Fig 1.
Distribution of |Δdn| and σMOD values.
Distributions of the |Δdn| (A) and σMOD (B) values observed in the AS models for the four HDDR groups of MODELLER. Beside the names of the restraints groups, their mean values are reported.
Fig 2.
Modeling with uniform σ values.
Average GDT-HA (A) and lDDT (B) scores of the AS models as a function of the uniform σ value (ranging from 0.01 to 7.0 Å) applied to their HDDRs. The horizontal dashed lines represent the average scores obtained with the original σMOD values.
Fig 3.
The use of optimal parameters for HDDRs improves 3D modeling quality.
(A) and (B) GDT-HA and lDDT scores of the AS models built with σMOD (reported on the x-axis) and with optimal |Δdn| (y-axis) values. (C) and (D) GDT-HA and lDDT scores for the AM models obtained with MODELLER-generated (x-axis) and optimal (y-axis) HDDRs.
Table 1.
3D modeling qualities of the AS single-template models built with optimal HDDRs and alignments.
Table 2.
3D modeling qualities of the AM multiple-template models built with optimal HDDRs and alignments.
Fig 4.
Correlation between σMOD and |Δdn| values in the AS models.
(A) Distributions for the PCCs between σMOD and |Δdn| values for the HDDRs of the 225 AS models. (B) PCC distributions for the AS models rebuilt with TM-align alignments.
Fig 5.
Effect of |Δdn| perturbation on 3D modeling.
(A) and (B) Average GDT-HA and lDDT scores of the AS models as a function of their average Cα-Cα PCCMODEL values (see the “Methods” section). (C) and (D) Similar data obtained for the multiple-templates AM models. In (A) through (D), the dashed horizontal lines represent the average quality scores obtained by the default MODELLER.
Fig 6.
Average quality scores of the models of the analysis set as a function of the wSP with which the DOPE potential has been included in the objective function of MODELLER.
(A) to (C) Quality scores of the AS models. (D) to (F) Quality scores of the AM models. (A) through (F) The horizontal dashed lines correspond to the scores obtained when modeling with MODELLER-generated (blue color) or optimal (orange) HDDRs without the use of DOPE.
Table 3.
3D modeling qualities of the AS single-template models built by including DOPE in the objective function of MODELLER.
Fig 7.
Effects on 3D modeling of optimal σ values and DOPE.
Effects brought by the use |Δdn| values and DOPE (with a wSP of 3.5) on the 3D modeling of target 1yd0_chain_A (colored in orange) using as a template 1yd6_chain_D (pale green). In the model built using the default MODELLER (colored in white, superposed to its target and template on the left image) the three helices shown in the image are positioned in the same conformation of the template. In the model built employing |Δdn| values and DOPE with a wSP of 3.5 (pale cyan, shown on the right) the helices are repositioned in a native-like conformation. Figures rendered with PyMOL [39].
Fig 8.
DOPE energy landscapes for target (A) 1dk8_chain_A and (B) 1lam_chain_A modeled using different strategies. 100 decoys were built for each strategy and their GDT-HA scores are plotted here against their DOPE energies. The strategies with the “MOD-ST” prefix adopted MODELLER-generated HDDRs and a single template (blue-shaded dots), those with the “OPT-ST” prefix adopted optimal HDDRs and a single template (orange-shaded dots) and those with the “OPT-MT” prefix adopted optimal HDDRs and multiple templates (red-shaded dots). The “SP-X.X” suffix indicates the use of DOPE with a wSP of X.X. The green dots correspond to the DOPE-minimized native target structure.
Table 4.
3D modeling qualities of the AM multiple-template models built by including DOPE in the objective function of MODELLER.