Fig. 2: Protonation pathways and modulation of proton transfer barriers.
a Proton pathways from MD simulations of Nqo12ΔTH. Top inset: MD snapshot showing water-mediated connectivity from Lys329 to Lys385 and conserved polar residues stabilising the proton pathways. Bottom inset: The Glu132/Arg163 - Asp166/Lys216 ion-pair conformation in the WT (cyan) and E132Q (orange) variants. b Proton pathways from MD simulations of Nqo13. Top inset: MD snapshot of water-mediated connectivity from Lys235 to Glu377 via His292, and conserved polar residues stabilising the proton pathway. Bottom inset: the Glu123/Lys204 ion-pair conformation in WT (cyan) and E123Q (orange) variants. c, e Ion-pair dynamics and d, f hydration level along the proton pathways in the WT and E132Q/E123Q variants of Nqo12ΔTH (c, d) and Nqo13 (e, f); symbols in (d, f) refer to the pathway region indicated in panel (a) and (b), respectively. g, i Free energy profiles of proton transfer along the proton channel in the WT (blue) and E132Q (E123Q, orange) variants of (g) Nqo12ΔTH and (i) Nqo13. h, j Modulation of proton transfer barrier with ion-pair distance based on QM/MM calculations (black dots) and a fit from a theoretical model (see Supplementary Information). Inset: dissociation of the ion-pair induces an electric field (green dots) along the proton pathways. Data are provided in the Source Data file.
