The function of linear motifs strongly depends on the context, e.g. functional instances mainly occur inside flexible regions that are accessible for interaction.
It has previously been shown that functional instances of protein motifs tend to lie in intrinsically disordered regions of protein sequence [12], [13], [14].
Additionally, conservation of LMs in closely and distantly related proteins has been used to improve the identification of functional instances of known LM patterns [11], [21], [22], [23].
Conservation patterns of regions flanking 116 LM functional instances were examined in relation to the presence/absence of the LM inside protein families.
Although the functional instances are enriched in the test sequences compared with control sequences, some functional instances may be present in the control sequences, because of possible false negatives in ChIP data.
The majority of these interfaces are likely to be true negatives, however, since our knowledge of SLiMs and PPIs is incomplete, this set will undoubtedly contain functional instances and true interactions.
Nevertheless, binding sites do show characteristic patterns of evolution, and it should be possible to take these into account in attempting to distinguish the functional instances of the motif.
Then, the numerator in Equation (e1) is e5 Because functional instances of word W are over-represented in the test set of sequences compared with control, the final sum in Equation (e5) is always positive and the difference (T pi − C pi ) is proportional to f pi.
Because we can assume that non-functional instances of the word are not affected by the ChIP procedure, their counts are equal in the test and control sets of sequences: NT W pi ) = NC W pi ).
A fully functional demonstration instance of our system can be found at http://viramp.com/.
