We have explored a strategy to identify potential proton transfer channels using computational analysis of a protein structure based on Voronoi partitioning and applied it for the analysis of proton transfer pathways in redox-driven proton-pumping respiratory complex I. The analysis results in a network of connected voids/channels, which represent the dual structure of the protein; we then hydrated the identified channels using our water placement program Dowser++. Many theoretical water molecules found in the channels perfectly match the observed experimental water molecules in the structure; some other predicted water molecules have not been resolved in the experiments. The channels are of varying cross sections. Some channels are big enough to accommodate water molecules that are suitable to conduct protons; others are too narrow to hold water but require only minor conformational changes to accommodate proton transfer. We provide a preliminary analysis of the proton conductivity of the network channels, classifying the proton transfer channels as open, closed, and partially open, and discuss possible conformational changes that can modulate, i.e., open and close, the channels.

中文翻译：

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在呼吸复合物 I 中寻找质子转移通道


我们探索了一种策略，使用基于 Voronoi 分配的蛋白质结构计算分析来识别潜在的质子转移通道，并将其应用于氧化还原驱动的质子泵呼吸复合物 I 中的质子转移途径分析。分析结果是一个由连接的空隙/通道组成的网络，代表蛋白质的双重结构;然后，我们使用我们的水放置程序 Dowser++ 水合了确定的通道。在通道中发现的许多理论水分子与结构中观察到的实验水分子完全匹配;其他一些预测的水分子在实验中没有得到解决。通道具有不同的横截面。一些通道足够大，可以容纳适合传导质子的水分子;其他的太窄而无法容纳水，但只需要微小的构象变化即可适应质子转移。我们对网络通道的质子电导率进行了初步分析，将质子转移通道分为开放、闭合和部分开放，并讨论了可以调节通道（即打开和关闭）通道的可能构象变化。