Effects of two solvent conditions on the free energy landscape of the BBL peripheral subunit binding domain.
Effects of two solvent conditions on the free energy landscape of the BBL peripheral subunit binding domain.
复制标题
两种溶剂条件对 BBL 外围亚基结合域自由能景观的影响。
DOI：
10.1021/jp209791a
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Huo,Shuanghong
中科院分区：
文献类型：
--
作者：
Liu,Hanzhong;Huo,Shuanghong
BBL是具有两个主要平行螺旋的小的独立折叠结构域。Cα二级位移的实验表明，将pH值从107改变到105会导致螺旋2的C-末端的螺旋度降低。结合恒定pH分子动力学与复制交换，我们采样的蛋白质构象空间和质子化状态广泛的中性pH条件下和酸性条件下。我们的研究结果表明，溶剂条件影响的自由能景观。在中性pH条件下，变性态和天然态分离良好。酸性pH的条件重塑自由能表面，导致广泛分布的变性状态盆地和变性状态和天然状态之间的低自由能势垒。酸性pH使变性状态和天然状态之间的平衡向有利于变性状态的方向移动。在酸性条件下解释实验数据时必须谨慎，因为变性状态的贡献是显著的。计算的化学位移与实验数据吻合较好，这一事实支持了我们的模拟结果。
BBL is a small independently folding domain with two main parallel helices. The experiment of Cαsecondary shifts has shown that changing the pH from ∼7 to ∼5 results in the reduced helicity at the C-terminus of helix 2. Combining constant pH molecular dynamics with replica exchange, we sampled the protein conformation space and protonation states extensively under a neutral pH condition and an acidic condition. Our results reveal that the solvent conditions influence the free energy landscape. Under the neutral pH condition, the denatured state and the native state are well separated. The condition of the acidic pH reshapes the free energy surface, leading to a broadly populated denatured-state basin and a low free energy barrier between the denatured state and the native state. The acidic pH shifts the equilibrium between the denatured state and the native state in favor of the denatured state. Caution must be used to interpret experimental data under the acidic condition because the contribution of the denatured state is significant. Our simulation results are supported by the fact that the calculated chemical shifts are in good agreement with the experiment data.