Figure 8.
Water density at the PM P450BM3 substrate channel, with the reference structure averaged from the MD simulation. (A) Dextromethorphan is positioned for N-dealkylation. MDMA is positioned for N- and O-dealkylation in (B) and (C). Astemizole is positioned for N- and O-dealkylation in (D) and (E) and C-H hydroxylation in (F). (G) Diclofenac, (H) S-warfarin, and (I) R-warfarin are positioned for C-H hydroxylation. T268, located at the distal side of the heme (helix I) and believed to play a role in proton delivery and oxygen activation, is also shown. Water density is relatively lower in the presence of palmitic acid, naproxen, lovastatin, nicotine, and cotinine (Fig. S6).