APE-Gen2.0

APE-Gen2.0 models peptide–MHC class I (pMHC-I) complexes to predict structures and assess the effects of post-translational modifications and non-canonical peptide geometries relevant to neoantigen recognition.

Key Features:

• Comprehensive Modeling of PTMs: Models post-translational modifications including phosphorylation, nitration, and citrullination to predict effects on peptide–MHC-I binding affinity and stability.
• Non-canonical Anchor Identification: Employs an anchor identification routine to detect and model peptides with non-standard anchor conformations within the MHC binding cleft.
• Enhanced Structural Accuracy: Produces improved pMHC-I structural predictions that extend the range of peptide cases modeled and better capture interactions relevant to T-cell receptor recognition.

Scientific Applications:

• Cancer neoantigen analysis and immunotherapy design: Structural modeling of PTM-bearing and non-canonical peptides to inform vaccine and therapeutic design targeting cancer neoantigens.
• Mechanistic studies of antigen presentation: Assessment of how PTMs and peptide geometries influence MHC-I binding affinity, complex stability, and potential impacts on T-cell activation and antigen presentation.

Methodology:

Structural modeling of pMHC-I interactions with explicit handling of PTMs (phosphorylation, nitration, citrullination) and a computational anchor identification routine for non-canonical anchor conformations.