TOP-IDP-Scale: A New Amino Acid Scale Measuring Propensity for Intrinsic Disorder

Abstract

Intrinsically disordered proteins carry out various biological functions while lacking ordered secondary and/or tertiary structure. In order to find general intrinsic properties of amino acid residues that are responsible for the absence of ordered structure in intrinsically disordered proteins we surveyed 517 amino acid scales. Each of these scales was taken as an independent attribute for the subsequent analysis. For a given attribute value X, which is averaged over a consecutive string of amino acids, and for a given data set having both ordered and disordered segments, the conditional probabilities P(s o | x) and P(s d | x) for order and disorder, respectively, can be determined for all possible values of X. Plots of the conditional probabilities P(s o | x) and P(s d | x) versus X give a pair of curves. The area between these two curves divided by the total area of the graph gives the area ratio value (ARV), which is proportional to the degree of separation of the two probability curves and, therefore, provides a measure of the given attribute's power to discriminate between order and disorder. As ARV falls between zero and one, larger ARV corresponds to the better discrimination between order and disorder. Starting from the scale with the highest ARV, we applied a simulated annealing procedure to search for alternative scale values and have managed to increase the ARV by more than 10%. The ranking of the amino acids in this new TOP-IDP scale is as follows (from order promoting to disorder promoting): W, F, Y, I, M, L, V, N, C, T, A, G, R, D, H, Q, K, S, E, P. A web-based server has been created to apply the TOP-IDP scale to predict intrinsically disordered proteins (http://www.disprot.org/dev/disindex.php).

A Proline-Tryptophan Turn in the Intrinsically Disordered Domain 2 of NS5A Protein Is Essential for Hepatitis C Virus RNA Replication

“…Whereas no special features are detected with the latter method or with MoRF predictors for residues Pro 314 , Trp 316 , and Ala 317 , we demonstrate here that these residues are part of a minimal structural element that we name a PW turn. Among these crucial residues, the proline corresponds to the major disorder-promoting amino acid, whereas the tryptophan is the main order-promoting residue (34,56,57), which might explain why the PW turn escapes to the MoRF predictors. Residues Met 313 to Ala 317 of NS5A-D2 fold as a turn, which is mainly characterized by the hydrophobic interaction between the cyclic Pro 314 residue and the aromatic side chain of Trp 316 (Fig.…”

Slide-and-exchange mechanism for rapid and selective transport through the nuclear pore complex

“…The spacer residues are strongly hydrophilic (17) and rich in disorder-promoting residues, such as proline, serine, lysine, and glutamine ( Fig. 1) (18). Each NPC contains thousands of individual FG motifs that function as potential interaction sites for TFs during transport (19,20).…”

Missing strings of residues in protein crystal structures

“…8 The amino acid propensities to be in a missing string correlate quite well with the TOP-IDP amino acid scale that discriminates between order and disorder, 9 despite the latter one is based not only on the Protein Data Bank but also on other data (for example, circular dichroism or protease digestion). Apart the methionine, which is extremely frequent in the N-terminal missing strings despite its small TOP-IDP value, discrepancies are observed also for serine, glycine, asparagine, and histidine.…”