Fig. 5: Evaluation of Prosit-XL for analyzing 3D protein structures and protein-protein interactions.

a Unique number of identified interactions; inter-protein-protein interaction (green), intra-protein-protein interaction (orange), and intra-protein-protein connection (dark blue). The bars represent the number of PPIs and self-links for human-human, human-viral, and viral-viral interactions identified by data-driven rescoring of xiSEARCH results (left) and as reported in the original study by XlinkX (right). Source data are provided in Supplementary Data 5. b Venn diagrams comparing shared PPIs and UXLs between the rescoring results and the XlinkX results. The top left Venn diagram shows the PPI-level comparison for all types of PPIs. In parentheses, the total number of UXLs detected for the corresponding PPIs is shown. Top right Venn shows the UXL-level comparison for UXLs extracted from shared PPIs only (intersection in top left Venn). The bottom Venn diagram compares the UXLs in the unfiltered search results from xiSEARCH with the UXLs that were uniquely identified by XlinkX (combination of unique PPIs and missed UXLs from shared PPIs). c Correlation between UXL counts per PPI by rescoring versus XlinkX, separated by interaction type for human-human (blue), human-viral (orange), and viral-viral (green). The diagonal and regression lines are shown in dashed black and solid blue, respectively. The shaded blue area around the regression line indicates the 95% confidence interval of the regression. Data are presented as mean ± SEM for the shared set of PPIs identified by both methods: rescoring shows a mean of 4.54 ± 0.33 UXLs per PPI, and XlinkX shows a mean of 3.52 ± 0.25 UXLs per PPI. d Network representations of the interactions among the viral proteins UL25, and UL83, as well as the human protein DDX3X, comparing results from rescoring and XlinkX. Solid green, blue, and orange lines present confidently identified UXLs by rescoring or XlinkX that were gained, shared, or lost when comparing rescoring to XlinkX, respectively. The network was visualized using xiView⁵⁴ and modified. e Structural representations of the post-fusion (PDB: 7KDD) and the pre-fusion (PDB 7KDP) conformations of the viral proteins UL55. Lines indicate confidently identified UXLs by rescoring, highlighting the distance of the interacting sites. Colors represent individual interactions mapped onto the structure. The residue alpha carbons were depicted as gray spheres. The UXL distances shown were calculated using PyMOL.