Thermodynamic information is often derived from MD simulations based on the ergodic hypothesis, which assumes that a sufficiently long simulation will sample a representative population of states. From these, free energy differences can be inferred by analyzing the probability of the system occupying each state. To demonstrate that our ML/MM implementation can accurately reproduce realistic phase spaces (and thus realistic free energy landscapes) For oxazole-4-carbaldehyde, both the ML/MM implementation utilizing MBIS charges and the simpler ML/MM (ME) approach demonstrated good agreement with reference QM/MM simulations (Figure , Panel B). The differences in barrier heights and free energy changes between these methods were within approximately 1 kcal/mol. Using on-the-fly MBIS charges but without polarization nor distortion corrections retrieved similar results the ML/MM (ME) simulations (Figure ). This consistency suggests that variations in solvation patterns likely mitigate the impact of omitted corrections in both the ML/MM (ME) and ML/MM results without polarization corrections.