Inter-residue and solvent-residue interactions in proteins: a statistical study on experimental structures

Area of Science:

• Structural biology
• Computational chemistry
• Biophysics

Background:

• Protein Data Bank (PDB) provides structural data for X-ray and NMR resolved proteins.
• Understanding protein stability involves analyzing side chain and solvent-residue interactions.
• Knowledge-based potentials are crucial for protein structure prediction.

Purpose of the Study:

• To investigate the role of solvent-residue interactions in protein stability.
• To evaluate the inclusion of solvent effects in knowledge-based potentials.
• To assess the contribution of solvent-residue interactions to protein structure discrimination.

Main Methods:

• Statistical analysis of protein structures from the Protein Data Bank.
• Voronoi's polyhedron analysis for solvent-residue contacts.
• Gapless threading experiments to test knowledge-based potentials.

Main Results:

• Hydrophobic residues are key to protein stability, with hydrophobic-hydrophobic and aromatic-aromatic contacts often separated in sequence.
• A proposed relation links protein free energy to residue number, incorporating residue-residue and solvent-residue contributions.
• Solvent-residue potentials significantly improve native structure discrimination, particularly for small proteins.

Conclusions:

• Solvent-residue interactions are vital components of knowledge-based potentials for protein structure prediction.
• The inclusion of solvent effects enhances the free energy gap between native structures and decoys.
• Hydrophobic interactions remain dominant for large proteins, while solvent effects are comparable for small proteins.