Conformational dynamics of CYP3A4 demonstrate the important role of Arg212 coupled with the opening of ingress, egress and solvent channels to dehydrogenation of 4-hydroxy-tamoxifen

► MD-refined P450 structures identify the importance of channels in CYP3A4 docking. ► A unique configuration is identified involving Arg212 in the dehydrogenation of 4OHT. ► CYP3A4 and CYP3A4-R212A show a decreased rate of dehydrogenation versus oxygenation.