8th Liquid Matter Conference September 6-10, 2011 Wien, Austria ...

P10.26Tue 611:23-14:00Binding of tetraethylammonium to KcsA channel studyby 3D-RISMSaree Phongphanphanee, 1 Norio Yoshida, 1 and Fumio Hirata 11 Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, 444-8585, Okazaki,JapanTetraethylammonium (TEA) and other quaternary ammonium have been known to block ion currentthrough K channels, and used as tools to investigate gating and conducting function of Kchannel. It was found that blocking efficacy of TEA was decrease when Tyr at position 82 ofKcsA was substituted by Thr. Therefore, the cation-pi interaction of aromatic residues was believedto encourages the binding affinity between TEA and K channel. However, X-ray structuresof KcsA and other K channels reveal the position of the Tyr that is too far to create cation-pi interactionwith TEA at its binding site. In this work, we have applied the statistical theory of molecularliquid, or 3D-RISM, to study the binding of TEA to the channel. The distribution functions of TEAinside and around the wild type and Y82T mutant were calculated. Our results indicated that TEAbinding at the extracellular mount of the channel, which consistent to an experimental result. Theabsence of Y82 does not decrease the binding energy, but it causes the blocker to loose ability totightly fit the channel pore. We conclude that missing of Tyr causes TEA to mobilize around itsbinding site that allows other ion could move through the channel.26