The partition and transport behavior of cytotoxic ionic liquids (ILs) through the DPPC bilayer: Insights from molecular dynamics simulation

Abstract

A molecular dynamics (MD) simulation with atomistic details was performed to examine the partitioning and transport behavior of moderately cytotoxic ionic liquids (ILs), namely choline bis(2-ethylhexyl) phosphate (CBEH), choline bis(2,4,4-trimethylpentyl) phosphinate (CTMP) and choline O,O-diethyl dithiophosphate (CDEP) in a fully hydrated dipalmitoylphosphatidylcholine (DPPC) bilayer in the fluid phase at 323 K. The structure of ILs was so selected to understand if the role of dipole and dispersion forces in the ILs distribution in the membrane can be possible. Several analyses including mass density, electrostatic potential, order parameter, diffusion coefficients and hydrogen bond formation, was carried out to determine the precise location of the anionic species inside the membrane. Moreover, the potential of the mean force (PMF) method was used to calculate free energy profile for transferring anionic species from the DPPC membrane into the bulk water. While less cytotoxic DEP is located within the bulk water, more cytotoxic TMP and BEH ILs were found to remain in the membrane and the energy barrier for crossing through the bilayer center of BEH was higher. Various ILs have no significant effect on P-N vector. The thickness of lipid bilayer decreased in all systems comprising ILs, while area per lipid increased.

Elucidating anticancer drugs release from UiO-66 as a carrier through the computational approaches

“…This is essential for understanding the arrangement and organization of molecules in a specic region. 76,77 As can be seen in Fig. 5, the density of drugs, especially TMZ and 5-FU along the z-axis, was reduced.…”

De novo antioxidant peptide design via machine learning and DFT studies

“…To comprehensively study and evaluate the thermodynamic behavior of different antioxidant compounds binding to protein residues, we conducted an assessment of the thermodynamic favorability of these interactions using free energy calculations, as presented in Table S2 70 . In addition, considering that hydrogen bond formation in molecular dynamics simulations typically occurs within distances less than 3.5 Å 71 – 73 , we assessed the residues binding to each antioxidant by examining distances between their center of mass (COM) and nearby protein residues, as detailed in Fig. S3 and Table S3 (Supporting Information File).…”

Molecular Dynamics and Metadynamics Insights of 1,4-Dioxane-Induced Structural Changes of Biomembrane Models

“…Throughout this work, pure systems will be referred to as “clear”, and 1,4-dioxane-containing systems as “polluted” systems. Initial membrane configurations have been generated using automated online membrane builder, CHARMM-GUI. , The simulated systems consisted of 128 ( n lipid = 128, 64–64 lipid molecules in each membrane leaflet, whose size have been proven to be sufficiently large to reproduce membrane structural parameters ,,,, ) either DPPC or IPPC molecules, with 50 water molecules per headgroup ( n water = 6400 in total), which is well above the value of the water molecules needed for total hydration of bilayer . In the case of polluted systems, an additional 100 molecules of 1,4-dioxane have been inserted into the simulation box in random positions.…”