Physics Department T38, Technical University of Munich, 85748, Garching, Germany.
Angew Chem Int Ed Engl. 2019 Apr 23;58(18):5967-5972. doi: 10.1002/anie.201900935. Epub 2019 Mar 26.
Sac7d is a small, thermostable protein that induces large helical deformations in DNA upon association. Starting from multiple initial placements of the unbound Sac7d structure relative to a B-DNA oligonucleotide, molecular dynamics (MD) simulations were employed to directly follow several successful binding events at atomic resolution that resulted in structures in close agreement with the native complex geometry. The final native complex formed rapidly within tenths of nanoseconds and included simultaneous large-scale kinking, groove opening, twisting, and intercalation in the target DNA. The simulations indicate that the complex formation process involves initial non-native contacts that helped in reaching the final bound state, with residues intercalated at the center of the kinked DNA. It was also possible to identify several long-lived trapped intermediate states of the binding process and to follow sliding processes of Sac7d along the DNA minor groove.
Sac7d 是一种小型热稳定蛋白，与 DNA 结合时会诱导其产生大的螺旋形变。从未结合的 Sac7d 结构相对于 B-DNA 寡核苷酸的多个初始位置开始，采用分子动力学（MD）模拟直接跟踪了几个以原子分辨率成功发生的结合事件，这些事件导致的结构与天然复合物的几何形状非常吻合。最终的天然复合物在十分之几纳秒内迅速形成，并包括靶 DNA 中的大规模扭曲、沟道打开、扭转和嵌入。模拟表明，复合物形成过程涉及最初的非天然接触，这些接触有助于达到最终的结合状态，插入到扭曲 DNA 中心的残基。还可以识别结合过程中的几个长寿命的捕获中间状态，并跟踪 Sac7d 沿 DNA 小沟的滑动过程。
