In the field of molecular dynamics (MD) simulations, much work has contributed to improving molecular mechanics force fields (MMFF) to achieve higher accuracy in reproducing experimental metrics. Efforts include extending general small molecule force fields, 1,2 developing new protein force fields, and creating force fields for other biomolecules, such as DNA and lipids. Classical force fields aim to reproduce quantum mechanics (QM) results, however, it remains a challenge to accurately matching these QM results, especially when chemical reactions are involved. To overcome the challenge, a feasible solution is to combine the computational efficient MMFF method with the accurate QM methods. In the 1970s, Warshel Arieh and Levitt Michael proposed quantum mechanics/molecular mechanics (QM/MM) molecular dynamics, which applies a QM model which includes density functional theory (DFT) to describe the essential part of the system (such as atoms involved in a chemical reaction), and MMFF to describe the rest of the system. This multi-scale simulation technology make the investigation of electronic structures and chemical reactions in a large system come true.