title: Recent developments in computational prediction of HERG blockage.
abstract: The blockage of the voltage dependent ion channel encoded by human ether-a-go-go related gene (hERG) may lead to drug-induced QT interval prolongation, which is a critical side-effect of non-cardiovasular therapeutic agents. Therefore, identification of potential hERG channel blockers at the early stage of drug discovery process will decrease the risk of cardiotoxicity-related attritions in the later and more expensive development stage. Computational approaches provide economic and efficient ways to evaluate the hERG liability for large-scale compound libraries. In this review, the structure of the hERG channel is briefly outlined first. Then, the latest developments in the computational predictions of hERG channel blockers and the theoretical studies on modeling hERG-blocker interactions are summarized. Finally, the challenges of developing reliable prediction models of hERG blockers, as well as the strategies for surmounting these challenges, are discussed.
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM) and Jiangsu Key Laboratory for Carbon- Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Sichao
authors.initials: S
authors.lastname: Wang
authors.forename: Youyong
authors.initials: Y
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Tingjun
authors.initials: T
authors.lastname: Hou
mesh_terms: D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D015195:Drug Design; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015507:Drugs, Investigational / Q000009:adverse effects* / Q000737:chemistry; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000009:adverse effects* / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D040681:Structural Homology, Protein
chemical_list: D015507:Drugs, Investigational; D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers; D011188:Potassium