HADDOCK is one of the few docking programs that can explicitly account for water molecules in the docking process. Its solvated docking protocol starts from hydrated molecules and a fraction of the resulting interfacial waters is subsequently removed in a biased Monte Carlo procedure based on water-mediated contact probabilities. The latter were derived from an analysis of water contact frequencies from high-resolution crystal structures. Here, we introduce a simple water mediated amino acid - amino acid contact probability scale derived from the Kyte-Doolittle hydrophobicity scale and assess its performance on the largest high-resolution dataset developed to date for solvated docking. Both scales yield high-quality docking results. The novel and simple hydrophobicity scale, which should reflect better the physico-chemical principles underlying contact propensities, leads to a performance improvement of around 10% in ranking, cluster quality and water recovery at the interface compared to the statistics-based original solvated docking protocol.
|Journal||Proteins : Structure, Function, and Bioinformatics|
|Publication status||Published - 2013|
- ligand docking
- biomolecular complexes
- drug design