A novel structure-based virtual screening model for the hERG channel blockers
The hERG potassium channel is a key effector of cardiac repolarization and the blockade of this channel could cause arrhythmia. Thus, hERG channel blockade plays an important role for the potential pro-arrhythmic liability. In this report, binding of blockers to the hERG potassium channel is investigated using a combination of homology modeling, molecular docking, and molecular simula tions, where blockade activities are evaluated using the linear regression model of GoldScore fitness. This structure-based virtual screen ing model is able to estimate the pIC50 value of a wide range of ligands for the hERG potassium channel. The docked poses for ligands are also consistent with published mutation. Therefore, this model for the prediction of hERG channel blockade has the potential to provide cost-effective virtual screening tools for the evaluation of the cardiac liability of new chemical entities.
hERG Potassium channel Homology model Molecular docking Prediction Virtual screening
Lupei Du Minyong Li Qidong You Lin Xia
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China
国际会议
广州
英文
260-265
2008-11-01（万方平台首次上网日期，不代表论文的发表时间）