Interior and surface of monomeric proteins

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• Understanding protein structure-function relationships is crucial in molecular biology.
• Solvent-accessible surface area (As) is a key biophysical parameter influencing protein stability and interactions.
• Accurate determination of As and residue accessibility is essential for predicting protein behavior.

Purpose of the Study:

• To calculate and analyze the solvent-accessible surface area (As) of monomeric proteins using high-resolution structural data.
• To establish correlations between protein As, molecular weight (Mr), and residue accessibility.
• To investigate the compositional differences between protein surfaces and interiors and their relation to hydrophobicity.

Main Methods:

• Atomic coordinates from 46 high-resolution crystal structures were used to calculate As.
• Statistical analysis was employed to determine the accuracy of As calculations and identify correlations.
• Residue burial and surface accessibility were quantified and analyzed in relation to molecular weight and amino acid composition.

Main Results:

• Protein As correlates with Mr via the power law As = 6.3 M^0.73, predicting values within 4% accuracy.
• The water-accessible surface is predominantly non-polar (57%), while the buried surface is richer in polar groups (39%) but lower in charged groups (4%).
• The fraction of buried residues increases with Mr, and residue burial correlates well with hydrophobicity, though with low correlation within residue groups.

Conclusions:

• A predictive model for protein As based on molecular weight has been established.
• Significant differences in chemical composition exist between protein surfaces and interiors, with implications for protein folding and stability.
• Hydrophobicity is a primary driver for residue burial, but other factors also influence the partitioning of residues within proteins.