Automatic Rhodopsin Modeling with Multiple Protonation Microstates

Automatic Rhodopsin Modeling (ARM) is a simulation protocol providing QM/MM models of rhodopsins, capable of reproducing experimental electronic absorption and emission trends. Currently, ARM is restricted to a single protonation microstate for each rhodopsin model. Herein, we incorporate an extension of the minimal electro- static model (MEM) into the ARM protocol to account for all relevant protonation microstates at a given pH. The new ARM+MEM protocol determines the most impor- tant microstates contributing to the description of the absorption spectrum. As a test case, we have applied this methodology to simulate the pH-dependent absorption spec- trum of a toy model, showing that the single microstate picture breaks down at certain pH values. Subsequently, we applied ARM+MEM to Anabaena Sensory Rhodopsin, confirming an improved description of its absorption spectrum when the titration of several key residues is considered.