Solvated protein-DNA docking using HADDOCK.

Area of Science:

• Computational Biology
• Structural Biology
• Biophysics

Background:

• Interfacial water molecules are critical for protein-DNA specificity and recognition.
• Computational models of protein-DNA complexes have largely neglected the role of these interfacial water molecules.
• Accurate modeling of these interactions is essential for understanding biological processes.

Purpose of the Study:

• To present a novel solvated docking protocol for protein-DNA complexes that explicitly includes water molecules.
• To demonstrate the feasibility and effectiveness of this protocol using a benchmark dataset.
• To improve the computational modeling of protein-DNA interactions by incorporating solvation effects.

Main Methods:

• Development of a solvated docking protocol enabling explicit inclusion of water molecules.
• Validation using a benchmark of 30 high-resolution protein-DNA complexes with crystallographically-determined interfacial water.
• Application to real cases using unbound protein coordinates, model-built DNA, and knowledge-based restraints.

Main Results:

• The protocol successfully reproduces interfacial solvation patterns.
• Hydrogen-bonded water-mediated contacts are recovered in numerous benchmark cases.
• Solvated docking enhances the quality of protein-DNA models, particularly for complexes with limited conformational changes.

Conclusions:

• The developed solvated docking protocol accurately models interfacial water in protein-DNA complexes.
• This approach improves the accuracy of computational models for protein-DNA recognition.
• The protocol is applicable to both docking and NMR-based structure calculations, broadening its utility.