Stability of Complex Biomolecular Structures: van der Waals, Hydrogen Bond Cooperativity, and Nuclear Quantum Effects.
Stability of Complex Biomolecular Structures: van der Waals, Hydrogen Bond Cooperativity, and Nuclear Quantum Effects.
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DOI：
10.1021/acs.jpclett.5b01899
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
M. Rossi;W. Fang;A. Michaelides
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文献类型：
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作者：
M. Rossi;W. Fang;A. Michaelides
生物分子是通过弱相互作用的微妙平衡来稳定的复杂系统，因此准确评估所有能量贡献非常重要。然而，目前还不清楚哪些贡献能产生更大的影响。在这里，我们检查了堆积的聚谷氨酰胺 (polyQ) 链，这是淀粉样蛋白聚集体中常见的肽重复序列。我们研究氢键 (HB) 协同性、范德华 (vdW) 色散相互作用以及量子对自由能的贡献，包括通过密度泛函理论和从头算路径积分模拟的非谐性。在这些不同的因素中，我们发现对结构稳定的最大影响来自 vdW 相互作用。随着堆叠链规模的增长，HB 协同性是第二大贡献。竞争性核量子效应使净量子贡献很小，但对非谐性、vdW 和 HB 数量非常敏感。我们的结果表明，只有考虑所有这些组件才能实现对这些系统的可靠处理。
Biomolecules are complex systems stabilized by a delicate balance of weak interactions, making it important to assess all energetic contributions in an accurate manner. However, it is a priori unclear which contributions make more of an impact. Here, we examine stacked polyglutamine (polyQ) strands, a peptide repeat often found in amyloid aggregates. We investigate the role of hydrogen bond (HB) cooperativity, van der Waals (vdW) dispersion interactions, and quantum contributions to free energies, including anharmonicities through density functional theory and ab initio path integral simulations. Of these various factors, we find that the largest impact on structural stabilization comes from vdW interactions. HB cooperativity is the second largest contribution as the size of the stacked chain grows. Competing nuclear quantum effects make the net quantum contribution small but very sensitive to anharmonicities, vdW, and the number of HBs. Our results suggest that a reliable treatment of these systems can only be attained by considering all of these components.