Many template-based docking predictions fall into acceptable quality category, according to the CAPRI criteria, even for highly inaccurate proteins (5 C 6 ? RMSD), although the number of such models (and, consequently, the docking success rate) drops significantly for models with RMSD 4 ?. criteria, even for highly inaccurate proteins (5 C 6 ? RMSD), although the number of such models (and, consequently, the docking success rate) drops significantly for models with RMSD 4 ?. The results show that the existing docking methodologies can be successfully applied to protein models with a broad range of structural accuracy, and TDZD-8 the template-based docking is much less sensitive to inaccuracies of protein models than the free docking. and 6.7% in human.1 Thus, the structure of most known protein interactions has to be determined by computational PPI modeling (protein docking).2 Current protein docking methods generally belong to two major categories: (a) free docking, where relative positions of the two proteins are sampled and systematically, generally, no given information other than the structure of the two proteins, is assumed to be TDZD-8 known of the protein-protein complex is characterized by a set of pairwise contacts =?{(of the receptor (the larger protein in the complex) and of the ligand (the smaller protein in the complex) interacting across the interface. The similarity between configurations and (fraction of shared contacts), can be calculated as the Jaccard index of the two sets and between similar docking modes does not have substantial variation from complex to complex (see Supporting Information, Figure S1). The fraction of the native contacts (fnat), in CAPRI definition,31 Rabbit polyclonal to ITM2C cannot be directly used TDZD-8 for pairwise comparison of model-model docking predictions because of the required reference set of the native interface residues/contacts, which varies in different docking models. In this regard, FSC(Eq. 2) can be considered a modification of fnat, such that the number of shared contacts is normalized by the number of contacts in either of the two models, making the score symmetric (FSC= FSC(Eq. 2) the FSC-score needs an additional rule for finding contacts shared by the two complexes with different monomers. We considered the template contacts (values suggest preservation of the docked monomers position with the increasing model inaccuracy. Such trend is similar for both good (acceptable and higher quality) and bad (incorrect) predictions with a slightly less pronounced effect for the latter (Figure S7), and with a fraction of the bad predictions (1.6% for the 1 ? models, to 6.1% for the 6 ? models) losing native contacts completely (minor peak in distributions at ~0, in Figure S7). Open in a separate window Figure 4 Comparison of free and template-based docking of models predictions with the docking of X-ray structures predictions in terms of fraction of shared contactsFor each level of the model TDZD-8 accuracy and each complex in the set, docking prediction of the X-ray structure with the maximum fraction of shared contacts FSCij (Eq. 2) was used for comparison with each of the top 1000 free docking of the models predictions. The resulting 1651000 FSCscores were plotted as gray box-and-whisker diagrams, separately for each distortion level (A). Box whiskers and areas contain 25 C 75 % and 5 C 95 % of data, respectively (outliers not shown). Lower bounds (blue) were estimated using 1000 randomly selected matches from the top 100,000 free docking of the models predictions. Upper bounds (red) were evaluated on a 1000-matches subset among 100,000 free docking of the models predictions with the maximum FSCij similarity to the top 1000 docking of the X-ray structures predictions. Darker and lighter areas of the upper and lower bounds correspond to whiskers and boxes respectively, and the dashed lines TDZD-8 indicate medians. For the template-based docking (B), only pairs of the model and the X-ray predictions that share the same template (dark gray bars in Figure 3, and numbers at the whiskers in this figure) were considered. Upper and lower limits for the template-based.