Improvement of Cyclophosphamide Activation by CYP2B6 Mutants: from in Silico to ex Vivo

Data Supplement

Files in this Data Supplement:

• Data Supplement - Video 1. Molecular dynamic (MD) simulation (2ns) of the CPA in a wild type model of CYP2B6. MD was performed under Gromacs. The video (length 16 sec, mpg format, 2.70 Mo) was generated using Movie Maker under VMD. A smooth filter has been applied to make a smooth rendering of the animation. Protein is shown in new cartoon representation. The non mutated residues I114 and V477 are shown in orange licorice representation. CPA and heme are shown in licorice representation. The active site is viewed from the B-C loop along the main channel (family 2 subclass). As discussed in the paper, in the wild type model, CPA is free to move in the active site. A change in orientation of CPA can be observed starting from the first third of the simulation. One can also notice the larger movements of the 2 branches of the CPA.
• Data Supplement - Video 2. Molecular dynamic simulation (2ns) of the CPA in a double muted (I114V/V477W) model of CYP2B6. MD was performed under Gromacs. The video (length 16 sec, mpg format, 2,54 Mo) was generated using Movie Maker under VMD. A smooth filter has been applied to make a smooth rendering of the animation. Protein is shown in new cartoon representation. The mutated residues V114 and W477 are shown in green licorice representation. CPA and heme are shown in licorice representation. The active site is viewed from the B-C loop along the main channel (family 2 subclass). Once mutated, active site seems narrower for the CPA, leading to restriction of motion as compared to the wild type. CPA seems to be stacked on the I helix by W477 side chain.