Here L CP/QMMM is the QM/MM Car-Parrinello Lagrangian as given in Eq. 1. The second term in Eq. 2 is the kinetic energy of auxiliary variables, where µ α is the fictitious mass of the auxiliary variable s α . N s number of auxiliary variables are coupled to the corresponding collective variables (CV) S α by harmonic potentials with coupling constant k α . Here W b h (s 1 )