Yang P K, Lee C Y, Hwang M J
Division of Structural Biology, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Biophys J. 1997 Jun;72(6):2479-89. doi: 10.1016/S0006-3495(97)78892-1.
Recent studies making use of channel-blocking peptides as molecular calipers have revealed the architecture of the pore-forming region of Shaker-type potassium channels. Here we show that the low-resolution, experimentally derived geometric information can be incorporated as restraints within the context of an annealed molecular dynamics simulation to predict an atomic structure for the channel pore which, by virtue of restraints, conforms to the experimental evidence. The simulation is reminiscent of the computational method employed by nuclear magnetic resonance (NMR) spectroscopists to resolve solution structures of biological macromolecules, but in lieu of restraints conventionally derived from NMR spectra, novel restraints are developed that include side-chain orientation of amino acid residues and assumed symmetry of protein subunits. The method presented here offers the possibility of expanding cooperation between simulation and experiment in developing structural models, especially for systems such as ion channels whose three-dimensional structures may not be amenable to determination by direct methods at the present time.
最近利用通道阻断肽作为分子卡尺的研究揭示了摇椅型钾通道孔形成区域的结构。在此我们表明，低分辨率的、通过实验获得的几何信息可以作为约束条件纳入退火分子动力学模拟中，以预测通道孔的原子结构，该结构由于约束条件而符合实验证据。该模拟让人联想到核磁共振（NMR）光谱学家用于解析生物大分子溶液结构的计算方法，但这里开发了新的约束条件来代替传统上从NMR光谱得出的约束条件，这些新约束条件包括氨基酸残基的侧链取向和假定的蛋白质亚基对称性。本文提出的方法为在开发结构模型时扩大模拟与实验之间的合作提供了可能性，特别是对于诸如离子通道等目前其三维结构可能无法通过直接方法确定的系统。
