How Quickly Do Proteins Fold and Unfold, and What Structural Parameters Correlate with These Values?

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• Protein folding and unfolding kinetics are crucial for protein function and stability.
• Understanding the relationship between protein structure and dynamics is essential for protein engineering.

Purpose of the Study:

• To investigate correlations between protein unfolding rates and various structural parameters.
• To compare folding and unfolding kinetics across different protein types (bacterial vs. eukaryotic, thermophilic vs. mesophilic) and kinetic models (two-state vs. multi-state).

Main Methods:

• Statistical analysis of the logarithm of unfolding rates for 108 proteins.
• Calculation of correlations between unfolding rates and structural parameters like size, radius of cross-section, contact order, and radius of gyration.

Main Results:

• Strong positive correlations were found between logarithm of folding and unfolding rates (0.79), and between protein stability and unfolding rate (0.79).
• Proteins with two-state kinetics exhibit higher folding and unfolding rates than those with multi-state kinetics.
• Bacterial two-state proteins fold and unfold significantly faster than eukaryotic two-state proteins.
• Thermophilic proteins have much lower unfolding rates than mesophilic proteins, despite similar folding rates.
• Unfolding rates correlate with protein size, radius of cross-section, logarithm of absolute contact order, and radius of gyration.

Conclusions:

• Protein folding and unfolding rates are closely linked and influenced by protein stability and kinetics.
• Bacterial and thermophilic proteins possess distinct kinetic properties compared to their eukaryotic and mesophilic counterparts.
• Structural parameters significantly influence protein unfolding rates, providing insights for protein design and engineering.