Network analysis of chromophore binding site in LOV domain

Abstract

Photoreceptor proteins are versatile toolboxes for developing biosensors for optogenetic applications. These molecular tools get activated upon illumination of blue light, which in turn offers a non-invasive method for gaining high spatiotemporal resolution and precise control of cellular signal transduction. The Light-Oxygen-Voltage (LOV) domain family of proteins is a well-recognized system for constructing optogenetic devices. Translation of these proteins into efficient cellular sensors is possible by tuning their photochemistry lifetime. However, the bottleneck is the need for more understanding of the relationship between the protein environment and photocycle kinetics. Significantly, the effect of the local environment also modulates the electronic structure of the chromophore, which perturbs the electrostatic and hydrophobic interaction within the binding site. This work highlights the critical factors hidden in the protein network linking with their experimental photocycle kinetics. It also presents an opportunity to quantitatively examine the alternation in chromophore equilibrium geometry and identify details which have substantial implications in designing synthetic constructs with desirable photocycle efficiency.