Petsko's past research interests have been in protein crystallography and enzymology. He is co-author with Dagmar Ringe of "Protein Structure and Function". He was also the author of a monthly column in Genome Biology modelled after an amusing column in Current Biology penned by Sydney Brenner. Petsko is best known for his collaborative work with Dagmar Ringe, in which they used X-ray crystallography to solve important problems in protein function including protein dynamics as a function of temperature and problems in mechanistic enzymology.