Bioinformatics approaches to the structure and function of intrinsically disordered proteins

Abstract

Intrinsically disordered proteins and protein regions (IDPs/IDRs) exist without a well-defined structure. They carry out their function by relying on their highly flexible conformational states and are mostly involved in signal transduction and regulation. By a battery of biophysical techniques, the structural disorder of about 600 proteins has been demonstrated, and functional studies have provided the basis of classifying their functions into various schemes. Indirect evidence suggests that the occurrence of disorder is widespread, and several thousand proteins with significant disorder exist in the human proteome alone. To narrow the wide gap between known and anticipated IDPs, a range of bioinformatics algorithms have been developed, which can reliably predict the disordered state from the amino acid sequence. Attempts have also been made to predict IDP function. However, due to their fast evolution, and reliance on short motifs for function, capturing sequence clues for IDP functions is a much more challenging task. In this chapter we give a brief survey of the IDP field, with particular focus on their functions and bioinformatics approaches developed for predicting their structure and function.