Molecular View of the Interaction of S-Methyl Methanethiosulfonate with DPPC Bilayer

MIGUEL, VIRGINIA;; DEFONSI LESTARD, MARIA E. ; TUTTOLOMONDO, MARIA E. ; DÍAZ, SONIA B. ; BEN ALTABEF, AIDA; PUIATTI, MARCELO; PIERINI, ADRIANA B

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 1858 p. 38 - 46

0005-2736

We presentmolecular dynamics (MD) simulation studies of the interaction of a chemopreventive and protective agent, S-methyl methanethiosulfonate (MMTS), with amodel bilayer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine(DPPC). We analyzed and compared its diffusion mechanisms with the relatedmolecule dimethyl sulfoxide (DMSO). We obtainedspatially resolved free energy profiles of MMTS partition into a DPPC bilayerin the liquid-crystalline phase through Potential of Mean Force (PMF)calculations using an umbrella sampling technique. These profiles showed aminimum for MMTS close to the carbonyl region of DPPC. The location of MMTSmolecules in the DPPC bilayer observed in the MD were confirmed by previousSERS studies.1 We decomposed PMF profiles into entropic andenthalpic contributions. These results showed that the driving force for thepartitioning of MMTS into the upper region of DPPC is driven by a favorableentropy change while partitioning into the acyl chains is driven by enthalpy. Onthe other hand, the partition of DMSO into the membrane is not favored, and isdriven by entropy instead of enthalpy. Free diffusion MD simulations using allatom and coarse grained (CG) models of DPPC in presence of MMTS were used toanalyze the effect of DPPC-MMTS interaction. Density profiles showed that MMTSlocates preferentially in the carbonyl region, as expected according to the PMFprofile and the experimental evidence. MMTSpresented two differential effects over the packing of DPPChydrocarbonate chains at low or at high molar ratios. An ordering effect wasobserved when a CG MMTS model was used. Finally, free diffusion MD and PMFdecomposition for DMSO were used for comparison.