The comparison to explicit-solvent reference simulations was conducted by taking the final conformers from the minimization workflow and considering them as separate conformational states. The reference simulation was then used to assign a population to each state by assigning each frame of the reference simulation to the closest conformer below an RMSD threshold of 0.1 nm. These populations were converted to free energies and compared to the free energy predicted by the GNN-based approach. The same procedure was performed with the conformer ensembles minimized in a vacuum and using the GB-Neck2 implicit solvent model.