A structure-based computational workflow to predict liability and binding modes of small molecules to hERG.

ABSTRACT: Off-target interactions of drugs with the human ether-à-go-go related gene 1 (hERG1) channel have been associated with severe cardiotoxic conditions leading to the withdrawal of many drugs from the market over the last decades. Consequently, predicting drug-induced hERG-liability is now a prerequisite in any drug discovery campaign. Understanding the atomic level interactions of drug with the channel is essential to guide the efficient development of safe drugs. Here we utilize the recent cryo-EM structure of the hERG channel and describe an integrated computational workflow to characterize different drug-hERG interactions. The workflow employs various structure-based approaches and provides qualitative and quantitative insights into drug binding to hERG. Our protocol accurately differenti

SUBMITTER: Kalyaanamoorthy S 

PROVIDER: S-EPMC7530726 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature