From Protein Structure to Function with Bioinformatics.pdf

5 Structure and Function of Intrinsically Disordered Proteins 121Fig. 5.3 Estimated pairwise interaction energies of globular proteins and IDPs. The total pairwiseinteraction energy of globular proteins (red +) and disordered proteins (blue ×) was estimated fromtheir amino acid composition and plotted as a function of their length. The negative directionrepresents increasing stabilization due to pairwise amino acid interactions. Averages in arbitraryenergy units (AEU) suggest more stabilization in the case of globular proteins (−0.81 AEU) thanIDPs (−0.07 AEU) (Reprinted from Dosztanyi et al. 2005b with permission from Elsevier)5.3.7 A Reduced Alphabet Suffices to Predict DisorderTo highlight key aspects of the underlying physical principles, it was shown that disorderedand ordered proteins can be discriminated by a reduced alphabet, i.e. by clusteringthe 20 amino acids into a smaller number of groups (Weathers et al. 2004). It was foundthat an SVM that incorporates amino acid composition has a prediction accuracy of87 ± 2%, underscoring that composition is the major feature distinguishing disorder.Progressive significant reductions of parameter space, however, by clustering physically/chemicallysimilar amino acids, had little effect on accuracy, down to four vectorsdescribing the 20 amino acids (84 ± 2%). In keeping with previous points, the compositionand relative weights of the vectors suggest that the primary determinants of disorderare simple general physicochemical features, rather than specific amino acids.