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The problem of hinge prediction is easiest when two or more sets of atomic coordinates
are available for a given protein in different conformations. In that case, it is possible to
visually inspect the pairs of structures (as we have done in this work) and manually
annotate the hinge location. It is also possible to automate this using FlexProt or (to
some extent) other algorithms[26, 28, 73]. Hinge detection based on two structures is
thus largely a solved problem. A much more challenging problem arises when only one
structure is known. In early work on this problem, Janin and Wodak[7] developed a
domain interface area calculation method. The more recent FIRST algorithm[62]
identifies rigid substructures based on graph theoretic calculations. FRODA uses these
rigid units to simplify the process of generating alternate structures which have been
shown to be consistent with NMR data for certain proteins.[30, 60] The Gaussian
Network Model (GNM)[64] is an approximate method for obtaining normal mode
displacements and consequent motional correlations of backbone α–carbon atoms.
Kundu et al. used the sign of the GNM first normal mode displacement, with some
postprocessing, to assign residues to structural domains.[74]
A yet more challenging problem arises when only sequence features (but no structural
coordinates) are known. In this article we evaluate one predictor that uses only sequence
information. Relatively little work has been reported on this largely unsolved problem,
but it is in some ways related to the more extensively studied problem of detection of
evolutionary domain boundaries (which may or may not be flexible)[33, 34, 39, 75].
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