Computer simulations have been used to probe the gating mechanism in the Salmonella serovar typhimurium chloride channel (st-ClC). Specifically, the recently developed metadynamics methodology has been exploited to construct free energy surfaces as a function of the positions of either one or two chloride ions inside the pore, the position and protonation state of the key E148 residue, and the number of water molecules coordinating the translocating ions. The present calculations confirm the multi-ion mechanism in which an ion-push-ion effect lowers the main barriers to chloride ion translocation. When a second anion is taken into account, the barrier for chloride passage through the E148 narrow region is computed to be 6 kcal/mol in the wild-type channel, irrespective of the protonation state of the E148 residue, which is shown to only affect the entrance barrier. In the E148A mutant, this barrier is much lower, amounting to 3 kcal/mol. The metadynamics calculations reported herein also demonstrate that before reaching the periplasmic solution, chloride ions have to overcome an additional barrier arising from two different effects, namely the rearrangement of their solvation shell and a flip in the backbone angles of the residues E148 and G149, which reside at the end of the alphaF helix.