Hree independent variables (the same number as the Euler representation). The

Hree independent variables (the same number as the Euler representation). The angular distance a of a 3D rotation is equivalent to the angle in the axis-angle representation and is related to the trace (tr) of the rotation matrix T: r(T){1?2 ! ??aT arccosAngular Distance in Protein-Protein MedChemExpress ASA-404 DockingFigure 5. IRMSD’s of the best predictions for the ADX48621 chemical information standard 66 rotational sampling run and the hybrid-resolution run, for the top 100 (top panel) and top 1000 (bottom panel) predictions. doi:10.1371/journal.pone.0056645.gAngular Distance in Protein-Protein Docking?Figure 6. Success rate for 156 and 66 rotational sampling, and for 66 rotational sampling with 196 angular distance pruning or 6 A RMSD pruning. doi:10.1371/journal.pone.0056645.gFigure 7. Average hit count for 156 and 66 rotational sampling, and for 66 rotational sampling with 196 angular distance pruning or ?6 A RMSD pruning. doi:10.1371/journal.pone.0056645.gAngular Distance in Protein-Protein DockingFigure 8. Success rate for 156 and 66 rotational sampling, the Intercept and Slope funnel properties (based on 10 closed neighbors using angular distance), and the scores and properties combined in a weighted linear function (training and testing using 22-fold cross validation). doi:10.1371/journal.pone.0056645.gThus we can express the rotation of a docking prediction specified by three Euler angles as a rotation matrix, from which we can then obtain the angular distance a between this prediction and the starting ligand orientation. The angular distance between the rotations of two docking predictions i and j, which are specified by two rotation matrices Ti and Tj respectively, is defined as: 3 2 n? 1 o tr Tj Ti {1 5 Da(i,j) arccos4ZDOCK score). We use this complex as an example because its top ZDOCK prediction is the closest to the native complex of all test cases in our benchmark. It is clear that the angular distance and RMSD are correlated. The correlation is particularly strong for shorter distances, which is the region that we are concerned with for most purposes.Hybrid-resolution Docking??We explored the possibility of reducing the computational cost of protein-protein docking by an approach consisting of two stages with different angular resolutions (Figure 2). A two-stage approach with different translational resolutions was explored previously in context of rigid-body protein-protein docking by Vakser and coworkers [4]. We argue that a first low-resolution stage can identify the regions in the angular space that contain near-native predictions. The second stage then refines the most promising regions using high-resolution sampling. Here we show results of a hybrid 15u/6u run. For each complex, we first took the 400 top predictions from a 15u sampling run. This corresponded to roughly 10 of the total number of 4392 predictions. We followed this with a 6u sampling run in which we only considered those angle sets that were within 10u of the 400 predictions identified in the first stage. Generating this reduced 6u angle list is computationally inexpensive as we used pre-computed lists of nearest neighbors based on angular distance defined by Equation 5. The average number of angle sets retained in the 6u run was 7173, resulting in an average total number of 11,565 angle sets (4392+7173) that needed to be evaluated. This corresponds toThe inverted matrix T21 (which for rotation matrices is identical to the transpose) is the rotation in the opposite direction of T. The product (T.Hree independent variables (the same number as the Euler representation). The angular distance a of a 3D rotation is equivalent to the angle in the axis-angle representation and is related to the trace (tr) of the rotation matrix T: r(T){1?2 ! ??aT arccosAngular Distance in Protein-Protein DockingFigure 5. IRMSD’s of the best predictions for the standard 66 rotational sampling run and the hybrid-resolution run, for the top 100 (top panel) and top 1000 (bottom panel) predictions. doi:10.1371/journal.pone.0056645.gAngular Distance in Protein-Protein Docking?Figure 6. Success rate for 156 and 66 rotational sampling, and for 66 rotational sampling with 196 angular distance pruning or 6 A RMSD pruning. doi:10.1371/journal.pone.0056645.gFigure 7. Average hit count for 156 and 66 rotational sampling, and for 66 rotational sampling with 196 angular distance pruning or ?6 A RMSD pruning. doi:10.1371/journal.pone.0056645.gAngular Distance in Protein-Protein DockingFigure 8. Success rate for 156 and 66 rotational sampling, the Intercept and Slope funnel properties (based on 10 closed neighbors using angular distance), and the scores and properties combined in a weighted linear function (training and testing using 22-fold cross validation). doi:10.1371/journal.pone.0056645.gThus we can express the rotation of a docking prediction specified by three Euler angles as a rotation matrix, from which we can then obtain the angular distance a between this prediction and the starting ligand orientation. The angular distance between the rotations of two docking predictions i and j, which are specified by two rotation matrices Ti and Tj respectively, is defined as: 3 2 n? 1 o tr Tj Ti {1 5 Da(i,j) arccos4ZDOCK score). We use this complex as an example because its top ZDOCK prediction is the closest to the native complex of all test cases in our benchmark. It is clear that the angular distance and RMSD are correlated. The correlation is particularly strong for shorter distances, which is the region that we are concerned with for most purposes.Hybrid-resolution Docking??We explored the possibility of reducing the computational cost of protein-protein docking by an approach consisting of two stages with different angular resolutions (Figure 2). A two-stage approach with different translational resolutions was explored previously in context of rigid-body protein-protein docking by Vakser and coworkers [4]. We argue that a first low-resolution stage can identify the regions in the angular space that contain near-native predictions. The second stage then refines the most promising regions using high-resolution sampling. Here we show results of a hybrid 15u/6u run. For each complex, we first took the 400 top predictions from a 15u sampling run. This corresponded to roughly 10 of the total number of 4392 predictions. We followed this with a 6u sampling run in which we only considered those angle sets that were within 10u of the 400 predictions identified in the first stage. Generating this reduced 6u angle list is computationally inexpensive as we used pre-computed lists of nearest neighbors based on angular distance defined by Equation 5. The average number of angle sets retained in the 6u run was 7173, resulting in an average total number of 11,565 angle sets (4392+7173) that needed to be evaluated. This corresponds toThe inverted matrix T21 (which for rotation matrices is identical to the transpose) is the rotation in the opposite direction of T. The product (T.