Dynamics of the Complex of Cytochrome P450 and Cytochrome P450 Reductase in a Phospholipid Bilayer: This project aims at understanding the interactions of CYP enzymes and their redox partner, namely cytochrome P450 reductase (CPR), in a phospholipid bilayer and identification of inter-protein electron transfer pathways. We investigated the interactions between models of membrane-bound CYP1A1 and CPR. We developed and reported a first ab-initio systematic protocol to build and simulate a CYP-CPR-membrane complex using Brownian dynamics (BD), coarse-grained and all-atom MD simulations.

The models from the study provided a starting point for understanding the association and dissociation of CYP and CPR in the native membrane-bound forms, the catalytic mechanism of the CYPs, and ligand access and egress in the CPR-bound form of CYP1A1. The overall results will improve the basis for accounting for CYP mediated metabolism in drug discovery and for considering CYPs as drug targets (High Performance Computing in Science and Engineering ´15 pp 255-264). The study provided important guidelines for modeling and studying protein-protein interactions in membrane using multi-scale MD simulations. Ongoing work reveals the mechanism of inter-protein electron transfer and residues involved in it. These residues can be targeted for CYP‑targeted anticancer drug design.