Correlation between calculated local stability and hydrogen exchange rates in proteins

Area of Science:

• Biophysics
• Structural Biology
• Protein Dynamics

Background:

• Hydrogen exchange rates offer insights into protein structure and dynamics.
• Understanding the factors influencing hydrogen exchange is crucial for protein folding and function studies.

Purpose of the Study:

• To establish novel correlations between local protein structural features and main-chain amide hydrogen exchange rates.
• To elucidate the underlying mechanisms of hydrogen exchange in proteins.

Main Methods:

• Analyzing the correlation between buried surface area of residues and hydrogen exchange rates in Bovine Pancreatic Trypsin Inhibitor (BPTI).
• Developing a model based on local unfolding energetics to predict hydrogen exchange rates.
• Validating predictions against experimental data for BPTI, ribonuclease S, hen lysozyme, and cytochrome c.

Main Results:

• A significant correlation was found between the buried surface area of residues and their main-chain amide hydrogen exchange rates in BPTI.
• The proposed model, incorporating local unfolding energetics, quantitatively predicted experimental hydrogen exchange rates for 80% of amides in BPTI.
• Similar high correlation levels were observed for ribonuclease S, hen lysozyme, and cytochrome c, and for crystal-based neutron diffraction data of ribonuclease A.

Conclusions:

• The energetics of local unfolding play a critical role in the mechanism of protein hydrogen exchange.
• The established correlations provide a robust method for predicting hydrogen exchange rates in proteins.
• This approach can be applied to various proteins, enhancing our understanding of their structural dynamics.