Thermodynamics of Structural Stability and Cooperative Folding Behavior in Proteins

Abstract

Publisher Summary This chapter provides an insight that quantitative predictions of the stability and cooperative folding behavior of proteins are within reach. The problem of predicting the structure of a protein from its amino acid sequence constitutes the classical “protein folding problem.” The thermodynamic aspects of this problem constitute the focus of the chapter. Experimental thermodynamic values for the fundamental forces that determine protein stability are refined to a point in which accurate calculations of the free energy of stabilization are possible, provided that the protein structure is known. The chapter also (1) predicts the overall stability of proteins based on structural information, (2) predicts the cooperative folding/unfolding behavior of proteins, (3) predicts the magnitude of the interactions among structural domains in proteins, and (4) predicts the presence of specific partially folded intermediates. Estimation of the folding/unfolding partition function using a hierarchical approximation and subsequent prediction of cooperative behavior is also increasingly feasible, as demonstrated for myoglobin and yeast phosphoglycerate kinase. Thermodynamic stability and cooperative interactions in proteins can be determined by hierarchical approach to partition functions, thermodynamic dissection of cooperative interactions, and classification of cooperative forces and mechanisms. The strategy used to dissect specific fundamental interactions is to isolate first the hydrophobic effects and subsequently other interactions. Some future work will extend the capability to proteins exhibiting other than pure α-helical structural motifs.