Thermodynamics and Kinetics of Protein Folding: An Evolutionary Perspective

This article appeals to an evolutionary model which postulates that primordial proteins were described by small polypeptide chains which (i) lack disulfide bridges, and (ii) display slow folding rates with multi-state kinetics, to determine relations between structural properties of proteins and their folding kinetics. We parameterize the energy landscape of proteins in terms of thermodynamic activation variables. The model studies evolutionary changes in these thermodynamic parameters, and we invoke relations between these activation variables and structural properties of the protein to predict the following correspondence between protein structure and folding kinetics. • e variability in both folding rates and stability of intermediates, multi-state kinetics. x02022; folding rates; unstable intermediates; two-state kinetics. x02022; rmediate rates; metastable intermediates; multi-state kinetics. x02022; rates; metastable intermediates; multi-state kinetics. volutionary model thus provides a kinetic characterization of one important subfamily of proteins which we describe by the following property: Folding dynamics of single-domain proteins which lack disulfide bridges are described by two-state kinetics. Folding rate of this class of proteins is positively correlated with the thermodynamic stability of the folded state.