Exploring channelrhodopsin-2 and gold nanocluster interaction: a route to control the protein photocycle

Hybrid light-matter platforms that combine biomolecular photochemistry with engineered electromagnetic fields offer a promising, largely unexplored way to extend optogenetic control beyond the limits of native chromophores. Channelrhodopsin-2 (ChR2), a widely used light-gated ion channel, serves as an ideal model to test whether metallic nanoclusters can interface with membrane photoreceptors without disrupting their structure or function. Using large-scale molecular dynamics simulations from multiple starting configurations, we simulate ChR2 in complex with a gold nanocluster, which does not exhibit plasmonic behavior but lies within the size regime where metallic nanoclusters begin to display plasmonic resonances. We find that these functionalized nanoclusters spontaneously form stable, physiologically relevant complexes with ChR2 while preserving its global structure, hydration, retinal binding pocket, and native dynamics. Protein network and contact perturbation analyses uncover an unreported allosteric link between nanocluster binding sites and the retinal cavity, suggesting a mechanism to tune photochemical behavior. Our results establish a molecular feasibility framework for integrating nanoclusters with optogenetic receptors, opening the way for the design of future nano-optogenetic platforms that could modulate photoreceptor photochemistry without genetic or chemical modification of the photoreceptor itself.