histo.fyi: A Useful New Database of Peptide:Major Histocompatibility Complex (pMHC) Structures

pMHCs are set to become a major target class in drug discovery; unusual peptide fragments presented by MHC can be used to distinguish infected/cancerous cells from healthy cells more precisely than over-expressed biomarkers. In this blog post, I will highlight a prototype resource: Dr. Chris Thorpe’s new database of pMHC structures, histo.fyi.

histo.fyi provides a one-stop shop for data on (currently) around 1400 pMHC complexes. Similar to our dedicated databases for antibody/nanobody structures (SAbDab) and T-cell receptor (TCR) structures (STCRDab), histo.fyi will scrape the PDB on a weekly basis for any new pMHC data and process these structures in a way that facilitates their analysis.

Today, histo.fyi covers pMHC structures from 18 species and spans 16 different peptide lengths. The database is still at the ‘alpha’ stage, a static timestamp containing only MHC Class I presented peptides, but already contains a lot of useful information. Current use cases include identifying apo pMHC equivalents for a TCR:pMHC complex of interest, stripping all examples of a given immunoglobulin:pMHC binding class of interest (e.g. antibodies bound to MHC Class I), rapidly curating peptide sequence:MHC associations to develop algorithms that predict peptide presentability by certain alleles, and mining structural bioinformatics features that could be valuable in improving our ability to predict unsolved peptide structures within the binding groove.

A real strength of the database is its beautiful visuals: all complexes are prealigned in a common reference frame allowing for helpful consistent views of the peptide. An example are the cutaway views of the binding groove that capture peptide ‘fitness’ for the MHC (Figs. 1 & 2). Information for each pMHC complex is displayed clearly, and is all freely downloadable in a section at the bottom of the page. This includes the metadata file used to generate the histo.fyi webpage for the entry, facilitating web scraping (all data is available under a CC-BY 4.0 license).

Fig. 1: A slice down the length of the peptide binding groove to demonstrate how closely each peptide residue is associating with a binding partner on the MHC.
Fig. 2: Top-down views of the peptide binding groove showing the pMHC contact neighbourhood by classical binding pocket.

Personally, I would love to see this database mature with enhanced searching capabilites as well as the intended addition of class II pMHCs. Chris has been extremely responsive to my feedback/suggestions, so I encourage anyone reading with interests in this area to explore histo.fyi and pass on your comments; it has the potential to become an invaluable community resource.

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