Permeability of antioxidants through a lipid bilayer model with coarse-grained simulations

AbstractOxidative stress caused by pollution and lifestyle changes causes an excess of free radicals that react chemically with cell constituents leading to irreversible damage. There are molecules known as antioxidants that reduce the levels of free radicals. Some pigments of fruits and vegetables known as anthocyanins have antioxidant properties. Their interaction with the cell membrane becomes a crucial step in studying these substances. In this research, molecular dynamics simulations, particularly, coarse-grained molecular dynamics (CGMD) were used. This technique aims to replace functional groups with corresponding beads that represent their level of polarity and affinities to other chemical groups. Also, umbrella sampling was carried out to obtain free energy profiles that describe well the orientation and location of antioxidants in a membrane considering Trolox, Cyanidin, Gallic Acid, and Resveratrol molecules to study the structural effects they cause on it. It was concluded in this study that an antioxidant when crossing the membrane does not cause either damage to the structural properties or the loss of packing and stratification of phospholipids. it was also observed that the most reactive part of the molecules could easily approach area A prone to lipid oxidation, which can describe the antioxidant capacity of these molecules.Communicated by Ramaswamy H. SarmaKeywords: antioxidantsmolecular dynamicscoarse-grainedmartiniDFT Acknowledgement(s)HAL gratefully acknowledges a Doctoral Fellowship from CONACYT. DGM and NFH are researchers of CIMAV and CONACYT from which partial support is also acknowledged.Disclosure statementNo potential conflict of interest was reported by the authors.Authors’ contributionsHAL and NFH conceived the concept and designed the study. HAL carried out the theoretical calculations and analysis. HAL, NFH, and DGM co-wrote the paper. All authors discussed the results and commented on the manuscript.Consent for publicationAll author have consented for the publication of this manuscript.Availability of data and materialsAll generated data is available from the authors under request.Code availabilityAll the MD inputs and data are available upon request to the corresponding author. The software used for this study are Groningen Machine for Chemical Simulations, version 5.0.7 (GROMACS), an open-source and free MD package, (https://www.gromacs.org/). Gaussian 09 Rev D.01 (https://gaussian.com), a licensed program that utilizes fundamental laws of quantum mechanics to predict energies, molecular structures, spectroscopic data as NMR, IR, UV, etc. Automated Topology Builder ATB 3.0 (https://atb.uq.edu.au/) is a tool to provide classical force fields for novel molecules. Scikit learn 1.0 (https://scikit-learn.org/stable/index.html) is an open-source machine-learning tool for analysis data. RStudio (https://www.rstudio.com/) is open-source software for code execution. INSANE (https://github.com/Tsjerk/Insane) is a python script tool to build coarse-grained input structures for molecular dynamics. pyCGTOOL (https://github.com/jag1g13/pycgtool), A Python program for automated generation of coarse-grained molecular dynamics models.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.