Journal article
Exploring peptide/MHC detachment processes using hierarchical natural move Monte Carlo
- Abstract:
- Motivation: The binding between a peptide and a major histocompatibility complex (MHC) is one of the most important processes for the induction of an adaptive immune response. Many algorithms have been developed to predict peptide/MHC (pMHC) binding. However, no approach has yet been able to give structural insight into how peptides detach from the MHC. Results: In this study, we used a combination of coarse graining, hierarchical natural move Monte Carlo and stochastic conformational optimization to explore the detachment processes of 32 different peptides from HLA-A*02:01. We performed 100 independent repeats of each stochastic simulation and found that the presence of experimentally known anchor amino acids affects the detachment trajectories of our peptides. Comparison with experimental binding affinity data indicates the reliability of our approach (area under the receiver operating characteristic curve 0.85). We also compared to a 1000 ns molecular dynamics simulation of a non-binding peptide (AAAKTPVIV) and HLA-A*02:01. Even in this simulation, the longest published for pMHC, the peptide does not fully detach. Our approach is orders of magnitude faster and as such allows us to explore pMHC detachment processes in a way not possible with all-atom molecular dynamics simulations. Availability and implementation: The source code is freely available for download at http://www.cs.ox.ac.uk/mosaics/.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, 376.9KB, Terms of use)
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- Publisher copy:
- 10.1093/bioinformatics/btv502
Authors
- Publisher:
- Oxford University Press
- Journal:
- Bioinformatics More from this journal
- Volume:
- 32
- Issue:
- 2
- Pages:
- 181-186
- Place of publication:
- England
- Publication date:
- 2015-09-22
- Acceptance date:
- 2015-08-21
- DOI:
- EISSN:
-
1367-4811
- ISSN:
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1367-4803
- Pmid:
-
26395770
- Language:
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English
- Keywords:
- Pubs id:
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585860
- Local pid:
-
pubs:585860
- Deposit date:
-
2021-03-16
Terms of use
- Copyright holder:
- Knapp et al.
- Copyright date:
- 2016
- Rights statement:
- Copyright The Author 2015. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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