InterEvDock

InterEvDock2 predicts protein–protein complex structures by performing ab initio rigid-body docking and integrating co-evolutionary information into consensus scoring to improve interface identification.

Key Features:

• Ab initio rigid-body docking (FRODOCK): Performs free rigid-body docking using the FRODOCK program to systematically explore potential interactions between unbound protein structures.
• Consensus scoring and InterEvScore: Re-scores docking decoys with a consensus of physics-based and statistical potentials, and incorporates co-evolutionary information via the InterEvScore function.
• Two- and three-body statistical potentials: Uses two- and three-body statistical potentials that allow residues to contribute within their local structural environment to improve discrimination of near-native interfaces.
• Support for sequence-based inputs: Accepts input protein sequences in addition to structural data to enable modeling when only sequences are available.
• Multimeric input and constraint specification: Accepts multimeric inputs and allows specification of interaction constraints based on prior knowledge.
• Automatic template search and comparative modeling: Includes modules for automatic template search and comparative modeling of input proteins when homologous structures are used.

Scientific Applications:

• Structural interactome analysis: Leverages co-evolutionary information to explore protein–protein interaction networks from an evolutionary perspective.
• Interaction model prediction: Generates ab initio docking models for predicting protein–protein complex structures and interfaces.
• Guiding experimental design: Identifies candidate interface residues to inform mutagenesis and validation experiments.
• Benchmarking performance: On 812 complexes with unbound homology models and co-evolutionary data, identified a correct model among the top 10 consensus models in 29% of cases, outperformed individual scoring functions (15–24%), and predicted at least one correct interface residue among the top 10 residues in 91% of cases.

Methodology:

Performs an initial free rigid-body docking search with FRODOCK followed by re-scoring with the InterEvScore function that combines physics-based terms and two- and three-body statistical potentials incorporating co-evolutionary information; includes automatic template search and comparative modeling modules for sequence inputs.