Solvated docking: introducing water into the modelling of biomolecular complexes

Area of Science:

• Computational Biology
• Structural Biology
• Biophysics

Background:

• Interfacial water is crucial for biomolecular interactions but often overlooked in modeling.
• Existing models of protein-protein complexes do not adequately account for the role of water at the interface.

Purpose of the Study:

• To develop and validate a novel computational approach, solvated docking, that explicitly incorporates interfacial water into protein-protein complex modeling.
• To improve the accuracy and scoring of protein-protein complex predictions by considering the hydration layer.

Main Methods:

• A solvated docking protocol was developed, focusing on the 'first encounter complex' with an explicit water layer.
• A biased Monte Carlo procedure was employed to simulate the expulsion of water molecules during complex formation.
• The method utilizes water-mediated contact propensities derived from crystal structure analysis.

Main Results:

• The solvated docking approach was successfully applied to protein-protein complexes with both 'wet' and 'dry' interfaces.
• The method demonstrated improvements in both the quality of predicted complex structures and scoring accuracy.
• Recovered water molecules in the models closely corresponded to those observed in experimental crystal structures.

Conclusions:

• Solvated docking offers a more realistic representation of protein-protein complex formation by including interfacial water.
• This method enhances the predictive power of computational docking for biomolecular interactions.
• The solvated docking approach will be integrated into future releases of HADDOCK (version 2.0).