Details

Autor(en) / Beteiligte

• Hernández‐Rodríguez, Erix W.
• Escorcia, Andrés M.
• Kamp, Marc W.
• Montero‐Alejo, Ana L.
• Caballero, Julio

Titel

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

Ist Teil von

• Journal of computational chemistry, 2020-10, Vol.41 (26), p.2278-2295

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2020

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• 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‐lighting‐absorbing proteic photosensitizers. Photosensitized singlet oxygen generation is probable in mutant rhodopsins. By combining computational tools such as implicit ligand sampling and multi‐scale QM/MM calculations, it is identified that an amino acid substitution can lead to sufficient energy and O2 accessibility in the retinal binding pocket to support the photosensitization.