界面限制对 GB1 发夹折叠景观的平滑作用。
Smoothing of the GB1 hairpin folding landscape by interfacial confinement.
机构信息
Department of Chemical Engineering, Lehigh University, Bethlehem, Pennsylvania.
Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
出版信息
Biophys J. 2012 Aug 8;103(3):596-600. doi: 10.1016/j.bpj.2012.07.005.
We study the effects of confinement between planar walls on the folding thermodynamics of a β-hairpin, using large-scale replica-exchange molecular-dynamics simulations with an all-atom model and explicit solvent. We find that the folding free-energy landscape of this peptide observed in bulk is significantly modified when the peptide is confined between the walls. Most notably, the propensity of the peptide to form a misfolded state observed in the bulk solution becomes negligible under confinement. The absence of the misfolded state under confinement can be explained by an increased tendency of hydrophobic aromatic side chains to stay near the walls, because the misfolded state is characterized by a nonnative arrangement of aromatic side chains. These results from a simple confinement model may provide clues about the role of chaperonin confinement in smoothing folding landscapes by avoiding trapped intermediates.
我们使用全原子模型和显式溶剂的大规模复制交换分子动力学模拟研究了平面壁之间的限制对 β-发夹折叠热力学的影响。我们发现，在大块中观察到的这种肽的折叠自由能景观在肽被限制在壁之间时会发生显著改变。值得注意的是，在限制下，肽在大块溶液中形成错误折叠状态的倾向变得可以忽略不计。在限制下不存在错误折叠状态可以通过疏水性芳族侧链增加的倾向来解释，因为错误折叠状态的特征是芳族侧链的非天然排列。这个简单的限制模型的结果可能为伴侣蛋白限制通过避免被困中间体来平滑折叠景观的作用提供线索。
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