Targeted molecular dynamics of an open-state KcsA channel
Targeted molecular dynamics of an open-state KcsA channel
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DOI：
10.1063/1.1869413
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Girardet, C
中科院分区：
文献类型：
--
作者：
Compoint, M;Picaud, F;Girardet, C
使用靶向分子动力学模拟研究 KcsA 通道的孔开放。确定蛋白质的构象变化，从X射线实验中确定的结晶精制2.0埃结构（pdb 1K4C）开始，到达基于电子顺磁共振波谱数据构建的开放态结构（pdb 1JQ1）。我们的结果证实了位于跨膜螺旋 M-2 上的末端残基所发挥的重要作用，而当时并未考虑到这一点。通道的孔径机构看起来是拉链状的。应用于位于细胞内侧的末端残基的小约束（大约 5x10(-2) kcal mol(-1) angstrom(-2)/C-alpha）足以初始化门最内侧部分的孔开口，但必须应用额外的约束来明确完成孔孔径。开放结构被证明是亚稳态，因为释放约束导致另一个松弛的开放构象，似乎达到了稳定。 (C) 2005 年美国物理研究所。
Pore opening of KcsA channel is studied using targeted molecular dynamics simulations. Conformational changes of the protein are determined, starting from the crystallized refined 2.0 angstrom structure (pdb 1K4C) determined in x-ray experiments and arriving to the open-state structure constructed on the basis of electron paramagnetic resonance spectroscopic data (pdb 1JQ1). Our results corroborate the essential role played by the terminal residues located on the transmembrane helices M-2 which were not taken into account at that time. The aperture mechanism of the channel appears to be ziplike. A small constraint (approximate to 5x10(-2) kcal mol(-1) angstrom(-2) per C-alpha) applied to the terminal residues located on the intracellular side is sufficient to initialize the pore opening at the innermost part of the gate, but additional constraint must be applied to definitely complete the pore aperture. The open structure is proved to be a metastable state since releasing the constraint leads to another relaxed open conformation which seems to reach stability. (C) 2005 American Institute of Physics.