Multi‐scale simulation reveals that an amino acid substitution increases photosensitizing reaction inputs in Rhodopsins

Evaluating the availability of molecular oxygen (O2) and energy of excited states in the retinalbinding site of rhodopsin is a crucial challenging first step to understand photosensitizing reactionsin wild-type (WT) and mutant rhodopsins by absorbing visible light. In the present work, energiesof the ground and excited states related to 11-cis-retinal and the O2 accessibility to the β-iononering are evaluated inside WT and human M207R mutant rhodopsins. Putative O2 pathways withinrhodopsins are identified by using molecular dynamics simulations, Voronoi-diagram analysis,and implicit ligand sampling while retinal energetic properties are investigated through densityfunctional theory, and quantum mechanical/molecular mechanical methods. Here, the predictionsreveal that an amino acid substitution can lead to enough energy and O2 accessibility in the corehosting retinal of mutant rhodopsins to favor the photosensitized singlet oxygen generation, whichcan be useful in understanding retinal degeneration mechanisms and in designing blue-lightingabsorbing proteic photosensitizers.