Unveiling the mechanisms of aquaglyceroporin-3 water and glycerol permeation by metadynamics

Water and glycerol permeation via human AQP3 are described exploiting advanced metadynamics approaches, which enabled to both explore the free energies involved in pore permeation, as well as to achieve a description of the mechanisms with an atomistic level of detail. Moreover, thanks to this technique, a basic water transport mechanism, single‐filed and bidirectional in nature was retrieved, on which glycerol molecules are inserted during channel permeation. Therein, activation energies result from static and dynamic effects involving hydrogen bonds within the water filament and among substrate molecules and pore internal residues