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MHC proteins and the immune system |
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Molecular Dynamics |
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Simulated Annealing is a molecular dynamics technique which involves rapid heating followed by slow cooling of a system (see Figure below). This allows molecules to sample many conformations and high energy geometries, then finally settle near the global energy minimum. There are many possible peptide sequences. For each chosen peptide, we simulate the dynamics of the complex in solvent. By studying the energetic interactions of each peptide we can discriminate between good and bad binders.
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Computational Challenge |
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Each person's immune system comprises a selection of slightly different MHC proteins, each of which can bind particular peptides. There are thousands of possible peptides which may bind. Furthermore, the full model system is large, and long time scales are required for the dynamics calculations. The simulations are therefore computationally demanding and produce large amounts of data. Hence, a Grid-based distributed computing approach is ideal.
Reference: "A Novel Predictive Technique for the MHC Class II-peptide binding interaction" Davies M et al. Medicine, 2004 (in press). |
When an individual is infected with a virus or bacterium,
an immune response is provoked that recognizes and
eliminates the infectious agent.
A critical step in the cellular response of the immune
system is the binding of short peptide fragments (from
broken down foreign proteins) to MHC Class II protein
molecules (see Figure on right). This complex is then presented to
helper T cell receptors for inspection at the cell surface.
Identifying peptides that bind to MHC, and hence trigger a
response, may help researchers produce a vaccine.
Rheumatoid arthritis and multiple sclerosis are common
diseases where MHC molecules play a role. Inappropriate
immune response can be equally harmful, for example in
the treatment of leukaemia.
