Many drug molecules inhibit the conduction of several families of cation channels by binding to a small cavity just below the selectivity filter of the channel protein.The exact mechanisms governing drug-channel binding and the subsequent inhibition of conduction are not well understood.Here the inhibition of two K+ channel isoforms, Kv1.2 and KCa3.1, by two drug molecules, lidocaine and TRAM-34, is examined in atomic detail using molecular dynamics simulations.A conserved valine-alanine-valine motif in the inner cavity is found to be crucial for drug binding in both channels, consistent with previous studies of similar systems.