Crouzy S, Woolf T B, Roux B
CENG, CEA, Grenoble, France.
Biophys J. 1994 Oct;67(4):1370-86. doi: 10.1016/S0006-3495(94)80618-6.
The gating transition of the RR and SS dioxolane ring-linked gramicidin A channels were studied with molecular dynamics simulations using a detailed atomic model. It was found that the probable reaction path, describing the transition of the ring from the exterior to the interior of the channel where it blocked the permeation pathway, involved several steps including the isomerization of the transpeptide plane dihedral angle of Val1. Reaction coordinates along this pathway were defined, and the transition rates between the stable conformers were calculated. It was found, in good accord with experimental observations, that the calculated blocking rate for the RR-linked channel was 280/s with a mean blocking time of 0.04 ms, whereas such blocking did not occur in the case of the SS-linked channel. An important observation is that the resulting lifetime for the blocked state of the RR-linked channel was in good accord with the experimental observations only when the calculations were performed in the presence of a potassium ion inside the channel.
利用详细的原子模型，通过分子动力学模拟研究了RR和SS二氧戊环环连接的短杆菌肽A通道的门控转变。研究发现，描述环从通道外部向内部转变（在此过程中环阻断渗透途径）的可能反应路径涉及几个步骤，包括Val1反式肽平面二面角的异构化。定义了沿此路径的反应坐标，并计算了稳定构象体之间的转变速率。结果发现，与实验观察结果高度一致的是，RR连接通道的计算阻断速率为280/s，平均阻断时间为0.04毫秒，而SS连接通道则未发生这种阻断。一个重要的观察结果是，只有当在通道内部存在钾离子的情况下进行计算时，RR连接通道阻断状态的所得寿命才与实验观察结果高度一致。
