Sidewinder

Sidewinder combines cross-linking mass spectrometry (XL-MS) with structural modeling to map antibody-antigen interactions, enabling high-throughput interrogation of antibody-antigen systems.

Key Features:

• Modular high-throughput pipeline: Integrates state-of-the-art computational structural prediction and molecular docking with rapid XL-MS analysis.
• Probabilistic ensemble querying: Generates and queries a large ensemble of interaction models probabilistically to identify well-defined monoclonal antibody epitopes.
• Low sample requirement: Maps protein-protein interactions from low sample amounts using XL-MS integrated with structural modeling.

Scientific Applications:

• Epitope mapping on bacterial virulence factors: Identified a well-defined monoclonal antibody epitope on Streptococcus pyogenes Streptolysin O.
• Analysis of complex antibody-antigen systems: Analyzed monoclonal antibodies targeting the cell wall-anchored M1 protein of Streptococcus pyogenes.
• Therapeutic antibody development: Provides a framework for studying complex antibody-antigen systems to advance targeted immunotherapy development against bacterial pathogens.

Methodology:

The pipeline combines cross-linking mass spectrometry with computational structural prediction and molecular docking, followed by probabilistic querying of a large ensemble of interaction models.