Cohen Jordi, Kim Kwiseon, King Paul, Seibert Michael, Schulten Klaus
Department of Physics and Beckman Institute, University of Illinois, Urbana, IL 61801, USA.
Structure. 2005 Sep;13(9):1321-9. doi: 10.1016/j.str.2005.05.013.
We report on a computational investigation of the passive transport of H2 and O2 between the external solution and the hydrogen-producing active site of CpI [FeFe]-hydrogenase from Clostridium pasteurianum. Two distinct methodologies for studying gas access are discussed and applied: (1) temperature-controlled locally enhanced sampling, and (2) volumetric solvent accessibility maps, providing consistent results. Both methodologies confirm the existence and function of a previously hypothesized pathway and reveal a second major pathway that had not been detected by previous analyses of CpI's static crystal structure. Our results suggest that small hydrophobic molecules, such as H2 and O2, diffusing inside CpI, take advantage of well-defined preexisting packing defects that are not always apparent from the protein's static structure, but that can be predicted from the protein's dynamical motion. Finally, we describe two contrasting modes of intraprotein transport for H2 and O2, which in our model are differentiated only by their size.
我们报告了对巴氏芽孢杆菌CpI [FeFe]-氢化酶外部溶液与产氢活性位点之间H2和O2被动运输的计算研究。讨论并应用了两种研究气体进入的不同方法：（1）温度控制的局部增强采样，以及（2）体积溶剂可及性图谱，结果一致。两种方法都证实了先前假设途径的存在和功能，并揭示了先前对CpI静态晶体结构分析未检测到的第二条主要途径。我们的结果表明，扩散到CpI内部的小疏水分子，如H2和O2，利用了明确存在的堆积缺陷，这些缺陷从蛋白质的静态结构中并不总是明显可见，但可以从蛋白质的动态运动中预测出来。最后，我们描述了H2和O2在蛋白质内运输的两种对比模式，在我们的模型中，它们仅通过大小来区分。
