Extended Data Fig. 6: Water conduction through GltPh-ClCS and setup of umbrella sampling simulations and convergence to capture Cl− movement through GltPh-ClCS.
From: Glutamate transporters have a chloride channel with two hydrophobic gates
a, The GltPh-ClCS structure was embedded into a lipid bilayer containing POPE, POPG and POPC lipids, mimicking experimental conditions. After an initial equilibration of 100 ns, the entire system was subjected to an external electric field of 800 mV, which resulted in a continuous water pathway through the interface of the scaffold and the transport domains. The GltPh-ClCS protomer is shown in cartoon representation, with the transport domain in blue and the scaffold domain in salmon. XL-2 residues L152 and G351 are shown in red and blue spheres, respectively. b, Residues lining the Cl− pathway have a higher solvent accessible surface area (SASA) in the GltPh-ClCS than in the OFS (calculated using the crystal structure of OFS PDB: 2NWX). c, Overlap between the corresponding windows used in umbrella sampling simulations. d, No substantial changes between the free-energy profile obtained at 10 ns (red), 15 ns (blue) and 20 ns (green) were observed, highlighting the convergence of umbrella sampling simulations.
