Accurate Simulation of Ubiquinone Partition and Diffusion in a Bacterial-Like Membrane Model: Towards Reliable Estimates of the Energetics Involved in the Q-Cycle Mechanism of Cytocrome Bc1

VANESA V. GALASSI; JOAO PAULO CAMARGO DA SILVA; GUILHERME MENEGON ARANTES

San Francisco

Congreso; 58th Annual Meeting of the Biophysical Society; 2014

Biophysical Society

Cytochrome bc1 complex is an ubiquitous component of electron transfer chains in prokariotic and eukariotic organisms. It catalyzes redox reactions of ubiquinone/ubiquinol (UQ) in a pathway called Q-cycle. We are performing computer simulations with molecular mechanical and hybrid quantum mechanical (QM) potentials in order to understand the energetics of several steps involved in this cycle. To start with, we have built and equilibrated a realistic model of a bacterial-like inner membrane, a mixture of phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) 3:1, both with palmitoyiloleoyl chains, using the novel CHARMM36 parameters. We have also parametrized tetraoleoyl cardiolipin (CL) and performed simulations of PE-PC bilayers with 10% CL. We have built a new potential for UQ by improving partial charges and torsional parameters from previously available UQ potentials [1,2]. In comparisons to high-level QM torsional and water or methane interaction profiles, our new UQ potential shows significant improvement over the previous potentials. Thus, we performed potential of mean force calculations with our new UQ potential to obtain the free energy of water/membrane partition of UQ with different isoprenil chain lengths and validated our model by comparison with experimental data [3]. This accurate ubiquinone and bacterial membrane model, is now in use to study the diffusion pathway of UQ through the membrane into Cytochrome bc1 and within its two UQ binding sites.[1] A. Aird et al. Biophysical Journal, 2007, 92(1), 23-33.[2] K. Kaszuba et al. Theor Chem Acc, 2013, 132, 1370-1383.[3] R. Fato et al. Biochemistry, 1996, 35, 2705-2716.