where S(p) is the solution vector of GFN2-xTB parameters to be optimized, and GrS, ChS, and EnS are the gradient, charge, and energy scores, respectively. The search is conducted in the decision-variables space, comprising the selected set of GFN2-xTB's element-specific parameters (see the SI). The objective space is defined by three scores that guide the optimization, these scores are aggregated into a global score (GS) according to the following equation: