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

Abstract

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

Multiscale QM/MM modelling of catalytic systems with ChemShell

“…165 QM/MM methods are now widely applied to the study of excited electronic states, in tandem with electronic structure software packages capable of time-dependent density functional theory or wavefunction-based excited state calculations. Light-sensitive proteins that have been simulated with Chem-Shell in recent studies include a wide range of rhodopsins, [166][167][168][169][170][171][172][173] photosystem II, [174][175][176] calcium-regulated photoproteins, 177 green fluorescent protein, 178 the phototoxic protein KillerRed, 179 bacterial phytochromes, 180,181 and cyanobacteriochromes. [182][183][184] Excited state calculations are typically used to simulate experimental UV-vis spectra, 185 and so are useful for characterising any molecular system containing a chromophore, including catalytic intermediates.…”