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Gcn4 is a transcription factor and a “master regulator” for gene expression which regulates close to one tenth of the yeast genome.<br />A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. Leucine zippers are a dimerization motif of the bZIP (Basic-region leucine zipper) class of eukaryotic transcription factors. Leucine zippers are present in both eukaryotic and prokaryotic regulatory proteins, but are mainly a feature of eukaryotes. They can also be annotated simply as ZIPs, and ZIP-like motifs have been found in proteins other than transcription factors and are thought to be one of the general protein modules for protein–protein interactions.<br />The energetics of formation of specific protein complexes with other proteins or nucleic acids is now attracting increasing attention since it actually represents a most basic biological function. The heat capacity plays a major role in the determination of the energetics of protein folding and molecular recognition. As such, a better understanding of this thermodynamic parameter and its structural origin will provide new insights for the development of better molecular design strategies.