<p>The docking model is based on the work of Yang et al., 2009 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142182#pone.0142182.ref077" target="_blank">77</a>] wherein Val1951 in the sensing domain of the DOCK9 GEF (dark green ribbon) was suggested to reduce nucleotide interaction with Mg<sup>2+</sup> via steric hinderance or ‘exclusion’ and thereby destabilize nucleotide binding to cause release from the GTPase active site. <b>(A-B)</b> The crystal structure of Cdc42-GDP in complex with the DOCK9 GEF (PDB ID 2WMN) was used to predict the active site docking of (<b>C-D</b>) 6-MNA, (<b>E-F</b>) R-, S-naproxen and (<b>G-H</b>) R-, S-ketorolac. (<b>B, D, F, H</b>) The carboxyl moiety in all compounds is proposed to interact with the Mg<sup>2+</sup>, thereby reducing interaction with GDP and reducing binding affinity analogous to Val1951 (teal). R-naproxen and R-ketorolac are shown in red. 6-MNA rust, S-naproxen and S-ketorolac are shown in green. R-enantiomers show more favorable interaction with Mg<sup>2+</sup> than S-enantiomers due to rotational constraints imposed on the carboxylate by the stereocenter. For quantification of free energy of ligand binding and distances see Table G in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142182#pone.0142182.s001" target="_blank">S1 File</a>.</p
