title: A novel structure-based virtual screening model for the hERG channel blockers.
abstract: 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 simulations, where blockade activities are evaluated using the linear regression model of GoldScore fitness. This structure-based virtual screening model is able to estimate the pIC(50) 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.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lupei
authors.initials: L
authors.lastname: Du
authors.forename: Minyong
authors.initials: M
authors.lastname: Li
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
authors.forename: Lin
authors.initials: L
authors.lastname: Xia
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D026902:Potassium Channel Blockers / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers