Computer simulation of the KvAP voltage‐gated potassium channel: steered molecular dynamics of the voltage sensor

FEBS Letters

Robertson, Kindal M.¹  MacCallum, Justin L.¹  Tieleman, D.Peter¹  Monticelli, Luca¹ 

[1] Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, AB, Canada T2N 1N4

关键词: Non-equilibrium molecular dynamics;    Molecular modeling;    Potassium channel;    Voltage gating;    Shaker;    Membrane protein;   

DOI  :  10.1016/S0014-5793(04)00271-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The recent crystal structures of the voltage-gated potassium channel KvAP and its isolated voltage-sensing ‘paddle’ (composed of segments S1–S4) challenge existing models of voltage gating and raise a number of questions about the structure of the physiologically relevant state. We investigate a possible gating mechanism based on the crystal structures in a 10 ns steered molecular dynamics simulation of KvAP in a membrane-mimetic octane layer. The structure of the full KvAP protein has been modified by restraining the S2–S4 domain to the conformation of the isolated high-resolution paddle structure. After an initial relaxation, the paddle tips are pulled through the membrane from the intracellular to the extracellular side, corresponding to a putative change from closed to open. We describe the effect of this large-scale motion on the central pore domain, which remains largely unchanged, on the protein hydrogen-bonding network and on solvent. We analyze the motion of the S3b–S4 portion of the protein and propose a possible coupling mechanism between the paddle motion and the opening of the channel. Interactions between the arginine residues in S4, solvent and chloride ions are likely to play a role in the gating charge.

【 授权许可】

Unknown