Faculty of Chemistry, Adam Mickiewicz University in Poznań, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland.
J Phys Chem B. 2022 Aug 11;126(31):5772-5780. doi: 10.1021/acs.jpcb.2c03502. Epub 2022 Aug 2.
The molecular mechanism of fibrillation is an important issue for understanding peptide aggregation. In our previous work, we demonstrated that the interchain attraction and intrachain bending stiffness control the aggregation kinetics and transient aggregate morphologies of a one-bead-per-residue implicit solvent peptide model. However, that model did not lead to fibrillation. In this work, we study the molecular origin of fibril formation using a two-beads-per-residue model, where one bead represents the backbone residue atoms and the other the side chain atoms. We show that the side chain geometry determines the fibrillation propensity that is further modulated by the modified terminal beads. This allows us to bring out the effects of side chain geometry and terminal capping on the fibrillation propensity. Our model does not assume a secondary structure and is, perhaps, the simplest bead-based chain model leading to fibrillation.
纤维形成的分子机制是理解肽聚集的一个重要问题。在我们之前的工作中，我们证明了链间吸引力和链内弯曲刚度控制着一个每残基一个珠子的隐溶剂肽模型的聚集动力学和瞬态聚集形态。然而，该模型并没有导致纤维形成。在这项工作中，我们使用每残基两个珠子的模型研究了纤维形成的分子起源，其中一个珠子代表主链残基原子，另一个珠子代表侧链原子。我们表明，侧链几何形状决定了纤维形成倾向，而修饰的末端珠子进一步调节了这种倾向。这使我们能够揭示侧链几何形状和末端帽对纤维形成倾向的影响。我们的模型不假设二级结构，也许是最简单的基于珠子的导致纤维形成的链模型。
