<p>NSAID docking on Rac1 was modeled on the ‘magnesium exclusion’ model proposed based on the crystal structure of Cdc42 complexed to DOCK9 GEF [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142182#pone.0142182.ref077" target="_blank">77</a>] and subsequently also validated for the crystal structure of Rac1 complexed to DOCK2 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142182#pone.0142182.ref078" target="_blank">78</a>]. <b>(A-B)</b> The crystal structure of Rac1-GDP in complex with the DOCK9 GEF (PDB ID 2YIN) was used to predict the active site docking of 6-MNA, (<b>C-D</b>) R-, S-naproxen and (<b>E-F</b>) R-, S-ketorolac. The carboxyl moiety in all compounds is proposed to interact with the Mg<sup>2+</sup>, thereby reducing interaction with GDP and binding affinity analogous to Val1539 (teal) in the DOCK2 GEF (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142182#pone.0142182.g009" target="_blank">Fig 9</a> for detail). 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
