How the hydrophobic factor drives protein folding

Area of Science:

• Biochemistry and Physical Chemistry
• Protein Folding Dynamics
• Hydrophobicity Studies

Background:

• Hydrophobicity (HY) is a key driver of protein folding.
• The traditional Nozaki-Tanford method for measuring HY has limitations.
• Understanding the nuances of HY is critical for protein science.

Purpose of the Study:

• To modify the Nozaki-Tanford method for easier HY measurement using gases.
• To differentiate and characterize two types of hydrophobicity: intrinsic and extrinsic.
• To investigate the role of hydration shells in alkane hydrophobicity and protein folding.

Main Methods:

• Modification of the Nozaki-Tanford method using gases as solutes.
• Measurement of hydrophobicity values for rare gases and alkanes.
• Analysis of transfer energetics of alkanes to cyclohexane.
• Development of a space-filling model for alkane hydration shells.

Main Results:

• A modified, user-friendly method for measuring hydrophobicity was developed.
• Rare gases exhibit intrinsic HY proportional to solvent-accessible surface area (ASA).
• Alkanes show extrinsic HY dependent on special hydration shells stabilized by van der Waals interactions.
• Evidence supports the presence of these shells and their role in protein folding.

Conclusions:

• Two distinct types of hydrophobicity (intrinsic and extrinsic) were identified.
• Extrinsic hydrophobicity in alkanes is driven by specific hydration shells, supporting Kauzmann's protein folding mechanism.
• The short lifetime of van der Waals interactions likely explains the difficulty in detecting alkane hydration shells via NMR.