MICROCALORIMETRY AND THE MOLECULAR RECOGNITION OF PEPTIDES AND PROTEINS

Isothermal titration (ITC) and differential scanning calorimetry (DSC) techniques are now routinely applicable to the study of non-covalent interactions in biomolecular recognition. Examples from our own current work on peptide antibiotic interactions and protein folding illustrate what may be achieved. ITC binding studies of vancomycin antibiotics with model peptides give information about the thermodynamics of group interactions, and also demonstrate possible complexities due to ligand-induced aggregation processes. The thermal stability of proteins in mixed aqueous solvents, studied by DSC, shows how the balance of forces responsible for folding stability may switch, without markedly perturbing the native structure. Separate experiments on the molecular recognition of unfolded polypeptide chains by cyclodextrins are consistent with simple binding of these cyclic polysaccharides to exposed aromatic groups on the thermally denaturated protein.