Solvation stabilizes intercarbonyl n→π* interactions and polyproline II helix
Solvation stabilizes intercarbonyl n→π* interactions and polyproline II helix
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溶剂化可稳定羰基间 n-β* 相互作用和聚脯氨酸 II 螺旋
DOI：
10.1039/d2cp00857b
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发表时间：
2022
影响因子：
3.3
通讯作者：
Zondlo, Neal J.
中科院分区：
文献类型：
--
作者：
Zondlo, Neal J.
连续羰基之间的n→π* 相互作用稳定蛋白质中的α-螺旋和聚脯氨酸II螺旋（PPII）构象。已经提出n→π* 相互作用对蛋白质的无序状态提供显著的构象偏差。为了理解溶剂化作用对n→π* 相互作用强度的作用，使用水和HF对模型n→π* 相互作用（扭转平行偏移甲醛二聚体）进行了计算研究，作为供体和受体羰基的显式溶剂化的函数。此外，还考察了尿素、硫脲、胍盐和一价阳离子对n→π* 相互作用强度的影响。受体羰基的溶剂化显著增强n→π* 相互作用，而供体羰基的溶剂化仅适度减弱n→π* 相互作用。在受体羰基上有两个溶剂分子时，n→π* 相互作用强度最大。尿素通过同时接合受体羰基上的两个氧孤对来稳定n→π* 相互作用。在模型肽Ac-Pro-NMe 2、Ac-Ala-NMe 2和Ac-Pro 2-NMe 2中进一步研究溶剂效应。肽中的溶剂效应与甲醛二聚体中的溶剂效应相似，受体羰基的溶剂化增加了n→π* 相互作用强度，并导致脯氨酸内和外环褶皱中更紧凑的构象，以及这些环褶皱之间的能量差减小。羰基溶剂化导致PPII的能量偏好超过α-螺旋和β/扩展构象，这与质子溶剂和蛋白质变性剂都促进PPII的实验数据一致。受体羰基的溶剂化削弱了稳定β构象的残基内C5氢键。
n→π* interactions between consecutive carbonyls stabilize the α-helix and polyproline II helix (PPII) conformations in proteins. n→π* interactions have been suggested to provide significant conformational biases to the disordered states of proteins. To understand the roles of solvation on the strength of n→π* interactions, computational investigations were conducted on a model n→π* interaction, the twisted-parallel-offset formaldehyde dimer, as a function of explicit solvation of the donor and acceptor carbonyls, using water and HF. In addition, the effects of urea, thiourea, guanidinium, and monovalent cations on n→π* interaction strength were examined. Solvation of the acceptor carbonyl significantly strengthens the n→π* interaction, while solvation of the donor carbonyl only modestly weakens the n→π* interaction. The n→π* interaction strength was maximized with two solvent molecules on the acceptor carbonyl. Urea stabilized the n→π* interaction via simultaneous engagement of both oxygen lone pairs on the acceptor carbonyl. Solvent effects were further investigated in the model peptides Ac-Pro-NMe2, Ac-Ala-NMe2, and Ac-Pro2-NMe2. Solvent effects in peptides were similar to those in the formaldehyde dimer, with solvation of the acceptor carbonyl increasing n→π* interaction strength and resulting in more compact conformations, in both the proline endo and exo ring puckers, as well as a reduction in the energy difference between these ring puckers. Carbonyl solvation leads to an energetic preference for PPII over both the α-helix and β/extended conformations, consistent with experimental data that protic solvents and protein denaturants both promote PPII. Solvation of the acceptor carbonyl weakens the intraresidue C5 hydrogen bond that stabilizes the β conformation.