Help with the Structure Tool
The Structure Tool provides users with the ability to compare the tertiary structure of MHC molecules. The structure are predicted through ESMFold, and and the modelled structure is aligned to a template structure that has been previously prepared with a poly-A peptide in the pocket.
Structure preparation
For class I molecules, a 9-mer peptide is inserted, while for class II a 12-mer is used. Additionally, for class II molecules, the missing chain is added to the model by identifying the closest matching sequence in the previously generated library. Finally, a molecular dynamics energy minimisation is performed. The final molecule is provided as a PDB file with two chains for class I molecules, or three chains for class II.
Structure visualization
A customised implementation of MolStar is available to visualise and compare MHC molecules. The page is available here and a link to each structure is provided in any page of alleles that have a structure available. The tool allows to load one or more alleles through the autocomplete field. As a result, alleles are automatically loaded and the structures are aligned.
References
Please check the following references for further details:
- Maccari G, Robinson J, Barker DJ, Yates AD, Hammond JA, Marsh SGE, The 2024 IPD-MHC database update: a comprehensive resource for major histocompatibility complex studies Nucleic Acids Research, 2024;, gkae932, DOI: 10.1093/nar/gkae932
- Lin Z, Akin H, Rao R, Hie B, Zhu Z, Lu W, Smetanin N, Verkuil R, Kabeli O, Shmueli Y, dos Santos Costa A. Evolutionary-scale prediction of atomic-level protein structure with a language model. Science. 2023 Mar 17;379(6637):1123-30. DOI: 10.1126/science.ade2574