Molecular Dynamics Simulation of Bioactive Complexes, Nanoparticles and Polymers

In this thesis, molecular dynamics (MD) simulations were performed to design inhibitors against viral pathogens, examine drug delivery systems and model dynamical nano-systems. Peptide based inhibitors against SARS-CoV-2 were designed by mimicking ACE2 (cellular receptor of SARS-CoV-2). MD simulations revealed that inhibitors with double α-helix bundle could provide specific geometry matching to the spike protein of SARS-CoV-2. The sequence of inhibitors can be evolved by a newly designed computational algorism to provide specificity to different strains. Protein based boosters were also designed aiming to trigger the immune reaction to SARS-CoV-2. The binding efficiencies of those boosters were examined by MD simulations. In collaboration with different experimental groups, various heparan sulfate (HS) mimics designed in their labs were examined through MD simulations to study the atomistic details of the coupling between HS mimics and viral proteins, where multivalent binding modes were found to dominate the enhanced affinity. The corresponding virucidal mechanisms were proposed based on calculations of free energy of binding. Polymers forming aggregates or micelles, synthesized in our collaborator’s lab, were also studied in atomistic details about their membrane permeability and serum stability, where the interactions between polymers and their targets were quantified. In addition to bio-related systems, nanomaterial systems were also designed and studied. Stretch healable nanofibers composed of coronene (or) perfluorocoronene molecules were designed and tested by MD simulations. Intermolecular interactions interpreted by ab initio calculations were found to be the driving factor in the self-assembly of nanofibers. The intermolecular interactions were also the key factors in determining the reaction rates of the slider-track systems and ligand effects of functionalized gold nanoparticle systems in other collaborative projects.