Abstract:
Thymoquinone, a phytochemical with antitumor activity, and its derivative aminothymoquinone were investigated using Molecular Dynamics (MD) Simulations to understand their interactions with simple and complex bilayer models. MD simulations of the models were performed using all atom (AA) and coarse-grained (CG) force fields, i.e., the OPLS-AA and MARTINI 3. Although the resolution of the molecules decreased during coarse-graining, the chemical and thermodynamic properties of the molecules were mostly retained. The bond and dihedral distributions validated the matching of AA and CG models, and the free energy calculations showed the reproducibility of new models apart from the agreement with the experimental logP values with less than 10% of error. AA and CG thymoquinone models were used with DOPC and POPC bilayers and the systems were compared with the sole bilayers. The structural properties of bilayers including area per lipid, bilayer thickness, order parameters, and lateral diffusion coefficients were computed. The interaction of CG molecules with two different normal and cancer membrane models was also investigated through the orientation of the molecules in the bilayers, the density distribution, and radial distribution function (RDF) in addition to the methods used for simple bilayer. Both molecules resulted in bilayer thinning with decreased bilayer thicknesses but increased the area per lipid values. Similarly, both molecules decreased the ordering of the bilayers, but the effect was slightly more significant with thymoquinone in normal membrane models. While thymoquinone diffused inside the model membranes, aminothymoquinone preferred to reside near the head groups of lipids. Overall, both molecules interacted similarly, in general, with the lipids of the model membranes, apart from small differences.
