Large Language Models as Tools for Molecular Toxicity Prediction: AI Insights into Cardiotoxicity

The importance of drug toxicity assessment lies in ensuring the safety and efficacy of the pharmaceutical compounds. Predicting toxicity is crucial in drug development and risk assessment. This study compares the performance of GPT-4 and GPT-4o with traditional deep-learning and machine-learning models, WeaveGNN, MorganFP-MLP, SVC, and KNN, in predicting molecular toxicity, focusing on bone, neuro, and reproductive toxicity. The results indicate that GPT-4 is comparable to deep-learning and machine-learning models in certain areas. We utilized GPT-4 combined with molecular docking techniques to study the cardiotoxicity of three specific targets, examining traditional Chinese medicinal materials listed as both food and medicine. This approach aimed to explore the potential cardiotoxicity and mechanisms of action. The study found that components in Black Sesame, Ginger, Perilla, Sichuan Pagoda Tree Fruit, Galangal, Turmeric, Licorice, Chinese Yam, Amla, and Nutmeg exhibit toxic effects on cardiac target Cav1.2. The docking results indicated significant binding affinities, supporting the hypothesis of potential cardiotoxic effects.This research highlights the potential of ChatGPT in predicting molecular properties and its significance in medicinal chemistry, demonstrating its facilitation of a new research paradigm: with a data set, high-accuracy learning models can be generated without requiring computational knowledge or coding skills, making it accessible and easy to use.