In Silico Prediction of Hemolytic Toxicity on the Human Erythrocytes for Small Molecules by Machine-Learning and Genetic Algorithm

摘要

Hemolytic toxicity of small molecules, as one of the important ADMET end points, can cause the lysis of erythrocytes membrane and leaking of hemoglobin into the blood plasma, which leads to various side effects. Thus, it is very crucial to assess the hemolytic potential of small molecules during the early stage of drug development process. However, so far there is no computational model to predict the human hemolytic toxicity of small molecules. To this end, we manually curate the hemolytic toxicity data set for the small molecules experimentally evaluated on the human erythrocytes, develop the first machine-learning (ML) based models to predict the human hemolytic toxicity of small molecules, harness the genetic algorithm (GA) and ML based model to optimize human hemolytic toxicity based on the molecular fingerprint to derive "optimal virtual fingerprints (OVFs)" with the desired hemolytic/nonhemolytic property, and finally implement a free software for the users to predict/optimize the human hemolytic toxicity with ML and GA in the automatic manner.