As shown in Figure , the ANI-2x model consistently outperforms MACE-OFF23(S) in terms of speed. Compared to ANI-2x, MACE is a larger model, capable of processing additional inputs such as environmental forces and cell size, and predicting properties like dipole moments and stress. Even though these features are not utilized in our current study, they do impact computational performance. Conversely, the ANI-2x model is designed for efficiency, focusing on the rapid prediction of molecular energies and atomic forces. Although MACE currently runs slower than ANI-2x, various methods, such as reducing model parameters and implementing the JAX MD framework, have been proposed to enhance its speed. Overall, compared to traditional QM/MM MD simulations, ML/MM enables nanosecond-timescale simulations with near-DFT level of accuracy.