v/v [%] 100 mM MES-BIS-TRIS pH 6.9 75 mM LiCl, 0.03 mM Mega8, 1 mM DTT 60 0.1 mM EDTA, 23% (v/v) MeOH MPD 30 1 M benzoic acid in DMSO 10 In Molecular dynamics simulations the protonated form of the benzoic acid fragment is stable in its X-ray determined binding pose whereas the deprotonated form rotates away from its original binding pose. Over the course of a 1 µs simulation protonated benzoic acid maintains two hydrogen bonds, namely between the backbone carbonyl of Glu 121 to the hydroxyl group of the fragment and secondly between the backbone amide of Val 123 and the carbonyl of the fragment. The hydrogen bond to the backbone amide of Val 121 had been identified based on X-ray structure [6] (LS need to check the paper again). We note that the 3D structure of PKA and specifically of the ligand binding site is stabilized by the presence of the protonated form of the fragment. In absence of protonated benzoic acid, there are some local structural rearrangement in PKA as shown by computing Root Mean Square Fluctuations (RMSFs) and Root mean square distances (RMSDs) to the initial structure (SI Fig ). The deprotonated acid fragment loses two hydrogen bonds with PKA, with the side chain OH group of Glu 121 and the backbone amide proton of Val 123.