Summary: Biochemistry 1994,33, 7505-7509 7505
Perspectives in Biochemistry
Kinetics versus Thermodynamics in Protein Folding
David Baked and David A. Agard'
Howard Hughes Medical Institute and the Department of Biochemistry and Biophysics,
University of California at San Francisco, San Francisco, California 94143-0448
Received March 4, 1994; Revised Manuscript Received April 11, 1994"
ABSTRACT: Until quite recently it has been generally believed that the observed tertiary structure of a
protein is controlled by thermodynamic and not kinetic proceses. In this essay we review several recent
resultswhich callintoquestionthe universality of thethermodynamichypothesis and discuss their implications
for the understanding of protein folding.
The thermodynamic hypothesis of protein folding has had
a long and venerable history. Christian Anfinsen in his 1972
Nobel prize acceptancelecturedescribed the "thermodynamic
hypothesis" of protein folding as follows (Anfinson, 1973):
"This hypothesisstatesthat thethree-dimensional structure
of a native protein in its normal physiological milieu (solvent,
pH, ionicstrength,presenceof other componentssuch asmetal
ions or prosthetic groups, temperature, and other) is the one
in which the Gibbs free energy of the whole system is lowest;