Conformer ensemble refinement. Due to the applied potential to force extensive sampling, geometric anomalies such as long bonds were observed in the selected structures during development. To avoid this issue, a two-step post-processing refinement was implemented. First, energy minimization using the GAFF2 force field in NAMD is performed (MM), limited to 500 steps to preserve the initial conformations. This is followed by quantum mechanical (QM) optimization using the semi-empirical GFN2-xTB method with XTB software, employing the "crude" optimization level with convergence criteria of 5×10 Eh for energy and 1×10 -2 Eh•α -1 for gradient, and a maximum of 1500 iterations. If QM optimization fails to converge, the MM conformation is retained to avoid excessive computational time. This refinement process effectively corrects geometric issues while maintaining the diversity of the conformer ensemble.