A two-component nucleation model of protein hydrophobicity

Area of Science:

• Biophysics
• Computational Biology
• Protein Science

Background:

• Soluble globular proteins exhibit a fundamental structure with a hydrophobic core and a hydrophilic exterior.
• The distribution of amino acid residue hydrophobicity is crucial for protein structure and function.
• Hydrophobic moments have emerged as a tool to profile this radial hydrophobicity distribution.

Purpose of the Study:

• To identify common features in the radial hydrophobicity distribution across diverse proteins.
• To investigate the origin of these common features using a simulation model.
• To understand the factors governing the hydrophobic-ratio of distances in protein structures.

Main Methods:

• Analysis of radial hydrophobicity distribution using hydrophobic moments for 30 diverse proteins.
• Development and application of a two-component nucleation model to simulate hydrophobicity rates.
• Comparison of model-generated profiles and ratios with observed protein data.

Main Results:

• Identified two common features: the shape of the second-order ellipsoidal hydrophobic moment and a quasi-invariant hydrophobic-ratio of distances.
• The two-component nucleation model successfully simulated the observed hydrophobic moment profiles and ratios.
• Demonstrated that a wide range of residue increase rates yields a narrow range of hydrophobic ratios.
• Identified decreasing residue density with distance from the protein interior as critical for observed hydrophobic ratios.

Conclusions:

• The study reveals fundamental principles governing protein hydrophobicity distribution.
• A simple nucleation model can explain key structural features of globular proteins.
• Decreasing residue density is a critical factor in determining protein structural characteristics and stability.