Efficient Exploration of Chemical Compound Space Using Active Learning for Prediction of Thermodynamic Properties of Alkane Molecules

We introduce an exploratory active learning (AL) algorithm using Gaussian process regression and marginalized graph kernel (GPR-MGK) to sample chemical compound space (CCS) at minimal cost. Targeting 251,728 enumerated alkane molecules with 4-19 carbon atoms, we applied the AL algorithm to select a diverse and representative set of molecules and then conducted high-throughput molecular simulations on these selected molecules. To demonstrate the power of the AL algorithm, we built directed message-passing neural networks (D-MPNN) using simulation data as the training set to predict liquid densities, heat capacities, and vaporization enthalpies of the CCS. Validations show that D-MPNN models built on the smallest training set considered in this work, which consists of 313 molecules or 0.124% of the original CCS, predict the properties with R-2 > 0.99 against the computational data and R-2 > 0.94 against the experimental data. The advantage of the presented AL algorithm is that the predicted uncertainty of GPR depends on only the molecular structures, which renders it compatible with high-throughput data generation.