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Exploring the unbinding of L eishmania ( L .) amazonensis CPB derived‐epitopes from H 2 MHC class I proteins
Author(s) -
Brandt Artur M. L.,
Batista Paulo Ricardo,
SouzaSilva Franklin,
Alves Carlos Roberto,
Caffarena Ernesto Raul
Publication year - 2016
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24994
Subject(s) - major histocompatibility complex , peptide , epitope , mhc class i , biology , computational biology , leishmania , chemistry , microbiology and biotechnology , immune system , biochemistry , antigen , genetics , parasite hosting , world wide web , computer science
New strategies to control Leishmania disease demand an extensive knowledge about several aspects of infection including the understanding of its molecular events. In murine models, cysteine proteinase B from Leishmania amazonensis promotes regulation of immune response, and fragments from its C‐terminus extension ( cyspep ) can play a decisive role in the host‐parasite interaction. The interaction between cyspep ‐derived peptides and major histocompatibility complex (MHC) proteins is a crucial factor in Leishmania infections. Seven cyspep ‐derived peptides, previously identified as capable of interacting with H‐2 (murine) MHC class I proteins, were studied in this work. We established a protocol to simulate the unbinding of these peptides from the cleft of H‐2 receptors. From the simulations, we estimated the corresponding free energy of dissociation (Δ G d ) and described the molecular events that occur during the exit of peptides from the cleft. To test the reliability of this method, we first applied it to a calibration set of four crystallographic MHC/peptide complexes. Next, we explored the unbinding of the seven complexes mentioned above. Results were consistent with Δ G d values obtained from surface plasmon resonance (SPR) experiments. We also identified some of the primary interactions between peptides and H‐2 receptors, and we detected three regions of influence for the interaction. This pattern was systematically observed for the peptides and helped determine a minimum distance for the real interaction between peptides and H‐2 proteins occurring at ∼25 Å. Proteins 2016; 84:473–487. © 2016 Wiley Periodicals, Inc.