Thermodynamic aspects of molecular recognition have been studied using yeast phosphoglycerate kinase (PGK) and two antibiotics, ristocetin and vancomycin, as model systems. The binding of 3 natural substrates, ADP, ATP and 3-phosphoglycerate to wild-type and two mutant forms of PGK was examined using kinetic techniques and isothermal titration microcalorimetry. The latter technique was also used to investigate the binding of various ligand molecules to PGK and to study the formation of the ternary complex- PGK.3-PG.ADP.