The displacement of water upon the recognition between a protein and a drug has a significant and often dominant contribution to the binding free energy. Docking programs, aimed at screening viable drug candidates, due to the difficulties in calculating free energies of displacement, tend to ignore this contribution or treat it with implicit models of water that neglect the molecular structure of water molecules. There has been hope that methods that explicitly treat water such as those based on Inhomogeneous fluid Solvation Theory (IST) will lead to increased accuracy in docking and other early stage computational drug discovery application. Here, we have integrated a grid based implementation of IST (GIST) into the scoring function of DOCK 3.7 and tested it retrospectively against 25 protein targets and prospectively on the model system Cytochrome c Peroxidase.

Incorporating solvation thermodynamic mapping into docking

254th National Meeting (2017)

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