Bioinformatics
Heidelberg Institute for Theoretical Studies
Molecular and Cellular Modeling
Cytochrome P450 (CYP) enzymes are key players in the metabolism of drugs and the biosynthesis of compounds such as steroids. Many are also drug targets. Cytochrome P450 reductases (CPR) transfer two electrons to CYPs. We are applying molecular simulation techniques to investigate the mechanism and determinants of electron transfer to membrane-bound eukaryotic CYPs. We have developed a multiresolution protocol, using Brownian dynamics and molecular dynamics (MD) simulations, to simulate membrane-bound CYP-redox protein complexes. This has enabled us to compute electron transfer pathways and rates consistent with experimental data. Here, we study CYP2B4, the eukaryotic CYP that has been most extensively characterized by biophysical and biochemical techniques. We will perform MD simulations of CYP2B4 and CPR in a membrane to investigate how the structure, dynamics and function are affected by the large conformational dynamics of CYP2B4 and truncation of the interdomain linker of CPR.