Prior to beginning this study, our OpenEye Scientific collaborators provided the SEH structure, the location of the binding site where ligands would be docked, and a set of 47 ligands in the form of SMILES strings. The initial SEH structure from OpenEye Scientific was missing residues. We found the apo SEH structure in the Protein Data bank (PDBID:5AHX), built in the missing residues with PDBFixer, and used this structure for the remainder of the study. The apo SEH structure was altered using the PDB2PQR web server, 30 which uses PROPKA2.0 to assign residue protonation states. We protonated residues at pH 8.5 to match experimental conditions, using AMBER parameters and we removed crystallographic waters from the system. The PQR file was then converted back to a PDB file with ParmEd (v3.0.1). We aligned the corrected apo SEH structure to the SEH structure provided by OpenEye Scientific to ensure the pre-defined docking site was the same. The SEH protein contains 2 domains, a phosphatase domain (N-terminus) and a hydrolase domain (C-terminus) connected by a flexible proline rich linker. The pre-defined docking site was only located in the C-terminal hydrolase domain, so to reduce computational cost, we removed the N-terminal domain from residue 0 to residue 224 (Fig. ). We analyzed the structural integrity of the truncated protein by averaging the RMSD of the protein backbone over a 1 microsecond MD simulation. The average RMSD of the truncated protein backbone was 2.1 Angstroms suggesting the C-terminus was relatively unaffected by the removal of N-terminus. In Figure , we show the entire binding site located in the C-terminus domain as defined by our collaborators.