Fig. 10

Overall disorder analysis of 4792 human proteins interacting with all HIV-1 proteins. Information about these host proteins was retrieved from the HIV-1 Interaction Database accessible at the National Institutes of Health: National Center for Biotechnology Information (see https://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses/hiv-1/interactions/). A PONDR^® VSL2 mean disorder score vs. PONDR^® VSL2 (%) plot. Here, each point corresponds to a query protein, coordinates of which are evaluated from the corresponding PONDR^® VSL2 data as its mean disorder score (MDS) and percent of the predicted intrinsically disordered residues (PPIDR). MDS was calculated for each query protein as a protein length-normalized sum of all the per-residue disorder scores, whereas PPIDR was calculated as a protein length-normalized number of residues with the disorder scores of at least 0.5 multiplied by 100%. Color blocks are used to visualize proteins based on the accepted classification, with red, pink/light pink, and blue/light blue regions containing highly disordered, moderately disordered, and ordered proteins, respectively. Classification is based on the accepted practice, where a PPIDR value of less than 10% is taken to correspond to a highly ordered protein, PPIDR between 10 and 30% is ascribed to moderately disordered protein, and PPIDR greater than 30% corresponds to a highly disordered protein [148, 149]. Proteins can also be grouped based on their corresponding MDS values, being classified as highly ordered (MDS < 0.15), moderately disordered of flexible (MDS between 0.15 and 0.5) and highly disordered (MDS ≥ 0.5). Dark blue or pink regions correspond to the regions, where PPIDR agrees with MDS, whereas areas in which only one of these criteria applies are shown by light blue or light pink. Numbers within these segments reflect their protein content. B CH-CDF plot, where coordinates for a protein are calculated as the average distance of its CDF curve from the CDF boundary (X axis) and its distance from the CH boundary. Protein classification is based on the quadrant, where it is located: Q1, protein predicted to be ordered by both predictors. Q2, protein predicted to be ordered to by CH-plot and disordered by CDF. Q3, protein predicted to be disordered by both predictors. Q4, protein predicted to be disordered by CH-plot and ordered by CDF. CH-CDF analysis combines results from the charge-hydropathy (CH) and cumulative distribution function (CDF) plots, which are both binary predictors of disorder. For CH, net charge is plotted versus hydropathy for each protein [150]. Due to the observation that disordered proteins tend to have high net charge and low hydropathy, disordered and ordered proteins cluster two regions of the plot. A linear boundary separates disordered and ordered proteins [150, 151]. Proteins that are disordered appear above the boundary while ordered proteins appear below [150, 151]. In the CDF-plot predictor, PONDR scores for each residue of a single protein is plotted against their frequency within the sequence. If a CDF curve of a given protein is below the order–disorder boundary, this protein is considered disordered, and protein is ordered if the CDF curve is located above this boundary [151]. Data generated by CH- and CDF-plots are then combined to generate ΔCH-ΔCDF plot, which enables rapid discrimination between flavors of disorder [152, 153]. To this end, for each query protein, ΔCH, the vertical distance of the corresponding point in CH plot from the boundary, is calculated, whereas ΔCDF is computed as the average distance between the order–disorder boundary and the CDF curve. Then, ΔCH is plotted against ΔCDF resulting in a CH-CDF plot. Proteins in the top-left quadrant are predicted to be disordered by both CH and CDF, the ones in the bottom-left are predicted to be ordered by CH and disordered by CDF, the ones in the top-right are predicted to be disordered by CH and ordered by CDF, and in the bottom-right quadrant predicted to be ordered by both [152, 153]