Assessing hERG1 Blockade from Bayesian Machine-Learning-Optimized Site Identification by Ligand Competitive Saturation Simulations.

ABSTRACT: Drug-induced cardiotoxicity is a potentially lethal and yet one of the most common side effects with the drugs in clinical use. Most of the drug-induced cardiotoxicity is associated with an off-target pharmacological blockade of K⁺ currents carried out by the cardiac Human-Ether-a-go-go-Related (hERG1) potassium channel. There is a compulsory preclinical stage safety assessment for the hERG1 blockade for all classes of drugs, which adds substantially to the cost of drug development. The availability of a high-resolution cryogenic electron microscopy (cryo-EM) structure for the channel in its open/depolarized state solved in 2017 enabled the application of molecular modeling for rapid assessment of drug blockade by molecular docking and simulation techniques. More importan

SUBMITTER: Mousaei M 

PROVIDER: S-EPMC7839320 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature