Entropy and mutual information values are used to summarize the variability and covariability of amino acids sites comprising the bHLH DNA binding and dimerization domain. When integrated with crystal structure data, these measures provide important insight into the evolution of 3-D structure in these proteins. Amino acid sites in the bHLH domain known to pack against each other have very low entropy values indicating little residue diversity at these contact sites. Non-contact sites, on the other hand, exhibit significantly larger entropy values as well as statistically significant levels of mutual information or association among sites. High levels of mutual information indicate significant amounts of intercorrelation among amino acid residues at these various sites. Using computer simulations based on a parametric bootstrap procedure, we partition the observed covariation among various amino acid sites into that arising from phylogenetic (common ancestry) and stochastic causes and that due to structural and functional constraints. These results show that a significant amount of the observed covariation among amino acid sites is due to structural/functional constraints, over and above the covariation arising from phylogenetic constraints. These quantitative analyses provide a highly integrated evolutionary picture of the multidimensional dynamics of sequence diversity and protein structure.