Importance of the Peptide Backbone Description in Modeling the Selectivity Filter in Potassium Channels
Importance of the Peptide Backbone Description in Modeling the Selectivity Filter in Potassium Channels
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DOI：
10.1016/j.bpj.2009.02.041
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发表时间：
2009-05-20
影响因子：
3.4
通讯作者：
Kuyucak, Serdar
中科院分区：
文献类型：
--
作者：
Bastug, Turgut;Kuyucak, Serdar
二面角能量校正（CMAP）项最近已被纳入CHARMM力场，以获得更准确的描述的肽骨架。它的重要性，在改善蛋白质的动力学性质，并保持其稳定性，在长期的分子动力学模拟已经建立了几个球状蛋白质。在这里，我们调查其在维持两个钾通道，振荡器K（V）1.2和KcsA的结构和功能的作用，通过进行分子动力学模拟，在其他相同的系统中的CMAP校正。我们表明，没有CMAP，它是不可能的，以保持实验观察到的取向的羰基在选择性过滤器中的振荡器，和通道失去其选择性。在KcsA的情况下，即使没有CMAP，通道也保留了一些选择性，因为与Shaker相比，羰基取向相对更好地保留。
A dihedral energy correction (CMAP) term has been recently included in the CHARMM force field to obtain a more accurate description of the peptide backbone. Its importance in improving dynamical properties of proteins and preserving their stability in long molecular-dynamics simulations has been established for several globular proteins. Here we investigate its role in maintaining the structure and function of two potassium channels, Shaker K(v)1.2 and KcsA, by performing molecular-dynamics simulations with and without the CMAP correction in otherwise identical systems. We show that without CMAP, it is not possible to maintain the experimentally observed orientations of the carbonyl groups in the selectivity filter in Shaker, and the channel loses its selectivity property. In the case of KcsA, the channel retains some selectivity even without CMAP because the carbonyl orientations are relatively better preserved compared to Shaker.