Figure 1. Results for the penicillopepsin test calculations using the MLHL target function (experimental phase information).

In all panels, black lines refer to DEN refinements, whereas red lines refer to noDEN refinements. (a) Showing how the (γ, w_DEN) grid-search determines the values that give the best R_free value for the synthetic diffraction data set at d_min=4.5 Å. The R_free value is contoured using values calculated on a 6 × 5 grid (marked by small ‘+’ signs) where the parameter γ was [0.0, 0.2, 0.4, 0.06, 0.8, 1.0] and w_DEN was [3, 10, 30, 100, 300]. For each parameter pair we performed an extensive refinement protocol (Online Methods). The contour plot shows clear minima and maxima with the value of R_free varying from 0.295 to 0.35. (b) Showing the contour map of the all-atom RMSD between the target structure 3app and the DEN-refined structure (repeat with the lowest R_free value) at each grid point in (a). Again there are clear minima and maxima with the RMSD varying from 1.47 to 1.60 Å. (c) Showing the R_free value as a function of d_min of the four synthetic diffraction data sets. Thick lines mark the lowest R_free values obtained from the ten repeats using the optimum parameters; the corresponding thin lines mark the highest R_free values. For the synthetic data sets at d_min ≥ 4 Å, DEN refinement performs much better than noDEN reaching lower R_free values. (d) Showing how Zemla’s GDT (<1 Å) score¹⁷, which measures structural similarity to the target structure 3app, varies as a function of d_min; the dashed line indicates the GDT score of the initial model. At all resolutions, DEN out-performs noDEN and gives GDT values that are more favorable (higher) than those of the initial structure. (e) Showing how the RMSD of all atoms to the 3app target structure varies vs. d_min of the four synthetic diffraction data sets. Once again DEN gives lower RMSD values, especially at low-resolution. The DEN-refined models used in (d), and (e) correspond to the best models among ten repeats as assessed by R_free (black dots in panel (c)). Black ellipses indicate on the contour maps values corresponding to the structure with lowest R_free value obtained for d_min=4.5Å.