Protein Domain Boundary Predictions: A Structural Biology Perspective

Kirillova, Svetlana; Kumar, Suresh; Carugo, Oliviero

Although it is impossible to consider it a rule, it is generally easier to work with single-domain proteins than with multi-domain proteins, since the latter ones tend to be conformationally more flexible [46] . For example, the reciprocal orientation of the domains can vary and depend on the presence of other molecules. Multi-domain proteins may also be little prone to refold if, by chance, they had been overexpressed in cells lacking proper chaperones. This does not mean that multi-domain proteins cannot be studied but it implies that some care must be paid in structural biology experiments and that longer time and larger funding can be expected to be necessary to solve multi-domain proteins. It is thus extremely important to be able to predict, on the basis of its amino acid sequence, if a protein contains one or more structural domains.