Nanoscale dewetting transition in protein complex folding
Nanoscale dewetting transition in protein complex folding
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DOI：
10.1021/jp0704923
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发表时间：
2007-08-02
影响因子：
3.3
通讯作者：
Berne, Bruce J.
中科院分区：
文献类型：
--
作者：
Hua, Lan;Huang, Xuhui;Berne, Bruce J.
在之前的一项研究中，观察到蜂毒肽四聚体的纳米级疏水通道内发生了令人惊讶的干燥转变。本文的目的是确定是否有其他蛋白质复合物能够在折叠的最后阶段表现出去湿转变。我们在整个蛋白质数据库 (PDB) 中搜索了所有可能的候选蛋白，包括蛋白质四聚体、二聚体和双结构域蛋白，然后对通过基于对齐疏水表面积的简单疏水评分函数识别的最佳候选蛋白进行分子动力学 (MD) 模拟。我们的大规模MD模拟发现了更多蛋白质，包括三个四聚体、六个二聚体和两个双结构域蛋白质，它们在折叠的最后阶段表现出纳米级的去湿转变。尽管单独的评分函数不足以识别去湿候选者（即，高分是必要的，但还不够），但它确实为去湿所需的复杂界面的特征提供了有用的见解。所有顶级候选者都有两个共同特征：（1）两个相应表面之间的大对齐（匹配）疏水区域，以及（2）同一表面上的大连接疏水区域。我们还研究了不同水模型和长程静电相互作用（截止与 PME）的不同处理对去湿的影响，发现去湿现象相当稳健。这项工作提出了除蜂毒肽四聚体之外的一些蛋白质，用于进一步实验研究去湿在蛋白质折叠末期的作用。
In a previous study, a surprising drying transition was observed to take place inside the nanoscale hydrophobic channel in the tetramer of the protein melittin. The goal of this paper is to determine if there are other protein complexes capable of displaying a dewetting transition during their final stage of folding. We searched the entire protein data bank (PDB) for all possible candidates, including protein tetramers, dimers, and two-domain proteins, and then performed the molecular dynamics (MD) simulations on the top candidates identified by a simple hydrophobic scoring function based on aligned hydrophobic surface areas. Our large scale MD simulations found several more proteins, including three tetramers, six dimers, and two two-domain proteins, which display a nanoscale dewetting transition in their final stage of folding. Even though the scoring function alone is not sufficient (i.e., a high score is necessary but not sufficient) in identifying the dewetting candidates, it does provide useful insights into the features of complex interfaces needed for dewetting. All top candidates have two features in common: (1) large aligned (matched) hydrophobic areas between two corresponding surfaces, and (2) large connected hydrophobic areas on the same surface. We have also studied the effect on dewetting of different water models and different treatments of the long-range electrostatic interactions (cutoff vs PME), and found the dewetting phenomena is fairly robust. This work presents a few proteins other than melittin tetramer for further experimental studies of the role of dewetting in the end stages of protein folding.