Potassium and sodium binding to the outer mouth of the K+ channel

Molecular dynamics simulations of the K+ channel from Streptomyces lividans (KcsA channel) were performed in a membrane-mimetic environment with Na+ a nd K+ in different initial locations. The structure of the channel remained stable and well preserved for simulations lasting up to 1.5 ns. Salt bridg es between Asp80 and Arg89 of neighboring subunits, not detected in the X-r ay structure, enhanced the stability of the tetrameric structure. Na+ or K ions located in the channel vestibule lost part of their hydration shell a nd diffused into the channel inner pore in less than a few hundred picoseco nds. This powerful catalytic action was caused by strong electrostatic inte ractions with Asp80 and Glu71. The hydration state of the metal ions turned out to depend significantly on the conformational flexibility of the chann el. Furthermore, Na+ entered the channel inner pore bound to more water mol ecules than K+. The different hydration state of the two ions may be a dete rminant factor in the ion selectivity of the channel.