IsUnstruct: prediction of the residue status to be ordered or disordered in the protein chain by a method based on the Ising model

Intrinsically disordered proteins (IDPs) were found in the main kingdoms of life and their percentage was shown to increase with the organism complexity: according to our estimates, 12, 3, and 2% of the proteins in eukaryotic, bacterial, and archean proteomes are totally disordered for 19 archean, 159 bacterial, and 17 eukaryotic proteomes, respectively (Bogatyreva, Finkelstein, & Galzitskaya 2006); in the other estimations about one-third of all eukaryotic proteins were predicted to be disordered (Dunker, Obradovic, Romero, Garner, & Brown 2000; Liu & Rost, 2001; Tompa, 2003; Xie et al., 2007). In addition to proteins which are completely disordered, there are ordered proteins with some local disordered regions (from whole disordered domains to a few disordered amino acid residues) (Dyson & Wright, 2005). Thus, there is a continuous range between completely ordered and completely disordered proteins where intermediate cases are rather common (Dyson & Wright, 2005). Intrinsically disordered proteins have certain properties that distinguish them from proteins with the welldefined structures (Fong et al., 2009; Serdiuk, 2007): (1) they have no unique three-dimensional structure in an isolated state and can fold upon binding to their interaction partners (Draper & Reynaldo, 1999; Dunker, Brown, Lawson, Iakoucheva, & Obradovic, 2002; Fink, 2005; Gunasekaran, Tsai, Kumar, Zanuy, & Nussinov, 2003; Tompa, 2002; Wright & Dyson, 1999); (2) conformational changes in proteins with disordered regions upon binding are much larger than those in structured proteins; (3) the conformations of disordered regions in a complex are determined not only by the amino acid sequence but also by the interacting partners; (4) disordered proteins can have many different functions and can bind to many different partners using the same or different interfaces; (5) disordered proteins can accommodate larger interfaces on smaller scaffolds compared to proteins with well-defined structure (Gunasekaran et al. 2003; Gunasekaran, Tsai, & Nussinov, 2004); and (6) disordered regions have a low aromatic content and high net charge as well as low sequence complexity and high flexibility (Romero et al., 2001; Uversky, Gillespie, & Fink, 2000; Xie et al., 2007). At present, 653 (Disprot 5.9) proteins with disordered regions are known (Sickmeier et al., 2007). These proteins and domains are either entirely disordered in the native state (the so-called intrinsically disordered proteins, IDP) or have lengthy intrinsically disordered regions (IDRs). Since disordered regions of the protein chain play an important role in the protein functioning (see reviews Tompa, 2002; Wright & Dyson, 1999), much attention is being paid to their prediction. It should be noted that recently the new published methods for the prediction of disordered regions are usually meta-servers that combine multiple disorder predictors, e.g. MD (Schlessinger, Punta, Yachdav, Kajan, & Rost 2009), PONDR-FIT (Xue, Dunbrack, Williams, Dunker, & Uversky, 2010), and MFDp (Mizianty et al., 2010) or are based on the network trained [Espritz (Walsh, Martin, Di Domenico, & Tosatto, 2012), SpineD, methods based on machine