K+-channels are responsible for the efficient and selective conduction of K+ ions across the plasma membrane. The bacterial K+ channel KcsA has historically been used to characterize various aspects of K+ conduction via computational means. The energetic barriers associated with ion translocation across the KcsA selectivity filter have been computed in various studies, leading to the proposal of two alternate mechanisms of conduction, involving or neglecting the presence of water molecules in between the permeating ions. Here, the potential of mean force of K+ permeation is evaluated for KcsA in lipid bilayers containing anionic lipids, which is known to increase the open probability of the channel. In addition, the effect of the protonation/deprotonation of residue E71, which directly interacts with the selectivity filter sequence, is assessed. Both conduction mechanisms are considered throughout. The results obtained provide novel insights into the molecular functioning of K+ channels including the inactivation process.