Modeling of Therapeutic Drugs, Polymers, and Self-Assembling Peptides

In this thesis, we collaborated with several experimental groups on designing and testing of new therapeutics and peptide-based materials. In particular, we conducted atomistic molecular dynamics simulations to study systems in three main areas: A) small drugs and therapeutic polymers, B) therapeutic peptides, and C) materials based on self-assembled peptides. A) We designed and investigated antivirals based on sulfoglycodendrimers and polystyrene sulfonate polymers of different topologies and sizes that can mimic heparan sulfate proteoglycans. We also investigated cucurbit[n]urils and small drugs capable of encapsulating charged viral residues and performing other inhibitory activities. B) First, we developed methods capable of designing small therapeutic peptides. These methods were used to design peptides for proteins involved in immune evasion by tumor cells. Second, we explored self-assembling functionalized peptides as localized therapeutics against viruses, bacteria, and fungi. These fibril-forming peptides were also examined as binders for human proteins to promote endogenous activity. Finally, we studied a hypothetical coupling between amyloids and Spike proteins of SARS-CoV-2. C) We explored materials based on peptides self-assembled into porous crystals. We examined how mutations introduced in these peptides affect the stability of the observed modified crystals. We also investigated how small molecules intercalated in these crystals influenced their structural changes.