Fig. 7: Short residence time inhibitor SB203580.
From: Decisive role of water and protein dynamics in residence time of p38α MAP kinase inhibitors
a Structure of SB203580 is chemically diverse from 1 or 2. b Biological activity of SB203580 in selected assays. (ADP-Glo, ELISA, DLD1, HCT116, FP: n = 3; SPR n = 2) c WaterMap ligand scores based on the ligand displaced waters in the MSM derived metastable state derived conformations (see Fig. 6 for further details). *P < 0.05 (two-tailed t-test). d Displaced waters by SB203580 in the SB2-S2 conformation II (hydration sites with overlap factor >0.5 with the ligand are shown). The hydration sites are shown in spheres together with their estimated energies (kcal/mol, ΔG relative to bulk water) and are colored with the green-brown-red scale from low to high energy. SB203580 is shown with ball and stick representation (nonpolar hydrogens are hidden). e Buried surface areas of 1, 2 and SB203580. Simulation data was analysed for each 1 ns i.e., data in e consist of 91,328, 86,505, and 91,090 individual data points for 1, 2 and SB203580, respectively. The black horizontal line in the box represents the median. Box displays the quartiles of the dataset (25–75%) and whiskers the rest of the data with maximum 1.5 IQR. Outliers are indicated with black diamonds. Source data are provided as a Source Data file.
