Retinylidene conformations and rearrangements of the hydrogen-bond network in the vicinity of the protonated Schiff base (PSB) play a key role in the proton transfer process in the Heliorhodopsin photocycle. Photoisomerization of the Retinylidene chromophore and the formation of photoproducts corresponding to the early intermediates were modeled using a combination of molecular dynamics (MD) simulations and quantum mechanical/molecular mechanics (QM/MM) calculations. The resulting structures were refined, and the respective excitation energies were calculated. Aided by metadynamics simulations, we constructed a photoisomerized intermediate where 13-cis retinylidene chromophore is rotated about a parallel pair of double bonds at C13=C14 and C15=N_Z double-bonds, following an ‘aborted bicycle-pedal’ motion. We demonstrate how the deprotonation of the Schiff base and the concomitant protonation of the Glu107 counterion are only favored because of these rearrangements.

Graphical Abstract

Free energy profile obtained from the metadynamics simulation. (CV1, CV2) are defined as the dihedrals CV1 = C12-C13-C14-C15 and CV2 = C14-C15-N_z-C_ε.

Typical snapshots along equilibrium MD simulations whose starting geometries are taken from the free energy basins from the metadynamics free energy profile representing the dark, K, L and M states, respectively.

Nimesha Wijesiri

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