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.