title: Toward the atomistic simulation of T cell epitopes automated construction of MHC: peptide structures for free energy calculations.
abstract: Epitopes mediated by T cells lie at the heart of the adaptive immune response and form the essential nucleus of anti-tumour peptide or epitope-based vaccines. Antigenic T cell epitopes are mediated by major histocompatibility complex (MHC) molecules, which present them to T cell receptors. Calculating the affinity between a given MHC molecule and an antigenic peptide using experimental approaches is both difficult and time consuming, thus various computational methods have been developed for this purpose. A server has been developed to allow a structural approach to the problem by generating specific MHC:peptide complex structures and providing configuration files to run molecular modelling simulations upon them. A system has been produced which allows the automated construction of MHC:peptide structure files and the corresponding configuration files required to execute a molecular dynamics simulation using NAMD. The system has been made available through a web-based front end and stand-alone scripts. Previous attempts at structural prediction of MHC:peptide affinity have been limited due to the paucity of structures and the computational expense in running large scale molecular dynamics simulations. The MHCsim server (http://igrid-ext.cryst.bbk.ac.uk/MHCsim) allows the user to rapidly generate any desired MHC:peptide complex and will facilitate molecular modelling simulation of MHC complexes on an unprecedented scale.
authors.affiliation: Department of Crystallography, University of London, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Todman
authors.forename: Mark D
authors.initials: MD
authors.lastname: Halling-Brown
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Davies
authors.forename: Darren R
authors.initials: DR
authors.lastname: Flower
authors.forename: Melis
authors.initials: M
authors.lastname: Kayikci
authors.forename: David S
authors.initials: DS
authors.lastname: Moss
mesh_terms: D000818:Animals; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D015203:Reproducibility of Results; D012985:Software Design; D013816:Thermodynamics
chemical_list: D018984:Epitopes, T-Lymphocyte; D010455:Peptides