Insights from Void Volumes and Hydration Dynamics on Protein Spontaneous Rupture via Dynamic Internal Impact Forces:...

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• Mechanical forces are crucial for protein conformational changes.
• Protein compressibility, influenced by internal cavities and hydration, dictates responses to stress.
• Understanding protein mechanical stability is vital for biomaterial development.

Purpose of the Study:

• To investigate changes in internal void volumes and hydration dynamics of epidermal growth factor receptor (EGFR) under compressive force.
• To model tertiary structural rupture of EGFR using all-atom steered molecular dynamics (SMD) simulations.
• To elucidate the mechanisms behind protein rupture under pN compressive forces.

Main Methods:

• All-atom steered molecular dynamics (SMD) simulations were employed.
• EGFR was used as a model system to study compressive force-induced structural rupture.
• Analysis focused on internal void volumes, hydration dynamics, and surface properties.

Main Results:

• Tertiary structure-ruptured EGFR showed reduced internal cavity volumes and increased surface hydrophobicity.
• The ruptured state exhibited a more ordered hydration shell, enhanced hydration, and altered surface electrostatic potential.
• EGFR adopted a mechanically less compressible conformation upon rupture, suggesting internal force redistribution.

Conclusions:

• EGFR's mechanical response to rupture involves changes in void volumes and hydration, leading to reduced compressibility.
• These findings are likely applicable to other proteins and complexes under pN compressive forces.
• The study provides insights into stochastic protein rupture mechanisms and informs biomaterial design.