Globular-disorder transition in proteins: a compromise between hydrophobic and electrostatic interactions?

Area of Science:

• Biophysics
• Computational Biology
• Protein Science

Background:

• Proteins exist as either folded globular structures or intrinsically disordered proteins.
• The interplay between protein sequence properties like charge and hydrophobicity influences protein structure and function.
• Understanding the factors governing protein folding versus disorder is crucial for molecular biology.

Purpose of the Study:

• To investigate the correlation between charge and hydrophobicity in globular and disordered proteins.
• To identify the dominant interactions driving protein folding and disorder.
• To explore the principle of minimal frustration in both protein folding and disorder.

Main Methods:

• Utilized a generalized self-consistent field theoretical method.
• Employed Metropolis Monte Carlo simulations to generate protein conformations.
• Designed protein sequences with varying mean net charge and mean hydrophobicity.

Main Results:

• Identified a charge-hydrophobicity boundary separating globular and disordered protein behaviors.
• Observed that attractive interactions (hydrophobic) dominate globular protein folding.
• Found that repulsive interactions (electrostatic) prevail in disordered proteins, leading to expanded conformational ensembles.

Conclusions:

• The charge-hydrophobicity boundary represents a balance between attractive and repulsive forces.
• Both protein folding and protein disorder adhere to the principle of minimal frustration.
• The developed algorithm can effectively probe the conformational characteristics of disordered proteins.