State Key Laboratory of Surface Physics, and Department of Physics, Fudan University, 220 Handan Road, Shanghai 200433, China.
J Chem Phys. 2012 Jul 14;137(2):025101. doi: 10.1063/1.4732761.
Characterizing the early formed oligomeric intermediates of amyloid peptides is of particular interest due to their links with neurodegenerative diseases. Here we study the NNQQ peptide, known to display parallel β-strands in amyloid fibrils by x-ray microcrystallography, and investigate the structural, thermodynamical, and dynamical properties of 20 NNQQ peptides using molecular dynamics and replica exchange molecular dynamics simulations coupled to a coarse-grained force field. All simulations are initiated from randomized and fully dispersed monomeric conformations. Our simulations reveal that the phase transition is characterized by a change in the oligomer and β-sheet size distributions and the percentage of mixed parallel/antiparallel β-strands when the sheets are formed. At all temperatures, however, the fraction of parallel β-strands remains low, though there are many association/fragmentation events. This work and a growing body of computational studies provide strong evidence that the critical nucleus goes beyond 20 chains and reordering of the β-strands occurs in larger oligomers.
由于其与神经退行性疾病的关联，研究淀粉样肽早期形成的寡聚中间体具有特别的意义。在这里，我们研究了 NNQQ 肽，其通过 X 射线微晶体学显示出在淀粉样原纤维中具有平行β-折叠结构，并使用分子动力学和 replica 交换分子动力学模拟结合粗粒度力场研究了 20 个 NNQQ 肽的结构、热力学和动力学性质。所有模拟都是从随机和完全分散的单体构象开始的。我们的模拟表明，相转变的特征是寡聚体和β-折叠大小分布的变化，以及当形成片层时混合平行/反平行β-折叠的百分比。然而，在所有温度下，平行β-折叠的分数仍然较低，尽管存在许多缔合/片段化事件。这项工作和越来越多的计算研究提供了有力的证据，表明关键核超过 20 个链，并且较大的寡聚体中β-链发生重新排列。
