In the multiple sequence alignment (MSA) of a protein family, non-conserved positions can be very important because the destabilizing effects of a given amino acid at one position can be compensated by the stabilizing effect of another amino acid at a different position. As a consequence these positions are often coevolving. Several methods are available for the detection of coevolving positions from the analysis of MSAs. Information about coevolution in combination with information on the changes in folding free-energy produced by all possible point mutations of each residue can be very valuable to understand the protein mechanism and dynamic properties, and to design mutagenesis studies. Using an example based on the family of KDO8P synthase, an enzyme involved in the synthesis of bacterial endotoxin, we describe a general strategy to assess the contribution of coevolving residues to protein stability by computational means.