Publisher Summary This chapter describes an approach for modeling the three-dimensional structure of a protein from the tertiary structure of a homologous protein determined by X-ray or Nuclear magnetic resonance analysis. In this approach, a known structure as an archetype is considered for the unknown structure of another protein. The structure of a protein of homologous sequence is then modeled on the basis of the similarity with its archetype. The two problems that arise in this modeling approach are the a priori univocal assignment of the correspondence between model and tethering structure equivalent atoms and the most efficient search algorithm to describe the changes from the initial structure to the homologous one. A novel technique is also described, which simultaneously solves the problem of assignment and search by relying on a self-consistent procedure of restraint assignment during a biased molecular dynamics trajectory. The technique is exemplified by its application to several unrelated systems ranging from very small peptides to domain movements in large proteins.