Toward the atomistic simulation of T cell epitopes Automated construction of MHC: Peptide structures for free energy calculations

Department of Crystallography, University of London, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom.
Journal of Molecular Graphics and Modelling (Impact Factor: 2.02). 03/2008; 26(6). DOI: 10.1016/j.jmgm.2007.07.005
Source: OAI

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 ( allows the user to rapidly generate any desired MHC:peptide complex and will facilitate molecular modelling simulation of MHC complexes on an unprecedented scale.

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    • "The selected peptides obtained by the above bioinformatics tools were listed with their anchor residues. For structural simulations, the molecular models of the peptides were constructed using a web based interface MHCsim (Todman et al., 2008) available online. Sample peptides of HIGH affinity binders for a few alleles whose crystal structures are known (HLA-B*5102, HLA-B*2705, HLA-DRBI*0101) were obtained from the Protein Data Bank (Bergman et al., 2000) and modelled employing structural templates (viz. "
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