Structural models of human big conductance calcium- and voltage-gated potassium channels

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• 作者：Agata Kranjc ; Claudio Anselmi ; Paolo Carloni ; Frank E. Blaney
• 关键词：Human big conductance calcium- and voltage-gated potassium channel (hBK) ; RCK1 domain (Regulate the Conductance of K⁺) ; Calcium bowl (CB) ; Homology modeling ; Molecular dynamics (MD)
• 刊名：Computer Physics Communications
• 出版年：2007
• 出版时间：July 2007
• 年：2007
• 卷：177
• 期：1-2
• 页码：21-26
• 全文大小：543 K

文摘

Human big conductance Ca²⁺- and voltage-gated K⁺ channels (hBK) are putative drug targets for cardiovascular, respiratory and urological diseases. Here we have used molecular simulation and bioinformatics approaches to construct models of two domains important for Ca²⁺ binding and channel gating, namely the regulator of conductance for K⁺ (RCK1) domain and the so-called calcium bowl (CB). As templates for RCK1 were used the corresponding domains from a K⁺ channel from E. coli and the K⁺ channel from Methanobacterium thermoautothropicum (MthK). CB was modeled upon the structure of the human thrombospondin-1 C-terminal fragment and allowing the domain to relax in a simulated aqueous environment for 10-ns molecular dynamics simulations. The relevance of these models for interpreting the available molecular biology data is then discussed.