title: Human Aquaporin 4 Gating Dynamics under Perpendicularly-Oriented Electric-Field Impulses: A Molecular Dynamics Study.
abstract: Human aquaporin 4 has been studied using molecular dynamics (MD) simulations in the absence and presence of pulses of external static electric fields. The pulses were 10 ns in duration and 0.012-0.065 V/Å in intensity acting along both directions perpendicular to the pores. Water permeability and the dipolar response of all residues of interest (including the selectivity filter) within the pores have been studied. Results showed decreased levels of water osmotic permeability within aquaporin channels during orthogonally-oriented field impulses, although care must be taken with regard to statistical certainty. This can be explained observing enhanced "dipolar flipping" of certain key residues, especially serine 211, histidine 201, arginine 216, histidine 95 and cysteine 178. These residues are placed at the extracellular end of the pore (serine 211, histidine 201, and arginine 216) and at the cytoplasm end (histidine 95 and cysteine 178), with the key role in gating mechanism, hence influencing water permeability.
authors.affiliation: Department of Information Engineering, Electronics and Telecommunications, La Sapienza University, 00184 Rome, Italy. marracino@diet.uniroma1.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marracino
authors.affiliation: Department of Information Engineering, Electronics and Telecommunications, La Sapienza University, 00184 Rome, Italy. liberti@diet.uniroma1.it.
authors.forename: Micaela
authors.initials: M
authors.lastname: Liberti
authors.affiliation: Department of Information Engineering, Electronics and Telecommunications, La Sapienza University, 00184 Rome, Italy. erikatrapani@gmail.com.
authors.forename: Erika
authors.initials: E
authors.lastname: Trapani
authors.affiliation: School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, D4 Dublin, Ireland. christian.burnham@ucd.ie.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Burnham
authors.affiliation: Department of Information Engineering, Electronics and Telecommunications, La Sapienza University, 00184 Rome, Italy. massimilianoavena@icloud.com.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Avena
authors.affiliation: Computational Biology Laboratory, Life Sciences Foundation, 7750000 Santiago, Chile. garate.j.a@gmail.com.|Centro Interdisciplinario de neurociencia de Valparaiso, Universidad de Valparaiso, 05101 Valparaiso, Chile. garate.j.a@gmail.com.
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Garate
authors.affiliation: Department of Information Engineering, Electronics and Telecommunications, La Sapienza University, 00184 Rome, Italy. apollonio@diet.uniroma1.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Apollonio
authors.affiliation: School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, D4 Dublin, Ireland. niall.english@ucd.ie.
authors.forename: Niall J
authors.initials: NJ
authors.lastname: English
mesh_terms: D051401:Aquaporin 4 / Q000737:chemistry*; D004560:Electricity; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D014867:Water / Q000737:chemistry*
chemical_list: D051401:Aquaporin 4; D014867:Water
keywords: aquaporin; electric field; molecular dynamics; permeability; water