Design, Modeling, and Synthesis of Active Nanosystems and Therapeutics

In this thesis, I studied, through computational and experimental means, materials and therapeutics. Using molecular dynamics (MD) simulations, we examined: 1) dynamics of silver-alkaloid molecular motors, 2) bioinspired polymer separators, 3) amyloid inhibitors, 4) dendrimer-peptide conjugates, 5) phosphoethanolamine (pEtN) functionalized cellulose, and 6) synthesis of early-stage autophagy inhibitors. In 1), we identified the mechanism behind chirality and pH-dependent molecular motor rotation to be asymmetric dissolution of adsorbed alkaloid crystals. These alkaloids also fit a quantum ratchet model, where in an asymmetric system, under non-equilibrium conditions, they will move asymmetrically. In 2), we examined the transport of lithium ions near poly(ethylene-co-acrylic acid) separators. We showed that the separator immobilizes PF6- anions and desolvates Li+ cations, increasing the relative mobility of Li+ and so decreasing lithium dendrite formation. In 3), we modeled native and inhibited model amyloid crystals. We showed that the inhibitor outcompetes dipeptide molecules for surface adsorption, favoring formation of the observed inhibited crystals. In 4), human ACE2 peptide-PAMAM dendrimer conjugates were simulated, showing that increased stability of the peptides results in improved binding with the SARS-CoV-2 spike protein. In 5), our collaborator previously discovered pEtN cellulose in bacterial biofilms. We confirmed computationally that pEtN cellulose binds tightly with curli fibers and forms hydrogen bonds with neighboring pEtN chains as well as nearby water, forming hydrogels seen experimentally. In 6), I developed a synthetic pathway for an ATG5-ATG16L1 protein-protein interaction inhibitor for early-stage autophagy inhibition.