By comparison, the Vinardo score for the native ligand cocrystallized in the 8ABX structure-after a reasonably accurate self-docking that yielded a heavy-atom RMSD of 0.41 Å from the experimental pose-is -12.53 kcal/mol; the native ligand's DFT-derived conformational strain energy is approximately 0.9 kcal/mol, leading to a net binding energy of roughly -11.63 kcal/mol. Therefore, our top-scoring natural compound binds nearly as strongly-or slightly more strongly-than the native ligand, even before accounting for any improvements from local geometric refinements of the ligand and interacting residues.