Abstract
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.
Original language | English |
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Pages (from-to) | 510-518 |
Journal | Proteins : Structure, Function, and Bioinformatics |
Volume | 81 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2013 |
Keywords
- ligand docking
- biomolecular complexes
- globular-proteins
- drug design
- molecules
- recognition
- interfaces
- solvent
- haddock
- challenges