For each protein target, a ligand-bound co-crystal structure with high quality metrics was imported from the PDB to Maestro and processed with the Protein Preparation Wizard . For BACE1, a monomeric unit from PDB entry 6UWP was kept, and the protein was protonated for pH 4.5. For CDK2, the kinase and its bound cyclin from PDB entry 3DDQ were kept and were protonated for pH 7.0. For thrombin, a unit containing the heavy chain, the light chain, hirudin, and the bound ions from PDB entry 5JZY were kept and protonated for pH 7.5. These pH values were chosen to be typical of those used in the affinity assays for each respective protein . For all targets, crystal waters were retained during structure preparation.