Cooperative folding mechanism of a β‐hairpin peptide studied by a multicanonical replica‐exchange molecular dynamics simulation
Cooperative folding mechanism of a β‐hairpin peptide studied by a multicanonical replica‐exchange molecular dynamics simulation
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DOI：
10.1002/prot.21264
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发表时间：
2006-12
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影响因子：
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通讯作者：
T. Yoda;Y. Sugita;Y. Okamoto
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文献类型：
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作者：
T. Yoda;Y. Sugita;Y. Okamoto
G肽是链球菌蛋白G B1结构域C末端的16个残基肽，已知其在6 μs内折叠成特定的β发夹。在这里，我们研究了分子机制的稳定性和折叠的G肽进行多正离子复制交换（MUCAREM）分子动力学模拟与显式溶剂。与之前相同肽的模拟不同，模拟从未折叠构象开始，没有关于天然构象的任何实验信息。在278 ns的轨迹中，我们观察到三个独立的折叠事件。因此，MUCAREM可以估计加速折叠反应超过60倍，比传统的分子动力学模拟。肽在室温下的自由能图显示，在折叠途径中有三个基本的子事件来构建天然样β发夹构象：（i）在Tyr45和Phe52之间的侧链接触下发生肽的疏水性塌陷，（ii）然后，形成天然样转角，伴随着转角区域周围的氢键网络，和（iii）最后，形成其余的骨架氢键。许多稳定的天然氢键在第二阶段的合作形成，这表明了特定的转弯结构的形成的重要性。这也支持的非天然构象的积累，只有周围的Tyr45和Phe52的疏水簇。这些模拟结果与实验观察到的转弯区域的高λ值一致。Proteins 2007.© 2006 Wiley利斯公司
G‐peptide is a 16‐residue peptide of the C‐terminal end of streptococcal protein G B1 domain, which is known to fold into a specific β‐hairpin within 6 μs. Here, we study molecular mechanism on the stability and folding of G‐peptide by performing a multicanonical replica‐exchange (MUCAREM) molecular dynamics simulation with explicit solvent. Unlike the preceding simulations of the same peptide, the simulation was started from an unfolded conformation without any experimental information on the native conformation. In the 278‐ns trajectory, we observed three independent folding events. Thus MUCAREM can be estimated to accelerate the folding reaction more than 60 times than the conventional molecular dynamics simulations. The free‐energy landscape of the peptide at room temperature shows that there are three essential subevents in the folding pathway to construct the native‐like β‐hairpin conformation: (i) a hydrophobic collapse of the peptide occurs with the side‐chain contacts between Tyr45 and Phe52, (ii) then, the native‐like turn is formed accompanying with the hydrogen‐bonded network around the turn region, and (iii) finally, the rest of the backbone hydrogen bonds are formed. A number of stable native hydrogen bonds are formed cooperatively during the second stage, suggesting the importance of the formation of the specific turn structure. This is also supported by the accumulation of the nonnative conformations only with the hydrophobic cluster around Tyr45 and Phe52. These simulation results are consistent with high ϕ‐values of the turn region observed by experiment. Proteins 2007. © 2006 Wiley‐Liss, Inc.