title: Human aquaporin 4 gating dynamics in dc and ac electric fields: a molecular dynamics study.
abstract: Water self-diffusion within human aquaporin 4 has been studied using molecular dynamics (MD) simulations in the absence and presence of external ac and dc electric fields. The computed diffusive (p(d)) and osmotic (p(f)) permeabilities under zero-field conditions are (0.718 ± 0.24) × 10(-14) cm(3) s(-1) and (2.94 ± 0.47) × 10(-14) cm(3) s(-1), respectively; our p(f) agrees with the experimental value of (1.50 ± 0.6) × 10(-14) cm(3) s(-1). A gating mechanism has been proposed in which side-chain dynamics of residue H201, located in the selectivity filter, play an essential role. In addition, for nonequilibrium MD in external fields, it was found that water dipole orientation within the constriction region of the channel is affected by electric fields (e-fields) and that this governs the permeability. It was also found that the rate of side-chain flipping motion of residue H201 is increased in the presence of e-fields, which influences water conductivity further.
authors.affiliation: SEC Strategic Research Cluster and Centre for Synthesis and Chemical Biology, School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: J-A
authors.initials: JA
authors.lastname: Garate
authors.forename: Niall J
authors.initials: NJ
authors.lastname: English
authors.forename: J M D
authors.initials: JM
authors.lastname: MacElroy
mesh_terms: D051401:Aquaporin 4 / Q000737:chemistry / Q000378:metabolism*; D004560:Electricity; D006801:Humans; D056004:Molecular Dynamics Simulation; D010539:Permeability; D014867:Water / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051401:Aquaporin 4; D014867:Water