A Computational Study of Novel Cationic Oligomers and their Interactions with Viral Capsids

The treatment and neutralization of pathogenic bacteria, spores, and viruses continues to be an ongoing challenge that will require novel developments in biomedical technology. A particular class of cationic synthetic oligomers termed Oligo-p-Phenylene-Ethynylenes (OPEs) exhibit potential as biocidal agents against antibiotic-resistant bacteria and viral mutations. OPEs offer a wide range of variation in functional and end groups with an array of chemical properties. We have used computational chemical techniques to study the conformational landscape of a simple OPE, S-OPE-1(H), composed of a single monomer unit and cationic side groups. Optimized geometry calculations using density functional theory (DFT) at the 631g(d,p) level were performed on three conformations of S-OPE-1(H), where the cationic side chains were constrained to different geometries. Dihedral angle scans of triple bonds between rings of each molecule were then performed using DFT to investigate the effects of side group orientation on conformational energy. These potential energy surfaces provide a complete conformational energy landscape. The differences in total electronic energies of all conformations were compared to determine which is most energetically favorable. We have found that the lowest energy conformation where the side groups are maximally displaced from the backbone is 0.288eV lower than more constrained geometries. In solution at room temperature, this conformer is expected to dominate the population. However, when brought into contact with protein scaffolds, e.g. viral capsids, this may be changed significantly. Our future goal is to explore this interaction through classical Molecular Dynamics (MD) simulations, using AutoDock simulations as the starting point.