Unlocking chromophore excited state modulation in photoactive biohybrids using protein conformational dynamics
Year: 2026
Type: preprint
Abstract: Photoactive biohybrids offer a promising platform for photonic applications by merging the functional versatility of synthetic molecules with the tunable structure and dynamics of proteins. While unexpected excited-state relaxation in biohybrids has been attributed to complex protein motions, the intentional design and exploitation of such dynamics remain largely unexplored. Here, we demonstrated that the conformational landscape of biohybrids can be systematically tuned by exploiting the intrinsic flexibility of a de novo α3 protein scaffold. We develop the unfolding-refolding method to synthesize a series of four new thermodynamically stable biohybrids. Based on this approach, we showed that single-point aromatic mutations modulate the conformational exchange of our biohybrids on the microsecond timescale. By combining spectroscopic, structural, and computational studies, we showed that the engineered conformational dynamics correlate with changes in chromophore triplet-state relaxation. While environmental factors, such as polarity or steric forces within the protein pocket, can contribute to photoresponse, the observed trends highlight conformational dynamics as a key parameter linking protein structure to excited-state behavior. These findings reveal an unexplored strategy for controlling biohybrid photoresponses through engineered conformational changes, thereby opening new avenues for designing biohybrids with tunable photophysical properties.
Source: ChemRxiv
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7220383617