Allosteric Modulation of Fluorescence Revealed by Hydrogen Bond Dynamics
in a Genetically Encoded Maltose Biosensor
Abstract
Genetically encoded fluorescent biosensors (GEFBs) proved to be reliable
tracers for many metabolites and cellular processes. In the simplest
case, a fluorescent protein (FP) is genetically fused to a sensing
protein which undergoes a conformational change upon ligand binding.
This drives a rearrangement in the chromophore environment and changes
the spectral properties of the FP. Structural determinants of successful
biosensors are revealed only in hindsight when the crystal structures of
both ligand-bound and ligand-free forms are available. This makes the
development of new biosensors for desired analytes a long
trial-and-error process. In the current study, we conducted µs-long all
atom molecular dynamics (MD) simulations of a maltose biosensor in both
the apo (dark) and holo (bright) forms. We performed
detailed hydrogen bond occupancy analyses to shed light on the mechanism
of ligand induced conformational change in the sensor protein and its
allosteric effect on the chromophore environment. We find that two
strong indicators for distinguishing bright and dark states of
biosensors are due to substantial changes in hydrogen bond dynamics in
the system and solvent accessibility of the chromophore.