Effect of the location of the mutated site on the change in binding/folding free energies. On the x-axis: the probability of the wild type residue being in the given location to cause large change in binding/folding free energy (perturbation index, Pp) due to mutation. On the y-axis: the averaged absolute value of experimentally obtained binding/folding free energies provided with standard error of mean as an error bar and the total number of cases across appropriate databases. Experimentally determined values of binding/folding free energies were obtained from extended Skempi and ProTherm databases respectively. Five location types of mutation sites were considered for binding energy change analysis (COR, RIM, SUP, SUR, and INT), and three – for folding free energy analysis (Buried, Partially Buried, and Exposed). For details see Method section.