Peptide self-assembly has been used to design an array of nanostructures with attractive biomedical applications. Experimental studies have reported nanofilament and nanotube formation from peptide-based drug amphiphiles (DAs). Here each DA consists of an anticancer drug camptothecin (CPT) conjugated to a short peptide sequence via a biodegradable disulphide linker. These DAs have been shown to possess an inherently high drug loading with a tunable release mechanism. Recently, our laboratory reported long-time atomistic molecular dynamics (MD) simulations of supramolecular nanotubes composed of these DAs.   Based on these all-atomistic simulations we have parameterized a coarse grained (CG) model for these DAs to study the self-assembly process, as well as the structure and stability of these nanotubes at longer time-scales (microseconds). These CG models successfully recapitulate the radial density distribution of peptides, CPTs, and water compared to previously reported atomistic simulations. Furthermore, the orientation of the CPTs along the nanotube is also conserved. Through long-time CG MD simulation, we aim to study the nanotube formation and dominant intermolecular interactions required for stable nanotube structures. This study will assist in the rational design of peptide-based drug amphiphiles that self-assemble into defined nanostructures.<br/>

Coarse-grained molecular dynamics simulation of supramolecular anticancer nanotubes

2019 Spring National Meeting

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