Department of Chemistry, Georgetown University, Washington, DC, 20057.
Geophysical Laboratory, Carnegie Institution for Science, Washington, DC, 20015.
J Comput Chem. 2017 Jun 5;38(15):1174-1182. doi: 10.1002/jcc.24737. Epub 2017 Jan 19.
A critical question about piezophilic (pressure-loving) microbes is how their constituent molecules maintain function under high pressure. Here, factors are examined that may lead to the increased activity under pressure in dihydrofolate reductase from the piezophilic Moritella profunda compared to the homologous enzyme from the mesophilic Escherichia coli. Molecular dynamics simulations are performed at various temperatures and pressures to examine how pressure affects the flexibility of the enzymes from these two microbes, since both stability and flexibility are necessary for enzyme activity. The results suggest that collective motions on the 10-ns timescale are responsible for the flexibility necessary for "corresponding states" activity at the growth conditions of the parent organism. In addition, the results suggest that while the lower stability of many enzymes from deep-sea microbes may be an adaptation for greater flexibility at low temperatures, high pressure may enhance their adaptation to low temperatures. © 2017 Wiley Periodicals, Inc.
关于嗜压（喜欢压力）微生物的一个关键问题是，它们的组成分子如何在高压下保持功能。在这里，我们研究了一些因素，这些因素可能导致来自嗜压深海粘球菌的二氢叶酸还原酶在压力下的活性增加，而与其同源的来自中温的大肠杆菌的二氢叶酸还原酶的活性则没有增加。通过在不同温度和压力下进行分子动力学模拟，研究了压力如何影响来自这两种微生物的酶的灵活性，因为稳定性和灵活性对于酶活性都是必需的。结果表明，在 10-ns 的时间尺度上的集体运动是“对应状态”活性所必需的灵活性的原因，这种“对应状态”活性是在亲代生物体的生长条件下进行的。此外，结果表明，尽管来自深海微生物的许多酶的稳定性较低可能是适应低温下更大灵活性的一种方式，但高压可能会增强它们对低温的适应能力。© 2017 Wiley Periodicals, Inc.
