Hydrophobic regions on protein surfaces: definition based on hydration shell structure and a quick method for their...

Area of Science:

• Biophysics
• Computational Biology
• Protein Chemistry

Background:

• The hydrophobic surface of globular proteins is typically a large, interconnected region.
• Direct atom-wise delineation of hydrophobic patches is challenging.
• Proteins interact with bulk water as a unified entity with their first hydration shell.

Purpose of the Study:

• To investigate the organization of the hydrophobic surface of proteins when considering bound water molecules.
• To develop an accurate and rapid analytical technique for determining hydrophobic surface patches.
• To understand the role of these patches in molecular recognition processes.

Main Methods:

• Simulating the effect of tightly bound water by computationally increasing the radius of solvent-accessible polar atoms.
• Calculating the remaining exposed hydrophobic patches after accounting for bound water.
• Comparing computational results with experimental hydration data.

Main Results:

• Removing the surface area occupied by water bound to polar protein atoms reveals that only two-thirds of the hydrophobic surface remains accessible to bulk solvent.
• The single large hydrophobic region disintegrates into multiple smaller patches.
• A radial increase of 0.35-0.50 Å accurately simulates the effect of bound water on hydrophobic surface organization.

Conclusions:

• The first hydration shell significantly alters the organization of a protein's hydrophobic surface.
• The identified hydrophobic patches are crucial for intra- and intermolecular recognition, including ligand binding and protein association.
• A novel, accurate, and quick analytical technique for determining hydrophobic surface patches has been developed.