Unfavourable binding entropy changes have also been used to support the presence of conformational changes (or reductions in flexibility) occurring upon TCR recognition of pMHC.
ITC measurements provide detailed information [58] on thermodynamic quantities like enthalpy of binding (ΔH), the entropy contribution to the binding (TΔS) and also the affinity and stoichiometry that can be correlated to the results of other experiments.
In contrast to the small changes in binding free energy, a closer look at the thermodynamic data of the Y313A and R324A mutants revealed much greater changes in binding enthalpy and binding entropy from those of the wild type.
The empirical scoring function considers energy terms, such as hydrogen bonds, ionic interactions, hydrophobic effects, and binding entropy.
We hypothesized that such conformational stabilization of the otherwise flexible inhibitor would decrease the binding entropy of the resulting inhibitors, and thus increase affinity.
This result is also not surprising, as conformational dynamics are only one of many contributors to binding entropy changes (others include changes in solvation of polar and apolar surfaces and water/ion release/incorporation).
The first several TCR pMHC interactions studied thermodynamically all bound with unfavourable entropy changes at 25 °C [ 20, 43, 44], and, for a brief period, unfavourable binding entropy changes were presumed to serve as a 'thermodynamic signature' for TCR binding.
As shown in Hagan and Chandler (2006) much of the binding entropy penalty associated with adding a subunit to a capsid is incurred during the formation of the first bond, with smaller decreases in entropy associated with forming additional bonds.
A further dissection of the small binding entropy at 25 °C (–TΔS°bind = –0.6 (±0.1) kcal mol−1) suggests that a favourable desolvation of non-polar surface is almost completely balanced by unfavourable conformational entropy changes and loss of rotational and translational entropy.
This, in turn, would decrease I1's binding entropy.
