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A Multiscale Approach to Modelling Drug Metabolism by Membrane-Bound Cytochrome P450 Enzymes

Figure 3

Positioning of CYP3A4 in the lipid bilayer from atomistic MD simulations.

This configuration was generated from unbiased coarse grained simulations, in which a mixed POPC/POPE bilayer was self-assembled around the protein. The transmembrane helix spans the bilayer, with the A-anchor and F′ and G′ helices buried in the hydrophobic region of the membrane. This snapshot corresponds to the position of the protein with R-warfarin bound following conversion to full atomistic resolution, equilibration and simulation. Inset: active site region containing Compound I (Cpd I) and R-warfarin (WARF). The protein is shown in cartoon representation coloured by helix, lipids are shown in transparent grey stick representation, with the phosphate particles shown as orange transparent spheres. R-warfarin and Compound I are both shown in stick representation.

Figure 3