Correlations between internal mobility and stability of globular proteins

Area of Science:

• Biochemistry
• Structural Biology
• Physical Chemistry

Background:

• Protein conformation in solution is a dynamic ensemble, not a single static structure.
• Hydrophobic amino acid side chain clusters play a key role in protein architecture.
• Protein denaturation mechanisms correlate with internal mobility in native protein conformations.

Purpose of the Study:

• To survey recent work suggesting dynamic protein conformations and the role of hydrophobic clusters.
• To present preliminary data from new methods for characterizing proteins in solution.
• To evaluate the compatibility of the hydrophobic cluster model with new experimental data.

Main Methods:

• High-resolution 1H nuclear magnetic resonance (NMR) studies of aromatic ring mobility and amide proton exchange.
• Thermal denaturation studies of basic pancreatic trypsin inhibitor and related proteins.
• Computer graphics for outlining hydrophobic clusters.
• 1H-NMR experiments at variable hydrostatic pressure.
• 13C-NMR relaxation measurements.

Main Results:

• Original conclusions suggested dynamic protein ensembles and the importance of hydrophobic clusters.
• New methods, including computer graphics and advanced NMR techniques, were applied.
• Preliminary data from these new investigations are presented.
• The hydrophobic cluster model appears compatible with the early data.

Conclusions:

• Protein conformation in solution is a dynamic ensemble.
• Hydrophobic clusters are crucial for globular protein architecture.
• Internal protein mobility is linked to denaturation mechanisms.
• The hydrophobic cluster model is supported by preliminary data from new characterization techniques.