Overview
Drug-target interaction site identification uses crosslinking mass spectrometry (XL-MS), LiP-MS combined with molecular docking, and other technologies to precisely locate binding sites between small-molecule drugs and target proteins, revealing the molecular mechanism of drug action.
Technical Approach
- Crosslinking MS (XL-MS): Chemical crosslinkers capture protein-ligand complexes; MS analyzes crosslinked peptides to determine spatial proximity
- LiP-MS Conformational Fingerprinting: Drug-induced conformational change peptide fingerprints localize binding regions
- Molecular Docking Validation: Computational prediction of binding modes cross-validated with experimental data
- Mutational Validation: Site-directed mutagenesis of candidate sites confirmed by functional assays
Applications
- Guide lead optimization: clarify key SAR sites
- Reveal selectivity mechanisms: explain compound selectivity differences across protein families
- Support patent strategy: provide novel structural biology evidence