Instituto de Ciencia Molecular, Universidad de Valencia, P.O. Box 22085, E-46071 Valencia, Spain.
Phys Chem Chem Phys. 2014 Mar 7;16(9):4369-77. doi: 10.1039/c3cp53551g.
We use large-scale MP2 calculations to analyze the interactions appearing in amyloid fibers, which are difficult to determine experimentally. To this end, dimers and trimers of the hexapeptide NNQQNY from the yeast prion-like protein Sup35 were considered as model systems. We studied the energy interactions present in the three levels of organization in which the formation of amyloid fibrils is structured. The structural changes in the hydrogen bonds were studied too. It was found that the most energetic process is the formation of the β-sheet, which is equally due to both hydrogen bonds and van der Waals interactions. The aromatic rings help stabilize these aggregates through stacking of the aromatic rings of tyrosine, the stability produced by the aromatics residues increasing with their aromaticity. The formation of the basic unit of the assembled proto-fiber, the steric zipper, is less energetic and is associated to both dispersion forces and hydrogen bonds. The interactions between pair of β-sheets across the peptide-to-peptide contact through the tyrosine rings are cooperative and due to dispersion effects. Moreover, the strength of this interaction can rationalize the variation of mobility of the aromatic ring in the tyrosine units found in solid NMR experiments.
我们使用大规模 MP2 计算来分析在实验中难以确定的淀粉样纤维中出现的相互作用。为此，我们考虑了来自酵母朊病毒样蛋白 Sup35 的六肽 NNQQNY 的二聚体和三聚体作为模型系统。我们研究了淀粉样纤维形成的三个组织层次中存在的能量相互作用。还研究了氢键的结构变化。结果发现，最具能量的过程是β-折叠的形成，这既归因于氢键又归因于范德华相互作用。芳环通过酪氨酸的芳环堆积帮助稳定这些聚集体，由芳基残基产生的稳定性随着其芳族性的增加而增加。组装原纤维的基本单元，立体拉链的形成所需的能量较少，与色散力和氢键都有关。通过酪氨酸环在肽-肽接触处的β-片层之间的相互作用是协同的，并且归因于色散效应。此外，这种相互作用的强度可以合理地解释固态 NMR 实验中发现的酪氨酸单元中芳环迁移率的变化。
