Thermodynamics of protein folding

Being the 44th HUFFMAN MEMORIAL AWARD LECTUREof the Calorimetry Conference delivered 7 August 1996 at its 50th Annual Conference held in Vancouver, Canada The most surprising feature of proteins, which distinguishes them from all other types of large polymeric molecules and provides them with a broad range of special properties, is their unique structural order. The position of each atom in these macromolecules is unique relative to its neighboring atoms. Such ordered aperiodic macroscopic systems have never been dealt with before in physics and now attract rapidly increasing attention. This primarily concerns the thermodynamics of formation of their structure. What are the forces responsible for folding these molecules into such sophisticated constructions? Understanding the energetic basis of these structures has not only fundamental but also practical importance. This has required the measurement of the very small heat effects of intramolecular processes in proteins using microcalorimetric techniques, which have been developed specifically for this purpose.