Abstract：
:The recognition of peptide/MHC by T-cell receptors is one of the most important interactions in the adaptive immune system. A large number of computational studies have investigated the structural dynamics of this interaction. However, to date only limited attention has been paid to differences between the dynamics of peptide/MHC with the T-cell receptor bound and unbound. Here we present the first large-scale molecular dynamics simulation study of this type investigating HLA-B*08:01 in complex with the Epstein-Barr virus peptide FLRGRAYGL and all possible single-point mutations (n = 172). All of the simulations were performed with and without the LC 13 T-cell receptor for a simulation time of 100 ns, yielding 344 simulations and a total simulation time of 34 400 ns. Our study is 2 orders of magnitude larger than the average T-cell receptor/peptide/MHC molecular dynamics simulation study. This data set provides reliable insights into alterations of the peptide/MHC-I dynamics caused by the presence of the T-cell receptor. We found that simulations in the presence of T-cell receptors have more hydrogen bonds between the peptide and MHC, altered flexibility patterns in the MHC helices and the peptide, a lower MHC groove width range, and altered solvent-accessible surface areas. This indicates that without a T-cell receptor the MHC binding groove can open and close, while the presence of the T-cell receptor inhibits these breathing-like motions.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Knapp B,Deane CMdoi
10.1021/acs.jcim.5b00511subject
Has Abstractpub_date
2016-01-25 00:00:00pages
46-53issue
1eissn
1549-9596issn
1549-960Xjournal_volume
56pub_type
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