From NMR to AI: Designing a Novel Chemical Representation to Enhance Machine Learning Predictions of Physicochemical Properties
Arkadiusz Leniak, Wojciech Pietruś, Rafał Kurczab
Abstract
A novel approach to the utilization of nuclear magnetic resonance (NMR) spectroscopy data in the prediction of logD through machine learning algorithms is shown. In the analysis, a data set of 754 chemical compounds, organized into 30 clusters, was evaluated using advanced machine learning models, such as Support Vector Regression (SVR), Gradient Boosting, and AdaBoost, and comprehensive validation and testing methods were employed, including 10-fold cross-validation, bootstrapping, and leave-one-out. The study revealed the superior performance of the Bucket Integration method for dimensionality reduction, consistently yielding the lowest root mean square error (RMSE) across all data sets and normalization schemes. The SVR prediction models demonstrated remarkable computational efficiency and low cost, with the best RMSE value reaching 0.66. Our best model outperformed existing tools like JChem Suite's logD Predictor (0.91) and CplogD (1.27), and a comparison with traditional molecular representations yielded a comparable RMSE (0.50), emphasizing the robustness of our NMR data integration. The widespread availability of NMR data in pharmaceutical and industrial research presents an untapped resource for predictive modeling, highlighting the need for accessible methodologies like ours that complement the analytical toolbox beyond conventional 2D approaches. Our approach, designed to leverage the rich spatial data from NMR spectroscopy, provides additional insights and enriches drug discovery and computational chemistry with a freely accessible tool.