Free energy determinants of secondary structure formation: II. Antiparallel beta-sheets.
Free energy determinants of secondary structure formation: II. Antiparallel beta-sheets.
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二级结构形成的自由能决定因素：II。
DOI：
10.1006/jmbi.1995.0503
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Honig,B
中科院分区：
文献类型：
--
作者：
Yang,AS;Honig,B
通过对构象自由能的理论分析，讨论了决定反平行β折叠稳定性的因素。建立了一系列理想化的多聚丙氨酸β-折叠模型，并对模型进行了约束，使得氢键的角几何形状在蛋白质中观察到的范围内变化，而氢键距离保持不变。以这种方式产生的片材的构象具有范围从高度扭曲的左手到高度扭曲的右手取向的扭曲角的广泛分布。用气相CHARMM势和FDPB/γ溶剂化模型计算了各层的缔合自由能。左手结构被发现是不太稳定的右手结构，由于链内空间位阻在孤立的左手链。这就解释了为什么蛋白质中的反平行β折叠总是以右手方向扭曲。右手片的自由能表面表现出特别的偏好构象范围从平面到那些表现出明显的右手扭曲。这表明反平行β折叠可以采用多种右手构象，这一结果与已知蛋白质的观察结果一致。在我们对α-螺旋的研究中，我们发现货车范德华力和疏水相互作用是稳定聚丙氨酸β-折叠的主要因素，而静电相互作用包括氢键被发现是不稳定的。然而，与螺旋相反，仅涉及骨架-骨架相互作用（包括β-碳）的构象自由能的净变化不足以克服伴随片层形成的构型熵的损失。相反，我们认为，跨链非极性侧链侧链的相互作用是必不可少的片形成，解释为什么大的非极性氨基酸具有最大的片形成倾向。因此，片材倾向涉及成对相互作用，并且预期是上下文依赖的，如在最近的实验中已经观察到的。
The factors that determine the stability of antiparallel β-sheets are consideredviaa theoretical analysis of conformational free energies. A series of idealized model polyalanine β-sheets are built with constraints such that the angular geometry of hydrogen bonding varies in the range observed in proteins while hydrogen bonding distance remains fixed. The conformations of the sheets generated in this way have a broad distribution of twist angles ranging from highly twisted left-handed to highly twisted right-handed orientations. The association free energies of the sheets are calculated with a gas phase CHARMM potential and FDPB/γ solvation models. Left-handed structures are found to be less stable than right handed structures due to intrachain steric hindrance in isolated left-handed strands. This explains why antiparallel β-sheets in proteins are invariably twisted in the right-handed direction. The free energy surface for right-handed sheets shows particular preference for conformations ranging from flat to those that exhibit a pronounced right-handed twist. This suggests that antiparallel β-sheets can adopt a variety of right-handed conformations, a result that is consistent with observations on known proteins. In parallel with our study of α-helices we find that van der Waals and hydrophobic interactions are the primary factor stabilizing polyalanine β-sheets, while electrostatic interactions including hydrogen bonding are found to be destabilizing. However, in contrast to helices, the net change in conformational free energy involving only backbone-backbone interactions (including β-carbons) is not sufficient to overcome the loss in configurational entropy that accompanies sheet formation. Rather we suggest that cross-strand non-polar side-chain–side-chain interactions are essential for sheet formation, explaining why large non-polar amino acids have the greatest sheet forming propensities. Thus, sheet propensities involve pairwise interactions and are expected to be context dependent, as has been observed in recent experiments.