Bae Sehui, Oh Inrok, Yoo Jejoong, Kim Jun Soo
Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea.
LG Chem Ltd., LG Science Park, Seoul 07796, Republic of Korea.
ACS Omega. 2021 Jul 15;6(29):18728-18736. doi: 10.1021/acsomega.1c01709. eCollection 2021 Jul 27.
We present extensive molecular dynamics simulations of a cationic nanoparticle and a double-stranded DNA molecule to discuss the effect of DNA flexibility on the complex formation of a cationic nanoparticle with double-stranded DNA. Martini coarse-grained models were employed to describe double-stranded DNA molecules with two different flexibilities and cationic nanoparticles with three different electric charges. As the electric charge of a cationic nanoparticle increases, the degree of DNA bending increases, eventually leading to the wrapping of DNA around the nanoparticle at high electric charges. However, a small increase in the persistence length of DNA by 10 nm requires a cationic nanoparticle with a markedly increased electric charge to bend and wrap DNA around. Thus, a more flexible DNA molecule bends and wraps around a cationic nanoparticle with an intermediate electric charge, whereas a less flexible DNA molecule binds to a nanoparticle with the same electric charge without notable bending. This work provides solid evidence that a small difference in DNA flexibility (as small as 10 nm in persistence length) has a substantial influence on the complex formation of DNA with proteins from a biological perspective and suggests that the variation of sequence-dependent DNA flexibility can be utilized in DNA nanotechnology as a new tool to manipulate the structure of DNA molecules mediated by nanoparticle binding.
我们展示了阳离子纳米颗粒与双链DNA分子的广泛分子动力学模拟，以讨论DNA柔韧性对阳离子纳米颗粒与双链DNA形成复合物的影响。采用Martini粗粒化模型来描述具有两种不同柔韧性的双链DNA分子和具有三种不同电荷的阳离子纳米颗粒。随着阳离子纳米颗粒电荷的增加，DNA弯曲程度增加，最终在高电荷时导致DNA缠绕在纳米颗粒周围。然而，DNA持久长度仅小幅增加10纳米，就需要阳离子纳米颗粒电荷显著增加才能使DNA弯曲并缠绕。因此，更柔韧的DNA分子会弯曲并缠绕在具有中等电荷的阳离子纳米颗粒周围，而柔韧性较差的DNA分子则会在相同电荷下与纳米颗粒结合而无明显弯曲。这项工作提供了确凿证据，表明DNA柔韧性的微小差异（持久长度小至10纳米）从生物学角度对DNA与蛋白质形成复合物有重大影响，并表明序列依赖性DNA柔韧性的变化可在DNA纳米技术中用作一种新工具，来操纵由纳米颗粒结合介导的DNA分子结构。
