本文通过分子动力学模拟研究富勒烯在Aβ42低聚体表面的结合过程。在结合过程中， C60在Aβ表面经历一系列尝试过程，最终找到某个稳定的结合位点。根据结合的残基不同，这些结合位点可以分为六类，其中核心疏水区域(CHC)位点(17LVFFA21)及Turn 27-31位点(27NKGAI31)具有最强的结合稳定性。二者的结合主要通过范德华作用稳定，而溶剂化效应则起相反作用。在这六类位点中的两个位点，观察到C60会对Aβ二级结构起破坏作用。其一位于核心疏水区域， C60有挤入多肽β片层中间的趋势；另外一位点位于N端， C60能够破坏外侧Aβ的3-5号残基的主链氢键，瓦解其末端的β片结构。这两个过程对理解富勒烯抑制Aβ聚集的微观机制提供了帮助。此外，在Turn 27-31位点以及Y10-H14位点，发现了富勒烯与Aβ纤维样聚集体结合的沟槽滚动机制，即富勒烯能够在淀粉样低聚体表面形成的特定沟槽内滚动。这一特征有助于预测富勒烯在其它淀粉样多肽表面的结合位点及结合行为。%We investigated the binding process of ful erene to fibril-like Aβ42 oligomers by performing multiple molecular dynamics simulations. It was observed that the C60 molecule searched a series of positions on the surfaces of the Aβ42 oligomers before finding a stable binding state. Multi-binding sites have been identified and these can be classified into six types according to the type of residue in contact with the ful erene. The sites near the central hydrophobic core (CHC) (17LVFFA21) and the turn region (27NKGAI31) were identified as the most suitable sites with the lowest associated binding energies. These bound states were primarily stabilized by van der Waals interactions, while the solvation effect acted as a destabilizing factor. Structural disruption was observed under two conditions;in cases where the ful erene exhibited a tendency to insert into the CHC region of the Aββ-sheet bilayer and in situations where the ful erene molecule broke the main-chain hydrogen bond in the N-terminal region of the peptides. These two processes assist in understanding the mechanism whereby ful erene inhibits Aβ42 aggregation. Additional y, the groove-rol ing mechanism at the turn associated with the 27-31 and Y10-H14 sites was identified. Owing to the periodic features of amyloid fibrils, the ful erene could rol along the elongation direction of the Aβprotofibril on certain grooves. This mechanism could be helpful in predicting the interactions of ful erene with other amyloid peptides or proteins.
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