Harnessing Shannon entropy-based descriptors in machine learning models to enhance the prediction accuracy of molecular properties

Accurate prediction of molecular properties is essential in the screening and development of drug molecules and other functional materials. Traditionally, property-specific molecular descriptors are used in machine learning models. This in turn requires the identification and development of target or problem-specific descriptors. Additionally, an increase in the prediction accuracy of the model is not always feasible from the standpoint of targeted descriptor usage. We explored the accuracy and generalizability issues using a framework of Shannon entropies, based on SMILES, SMARTS and/or InChiKey strings of respective molecules. Using various public databases of molecules, we showed that the accuracy of the prediction of machine learning models could be significantly enhanced simply by using Shannon entropy-based descriptors evaluated directly from SMILES. Analogous to partial pressures and total pressure of gases in a mixture, we used atom-wise fractional Shannon entropy in combination with total Shannon entropy from respective tokens of the string representation to model the molecule efficiently. The proposed descriptor was competitive in performance with standard descriptors such as Morgan fingerprints and SHED in regression models. Additionally, we found that either a hybrid descriptor set containing the Shannon entropy-based descriptors or an optimized, ensemble architecture of multilayer perceptrons and graph neural networks using the Shannon entropies was synergistic to improve the prediction accuracy. This simple approach of coupling the Shannon entropy framework to other standard descriptors and/or using it in ensemble models could find applications in boosting the performance of molecular property predictions in chemistry and material science. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13321-023-00712-0.