OWPCP: A Deep Learning Model to Predict Octanol-Water Partition Coefficient

Abstract

The physicochemical properties of chemical compounds have great importance in several areas, including pharmaceuticals, environmental and separation science. Among these are physicochemical properties such as the octanol-water partition coefficient, which has been considered an important index pointing out lipophilicity and hydrophilicity. It affects drug absorption and membrane permeability. Following Lipinski's rule of five, logP was identified as one of the key determinants of the stability of chemical entities and, as such, needed state-of-the-art methods for measuring lipophilicity. This paper presents a deep-learning model, OWPCP, developed to compute logP using Morgan fingerprints and MACCS keys as input features. It uses the interconnection of such molecular representations with logP values extracted from 26,254 compounds. The dataset was prepared to contain a wide range of chemical structures with differing molecular weights and polar surface area. Hyperparameter optimization was conducted using the Keras Tuner alongside the Hyperband algorithm to enhance the performance. OWPCP demonstrated outstanding performance compared to current computational methods, achieving an MAE=0.247 on the test set and outperforming all previous DL models. Remarkably, while one of the most accurate recent models is based on experimental data on retention time to make predictions, OWPCP manages computing logP efficiently without depending on these factors, being, therefore, very useful during early-stage drug discovery. Our model outperforms the best model, which leverages Retention Time, and our model does not require any experimental data. Further validation of the model performance was done across different functional groups, and it showed very high accuracy, especially for compounds that contain aliphatic OH groups. The results have indicated that OWPCP provides a reliable prediction of logP.