Best Robert B, Chen Yng-Gwei, Hummer Gerhard
Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Structure. 2005 Dec;13(12):1755-63. doi: 10.1016/j.str.2005.08.009.
Conformational transitions underlie the function of many biomolecular systems. Resolving intermediate structural changes, however, is challenging for both experiments and all-atom simulations because the duration of transitions is short relative to the lifetime of the stable species. Simplified descriptions based on a single experimental structure, such as elastic network models or Gō models, are not immediately applicable. Here, we develop a general method that combines multiple coarse-grained models to capture slow conformational transitions. Individually, each model describes one of the experimental structures; together, they approximate the complete energy surface. We demonstrate the method for the helix-to-sheet transition in Arc repressor N11L. We find that the transition involves the partial unfolding of the switch region, and rapid refolding into the alternate structure. Transient local unfolding is consistent with the low hydrogen exchange protection factors of the switch region. Also in agreement with experiment, the isomerization occurs independently of the global folding/dimerization transition.
构象转变是许多生物分子系统功能的基础。然而，解析中间结构变化对于实验和全原子模拟来说都具有挑战性，因为转变的持续时间相对于稳定物种的寿命较短。基于单一实验结构的简化描述，如弹性网络模型或Gō模型，并不直接适用。在此，我们开发了一种通用方法，该方法结合多个粗粒度模型来捕捉缓慢的构象转变。每个模型单独描述一种实验结构；它们共同近似完整的能量表面。我们展示了该方法用于Arc阻遏蛋白N11L的螺旋到片层转变。我们发现该转变涉及开关区域的部分解折叠，并迅速重新折叠成交替结构。瞬时局部解折叠与开关区域的低氢交换保护因子一致。同样与实验一致的是，异构化独立于全局折叠/二聚化转变发生。
