The settings to conduct docking with Glide and restrained energy minimization with OpenMM are provided in the Supporting Info. The Cuby4 input scripts to carry out ligand SQM geometry optimization, protein-ligand complex SQM optimization and scoring are considered proprietary and thus were excluded. However, the code to process SQM output, compute and prepare features for the training of SQM-ML, evaluate the results, plot them and explain the ML model, was open-sourced at , along with the final SQM-ML model for production runs.