Version 1
: Received: 14 November 2022 / Approved: 15 November 2022 / Online: 15 November 2022 (09:50:18 CET)
How to cite:
Mandado, M.; Alvarado, R.; Cardenas, G.; Nogueira, J.J.; Ramos-Berdullas, N. On the Permeation of Polychlorinated Dibenzodioxins and Dibenzofurans through Lipid Membranes: Classical MD and Hybrid QM/MM-EDA Analysis. Preprints2022, 2022110283. https://doi.org/10.20944/preprints202211.0283.v1
Mandado, M.; Alvarado, R.; Cardenas, G.; Nogueira, J.J.; Ramos-Berdullas, N. On the Permeation of Polychlorinated Dibenzodioxins and Dibenzofurans through Lipid Membranes: Classical MD and Hybrid QM/MM-EDA Analysis. Preprints 2022, 2022110283. https://doi.org/10.20944/preprints202211.0283.v1
Mandado, M.; Alvarado, R.; Cardenas, G.; Nogueira, J.J.; Ramos-Berdullas, N. On the Permeation of Polychlorinated Dibenzodioxins and Dibenzofurans through Lipid Membranes: Classical MD and Hybrid QM/MM-EDA Analysis. Preprints2022, 2022110283. https://doi.org/10.20944/preprints202211.0283.v1
APA Style
Mandado, M., Alvarado, R., Cardenas, G., Nogueira, J.J., & Ramos-Berdullas, N. (2022). On the Permeation of Polychlorinated Dibenzodioxins and Dibenzofurans through Lipid Membranes: Classical MD and Hybrid QM/MM-EDA Analysis. Preprints. https://doi.org/10.20944/preprints202211.0283.v1
Chicago/Turabian Style
Mandado, M., Juan J. Nogueira and Nicolás Ramos-Berdullas. 2022 "On the Permeation of Polychlorinated Dibenzodioxins and Dibenzofurans through Lipid Membranes: Classical MD and Hybrid QM/MM-EDA Analysis" Preprints. https://doi.org/10.20944/preprints202211.0283.v1
Abstract
The permeation of dioxin-like pollutants, namely, chlorinated dibenzodioxins and dibenzofurans, through lipid membranes has been simulated using classic molecular dynamics (CMD) combined with the umbrella sampling approach. The most toxic forms of chlorinated dibenzodioxin and dibenzofuran, 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF), and a dioleyl-phosphatidylcholine (DOPC) lipid membrane of 50 Å wide have been chosen for our study. The free energy profile shows the penetration process is largely favoured thermodynamically (DG≈-12 kcal/mol), with a progressively decrease of the free energy until reaching the energy minima at distances of 8Å and 9.5Å from the centre of the membrane for, respectively, TCDD and TCDF. At the centre of the membrane, both molecules display subtle local maxima with free energy differences of 0.5 and 1 kcal/mol with respect to the energy minima for TCDD and TCDF, respectively. Furthermore, the intermolecular interactions between the molecules and the lipid membrane have been characterized at the minima and the local maxima using hybrid quantum mechanics/molecular mechanics energy decomposition analysis (QM/MM-EDA). Total interaction energies of -17.5 and -16.5 kcal/mol have been found at the energy minima for TCDD and TCDF, respectively. In both cases, the dispersion forces govern the molecule-membrane interactions, no significant changes have been found at the local maxima, in agreement with the classical free energy profile. The small differences found in the results obtained for TCDD and TCDF point out the adsorption and diffusion processes through the cell membrane are not related to the different toxicity shown by these pollutants.
Chemistry and Materials Science, Theoretical Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
