Void distributions reveal structural link between jammed packings and protein cores

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• Protein stability is determined by dense packing of hydrophobic residues in globular protein cores.
• Previous work established protein cores have a packing fraction (ϕ≈0.56), matching dense, random packing of amino-acid-shaped particles.

Purpose of the Study:

• To conduct an in-depth comparison of structural properties between protein cores and jammed packings of amino-acid-shaped particles.
• To analyze local and connected void regions within these systems.

Main Methods:

• Measurement of surface Voronoi cell volumes and local porosities.
• Assessment of connected void region percolation probability as a function of spherical probe size.
• Calculation of the critical exponent (τ) for void cluster size distribution during percolation.

Main Results:

• Similar statistical distributions were observed for surface Voronoi cell volumes and local porosities in both protein cores and amino-acid-shaped particle packings.
• Both systems exhibited the same critical probe size for void percolation.
• Void percolation cluster size statistics for amino-acid-shaped particles aligned with randomly placed spheres but differed from jammed sphere packings.

Conclusions:

• Connected void regions are a defining structural characteristic of proteins.
• These findings suggest jammed packings of amino-acid-shaped particles are viable analogs for protein cores, useful for modeling responses to mutations.
• The study proposes using void region analysis to distinguish true protein structures from computational decoys.