*2.1. Structural and Dynamical Properties of YqhD Enzyme*

As mentioned in the Introduction section, the crystal structure has a modified NADPH(OH)<sup>2</sup> cofactor, but in this work, simulations were performed for the YqhD homodimer with oxidized NADP and reduced NADPH cofactors (separately) for comparison (see Figure 1 for details). First, we performed an equilibration step involving 20 ns MD simulation in isothermal-isobaric (NPT) ensemble with each state. During the equilibration step, the YqhD protein adopts a conformation suitable for the binding of NADP and NADPH cofactors. Starting with equilibrated structures, we performed five 200 ns long independent MD simulations for each state, starting with different initial velocities (generated through a random number seed) to check the structural convergence. First, analysis of structure and dynamics was done using the crystal structure as reference for three different types of structural data subsets within each state of the NADP/H-cofactor: the entire dimer, the monomers comprising dimer, and the domains (α-helical and Rossmann-type domains) within each monomer, in addition to dynamics during the simulations (see Figure 1 for cofactor-bound crystal structure of YqhD).
