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

Figure 7

Transition state geometries for hydrogen abstraction pathways with lowest barrier.

Left: profile calculated from membrane simulation; right: profile calculated from water simulation. Calculated at B3LYP-D:6-31G/CHARMM27 level of theory. Arg212 shown explicitly and has been proposed to play a role in substrate specificity of CYP3A4. In the lowest-energy profiles generated it is observed to hydrogen bond with the O2 atom of R-warfarin in the membrane-bound simulation but not in the soluble case where Arg212 shows increased flexibility.

Figure 7