*4.2. Modeling of NADP/H Cofactor*

In the crystal structure of YqhD homodimer, [7] NADP cofactor is present as NADPH(OH)<sup>2</sup> (see Figure 1b), with modification at the C5 and C6 positions of the nicotinamide moiety. The native oxidized cofactor (NADP) was modeled by removing the hydroxyl moieties at the fifth and sixth positions in the nicotinamide ring. The reduced cofactor (NADPH) was prepared by modifying the oxidation state of the C4 atom of the nicotinamide ring. Forcefield parameters come from CHARMM 36 force field [34] for Zn2+, NADP, and NADPH cofactors. Throughout this paper, NADP/H is used to signify the NADPH cofactor generally, whether in its oxidized (NADP<sup>+</sup> ) or reduced (NADPH) state. When a specific oxidation state is indicated, NADP and NADPH are specified.
