Toward the atomistic simulation of T cell epitopes automated construction of MHC: peptide structures for free energy calculations.
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.
Todman
Sarah J
SJ
Department of Crystallography, University of London, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom.
Halling-Brown
Mark D
MD
Davies
Matthew N
MN
Flower
Darren R
DR
Kayikci
Melis
M
Moss
David S
DS
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
D018984:Epitopes, T-Lymphocyte; D010455:Peptides