Unstructural biology of the Dengue virus proteins.

In this study, we used a wide spectrum of bioinformatics techniques to evaluate the extent of intrinsic disorder in the complete proteomes of genotypes of four human dengue virus (DENV), to analyze the peculiarities of disorder distribution within individual DENV proteins, and to establish potential roles for the structural disorder with respect to their functions. We show that several proteins (ER, E, 1, 2A and 4A) are predicted to be mostly ordered, whereas four proteins (C, 2k, NS3 and NS5) are expected to have high disorder levels. The profiles of disorder propensities are similar across the four genotypes, except for the NS5 protein. Cleavage sites are depleted in polymorphic sites, and have a high propensity for disorder, especially relative to neighboring residues. Disordered regions are highly polymorphic in type 1 DENV but have a relatively low number of polymorphic sites in the type 4 virus. There is a high density of polymorphisms in proteins 2A and 4A, which are depleted in disorder. Thus, a high density of polymorphism is not unique to disordered regions. Analysis of disorder/function association showed that the predominant function of the disordered regions in the DENV proteins is protein-protein interaction and binding of nucleic acids, metals and other small molecules. These regions are also associated with phosphorylation, which may regulate their function.