The re-parametrization of GFN2-xTB for CCR and DHFR systems was conducted using The CCR System. Our optimization strategy for CCR involved nine iterative steps using both CCR-IRC and CCR-SC data sets simultaneously (see Table in "GFN2-xTB's parameters optimization setup" section in SI). The GS showed remarkable improvement from the initial optimization stage, with continued refinements through subsequent steps (Figure ). Analysis of atomic gradient errors revealed an interesting optimization pattern (Figure ). While the main distribution of gradient errors exhibited a slight broadening from the original parametrization to the ninth step, the magnitude of extreme errors (outliers) decreased substantially from 0.032 a.u. to 0.024 a.u. This indicates that our strategy effectively addressed the most significant force prediction errors, despite a minor broadening in the overall distribution. Additionally, Mulliken charge errors not only decreased in magnitude but also achieved a more symmetric distribution around zero (Figure ), suggesting improved electronic structure description.