Related Experiment Video
Updated: Jul 2, 2025
11:17
Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin
Published on: March 10, 2021
6.4K
APE-Gen2.0: Expanding Rapid Class I Peptide-Major Histocompatibility Complex Modeling to Post-Translational
Romanos Fasoulis1, Mauricio M Rigo1, Gregory Lizée2
1Department of Computer Science, Rice University, Houston, Texas 77005, United States.
Journal of Chemical Information and Modeling
|February 28, 2024
Summary
APE-Gen2.0 accurately models complex peptide-MHC structures, including non-standard modifications crucial for cancer immunotherapy research. This tool enhances understanding of T-cell receptor recognition and immune response.
Area of Science:
- Immunology
- Computational Biology
- Structural Biology
Background:
- T-cell receptor (TCR) recognition of peptides bound to class I major histocompatibility complex (MHC-I) receptors initiates adaptive immune responses.
- While peptide-MHC (pMHC) structure is critical, existing modeling tools often fail with non-canonical peptides, including those with post-translational modifications (PTMs) or unusual geometries.
- Accurate modeling of these non-canonical cases is vital for advancing cancer immunotherapy, particularly for neoantigens.
Purpose of the Study:
- To develop an improved computational tool, APE-Gen2.0, for accurate structural modeling of peptide-MHC (pMHC) complexes.
- To enhance the modeling range to include non-canonical peptides with various post-translational modifications (PTMs) and non-standard anchor conformations.
- To provide an accessible web server for pMHC structural modeling.
Main Methods:
- Development of APE-Gen2.0, an advanced pMHC structural modeling tool.
- Incorporation of algorithms to model diverse PTMs (phosphorylation, nitration, citrullination).
- Implementation of an improved anchor identification routine for non-canonical peptide conformations.
- Establishment of a user-friendly web server for accessible pMHC modeling.
Main Results:
- APE-Gen2.0 demonstrates improved accuracy and expanded modeling capabilities for non-canonical pMHC cases compared to existing tools.
- The tool successfully models peptides with various PTMs and non-standard anchor geometries.
- Modeled structures from APE-Gen2.0 enable more accurate assessment of PTM effects on peptide-MHC binding affinity.
Conclusions:
- APE-Gen2.0 significantly advances pMHC structural modeling, particularly for complex and non-canonical peptides relevant to cancer immunotherapy.
- The tool's ability to model PTMs and unusual structures provides deeper insights into TCR recognition and immune responses.
- APE-Gen2.0 offers a valuable, accessible resource for researchers in immunology and computational biology.
More Related Videos
Related Concept Videos
01:25Protein Folding
8.0K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
8.0K
01:19Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K