Protein Structure and Function: Applications of Bioinformatics Methods - John Rigden 2014

Bioinformatics Methods for Studying the Structure and Function of Unordered Proteins
Properties of IDP Sequences
Low Sequence Complexity and Disorder

Another manifestation of the periodic nature of IDPs is the low sequence complexity of their polypeptide chains. Applying the Entropy function (Shannon 1948) to protein Amino acid sequences (Wootton 1994a, b) has demonstrated that Globular Proteins predominantly reside in a high-entropy (high-complexity) state, whereas many other proteins contain extensive low-complexity regions. Up to 25% of all Amino Acids in the SwissProt database reside within low-complexity regions, and 34% of all proteins possess at least one such segment (Wootton 1994a, b). The relationship between low sequence complexity and disorder has been examined in two studies. First, Romero et al. (1999) investigated the relationship between alphabet size (the number of amino acids), complexity, and folding capacity. They found that SwissProt proteins span the entire possible range of alphabet sizes (1–20) and entropy values (H = 0.0–4.5), whereas globular domains occupy only restricted regions (alphabet = 10–20, H = 3.0–4.2). Regions with lower values (down to an alphabet size of 3 and H = 1.5) correspond to structured Fibrous proteins, such as coiled coils, collagens, and fibroins. These findings imply that a minimum alphabet size of 10 and an entropy value of approximately 2.9 are necessary and sufficient conditions to specify a sequence capable of folding into a globular Structure. Extrapolating these studies to IDPs (Romero et al. 2001) revealed that the complexity distribution in disordered proteins is shifted toward lower values, yet largely overlaps with that of ordered proteins. Overall, regional disorder correlates with low complexity; both disordered regions and low-complexity regions are widespread in proteomes; however, low complexity and disorder should not be considered synonymous.