Structural dynamics of the lac repressor-DNA complex revealed by a multiscale simulation.
Structural dynamics of the lac repressor-DNA complex revealed by a multiscale simulation.
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DOI：
10.1073/pnas.0409387102
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发表时间：
2005-05
影响因子：
11.1
通讯作者：
E. Villa;A. Balaeff;K. Schulten
中科院分区：
文献类型：
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作者：
E. Villa;A. Balaeff;K. Schulten
一个多尺度模拟的乳糖阻遏蛋白（LacI）和一个107 bp长的DNA片段之间的复合物的报告。阻遏物和两个操纵基因DNA片段之间的复合物由全原子分子动力学描述;模拟系统的大小包括226，000或314，000个原子。连接操作者的DNA环被建模为一个连续的弹性带，数学描述的非线性基尔霍夫微分方程的边界条件从每个操作者的终端碱基对的坐标。来自环状DNA的力被包括在分子动力学模拟中;环结构和力被不断地重新计算，因为在模拟过程中蛋白质的运动改变了运算符和环的假定末端。这些模拟以前所未有的细节揭示了LacI-DNA复合物的结构动力学。LacI的多个域在模拟过程中表现出显着的结构稳定性，像刚体一样移动。LacI主要通过其移动的DNA结合头基从环状DNA中吸收应变。即使施加了很大的波动力，头部基团也会强烈倾斜并保持对操纵基因DNA的控制，而蛋白质的其余部分则保持其V形结构。由500 pN力的裂缝的LacI的模拟开放揭示了负责锁定LacI在V-构象的相互作用。
A multiscale simulation of a complex between the lac repressor protein (LacI) and a 107-bp-long DNA segment is reported. The complex between the repressor and two operator DNA segments is described by all-atom molecular dynamics; the size of the simulated system comprises either 226,000 or 314,000 atoms. The DNA loop connecting the operators is modeled as a continuous elastic ribbon, described mathematically by the nonlinear Kirchhoff differential equations with boundary conditions obtained from the coordinates of the terminal base pairs of each operator. The forces stemming from the looped DNA are included in the molecular dynamics simulations; the loop structure and the forces are continuously recomputed because the protein motions during the simulations shift the operators and the presumed termini of the loop. The simulations reveal the structural dynamics of the LacI-DNA complex in unprecedented detail. The multiple domains of LacI exhibit remarkable structural stability during the simulation, moving much like rigid bodies. LacI is shown to absorb the strain from the looped DNA mainly through its mobile DNA-binding head groups. Even with large fluctuating forces applied, the head groups tilt strongly and keep their grip on the operator DNA, while the remainder of the protein retains its V-shaped structure. A simulated opening of the cleft of LacI by 500-pN forces revealed the interactions responsible for locking LacI in the V-conformation.