Abstract
Tandem homologous domains in proteins are susceptible to misfolding through the formation of domain swaps, non-native conformations involving the exchange of equivalent structural elements between adjacent domains. Cutting-edge biophysical experiments have recently allowed the observation of tandem domain swapping events at the single molecule level. In addition, computer simulations have shed light into the molecular mechanisms of domain swap formation and serve as the basis for methods to systematically predict them. At present, the number of studies on tandem domain swaps is still small and limited to a few domain folds, but they offer important insights into the folding and evolution of multidomain proteins with applications in the field of protein design.