Insight into the Mechanism of Water Permeation through the Sodium-Galactose Transporter vSGLT from Long Molecular Dynamics Simulations


Sodium-glucose transporters (SGLTs) mediate sugar transport as well as water flow across the cell membrane. Using a series of long molecular dynamics simulations generated on the special-purpose Anton supercomputer totaling nearly 16 microseconds in aggregate, we investigated the mechanism of water permeation through the inward-facing state of the bacterial sugar transporter vSGLT from Vibrio parahaemolyticus. Our simulations reveal conformational changes in the extracellular gate that create a transient water channel through the transporter. We developed a novel channel detection algorithm to characterize water pathways through the protein and identify key residues that control water flow. The simulations contain multiple, independent instances in which the galactose, initially bound to the transporter, spontaneously exits to solution. By comparing water flow through vSGLT when the sugar is bound, exiting and free in solution, we show that water flow, while modulated by galactose occupancy, is not coupled to substrate release.

Biophys. J.