Accurate parametrization of ubiquinone to obtain a Charmm36 compatible model

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

Córdoba

Congreso; XLII Annual Meeting of the Argentinean Biophysical Society; 2013

Sociedad Argentina de Biofísica

P { margin-bottom: 0.21cm; direction: ltr; color: rgb(0, 0, 10); line-height: 115%; widows: 2; orphans: 2; }P.western { font-family: "Calibri",serif; font-size: 11pt; }P.cjk { font-family: "WenQuanYi Micro Hei"; font-size: 11pt; }P.ctl { font-size: 11pt; }A:link { color: rgb(0, 0, 255); }Cytochromebc1 complex is an ubiquitous component of electron transfer chains inprokariotic and eukariotic organisms. It catalyzes redox reactions ofubiquinone/ubiquinol (UQ) in a pathway called Q-cycle. We areperforming computer simulations with molecular mechanical and hybridquantum mechanical (QM) potentials in order to understand theenergetics of several steps involved in this cycle. To start with, wehave built and equilibrated a realistic model of a bacterial-likeinner membrane, a mixture of phosphatidylethanolamine (PE) andphosphatidylglycerol (PG) 3:1, both with palmitoyiloleoyl chains,using the novel CHARMM36 parameters. We have also parametrizedtetraoleoyl cardiolipin (CL) and performed simulations of PE-PCbilayers with 10% CL. We have built a new potential for UQ byimproving partial charges and torsional parameters from previouslyavailable UQ potentials (Schulten and Tietz 2007, Róg 2013). Incomparisons to high-level QM torsional and water or methaneinteraction profiles, our new UQ potential shows significantimprovement over the previous potentials. Thus, we performedpotential of mean force calculations with our new UQ potential toobtain the free energy of water/membrane partition of UQ withdifferent isoprenil chain lengths and validated our model bycomparison with experimental data (Lenaz 1996). This accurateubiquinone and bacterial membrane model, is now in use to study thediffusion pathway of UQ through the membrane into Cytochrome bc1 andwithin its two UQ binding sites.