To compare our protocol to a system with known binders, we targeted the ATP binding site of HSP90 (heat-shock protein 90), known for the folding of other proteins in a cell . HSP90, with its extremely well-conserved ATP-binding domain, is an important therapeutic target and has been targeted for cancer treatment . We targeted this ATP binding site using SPOTLIGHT. Because there are known ligands for this protein , it is a good benchmark system having a well-established 3D crystal structure of the active site. The crystal structure of HSP90 was obtained from the protein data bank (PDB) with PDB ID 2VCI. All ligands and water molecules were removed from the PDB file, and the protein structure was provided to SPOTLIGHT. We marked the ATP binding region to be the active site (residues Leu33, Asn36, Ser37, Asp39, Ala40, Lys43, Asp78, Gly80, Ile81, Gly82, Met83, Thr84, Asp87, Leu92, Gly93, Thr94, Ile95, Gly120, Phe123, Val135, Thr137, His139, Thr169, and Val171). With the goal to create molecules that are varied, synthesizable, and strong binders to the HSP90 protein. we generated around 800 molecules each for all sizes between 16 to 26 heavy atoms.