DockTope: a Web-based tool for automated pMHC-I modelling.

The immune system is constantly challenged, being required to protect the organism against a wide variety of infectious pathogens and, at the same time, to avoid autoimmune disorders. One of the most important molecules involved in these events is the Major Histocompatibility Complex class I (MHC-I), responsible for binding and presenting small peptides from the intracellular environment to CD8(+) T cells. The study of peptide:MHC-I (pMHC-I) molecules at a structural level is crucial to understand the molecular mechanisms underlying immunologic responses. Unfortunately, there are few pMHC-I structures in the Protein Data Bank (PDB) (especially considering the total number of complexes that could be formed combining different peptides), and pMHC-I modelling tools are scarce. Here, we present DockTope, a free and reliable web-based tool for pMHC-I modelling, based on crystal structures from the PDB. DockTope is fully automated and allows any researcher to construct a pMHC-I complex in an efficient way. We have reproduced a dataset of 135 non-redundant pMHC-I structures from the PDB (Cα RMSD below 1 Å). Modelling of pMHC-I complexes is remarkably important, contributing to the knowledge of important events such as cross-reactivity, autoimmunity, cancer therapy, transplantation and rational vaccine design.