Drug Design Data Resource Grand Challenge 2015 Dataset: HSP90 - Heat shock protein 90

As detailed elsewhere [Symon Gathiaka, Shuai Liu, Michael Chiu, Jeanne A Stuckey, You Na Kang, Huanwang Yang, Stephen K. Burley, W. Patrick Walters, Jim Delproposto, Ginger Kubish, James B. Dunbar, Jr., Heather A. Carlson, Rommie E. Amaro, Victoria A. Feher and Michael K. Gilson. D3R Grand Challenge 2015: Evaluation of Protein-Ligand Pose and Affinity Predictions. JCAMD, 2016, (in press)], the HSP90 dataset is based on enzyme inhibition data contributed by Abbvie Pharmaceuticals to CSAR, D3R’s predecessor, which further developed the dataset by adding new compounds and binding data. The Abbvie dataset contains a set of small molecules with their IC50 values for binding to the protein’s N-terminal ATP-binding domain, measured with a time-resolved fluorescence energy transfer (TR-FRET) assay. The dataset was expanded to a total of 180 with an additional set of 17 ligands, which were designed by the CSAR team, synthesized by WuXi AppTech and assayed by the same TR-FRET method. Some of the compounds were analyzed further by isothermal titration calorimetry and the OctetRed method. These compounds may be classified into three chemical series: aryl-benzimidazolones, pyrimidin-2-amines and benzophenone-like compounds. Each series includes approximately 11 compounds for which binding was undetectable by the TR-FRET assay, corresponding to an IC50 greater than ~50µM. IC50 values ranged from 5.2 nM to >50μM. The CSAR team also obtained co-crystal structures using exactly the same truncated form of the protein used in the binding assays with eight of the ligands. Resolution limits for the resulting co-crystal structures range from 1.60 – 1.95 Å, and the crystallization methods and conditions can be found in www.RCSB.org.