TCRpMHCmodels - 1.0

MODELLER license key

To use TCRpMHCmodels you will need the license key for the modeling program MODELLER. To get the MODELLER license key you need to fill out the MODELLER License Agreement at http://salilab.org/modeller/registration.html.

Instructions

TCRpMHCmodels predicts the three-dimensional structure of TCR-pMHC class I complexes using comparative modelling. Upon submission, this tool automatically selects the best templates and provides within minutes a complete three-dimensional model.

1. Input sequences

The input must include all protein chains from the TCR-pMHC complex (the TCR alpha chain, the TCR beta chain, the peptide chain and the MHC chain), separated by a fasta header. The tool will automatically detect the chain types.

2. Submit job

Click on the "Submit" button. The status of your job (either 'queued' or 'running') will be displayed and constantly updated until it terminates and the server output appears in the browser window. At any time during the wait you may enter your e-mail address and simply leave the window. Your job will continue; you will be notified by e-mail when it has terminated. The e-mail message will contain the URL under which the results are stored; they will remain on the server for 24 hours for you to collect them.

3. View output

After the server successfully finishes the job, a summary page shows up. Use the "Download" button to download the generated PDB file.

Please cite:

Abstract

The interaction between the class I major histocompatibility complex (MHC), the MHC presented peptide and the T-cell receptor (TCR) is a key determinant of the cellular immune response. This interaction is therefore of paramount importance in infectious diseases and cancer. Here, we present TCRpMHCmodels, a method for accurate structural modeling of the TCR-pMHC complex. This TCR-pMHC modeling pipeline takes as input the amino acid sequence and generates models of the TCR-pMHC complex, with a median Cα RMSD of 2.3Å. TCRpMHCmodels significantly outperforms TCRFlexDock, a specialized method for docking pMHC and TCR models. TCRpMHCmodels is simple to use and the modeling pipeline takes, on average, only 2 minutes. Thanks to its ease of use and high modeling accuracy, we expect TCRpMHCmodels to provide insights into the underlying mechanisms of TCR and pMHC interactions and as an aid in the development of advanced T-cell based immunotherapies and rational design of vaccines.