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Molecular Dynamics Modeling of Sodium And Water Transport through a Claudin Pore
Author(s) -
Yu Alan,
Laghaei Rozita,
Rosenthal Rita,
Coalson Rob
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.970.13
Subject(s) - pore water pressure , molecular dynamics , water flow , water transport , permeability (electromagnetism) , chemistry , osmotic pressure , permeation , chemical physics , membrane , sodium , analytical chemistry (journal) , materials science , chromatography , soil science , geotechnical engineering , computational chemistry , biochemistry , organic chemistry , environmental science , engineering
Background Claudin‐2 is a paracellular channel. Na and water flow through it driven by an osmotic or Na concentration gradient, suggesting that Na and water pass through a common pore and that their fluxes are frictionally coupled. We investigated the mechanism by molecular dynamics simulations. Methods The claudin pore was modeled either as a double cone or a cylindrical nanotube with narrowest diameter of 6.5 Å and 6 negatively charged sites in the middle of the pore (each ‐0.2e). A hydrostatic pressure gradient was applied via an additional constant force in the channel axis direction to a layer of water molecules parallel to the membrane interface. Simulations were performed using the CHARMM27 force field and the TIP3P water model, with full electrostatics was included. Results With an osmotic gradient, water molecules oriented within the pore in 2 water wires and exhibited directional flow with Pf= 4.7 x 10‐13 cm 3 /s and a water:Na flux ratio of 233. Increasing the magnitude of the negative charge increased permeability only when the charges were smeared evenly along the pore surface. Application of a Na concentration gradient, also drove water flow with water:Na flux of 14.6. Increasing the pore diameter to 7Å also increased water flow significantly by allowing 3 water wires to form. Conclusions Our findings confirm that water can permeate through claudin‐2 via a water wire mechanism, demonstrate that water permeability is dependent on the magnitude and distribution of intrapore charges and on the pore diameter, and provide a molecular explanation for the frictional coupling of Na and water fluxes within the pore.