The recognition of specific epitopes (short peptides) bound to MHC proteins by T-cell receptors (TCRs) is an important step in the adaptive immune response. Understanding these interactions may lead to new vaccines.
The difference in the free energy of binding between two distinct epitopes can be relatively small yet lead to a qualitatively different response. Using a theoretically exact statistical mechanical technique, thermodynamic integration, we can compute the difference in binding free energy between two epitopes and a MHC-TCR system (see figure). This is especially challenging for a system of this size (100k atoms) and requires the use of High Performance Computing.
Wan,S., Coveney,P.V. & Flower,D.R. 2004 J. Comp. Chem. 25 1803-1813
Wan,S., Coveney,P.V. & Flower,D.R. 2005 submitted