The search for rhodopsins featuring large fluorescence quantum yields is an important topic in optogenetics. In this theoretical work we propose a novel method for designing a specific protein environment that blocks the ultrafast isomerization of a microbial rhodopsin, increasing its fluorescence quantum yield. The work has been performed employing high level QM/MM multiconfigurational models of Anabaena Sensory Rhodopsin with a simplified chromophore. First we present the application of the method on this minimal model and then we use the results as a guideline to propose a set of mutations for the full rhodopsin model. We exploit a typical feature of these chromophores photoreaction paths: the structures of an excited state intermediate have a different charge distribution with respect to the ones close to the conical intersection and, as a consequece of this, they are affected differently by an external electrostatic potential. The method calculates the optimal charge distribution in space that stabilizes the structures of the Franck-Condon region and destabilizes the ones close to the conical intersection. We study the effects and the consequences of this new potential applied on the system, via cavity sidechains polarization or full mutations. We show that it is possible to reshape the excited state potential energy surface, forming a new fluorescent species (a minimum) isolated from the conical intersection by a thermal transition state.

Towards the computational design of highly fluorescent rhodopsins

256th National Meeting (2018)

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