Peptide-based supramolecular filaments, in particular filaments self-assembled by drug amphiphiles (DAs), possess great potential in the field of drug delivery. These filaments possess one hundred percent drug loading, with a release mechanism that can be tuned based on the dissociation of the supramolecular filaments and the degradation of the DAs [Cheetham et al., J. Am. Chem. Soc., 2013, 135(8), 2907]. Recently, much attention has been drawn to the competing intermolecular interactions that drive the self-assembly of peptide-based amphiphiles into supramolecular filaments. Recently, we reported on long-time atomistic molecular dynamics simulations to characterize the structure and growth of chiral filaments by the self-assembly of a DA containing the aromatic anti-cancer drug camptothecin [Kang et al., Macromolecules, 2016, 49(3), 994]. We found that the π–π stacking of the aromatic drug governs the early stages of the self-assembly process, while also contributing towards the chirality of the self-assembled filament. Based on these all-atomistic simulations, we now build a chemically accurate coarse-grained model that can capture the structure and stability of these supramolecular filaments at long time-scales (microseconds). These coarse-grained models successfully recapitulate the growth of the molecular clusters (and their elongation trends) compared with previously reported atomistic simulations. Furthermore, the interfacial structure and the helicity of the filaments are conserved. Next, we focus on characterization of the disassembly process of a 0.675 μm DA filament at microsecond time-scales. These results provide very useful tools for the rational design of functional supramolecular filaments, in particular supramolecular filaments for drug delivery applications.

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肽基药物两亲丝的结构和稳定性的粗粒分子动力学研究

基于肽的超分子丝，特别是通过药物两亲物（DAs）自组装的丝，在药物递送领域具有巨大的潜力。这些细丝具有100％的载药量，其释放机理可根据超分子细丝的解离和DA的降解进行调整[Cheetham等人。，J。Am。化学 Soc。，2013，135（8），2907]。近来，引起竞争的分子间相互作用引起了很多关注，所述分子间相互作用驱使基于肽的两亲物自组装成超分子丝。最近，我们报道了长期的原子分子动力学模拟，以通过含有芳香族抗癌药物喜树碱的DA的自组装来表征手性长丝的结构和生长[Kang等。，高分子，2016，49（3），994]。我们发现芳香药物的π-π堆积控制着自组装过程的早期阶段，同时也有助于自组装长丝的手性。基于这些全原子模拟，我们现在建立化学上准确的粗粒度模型，该模型可以在较长的时间尺度（微秒）内捕获这些超分子细丝的结构和稳定性。与先前报道的原子模拟相比，这些粗粒度模型成功地概括了分子簇的生长（及其伸长趋势）。此外，保留了细丝的界面结构和螺旋度。接下来，我们将重点介绍微秒级时长为0.675μm的DA灯丝的拆卸过程。