School of Systems Biology, George Mason University, Manassas, VA 20110, USA.
J Mol Model. 2013 Feb;19(2):737-50. doi: 10.1007/s00894-012-1596-8. Epub 2012 Sep 29.
Using implicit solvent atomistic model and replica exchange molecular dynamics, we study binding of Aβ monomer to zwitterionic dimyristoylphosphatidylcholine (DMPC) lipid monolayer. Our results suggest that Aβ binding to the monolayer is governed primarily by positively charged and aromatic amino acids. Lysine residues tend to interact with surface choline and phosphorous lipid groups, whereas aromatic amino acids penetrate deeper into the monolayer, reaching its hydrophobic core. We show that binding to the DMPC monolayer causes a dramatic conformational transition in Aβ monomer, resulting in chain extension, loss of intrapeptide interactions, and formation of β-structure. This conformational transition is far more significant than that occurring during the initial stages of aggregation in water. We also found that Aβ binding perturbs surface ordering of lipids interacting with Aβ.
我们使用隐溶剂原子模型和复制交换分子动力学研究了 Aβ单体与两性离子二肉豆蔻酰磷脂酰胆碱（DMPC）脂质单层的结合。我们的结果表明，Aβ与单层的结合主要由带正电荷和芳香族氨基酸决定。赖氨酸残基倾向于与表面胆碱和磷脂质基团相互作用，而芳香族氨基酸则更深地渗透到单层中，到达其疏水性核心。我们表明，与 DMPC 单层的结合导致 Aβ单体发生剧烈的构象转变，导致链延伸、肽内相互作用丧失和β-结构形成。这种构象转变比在水中初始聚集阶段发生的转变更为显著。我们还发现，Aβ结合会扰乱与 Aβ相互作用的脂质的表面有序性。
