Exploring Strategies for Labeling Viruses with Gold Nanoclusters through Non-equilibrium Molecular Dynamics Simulations

Biocompatible
gold nanoclusters can be utilized as contrast agents
in virus imaging. The labeling of viruses can be achieved noncovalently
but site-specifically by linking the cluster to the hydrophobic pocket
of a virus via a lipid-like pocket factor. We have estimated the binding
affinities of three different pocket factors of echovirus 1 (EV1)
in molecular dynamics simulations combined with non-equilibrium free-energy
calculations. We have also studied the effects on binding affinities
with a pocket factor linked to the Au102pMBA44 nanocluster in different protonation states. Although
the absolute binding affinities are over-estimated for all the systems,
the trend is in agreement with recent experiments. Our results suggest that the natural pocket factor (palmitic
acid) can be replaced by molecules pleconaril (drug) and its derivative
Kirtan1 that have higher estimated binding affinities. Our results
also suggest that including the gold nanocluster does not decrease
the affinity of the pocket factor to the virus, but the affinity is
sensitive to the protonation state of the nanocluster, i.e., to pH
conditions. The methodology introduced in this work helps in the design
of optimal strategies for gold–virus bioconjugation for virus
detection and manipulation.