.
Looping of double-stranded DNA molecules with 100-200 base pairs into minicircles, catenanes, and rotaxanes has been suggested as a potential tool for DNA nanotechnologies. However, sharp DNA bending into a minicircle with a diameter of several to ten nanometers occurs with alterations in the DNA helical structure and may lead to defective kink formation that hampers the use of DNA minicircles, catenanes, and rotaxanes in nanoscale DNA applications. Here, we investigated local variations of a helical twist in sharply bent DNA using microsecond-long all-atom molecular dynamics simulations of six different DNA minicircles, focusing on the sequence dependence of the coupling between DNA bending and its helical twist. Twist angles between consecutive base pairs were analyzed at different locations relative to the direction of DNA bending and, among 10 unique dinucleotide steps, we identified four dinucleotide steps with strong twist-bend coupling, the pyrimidine-purine dinucleotide steps of TA/TA, CG/CG, and CA/TG and the purine-purine dinucleotide step of GA/TC. This work suggests the sequence-dependent structural responses of DNA to strong mechanical deformation, providing new molecular-level insights into the structure and stability of sharply bent DNA minicircles for nanoscale applications.
双链 DNA 分子的环化形成迷你环、连接体和轮烷，被认为是 DNA 纳米技术的一种潜在工具。然而，直径为数纳米至数十纳米的迷你环的尖锐 DNA 弯曲会导致 DNA 螺旋结构发生改变，可能导致缺陷的扭结形成，从而阻碍了 DNA 迷你环、连接体和轮烷在纳米尺度 DNA 应用中的使用。在这里，我们使用长达微秒的六个不同 DNA 迷你环的全原子分子动力学模拟研究了尖锐弯曲 DNA 中螺旋扭曲的局部变化，重点关注 DNA 弯曲与其螺旋扭曲之间的耦合的序列依赖性。在相对于 DNA 弯曲方向的不同位置分析了连续碱基对之间的扭转角，并在 10 个独特的二核苷酸步骤中，我们确定了四个具有强烈扭转-弯曲耦合的二核苷酸步骤，即 TA/TA、CG/CG、CA/TG 和 GA/TC 的嘧啶-嘌呤二核苷酸步骤和嘌呤-嘌呤二核苷酸步骤。这项工作表明 DNA 对强机械变形的序列依赖性结构响应，为纳米尺度应用中尖锐弯曲的 DNA 迷你环的结构和稳定性提供了新的分子水平见解。
