Biology Reference
In-Depth Information
Fig. 6.
Structure of a complex between a TCR and a p-MHC. The peptide, shown
in the context of the MHC molecule, is in ball-and-stick representation.
only at the structural level but also from a thermodynamic point of view,
are of major interest. Such molecular modeling approaches can be used
to guide new experimental investigations, and to rationally optimize
tumor-specific TCRs.
Recently, we performed a study of the 2C TCR/SIYR/H-2Kb system
using a binding free energy decomposition based on the MM-GBSA
approach (see above). The results show that the TCR-p-MHC binding
free energy decomposition including entropic terms provides a detailed and
reliable description of the interactions between the TCR and p-MHC mol-
ecules at an atomistic level.
59
Comparison of the calculated binding free
energy changes upon mutation with experimentally determined activity dif-
ferences for alanine mutants yields a correlation of 0.67 when the entropy
is neglected, and 0.72 when the entropy is taken into account.
