PDF(Pubmed)
Abstract：
Cryogenic electron microscopy (cryo-EM) has emerged as a powerful method for the determination of structures of complex biological molecules. The accurate characterisation of the dynamics of such systems, however, remains a challenge. To address this problem, we introduce cryoENsemble, a method that applies Bayesian reweighting to conformational ensembles derived from molecular dynamics simulations to improve their agreement with cryo-EM data, thus enabling the extraction of dynamics information. We illustrate the use of cryoENsemble to determine the dynamics of the ribosome-bound state of the co-translational chaperone trigger factor (TF). We also show that cryoENsemble can assist with the interpretation of low-resolution, noisy or unaccounted regions of cryo-EM maps. Notably, we are able to link an unaccounted part of the cryo-EM map to the presence of another protein (methionine aminopeptidase, or MetAP), rather than to the dynamics of TF, and model its TF-bound state. Based on these results, we anticipate that cryoENsemble will find use for challenging heterogeneous cryo-EM maps for biomolecular systems encompassing dynamic components.
摘要：
低温电子显微镜（cryo-EM）已成为确定复杂生物分子结构的强大方法。这些系统动力学的准确表征，然而,仍然是一个挑战。为了解决这个问题,我们介绍冷冻组，一种将贝叶斯重新加权应用于从分子动力学模拟得出的构象集合的方法，以改善它们与低温EM数据的一致性，从而可以提取动力学信息。我们说明了使用冷冻ENsemble来确定共翻译伴侣触发因子（TF）的核糖体结合状态的动力学。我们还表明，冷冻组可以帮助解释低分辨率，低温EM图的嘈杂或下落不明的区域。值得注意的是,我们能够将冷冻EM图谱的下落不明部分与另一种蛋白质（甲硫氨酸氨基肽酶，或MetAP)，而不是TF的动力学，并对其TF绑定状态进行建模。基于这些结果,我们预计CryoENsemble将用于包含动态组件的生物分子系统的具有挑战性的异质低温EM图。
