PoPMuSiC is an efficient tool for rational computer-aided design of single-site mutations in proteins and peptides. Two types of queries can be submitted. The first option allows to estimate the changes in folding free energy for specific point mutations given by the user. In the second option, all possible point mutations in a given protein or protein region are performed and the most stabilizing or destabilizing mutations, or the neutral mutations with respect to thermodynamic stability, are selected. For each sequence position or secondary structure the deviation from the most stable sequence is moreover evaluated, which helps to identify the most suitable sites for the introduction of mutations.