Analyses of protein cores reveal fundamental differences between solution and crystal structures

Area of Science:

• Structural biology
• Biophysics
• Computational biology

Background:

• Studies indicate significant structural discrepancies between protein structures determined by NMR spectroscopy and X-ray crystallography.
• The physical basis for these observed differences remains incompletely understood.

Purpose of the Study:

• To investigate the origin of structural differences between NMR and X-ray crystallography protein structures.
• To model protein cores using jammed packing principles to explain these discrepancies.

Main Methods:

• Assembled a database of high-quality protein structures solved by both NMR and X-ray crystallography.
• Modeled protein cores as jammed packings of amino acid-shaped particles.
• Varied the degree of thermalization in packing generation protocols.

Main Results:

• Confirmed significant differences in Cα atomic positions, core amino acid identity, dihedral angles, and packing fraction between NMR and crystal structures.
• Demonstrated that thermalization degree tunes the jammed packing fraction.
• Found athermal protocols match X-ray crystallography packing fractions, while highly thermalized protocols exceed NMR packing fractions.

Conclusions:

• Thermalized systems exhibit denser packing than athermal systems.
• This difference in packing density provides a physical explanation for structural variations observed between NMR and X-ray crystallography protein structures.
• The study offers a novel physical model for understanding protein structure determination artifacts.