Data associated with the publication: Protein stability is determined by single-site bias rather than pairwise covariance

Contains data in the publication with the title and authors above, which has been accepted for publication in Nature Chemical Biology in January of 2026. The data are of three types: (1) Guanidine-induced protein unfolding transitions monitored by circular dichroism and tryptophan fluorescence spectroscopies, (2) Isothermal titration calorimetry (ITC) of DNA binding by designed homeodomain proteins, and (3) enzyme kinetics data in the form of absorbance at 340 nanometers as a function of time, and initial reaction velocities as a function of substrate concentration. For the unfolding transitions there are four different protein families, including the homeodomain (HD) protein, adenylate kinase (AK), dihydrofolate reductase (DHFR), and phosphoglycerate kinase (PGK). For the ITC titrations there is only data for HD proteins. For enzyme kinetics there is data for AK, DHFR, and PGK, but not HD. The sequences of these proteins are given in the manuscript, and the scripts used to design the proteins are on our <a href=https://github.com/barricklab-at-jhu/Potts_analysis_Sternke_Tripp_Barrick>github site</a>