Non-interacting surface solvation and dynamics in protein-protein interactions

Area of Science:

• Biochemistry
• Structural Biology
• Computational Biology

Background:

• Protein-protein interactions (PPIs) are fundamental to cellular functions like proliferation and signal transduction.
• Understanding PPI energetics requires considering factors beyond traditional interface and rim regions.
• Previous work suggests global surface properties influence PPIs.

Purpose of the Study:

• To investigate the role of solvent effects on protein-protein surfaces using molecular dynamics simulations.
• To compare the dynamics of interface, rim, and non-interacting surface regions in protein complexes.
• To elucidate how surface properties and hydration layers impact PPI stability.

Main Methods:

• Molecular dynamics simulations of five protein complexes and their free components.
• Analysis of residue mobility in interface, rim, and non-interacting surface regions.
• Assessment of hydration layer properties and their correlation with surface chemistry.

Main Results:

• Non-interacting surface residues become more flexible in complexes, potentially offering entropic compensation.
• Polar residues exhibit lower fluctuations and are associated with stable water molecules compared to charged residues.
• The hydration layer's mobility, linked to complex stability, is influenced by local surface chemical properties.

Conclusions:

• The non-interacting surface contributes to the entropic balance of protein-protein complexes.
• The hydration layer's properties are critical for shielding protein complexes from unwanted interactions.
• Surface chemistry directly influences the hydration layer, impacting overall PPI stability.