Mechanisms of tetraethylammonium ion block in the KcsA potassium channel

We report results from automated docking and microscopic molecular dynamics simulations of the tetraethylammonium (TEA) complexes with KcsA, Binding m odes and energies for TEA binding at the external and internal sides of the channel pore are examined utilising the linear interaction energy method. Effects of the channel ion occupancy (based on our previous results for the ion permeation mechanisms) on the binding energies are considered. Calcula tions show that TEA forms stable complexes at both the external and interna l entrances of the selectivity filter. Furthermore, the effects of the Y82V mutation are evaluated and the results show, in agreement with experimenta l data, that the mutant has a significantly reduced binding affinity for TE A at the external binding site, which is attributed to stabilising hydropho bic interactions between the ligand and the tyrosines, (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All r ights reserved.