Reassessing buried surface areas in protein-protein complexes

Area of Science:

• Structural Biology
• Biophysics
• Computational Biology

Background:

• The interface in protein-protein complexes is often characterized by buried surface area (BSA).
• Accessible surface area (ASA) lost upon association is termed dissociation-induced surface area loss (DSA).
• Conformational changes can cause differences between BSA and DSA.

Purpose of the Study:

• To evaluate the DSA in protein-protein complexes.
• To quantify the differences between BSA and DSA.
• To investigate the impact of conformational changes on protein-protein interfaces.

Main Methods:

• Analysis of 144 protein-protein complexes from the Protein-Protein Interaction Affinity Database.
• Measurement of ASA for interface atoms in both bound and unbound states.
• Comparison of BSA and DSA to assess conformational changes.

Main Results:

• Differences between BSA and DSA exceeding 20% were observed.
• A systematic bias was found, with bound state ASA being 3.3% greater than unbound state ASA.
• BSA was, on average, 7% greater than DSA, even in complexes with minimal conformational changes.

Conclusions:

• Conformational changes significantly affect the interface area calculations in protein-protein complexes.
• Local movements optimize inter-component contacts at the expense of internal contacts.
• These interface dynamics may influence binding free energy, impacting protein interaction stability.