23] Probing structural and physical basis of protein energetics linked to protons and salt

Abstract

Publisher Summary This chapter outlines molecular mechanisms of salt- and pH-sensitive processes in proteins. The strategy employs experimental methods to measure and dissect the energetics of chemical equilibria that are sensitive to salts and pH, and computational methods to understand the physicochemical and structural origins of the measured energetics. The regulation of function and structure of human hemoglobin by protons and anions is used to illustrate the nature, utility, and limitations of molecular mechanisms that can be defined at present. The spectacular success of macromolecular crystallography has had a strong impact on how proteins are understood. Crystallographic structures are gold mines of information and provide invaluable insights into the origins of protein stability and function. Molecular mechanisms defined from the strictly structural perspective can be invaluable heuristically. Proteins, however, are energy-transducing machines, capable of interconverting energy in its different forms for biochemical purposes. Energetics rule, all aspects of the structure, function, and regulation of macromolecules. Useful and realistic molecular mechanisms of stability or function of proteins must consider energetics explicitly.