Exploration of the Nucleation Pathway for Supramolecular Fibers
Exploration of the Nucleation Pathway for Supramolecular Fibers
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DOI：
10.1021/acs.jcim.3c00049
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发表时间：
2023-04-05
影响因子：
5.6
通讯作者：
Loverde，Sharon M.
中科院分区：
文献类型：
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作者：
Tang，Phu K.;Khatua，Prabir;Loverde，Sharon M.
超分子纤维形成的途径与自组装分子的潜在顺序相耦合。在这里，我们报告原子分子动力学模拟表征的初始阶段的模型药物两亲物在水溶液中的自组装。我们用二维的元吸附理论计算了该模型药物两亲物Tubustecan，TT 1的组装空间。TT1由疏水性抗癌药物喜树碱（CPT）与亲水性聚乙二醇（PEG）链结合组成。我们发现，CPT的芳香堆积驱动形成更高密度的液滴。该液滴伸长，并且可以在重组和形成药物的界面和额外的芳香族堆叠时形成更高级有序的超分子组装体。我们表明，新的反应坐标适合这类分子是必不可少的捕获组装后的分子顺序的程度。这种方法可以改进和扩展，以表征其他分子的芳香族化合物的超分子组装途径。
The pathway for supramolecular fiber formation is coupled with the underlying order of the self-assembling molecules. Here, we report on atomistic molecular dynamics simulations to characterize the initial stages of the self-assembly of a model drug amphiphile in an aqueous solution. We perform two-dimensional metadynamics calculations to characterize the assembly space of this model drug amphiphile─Tubustecan, TT1. TT1 is composed of the hydrophobic anticancer drug, Camptothecin (CPT), conjugated to a hydrophilic polyethylene glycol (PEG) chain. We find that the aromatic stacking of CPT drives the formation of a higher-density liquid droplet. This droplet elongates and can form a higher-ordered supramolecular assembly upon reorganizing and forming an interface and additional aromatic stacking of the drugs. We show that novel reaction coordinates tailored to this class of molecules are essential in capturing the underlying degree of molecular order upon assembly. This approach can be refined and extended to characterize the supramolecular assembly pathway of other molecules containing aromatic compounds.