hERGBoost: A gradient boosting model for quantitative IC₅₀ prediction of hERG channel blockers

The human ether-a-go-go-related gene (hERG) potassium channel is pivotal in drug discovery due to its susceptibility to blockage by drug candidate molecules, which can cause severe cardiotoxic effects. Consequently, identifying and excluding potential hERG channel blockers at the earliest stages of drug development is crucial. Most traditional machine learning models predict a molecule's cardiotoxicity or non-cardiotoxicity typically at 10 μM, which doesn't account for compounds with low IC₅₀ values that are non-toxic at therapeutic levels due to their high effectiveness at lower concentrations. To address the need for more precise, quantitative predictions, we developed hERGBoost, a cutting-edge machine learning model employing a gradient-boosting algorithm. This model demonstrates superior accuracy in predicting the IC₅₀ of drug candidates. Trained on a specially curated dataset for this study, hERGBoost not only exhibited excellent performance in external validation, achieving an R² score of 0.394 and a low root mean square error of 0.616 but also significantly outstripped previous models in both qualitative and quantitative assessments. Representing a notable leap forward in the prediction of hERG channel blockers, the hERGBoost model and its datasets are freely available to the drug discovery community on our web server at. http://ssbio.cau.ac.kr/software/hergboost This resource promises to be invaluable in advancing safer pharmaceutical development.