Parametrization of an ubiquinone force eld and simulation of membrane partition, diusion and redox potentials

VANESA V. GALASSI; GUILHERME MENEGON ARANTES

Santiago de Chile

Congreso; 10th Congress of the World Association of Theoretical and Computational Chemists; 2014

World Association of Theoretical and Computational Chemists

P { margin-bottom: 0cm; direction: ltr; color: rgb(0, 0, 0); text-align: justify; widows: 2; orphans: 2; }P.western { font-family: "Helvetica","Arial",sans-serif; font-size: 10pt; }P.cjk { font-family: "Times New Roman",serif; font-size: 10pt; }P.ctl { font-family: "Helvetica","Arial",sans-serif; font-size: 10pt; }A:visited { color: rgb(128, 0, 128); }A.western:visited { }A.cjk:visited { }A.ctl:visited { font-family: "Times New Roman",serif; }A:link { color: rgb(0, 0, 255); }A.ctl:link { font-family: "Times New Roman",serif; }Ubiquinone(UQ) is involved in the transport of charge through mitochondrial andbacterial membranes, playing an essential role in molecularrespiration. It takes part in the electron/proton transfer processescatalyzed by both respiratory complexes I (NADH:ubiquinoneoxidoreductase) and III (cytochrome bc1). This function is related toits interfasial properties: membrane affinity and diffusion, apartfrom its redox properties.Performingsimulations with these complexes require parameters that accuratelydescribe this cofactor, which correctly reproduce experimentalmembrane partitioning and diffusion, as well as red-ox potentials.Wehave built a new CHARMM compatible force field for UQ in its reducedand oxidized forms, by improving partial charges, Lennard Jones andtorsional parameters, in comparisons to high-level QM torsional andintermolecular interaction profiles. For validation of the model, weperformed potential of mean force calculations for the insertion ofUQ with different isoprenil chain lengths in amitochondrial/bacterial-like membrane model (a bilayer made of amixture of POPE-POPG 3:1), obtaining the free energy ofwater/membrane partition and compared it with experimental data.Diffusion coefficients were obtained from mean squared displacementcalculations at the plane of preferred localization in the membranetransversal axis. We also performed calculations with quantumchemical/molecular mechanics (QC/MM) hybrid potentials to estimate UQred-ox potentials in the membrane.Thisubiquinone-membrane model, is now in use to study the diffusionpathway of UQ through the membrane into cytochrome bc1.