QM/MM Photodynamics of Retinal in the Channelrhodopsin Chimera C1C2 with OM3/MRCI

Abstract

The photoisomerization of all‐trans retinal in channelrhodopsins triggers the opening of a cation channel in the membrane of certain green algae. The stimulus resulting from cell depolarization enables the algae to perceive and react to the present lighting conditions. This property makes channelrhodopsins especially interesting for neuroscientific applications in optogenetics. We investigate the initial photoreaction in the channelrhodopsin chimera C1C2 with a combined quantum mechanical/molecular mechanical (QM/MM) strategy. For geometry optimizations, the OM3/RHF and OM3/MRCI/Amber protocols are used. Trajectory surface hopping calculations are performed with OM3/MRCI/Amber and a statistically relevant number of molecules to obtain reaction rates and quantum yields. The utilized models include a direct hydrogen bond of the retinal Schiff base to the proposed counterions in C1C2, i. e. either toward glutamate or aspartate. Static and dynamic aspects are compared to experimental findings including time constants and spectral traces. The calculations provide a rationale for the observed short and long time components in the photokinetics of C1C2 and yield detailed insight into the photoreaction mechanisms that include bicycle pedal and hula twist motions.

From Light Absorption to Cyclization: Structure and Solvent Effects in Donor‐Acceptor Stenhouse Adducts

“…Retinal photoisomerization, both in solution and embedded in different types of rhodopsin, is a prototypical example of such type of excited state topology. The environment mainly determines, through steric and electrostatic interactions with the chromophore, if an energy barrier is present (as in channelrhodopsin) or not (as in visual rhodopsin) . Nevertheless, other photoswitches, such stilbene, are characterized by a second S 1 minimum, corresponding to a 90 degrees rotation of the isomerizable double bond .…”

Insight into the isomerization mechanism of retinal proteins from hybrid quantum mechanics/molecular mechanics simulations

“…In a subsequent study, the authors performed the QM/MM surface hopping dynamics to investigate the C1C2 Channelrhodopsin photoisomerization using the OM3(20,20)/MRCI/Amber method. 99 More than 1000 trajectories were computed, 34% of them showed successful isomerization, while 37% aborted the isomerization and regenerated the all-trans isomer after the excited state decay. The residual 29% remained on the excited state during the entire simulation.…”

Nonadiabatic Photodynamics of Retinal Protonated Schiff Base in Channelrhodopsin 2

“…In addition, we note that the S 2 state is currently not included in our simulation. However, in a recent paper by Dokukina et al, 16 it was found that the S 2 state population rapidly decays to zero after ∼100 fs for RPSB photoisomerization in C1C2. 16 Therefore, we expect that including the S 2 state in our calculation will not significantly slow down the photoisomerization in ChR2.…”

“…The hydrogen bond acceptor of RPSB chromophore, i.e., the D253 or E123 residue, affects the directionality of isomerization, in agreement with a recent simulation of RPSB photoisomerization in C1C2. 16 The two hydrogen bond acceptors have similar effects on the excitedstate lifetime and quantum yield. Finally, we also conclude that RPSB photoisomerization facilitates its deprotonation (most likely through proton transfer to D253, although proton transfer to E123 is also possible) and partially increases channel hydration, which may eventually lead to full channel opening and ion conduction in ChR2.…”