Fluctuations within folded proteins: implications for thermodynamic and allosteric regulation

Area of Science:

• Biophysics
• Structural Biology
• Protein Dynamics

Background:

• Historically, X-ray crystallography provided static protein structures, overlooking dynamic fluctuations.
• Neglecting protein structural variability and its functional impact has been a limitation in understanding protein behavior.

Purpose of the Study:

• To review evidence highlighting the importance of protein structural rearrangements and fluctuations.
• To emphasize the role of these dynamics in protein function, stability, and response to environmental cues.

Main Methods:

• Review of experimental and computational studies on protein dynamics.
• Analysis of side-chain degrees of freedom and conformational heterogeneity.
• Comparison of protein dynamics to dense liquids and crystalline solids.

Main Results:

• Folded proteins exhibit substantial fluctuations influencing function.
• Side-chain motions generate conformational heterogeneity and contribute to thermodynamic stability.
• Correlated motions facilitate allosteric communication and are vital for protein functions.

Conclusions:

• Protein native state fluctuations are essential for biological activity.
• Understanding these dynamics offers pathways for manipulating biomolecular functions.
• Proteins behave more like dense liquids than crystalline solids due to correlated motions.