Supramolecular nanostructures formed by drug amphiphiles (DAs) containing the anticancer drug camptothecin (CPT) have been shown to possess great potential as self-delivery drug vehicles (Cheetham et al, JACS, 2013). Changes in the molecular design of the DA, such as attaching additional CPT drugs, modulate the intermolecular packing, shifting the morphology of a self-assembled filament to a nanotube. Using long-time all-atomistic molecular dynamics simulations, we probe the structure of these self-assembled nanotubes (Kang, Chakraborty, and Loverde, Journal of Chemical Information and Modeling, 2018) and filaments (Kang, Zhang, Cui, and Loverde, Macromolecules, 2016). Next, we describe efforts by our laboratory to build coarse-grained models of entire DA filaments (Kang, Cui, and Loverde, Soft Matter, 2017) and DA nanotubes as a method to characterize their stability, as well as their mechanical properties. Finally, we characterize the interactions of single nanotubes with model cellular membranes using advanced sampling methods in molecular dynamics. We also describe long-time (18 microseconds) atomistic simulations of individual DAs to characterize the interaction of these molecules with model cellular membranes. Insight from these simulations could guide the molecular level design of peptide amphiphiles and drug amphiphiles, optimizing their interaction with the cellular membrane.

Molecular modeling of peptide-drug amphiphiles

2019 Spring National Meeting

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