PDBcal: A Comprehensive Dataset for Receptor-Ligand Interactions with Three-Dimensional Structures and Binding Thermodynamics from Isothermal Titration Calorimetry"

Compounds designed solely based on structure often do not result in any improvement of the binding affinity because of entropy-enthalpy compensation. Thermodynamic data along with structure provide an opportunity to gain a deeper understanding of this effect and aid in the refinement of scoring functions used in computational drug design. Here, we scoured the literature and constructed the most comprehensive hand-curated calorimetry dataset to date. It contains thermodynamic and structural data for more than 400 receptor-ligand complexes. The dataset can be accessed through a web interface at http://www.pdbcal.org. The thermodynamic data consists of free energy, enthalpy, entropy and heat capacity as measured by isothermal titration calorimetry (ITC). The dataset also contains the experimental conditions that were used to carry out the ITC experiments. The chemical structures of the ligands are also provided. Analysis of the data confirms the existence of enthalpy-entropy compensation effect for the first time using strictly ITC data.

BioDrugScreen: A Docking Resource for Structure-Based Computational Drug Design

BioDrugScreen is a computational drug design and discovery resource and server. The portal contains the DOPIN (Docked Proteome Interaction Network) database. The DOPIN database contains millions of pre-docked and pre-scored complexes from thousands of targets from the human proteome and thousands of drug-like small molecules from the NCI diversity set and other sources. The portal is also a server that can be used to (i) customize scoring functions and apply them to rank molecules and targets in DOPIN; (ii) dock against pre-processed targets of the PDB; and (iii) search for off-targets. BioDrugScreen enables users to create their own scoring function - using affinity, structures, and pre-computed descriptors from existing databases such as PDBbind, BindingDB, and PDBcal - to validate these scoring functions with enrichment curves and ROC plots, and to apply these scores to rank molecules in the DOPIN database. The portal provides users the option to dock molecules to pre-identified cavities within targets of the PDB databank. In a few simple steps, the user submits the docking and GBSA scoring to the TeraGrid using our account. The jobs can be monitored within the portal. Finally, we provide off-target information for all molecules within DOPIN.