Protein structure modelling from remote sequence similarity.

Many methods exist for taking a sequence that exhibits similarity to another of known structure and building a molecular model. However, when the sequence similarity is very remote and fragmentary, this 'modelling-by-homology' approach is less reliable. Current methods that tackle this problem are reviewed below, taking as an example the construction of a predicted model for the retroviral protease. This earlier work, which was only partially automatic, identified many of the outstanding difficulties that have subsequently been automated in computer programs, developed both by the author and many others. Because of the rapid proliferation of methods and their variants, an exhaustive review of the literature has not been possible and the following survey concentrates on the developments of the author and colleagues to explain the basic methods.