Ligand conformation and flexibility

The affinity of ligand binding reflects both the enthalpy and entropy of complex formation. Importantly, this includes not only the change in entropy and enthalpy of the protein on losing solvent but also differences in the energy required to take the ligand out of solution and into the binding pocket. This can include entropic differences, depending on ligand solvation, but also differences in enthalpy and entropy if the ligand has preferred conformations or internal interactions that are lost on binding. For the abnormal amino acid series, KXK, we have been exploring whether there are differences between the ligands in NMR measurements such as chemical shift, J-J coupling and NOESY spectra (Davies et al., in preparation). To a first approximation, it would appear that the preferred conformations and order parameters for the free peptides in solution are essentially the same. NOESY experiments so far also indicate that the tri-peptides all have access to the same conformational space, except for those containing aromatic amino acids.

0 0

Post a comment