Characterization of binding site of closed-state KCNQ1 potassium channel by homology modeling, molecular docking, and pharmacophore identification.

Lü-Pei Du, Min-Yong Li, Keng-Chang Tsai, Qi-Dong You, Lin Xia

Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.

Biochemical and biophysical research communications 2005 Jul 8

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This investigation was performed to assess the importance of interaction in the binding of blockers to KCNQ1 potassium using molecular modeling. This work could be considered made up by three main steps: (1) the construction of closed-state structure of KCNQ1 through homology modeling; (2) the automated docking of three blockers: IKS-142, L-735821, and BMS-IKS, using DOCK program; (3) the generation and validation of pharmacophore for KCNQ1 ligands using Catalyst/HypoGen. The obtained results highlight the hydrophobic or aromatic residues involved in S6 transmembrane domain and the base of the pore helix of KCNQ1, confirming the mutagenesis data and pharmacophore model, and giving new suggestions for the rational design of novel KCNQ1 ligands.

Citation

Lü-Pei Du, Min-Yong Li, Keng-Chang Tsai, Qi-Dong You, Lin Xia. Characterization of binding site of closed-state KCNQ1 potassium channel by homology modeling, molecular docking, and pharmacophore identification. Biochemical and biophysical research communications. 2005 Jul 8;332(3):677-87