Drug-likeness scoring based on unsupervised learning

• Published in: Chemical science (Cambridge) 2022-01, Vol.13 (2), p.554-565
• Main Authors: Lee, Kyunghoon, Jang, Jinho, Seo, Seonghwan, Lim, Jaechang, Kim, Woo Youn
• Format: Article
• Language: English
• Subjects: Chemistry; Classification; Datasets; Extreme values; Neural networks; Recurrent neural networks; Training; Unsupervised learning
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d1sc05248a

Drug-likeness prediction is important for the virtual screening of drug candidates. It is challenging because the drug-likeness is presumably associated with the whole set of necessary properties to pass through clinical trials, and thus no definite data for regression is available. Recently, binary classification models based on graph neural networks have been proposed but with strong dependency of their performances on the choice of the negative set for training. Here we propose a novel unsupervised learning model that requires only known drugs for training. We adopted a language model based on a recurrent neural network for unsupervised learning. It showed relatively consistent performance across different datasets, unlike such classification models. In addition, the unsupervised learning model provides drug-likeness scores that well separate distributions with increasing mean values in the order of datasets composed of molecules at a later step in a drug development process, whereas the classification model predicted a polarized distribution with two extreme values for all datasets presumably due to the overconfident prediction for unseen data. Thus, this new concept offers a pragmatic tool for drug-likeness scoring and further can be applied to other biochemical applications. A new quantification method of drug-likeness based on unsupervised learning. The method only uses drug molecules as training set without any non-drug-like molecules.