Alchemical free energy calculations based on first principle statistical mechanics may serve as an optimal input for such AL applications. While computationally demanding, nowadays these calculations are readily accessible even at large scale: the predictions for hundreds to thousands of ligands can be obtained in a matter of days. Also, the accuracy of alchemical predictions draws close to the experimental measurements. Therefore, using these calculations as an oracle to construct ML models could allow describing binding affinities of large chemical libraries with high accuracy, while only a small fraction of the library needs to be evaluated with the computationally expensive alchemical method.