Structure–activity relationship for extracellular block of K+ channels by tetraalkylammonium ions

FEBS Letters

Åqvist, Johan¹  Luzhkov, Victor B¹  Österberg, Fredrik¹ 

[1] Department of Cell and Molecular Biology, Uppsala University, BMC, Box 596, SE-751 24 Uppsala, Sweden

关键词: Potassium channel;    Blocking;    Tetraethylammonium;    Free energy calculation;    Molecular dynamics;   

DOI  :  10.1016/S0014-5793(03)01117-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

External tetraalkylammonium ion binding to potassium channels is studied using microscopic molecular modelling methods and the experimental structure of the KcsA channel. Relative binding free energies of the KcsA complexes with Me₄N⁺, Et₄N⁺, and n-Pr₄N⁺ are calculated with the molecular dynamics free energy perturbation approach together with automated ligand docking. The four-fold symmetry of the entrance cavity formed by the Tyr82 residues is found to provide stronger binding for the D _2d than for the S ₄ conformation of the ligands. In agreement with experiment the Et₄N⁺ blocker shows several kcal/mol better binding than the other tetraalkylammonium ions.

【 授权许可】

Unknown