Automated QM/MM Screening of Rhodopsin Variants with Enhanced Fluorescence.

ABSTRACT

We present a computational protocol for the fast and automated screening of excited-state hybrid quantum mechanics/molecular mechanics (QM/MM) models of rhodopsins to be used as fluorescent probes based on the automatic rhodopsin modeling protocol (a-ARM). Such "a-ARM fluorescence screening protocol" is implemented through a general Python-based driver, PyARM, that is also proposed here. The implementation and performance of the protocol are benchmarked using different sets of rhodopsin variants whose absorption and, more relevantly, emission spectra have been experimentally measured. We show that, despite important limitations that make unsafe to use it as a black-box tool, the protocol reproduces the observed trends in fluorescence and it is capable of selecting novel potentially fluorescent rhodopsins. We also show that the protocol can be used in mechanistic investigations to discern fluorescence enhancement effects associated with a near degeneracy of the S1/S2 states or, alternatively, with a barrier generated via coupling of the S0/S1 wave functions.