The gating process of the KcsA protein is simulated using targeted molecular dynamics. Calculations show that the residues at the innermost part of the M-2 helices act as precursors of a zipper aperture. A sudden disruption of the narrow part of the gate is observed for a position restraint force constant equal to 0.5 kcal mol(-1) &ANGS;(-2). The gate diameter reaches its maximum of about 5.0 &ANGS; by doubling the restraint value. The opening energy corresponds to about 14 kT per C-α atom at 300 K. © 2005 Elsevier B.V. All rights reserved.