The first Dockbox package (DBX) was utilized to generate binding poses with AutoDock , AutoDock Vina and DOCK 6 (DOCK) , and rescore with their scoring function in addition to Gnina and DSX . The DBX configuration file used for generating binding pose from PDBbind v2016 and the test sets is illustrated in Figure S1; a maximum of 140 binding poses were generated for each system, 60 from AutoDock, 20 from Vina, and 60 from DOCK. For AutoDock, grid spacing was set to 0.3 Å, and the Lamarckian genetic algorithm was employed to generate poses. For Vina, the energy range for final poses was set to 3 kcal/mol. In DOCK, a grid-based scoring method was applied with a spacing of 0.3 Å. Docking with any of the above programs was followed by energy minimization, starting with 500 steps of the steepest descent method followed by 1,000 steps combining steepest descent and conjugate gradient methods. Energy minimization was performed using AmberTools 17 to prevent structural clashes and ensure appropriate rescoring with different programs. Rescoring was then conducted with AutoDock, Vina, DOCK, and DSX scoring functions. . Two nodes are connected by an edge if the root mean square deviation (RMSD) between the two poses is below a predefined threshold (usually 5Å or more) while the RMSD value is kept as edge feature.