NMR relaxation in proteins with fast internal motions and slow conformational exchange: model-free framework and Markov state simulations.
NMR relaxation in proteins with fast internal motions and slow conformational exchange: model-free framework and Markov state simulations.
复制标题
具有快速内部运动和慢速构象交换的蛋白质的 NMR 弛豫：无模型框架和马尔可夫态模拟。
DOI：
10.1021/jp400797y
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Levy,RonaldM
中科院分区：
文献类型：
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作者：
Xia,Junchao;Deng,Nan-jie;Levy,RonaldM
基于传统的分子动力学模拟，计算具有多个时间尺度上的动力学的蛋白质的NMR弛豫效应通常需要非常长的轨迹。在这份报告中，我们已经建立了马尔可夫状态模型，从多个MD轨迹，并使用由此产生的MSM捕获非常快速的内部运动的蛋白质内的自由能盆地的时间尺度高达数百皮秒和超过3个数量级的慢宏态之间的构象交换。为了解释弛豫数据，我们推导出新的方程使用无模型框架，其中包括两个缓慢交换的宏态，其中每个也表现出快速的局部运动。以HIV-1蛋白酶模拟为例，我们展示了如何从NMR弛豫数据中确定缓慢交换构象状态的种群以及不同状态的序参数。
Calculating NMR relaxation effects for proteins with dynamics on multiple time scales generally requires very long trajectories based on conventional molecular dynamics simulations. In this report, we have built Markov state models from multiple MD trajectories and used the resulting MSM to capture the very fast internal motions of the protein within a free energy basin on a time scale up to hundreds of picoseconds and the more than 3 orders of magnitude slower conformational exchange between macrostates. To interpret the relaxation data, we derive new equations using the model-free framework which includes two slowly exchanging macrostates, each of which also exhibits fast local motions. Using simulations of HIV-1 protease as an example, we show how the populations of slowly exchanging conformational states as well as order parameters for the different states can be determined from the NMR relaxation data.