The dimer interaction site lies within two of the FAD-binding sites of two TrxR protomers and is formed by 60 amino acids, allowing different interaction patterns with potential ligands. Eleven fragments were found that bind to the dimer interaction site (Figure ). The amino acid residues of Arg266, Gly279 and Thr291 play important roles in the formation of the binding site and the latter two are showing hydrogen bonds to two of the bound fragments. Also, all fragments bind symmetrically mirrored in the pocket regarding the other protomer. For clarity, only one binding mode per fragment is shown in Figure A. As stated above, the NADPHand FAD-binding domains must rotate against each other to allow the reaction cascade and binding of Trx. By stabilising the FO conformation through a ligand in the dimer interaction site which connects the protomers, the functionality of the enzyme might be inhibited. Further investigation of this binding pocket and the influence of ligand binding on the conformational change are needed. An example of one binding fragment in the dimer interaction site is shown in the upper left corner of Figure . This comparatively small fragment has six possible exit vectors. Since it shows a hydrogen bond to Gly279, only five of them might be used for further development to keep this interaction. A great number of possible follow-up compounds are available for this fragment with some exemplary possible substituents for extension at each exit vector shown in the blue boxes. Larger follow-up compounds are shown in the yellow boxes. Also, it might be possible to alter the scaffold of the fragment easily with some possibilities shown in the red box of Figure . These scaffold modifications stem from the other members of the respective cluster having similar shape and feature alignments.