As described previously , the choice of the protein and RNA force field depends on many factors of the studied system. There was no single force field that would outperform others in all of our studied complexes, and thus the selection of the force field should happen based on the studied system and the research question. Especially the flexibility of the system affected the force field performance in this study: the flexible Cas12j system displayed some structural instability with the AMOEBA force field and O3P water model, whereas this was not as obvious with the more stable and globular Ago2 system. The instability was most notably observed in the O3P water model simulations, where even some of the Ago2 systems displayed large fluctuations and lower number of hydrogen bonds. It is possible that the very recently published fine-tuned van der Waals parameters of the AMOEBA force field would alleviate instability issue in the AMOEBA force field.