Molecular dinamycs study of the interaction of S-methyl methanesulfonate with DPPC membrane

Abstract

Different experimental1 and theorithical2 methods can be employed for studying the interaction of different compounds with the cell membrane. Molecular dynamics simulations (MD) could bring a useful description of the phenomena at an atomic detail.2 In this work the interaction of S-methyl methanesulfonate (MMTS) with dipalmitoylphosphatidylcholine (DPPC) bilayers is studied by using MD simulations. The interest in MMTS relay in its antioxidant activity against lipid peroxidation and its a strong protective effect toward carcinogenesis.1 The parameters for the lipids employed in the simulations were a combination of the all atoms GAFF parameters with the charges used by Sonne et al for the DPPC.3 Different simulations of 20 ns of an hydrated DPPC bilayer of 128 units were performed in order to get the most appropriate conditions. The best results were obtained by applying anisotropic pressure, without fixing the area of the x-y lipid plane, and without applying an external artificial surface tension as is usually done.3 In the next stage 5 simulations of 25 ns of the DPPC bilayer with only one molecule of MMTS were performed. In three of these simulations the MMTS molecule, initially located at 10 Å above the bilayer, enter the membrane crossing the polar heads of the lipids, interacting with carbonyl groups of DPPC. The MMTS did not cross the bilayer to other side. Finally two simulations of 50 ns with 81 and 100 molecules of MMTS were done. In these simulations between 60 and 75 % of the MMTS units passed the polar head group of the bilayer interacting once again with the carbonyl groups and with the phosphates and amide group the choline. The observed results are in total accordance with experimental results obtained by studying the interaction of MMTS with DPPC liposomes by using FT-IR and IR-Raman.