title: Exploring peptide/MHC detachment processes using hierarchical natural move Monte Carlo.
abstract: BACKGROUND
  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.
  
  
  METHODS
  The source code is freely available for download at http://www.cs.ox.ac.uk/mosaics/.
  
  
  BACKGROUND
  bernhard.knapp@stats.ox.ac.uk
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Statistics, University of Oxford, 1 South Parks Road, Oxford, OX1 3TG, UK and.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Knapp
authors.affiliation: Department of Computer Science, University of Oxford, Wolfson Building, Parks Road, Oxford, OX1 3QD, UK.
authors.forename: Samuel
authors.initials: S
authors.lastname: Demharter
authors.affiliation: Department of Statistics, University of Oxford, 1 South Parks Road, Oxford, OX1 3TG, UK and.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Deane
authors.affiliation: Department of Computer Science, University of Oxford, Wolfson Building, Parks Road, Oxford, OX1 3QD, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Minary
mesh_terms: D000465:Algorithms; D006680:HLA Antigens / Q000737:chemistry*; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D006680:HLA Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides