Structure-Based Prediction of hERG-Related Cardiotoxicity: A Benchmark Study.

ABSTRACT: Drug-induced blockade of the human ether-à-go-go-related gene (hERG) channel is today considered the main cause of cardiotoxicity in postmarketing surveillance. Hence, several ligand-based approaches were developed in the last years and are currently employed in the early stages of a drug discovery process for in silico cardiac safety assessment of drug candidates. Herein, we present the first structure-based classifiers able to discern hERG binders from nonbinders. LASSO regularized support vector machines were applied to integrate docking scores and protein-ligand interaction fingerprints. A total of 396 models were trained and validated based on: (i) high-quality experimental bioactivity information returned by 8337 curated compounds extracted from ChEMBL (version 2

SUBMITTER: Creanza TM 

PROVIDER: S-EPMC9282647 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature