Department of Physics, University of California Santa Barbara, Santa Barbara, California 93106, USA.
J Chem Phys. 2012 Feb 14;136(6):065103. doi: 10.1063/1.3682986.
Mechanisms of peptide aggregation on hydrophobic surfaces are explored using molecular dynamics simulations with a coarse-grained peptide representation. Systems of peptides are studied with varying degrees of backbone rigidity (a measure of β-sheet propensity) and degrees of attraction between their hydrophobic residues and the surface. Multiple pathways for aggregation are observed, depending on the surface attraction and peptide β-sheet propensity. For the case of a single-layered β-sheet fibril forming on the surface (a dominant structure seen in all simulations), three mechanisms are observed: (a) a condensation-ordering transition where a bulk-formed amorphous aggregate binds to the surface and subsequently rearranges to form a fibril; (b) the initial formation of a single-layered fibril in the bulk depositing flat on the surface; and (c) peptides binding individually to the surface and nucleating fibril formation by individual peptide deposition. Peptides with a stiffer chiral backbone prefer mechanism (b) over (a), and stronger surface attractions prefer mechanism (c) over (a) and (b). Our model is compared to various similar experimental systems, and an agreement was found in terms of the surface increasing the degree of fibrillar aggregation, with the directions of fibrillar growth matching the crystallographic symmetry of the surface. Our simulations provide details of aggregate growth mechanisms on scales inaccessible to either experiment or atomistic simulations.
使用粗粒肽表示的分子动力学模拟探索疏水性表面上肽聚集的机制。研究了具有不同程度的骨架刚性（β-折叠倾向的度量）和疏水性残基与表面之间吸引力的肽系统。根据表面吸引力和肽β-折叠倾向，观察到了多种聚集途径。对于在表面上形成单层β-折叠原纤维的情况（所有模拟中都可见到的主要结构），观察到了三种机制：（a）凝聚-有序转变，其中体相形成的无定形聚集体结合到表面上，随后重新排列形成原纤维；（b）在体相中原纤维的单层初始形成并沉积在表面上；和（c）肽单独结合到表面上，并通过单个肽沉积引发原纤维形成。具有刚性手性骨架的肽更倾向于机制（b）而不是（a），并且更强的表面吸引力更倾向于机制（c）而不是（a）和（b）。我们的模型与各种类似的实验系统进行了比较，并且在表面增加原纤维聚集程度方面以及原纤维生长方向与表面的晶体学对称性匹配方面达成了一致。我们的模拟提供了在实验或原子模拟都无法达到的尺度上的聚集体生长机制的详细信息。
