Fernández Ariel
Department of Bioengineering, Rice University, Houston, TX 77005, United States.
FEBS Lett. 2005 Dec 5;579(29):6635-40. doi: 10.1016/j.febslet.2005.10.058. Epub 2005 Nov 9.
The identification of the driving factor for fibril formation is paramount to understand the molecular basis of amyloidogenic disease. Recently, an atomic-detail structure of a fibrillogenic aggregate was reported and revealed a tight packing of beta-sheets. However, there is not a single pair-wise interaction of significance between the beta-sheets, no hydrogen bond and no hydrophobic interaction. Instead, there is extensive burial of polar groups at the interface. These observations lead to the question: What factor drives the association of beta-sheets? This issue is addressed by combining all-atom molecular dynamics with an implicit-solvent analysis. The driving force for the association arises from the mechanical equivalent of the dehydration propensity of pre-formed intra-sheet hydrogen bonds and dipole-dipole interactions.
确定原纤维形成的驱动因素对于理解淀粉样变性疾病的分子基础至关重要。最近，报道了一种纤维状聚集体的原子细节结构，揭示了β-折叠片的紧密堆积。然而，β-折叠片之间没有一对显著的相互作用，没有氢键，也没有疏水相互作用。相反，在界面处有大量极性基团被掩埋。这些观察结果引发了一个问题：是什么因素驱动了β-折叠片的缔合？通过将全原子分子动力学与隐式溶剂分析相结合来解决这个问题。缔合的驱动力源于预先形成的片内氢键的脱水倾向和偶极-偶极相互作用的力学等效物。
