For simulations in chloroform and DMSO, all protonatable groups were assigned the neutral charge state. For the five compounds that were simulated in water, the most probable protonation state at pH 7 was used. This means that the tertiary amines in spiramycin, rifampicin, roxithromycin, and telithromycin were set to the protonated state, while E2-enant was kept in a neutral charge state. Additionally, we tested the best-performing force field on six in-house compounds for validation. While we cannot disclose the full structure of these molecules, Table lists some of their properties.