<br/>Oligo-<i>p</i>-phenylene ethynylenes (OPEs) are a novel class of synthetic compounds that have shown efficient biocidal activities against a broad-spectrum of pathogens, including bacteria, spores, and viruses. We have previously shown that a series of cationic OPEs effectively inactivated both MS2 and T4 viruses. In order to gain insights to the antiviral activity of the OPEs, we have used molecular docking and dual layer QM/MM electronic structure calculations to study the interactions of a range of OPEs with the MS2 protein capsid. Using a docking software, frequent binding locations of the OPEs on the capsid were observed in which binding occurred along the outer protein surface with a distinct preference and relatively large binding affinity relative to the unbound OPEs. For each of the clusters, electrostatic surfaces of the capsid showed binding of the positively charged OPEs in close proximity to negatively charged amino acid residues. Additionally, it appears that sterics also plays a significant role in binding preference. In order to corroborate the docking results and obtain more accurate binding affinities, QM/MM optimizations were conducted on the strongest OPE binding conformations predicted from docking, in addition to the surrounding capsid amino acid residues. Results so far show that the OPEs optimized using the dual layer QM/MM approach exhibit minimal structural change compared to the docking conformation, confirming the docking results for this series of OPEs. Currently, we are utilizing energetic properties obtained from QM/MM to generate more accurate binding affinities. Findings from this computational study will shed light on the mechanism of the antivirial activity of the OPEs.

Dual layer QM/MM binding study of antimicrobial oligomer-viral capsid complexes

249th National Meeting (2015)

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