Abstract
We describe a transferable multiresolution computational approach to build and simulate complexes of two proteins—cytochrome P450 (CYP) and CYP reductase (CPR)—in a membrane bilayer using Brownian dynamics (BD) and all-atom molecular dynamics (MD) simulations. Our benchmarks showed that MD simulations of these systems could be carried out efficiently with up to 180 nodes (4320 cores) using NAMD version 2.12. Our results provide a basis for defining the ensemble of electron transfer-competent arrangements of CYP-CPR-membrane complexes and for understanding differences in the interactions with CPR of different CYPs, which have implications for CYP-mediated drug metabolism and the exploitation of CYPs as drug targets. This work was carried out in the DYNATHOR (DYNAmics of THe complex of cytOchrome P450 and cytochrome P450 Reductase in a phospholipid bilayer) project at HLRS.
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Acknowledgements
We gratefully acknowledge the financial support of the Klaus-Tschira Foundation, Heidelberg University Frontiers Innovation Fund, the BIOMS Center for Modelling and Simulation in the Biosciences (Go.M.), and the German Academic Exchange Service (Gh.M., P.N.). Finally, we thank HLRS for providing computing time for the DYNATHOR project.
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Mukherjee, G., Nandekar, P., Mustafa, G., Richter, S., Wade, R.C. (2019). A Multi-resolution Approach to the Simulation of Protein Complexes in a Membrane Bilayer. In: Nagel, W., Kröner, D., Resch, M. (eds) High Performance Computing in Science and Engineering ' 18. Springer, Cham. https://doi.org/10.1007/978-3-030-13325-2_32
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DOI: https://doi.org/10.1007/978-3-030-13325-2_32
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