Conservation of water molecules in protein binding interfaces

Area of Science:

• Structural biology
• Computational biophysics
• Bioinformatics

Background:

• Interfacial water molecule conservation is understudied in large datasets.
• Previous analyses were limited by structural alignment challenges in large protein interface datasets.
• General conclusions on water conservation across diverse interfaces remain elusive.

Purpose of the Study:

• To develop a novel method for analyzing water conservation in protein interfaces without structural alignment.
• To investigate the role of interfacial water molecules in protein-protein interactions.
• To draw large-scale conclusions on water conservation patterns in protein interfaces.

Main Methods:

• Proposed a 'solvated sequence method' for analyzing protein interfaces.
• Labeled interfacial residues based on water contact information.
• Aligned interfacial residues using a sequence alignment-like approach.
• Analyzed the impact of residue substitution on local solvation.

Main Results:

• Substituting water-contacting interfacial residues with hydrophobic ones typically desolvates the local area.
• Residues with short side chains demonstrate a tendency to retain contacting water molecules.
• Deeply buried water molecules exhibit higher conservation in their contacts with interfacial residues.
• Water plays a significant role in shaping the structure and function of protein binding sites.

Conclusions:

• The solvated sequence method offers a scalable approach to study water conservation in protein interfaces.
• Interfacial water molecules are crucial for maintaining protein binding site integrity and function.
• Understanding water conservation provides insights into protein-protein interactions and binding site design.