Oxygen diffusion pathways in mutated forms of a LOV photoreceptor from : A molecular dynamics study.

4511 from is a photoreceptor of the light, oxygen voltage (LOV) family, binding flavin mononucleotide (FMN) as a chromophore. It exhibits the prototypical LOV photocycle, with the reversible formation of an FMN-Cys71 adduct via fast decay of the FMN triplet state. 4511 has high potential as a photosensitiser for singlet oxygen (SO) upon mutation of C71. 4511-C71S shows a triplet lifetime ( ) of several hundreds of microseconds, ensuring efficient energy transfer to dioxygen to form SO. In this work, we have explored the potential diffusion pathways for dioxygen within 4511 using molecular dynamics (MD) simulations. The structural model of wild-type (wt) 4511 showed a dimeric structure stabilised by a strong leucine zipper at the two C-terminal helical ends. We then introduced the C71S mutation and analysed transient and persistent oxygen channels. MD simulations indicate that the chromophore binding site is highly accessible to dioxygen. Mutations that might favour SO generation were designed based on their position with respect to FMN and the oxygen channels. In particular, the C71S-Y61T and C71S-Y61S variants showed an increased diffusion and persistence of oxygen molecules inside the binding cavity.