More compact protein globules exhibit slower folding rates

Area of Science:

• Protein structure and folding dynamics
• Biophysics
• Evolutionary biology

Background:

• Protein structural classes (all-alpha, all-beta, alpha/beta, alpha+beta) exhibit varying structural properties.
• The relationship between protein structure, residue contacts, and folding rates is a key area of biophysical research.
• Alpha/beta proteins are evolutionarily ancient, prompting investigation into their structural and kinetic characteristics.

Purpose of the Study:

• To investigate the correlation between protein structural class and the average number of contacts per residue.
• To examine the relationship between residue contacts, protein structural class, and protein folding rates.
• To explore potential evolutionary implications of structural and kinetic properties in globular proteins.

Main Methods:

• Comparative analysis of globular protein structures across different classes (all-alpha, all-beta, alpha/beta, alpha+beta).
• Quantification of the average number of contacts per residue for proteins of similar size.
• Correlation analysis between residue contact density, protein structural class, and experimentally determined folding rates.

Main Results:

• Alpha/beta proteins exhibit a higher average number of contacts per residue compared to other structural classes, attributed to their compact, spherical structure.
• Alpha/beta proteins demonstrate the slowest folding rates among the investigated structural classes.
• A positive correlation is observed between the number of residue contacts and slower folding rates in alpha/beta proteins.

Conclusions:

• Protein structural class significantly influences residue contact density and folding kinetics.
• The compact structure of alpha/beta proteins contributes to a higher contact frequency but slower folding.
• Evolutionary trends suggest a shift towards faster folding and less compact structures over time, potentially driven by selection pressures.