Molecular Dynamics Simulations of the Eye Lens Water Channel Aquaporin 0 from Fish

Aquaporin 0 (AQP0) plays a key role in water circulation in the eye lens through a variety of functions. In contrast to mammalian genomes, zebrafish contains two aqp0 genes leading to a separation of AQP0 multiple functions between the two gene products, Aqp0a and Aqp0b. A notable feature of the zebrafish AQP0 paralogs is the increased water permeability of Aqp0b relative to Aqp0a as well as a severa lfold increase relative to mammalian AQP0. Here, we report equilibrium molecular dynamics (MD) simulations on the microsecond timescale to identify the structural basis underlying the differences in water permeability between zebrafish AQP0 paralogs and between AQP0 mammalian and fish orthologs. Our simulations are able to reproduce the experimental trends in water permeability. Our results suggest that a substitution of a key Y23 residue in mammalian AQP0 for F23 in fish AQP0 orthologs introduces significant changes in the conformational dynamics of the CS-I structural motif, which, in conjunction with different levels of hydration of the channel vestibule, can account for the differences in permeabilities between fish and mammalian AQP0 orthologs and between zebrafish AQP0 paralogs.