Buried and accessible surface area control intrinsic protein flexibility

Area of Science:

• Structural Biology
• Biophysics
• Computational Biology

Background:

• Protein conformational dynamics are essential for biological functions.
• Understanding how protein structure encodes flexibility is a key challenge.

Purpose of the Study:

• To investigate the relationship between protein structure and intrinsic flexibility.
• To develop a practical method for predicting protein flexibility.

Main Methods:

• Calculation of relative solvent-accessible surface area (Arel) as a proxy for flexibility.
• Comparison of Arel with experimental and computational measures of protein flexibility.
• Analysis of sequence and structural properties associated with flexibility.

Main Results:

• Protein flexibility is tightly coupled to the amount of buried surface area.
• Arel effectively predicts global protein flexibility.
• Flexibility correlates with multiple domains and alpha-helical content, not intrinsic disorder.
• Arel can identify errors in crystal structures and relates to resolution.

Conclusions:

• Buried surface area is a fundamental determinant of protein flexibility.
• Arel provides a simple and practical method for predicting protein flexibility from structure.
• This work offers mechanistic insights into protein dynamics and a tool for structural analysis.