Chapter 4 - Protein Folding Kinetics

Abstract

Publisher Summary This chapter discusses the protein folding kinetics. Protein folding is often described in terms of a two-state mass-action model, D↔N, where D and N are denatured (or unfolded, U) and native (or folded, F) states, respectively. In protein folding, there is no single microscopic reaction coordinate that every chain follows, and there may not be identifiable barriers of the traditional type because energy landscapes may be funnel shaped. The mechanism of protein folding has been addressed with mutational studies of folding rates and equilibrium constants. This methodology, developed as the fraction of energy difference (Φ)-value analysis, has been widely applied to many different proteins. The experiments on protein engineering and Φ-value analysis also provide the information about the transition state structures at the level of individual residues. A set of single mutants, strategically distributed over the molecule, is used to map out the structure of the transition state at the resolution of single amino acid residues. This approach may analogously be applied on proteins, with more complicated energy landscapes that contain intermediates on the reaction pathway, and on proteins that have residual structure in their unfolded states. The experimentally determined Φ-values upon amino acid substitutions has been used to predict critical residues in protein folding. The residues with high Φ-values form folding nuclei in protein structures, which have a critical set of interactions for folding and rapid assembly of their native states.