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Molecular Dynamics Studies of the Role of Protein Flexibility in Immunological Molecular Recognition
Author(s) -
Ayres Cory,
Scott Daniel,
Baker Brian,
Corcelli Steven
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.571.33
Subject(s) - t cell receptor , epitope , major histocompatibility complex , biology , computational biology , microbiology and biotechnology , antigen , population , t cell , immune system , immunology , medicine , environmental health
Activation of the cellular immune response involves the recognition of an antigenic peptide presented by either the class I or class II major histocompatibility complex (MHC) by T‐cell receptors (TCRs). Because of the large population of potential antigenic peptides in comparison to the number of available TCRs, TCRs must be cross‐reactive, yet must also maintain a degree of specificity to avoid indiscriminate T cell activation. A commonly implicated factor for TCR specificity and cross reactivity, as well as the current focus for this study, involves the flexibility of TCR complementarity‐determining region (CDR) loops. This study focuses on the DMF5 TCR, which is specific for epitopes of the MART‐1 protein, upregulated in the majority of melanomas. Beyond its potential utility in cancer therapy, this particular TCR is of interest because of the apparent rigidity of its CDR loops, which contrasts with what traditionally has been expected of TCR binding loops. Molecular Dynamics simulations of both the unligated and ligated DMF5 TCR were performed in order to assess its flexibility and to gain insight into the roles of mobility in DMF5 binding.