Exploring the Folding Free Energy Landscape of a β-Hairpin Miniprotein, Chignolin, Using Multiscale Free Energy Landscape Calculation Method
Exploring the Folding Free Energy Landscape of a β-Hairpin Miniprotein, Chignolin, Using Multiscale Free Energy Landscape Calculation Method
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DOI：
10.1021/jp2008623
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发表时间：
2011-07-14
影响因子：
3.3
通讯作者：
Kitao, Akio
中科院分区：
文献类型：
--
作者：
Harada, Ryuhei;Kitao, Akio
采用多尺度自由能景观计算方法（MSFEL），对β-发夹结构的微小蛋白质chignolin的折叠过程进行了自由能景观计算.首先，粗粒度分子动力学模拟搜索了广阔的构象空间，然后使用大规模分布式计算，使用显式溶剂进行多个独立的全原子分子动力学模拟，确定了详细的局部自由电子激光。这两种模型的结合使得能够有效地计算自由能景观。MSFEL分析表明，chignolin有一个中间状态，以及错误折叠状态。折叠过程由β-发夹转角的形成开始，随后在Tyr 2和Trp 9之间的疏水核心中形成接触。此外，Tyr 2的突变使群体向错误折叠构象转变。结果表明，疏水核在稳定天然状态的姜木酚素中起着重要作用。
The folding process for a beta-hairpin miniprotein, chignolin, was investigated by free energy landscape (FEL) calculations using the recently proposed multiscale free energy landscape calculation method (MSFEL). First, coarse-grained molecular dynamics simulations searched a broad conformational space, then multiple independent, all-atom molecular dynamics simulations with explicit solvent determined the detailed local FEL using massively distributed computing. The combination of the two models enabled efficient calculation of the free energy landscapes. The MSFEL analysis showed that chignolin has an intermediate state as well as a misfolded state. The folding process is initiated by the formation of a beta-hairpin turn, followed by the formation of contacts in the hydrophobic core between Tyr2 and Trp9. Furthermore, mutation of Tyr2 shifts the population to the misfolded conformation. The results indicate that the hydrophobic core plays an important role in stabilizing the native state of chignolin.