xComb

xComb generates a database of theoretically feasible chemically cross-linked peptides and enables identification and sequence assignment of cross-linked peptides from tandem mass spectra to analyze protein-protein interactions and structural arrangements.

Key Features:

• Database Creation: Systematically generates peptide FASTA files containing a curated subset of all theoretically feasible combinations of chemically cross-linked peptides derived from a specified set of proteins.
• Decoupled Search Process: Linearizes cross-linked peptides and creates a searchable library that allows standard proteomic search engines to match tandem mass spectral data to cross-linked peptides, reducing search time and decoupling the workflow from any specific search engine.
• Compatibility with Multiple Search Engines: Supports use with Phenyx, Sequest, OMSSA, Mascot, and X!Tandem to leverage existing proteomic scoring routines.
• Scalability: Supports protein cross-linking studies involving up to 50 proteins simultaneously.

Scientific Applications:

• Protein–Protein Interaction Mapping: Identification of chemically cross-linked peptides from tandem mass spectra to map interaction partners and contact sites.
• Structural Biology: Provides information on spatial arrangement and interaction networks within protein complexes to inform structural interpretation.

Methodology:

Creates a comprehensive library of theoretical cross-linked peptides represented as peptide FASTA files, linearizes cross-linked peptides into a searchable form, and uses standard proteomic search engines (Phenyx, Sequest, OMSSA, Mascot, X!Tandem) to match tandem mass spectral data to identify cross-links.