Intramolecular surface contacts contain information about protein-protein interface regions

Area of Science:

• Biochemistry
• Structural Biology
• Computational Biology

Background:

• Amino acid preferences at protein-protein interfaces are known and used for prediction.
• Previous methods focused on single amino acid propensities.
• The potential of residue pairs in interface prediction was unexplored.

Purpose of the Study:

• To systematically analyze intramolecular surface contacts within protein interfaces.
• To determine if considering amino acid pairs improves protein-protein interface prediction accuracy.
• To investigate the utility of intramolecular contact propensities.

Main Methods:

• Analysis of intramolecular surface contacts in protein interfaces.
• Development and application of intramolecular contact propensities.
• Blind testing of prediction accuracy using these propensities.
• Correction of contact propensities to account for single amino acid preferences.

Main Results:

• Specific pairs of amino acids show significant preferences for occurring within and around protein interfaces.
• Intramolecular contact propensities assigned higher scores to interface residues compared to non-interface residues in blind tests.
• This predictive effect remained significant even after correcting for single amino acid interface propensities.

Conclusions:

• Intramolecular contact propensities derived from amino acid pairs are valuable for protein-protein interface prediction.
• These propensities may offer an alternative or complementary approach to traditional single amino acid interface propensities.
• The findings suggest a new avenue for improving computational prediction of protein interactions.