PIZSA

PIZSA assesses protein-protein interactions by assigning a Z Score from interface residue contacts to quantify interaction strength using the optimal number of atoms mediating contact and distinctions between main-chain and side-chain atom interactions.

Key Features:

• Z Score scoring: Computes a Z Score that quantifies protein-protein interaction strength based on interface residue contacts.
• Contact criteria: Considers the optimal number of atoms mediating contact between residue pairs and distinguishes main-chain versus side-chain atom contacts.
• Residue pair-wise breakdown: Provides a detailed residue pair-wise breakdown of interaction contributions within complexes.
• Decoy benchmarking: Benchmarks performance using decoys generated with ZDOCK alongside native protein complexes.
• Performance metrics: Demonstrated ranking the native structure better than any decoy in 146 of 174 cases and within the top 95th percentile in 162 cases on a 174-case test set.
• Comparison to existing potentials: Compared performance with CIPS (Contact Potential for Interaction Score) and reported superior accuracy on the 174-case set and comparable results on CAPRI targets.
• CAPRI validation: Validated on 15 CAPRI targets with results comparable to CIPS.
• Higher-order complex support: Scores higher-order protein complexes without requiring explicit designation of receptor or ligand chains.
• User-supplied potentials: Accepts user-uploaded potentials for testing and developing alternative scoring schemes.

Scientific Applications:

• Docking model ranking: Ranking and discriminating native structures from docking decoys generated by ZDOCK.
• Scoring function benchmarking: Benchmarking and comparing scoring functions such as CIPS using quantitative ranking statistics.
• Interface analysis: Assessing residue-level and pair-wise contributions to protein-protein interfaces, including main-chain and side-chain effects.
• Higher-order complex evaluation: Evaluating interactions in multi-chain protein complexes without receptor/ligand assignment.
• Development of scoring schemes: Testing and refining novel or user-supplied interaction potential schemes.

Methodology:

Scores interfaces using residue-residue contact statistics that account for optimal atom-mediated contacts and main-chain versus side-chain interactions, and validates performance by benchmarking against native complexes and ZDOCK-generated decoys (174-case set) and 15 CAPRI targets with comparisons to CIPS.