Exploring structurally conserved solvent sites in protein families

Area of Science:

• Structural biology
• Computational biophysics
• Biochemistry

Background:

• Protein-bound water molecules significantly influence protein structure, function, and energetics.
• Previous studies on conserved solvent sites were limited by a lack of effective computational tools.

Purpose of the Study:

• To develop and validate a semiautomated computational approach for identifying conserved solvent sites in proteins with similar 3D structures.
• To assess the conservation patterns of water molecules across diverse protein families.

Main Methods:

• A semiautomated computational method was developed to identify conserved solvent sites.
• The method was applied to six protein families: monodomain cytochrome c, fatty-acid binding protein, lactate/malate dehydrogenase, parvalbumin, phospholipase A2, and serine protease.

Main Results:

• The method successfully identified known conserved solvent sites in all tested protein families.
• Twenty-two novel conserved solvent sites were discovered, some exhibiting higher conservation than previously known sites.
• Highly conserved solvent sites (>90% conservation) were found to be located in regions of high sequence conservation.

Conclusions:

• Conserved solvent sites are important structural features of protein families and folds.
• The proximity of conserved solvent sites to conserved residues underscores their role in maintaining protein structural integrity and function.
• This computational approach provides a valuable tool for comprehensive analysis of protein-bound water molecules.