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WATGEN: an algorithm for modeling water networks at protein-protein interfaces
Huynh-Hoa Bui1, Alexandra J Schiewe, Ian S Haworth
1Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
Journal of Computational Chemistry
|May 2, 2007
Summary
WATGEN accurately predicts water molecule locations at protein interfaces, crucial for understanding biomolecular association. This algorithm models bridging water sites, aiding in analyzing binding energetics and specificity.
Area of Science:
- Structural Biology
- Computational Biology
- Biophysics
Background:
- Water molecules at protein interfaces are vital for atomic packing, surface complementarity, and mediating polar interactions.
- Accurate modeling of interface water is essential for comprehending the structural basis of biomolecular association.
Purpose of the Study:
- To present WATGEN, an algorithm for predicting water molecule locations at protein-protein or protein-peptide interfaces.
- To evaluate WATGEN's ability to identify water sites capable of forming multiple hydrogen bonds bridging the interface.
Main Methods:
- Developed the WATGEN algorithm to predict water molecule positions based on protein and peptide atomic coordinates.
- Tested WATGEN on 126 protein-peptide interfaces with X-ray resolutions <= 2.0 A.
- Evaluated predicted water network energies using AMBER8 to refine WATGEN parameters.
Main Results:
- WATGEN predicted 72% and 88% of experimentally determined bridging water sites within 1.5 A and 2.0 A, respectively.
- Control experiments with random water placement showed significantly lower accuracy (22% and 40% within 1.5 A and 2.0 A).
- The algorithm predicted a higher number of water molecules than experimentally observed, suggesting a comprehensive modeling approach.
Conclusions:
- WATGEN accurately predicts water molecule locations at protein-peptide interfaces.
- The algorithm is valuable for understanding the energetics and specificity of biomolecular association.
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