Dynathor: Dynamics of the Complex of Cytochrome P450 and Cytochrome P450 Reductase in a Phospholipid Bilayer

The Dynathor project aims at understanding the interaction of cytochrome P450 (CYP, P450) enzymes and their redox partner, cytochrome P450 reductase (CPR), in a phospholipid bilayer. Through simulation studies on the HLRS CRAY systems (initially XE6, later on XC40), we investigated the interactions of models of membrane-bound P450s (CYP51 and CYP1A1) and CPR. A model of membrane-bound T. brucei CYP51 and the human CPR was successfully built and simulated for 217.5 ns. A model of human CYP1A1 and the human CPR in a phospholipid bilayer was also built and is being simulated. These models can be used as starting points to understand the selectivity of the interactions of CYPs with CPR in the native membrane-bound forms, and thus may aid drug discovery projects.