INQUINOA   21218
INSTITUTO DE QUIMICA DEL NOROESTE
Unidad Ejecutora - UE
artículos
Título:
Molecular view of the interaction of S-methyl methanethiosulfonate with DPPC bilayer?
Autor/es:
V. MIGUEL ; M. E. DEFONSI LESTARD; M. E. TUTTOLOMONDO; S. B. DÍAZ; A. BEN ALTABEF; M. PUIATTI ; A. B. PIERINI
Revista:
BIOCHIMICA AND BIOPHYSICA ACTA
Editorial:
ELSEVIER
Referencias:
Año: 2016 vol. 1858 p. 38 - 46
ISSN:
0006-3002
Resumen:
Wepresent molecular dynamics (MD) simulation studies of the interaction of a chemo preventive and protectiveagent, S-methyl methanethiosulfonate (MMTS), with a model bilayer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC).Weanalyzed and compared its diffusionmechanismswith the relatedmolecule dimethylsulfoxide (DMSO).Weobtained spatially resolved free energy profiles ofMMTS partition into a DPPC bilayer in the liquid-crystallinephase through potential of mean force (PMF) calculations using an umbrella sampling technique. These profilesshowed a minimumforMMTS close to the carbonyl region of DPPC. The location ofMMTS molecules in the DPPCbilayer observed in the MD was confirmed by previous SERS studies [1].We decomposed PMF profiles into entropicand enthalpic contributions. These results showed that the driving force for the partitioning of MMTSinto the upper region of DPPC is driven by a favorable entropy change while partitioning into the acyl chains isdriven by enthalpy. On the other hand, the partition of DMSO into the membrane is not favored, and is drivenby entropy instead of enthalpy. Free diffusion MD simulations using all atom and coarse grained (CG) modelsof DPPC in presence ofMMTSwere used to analyze the effect of DPPC-MMTS interaction. Density profiles showedthatMMTS locates preferentially in the carbonyl region, as expected according to the PMF profile and the experimentalevidence. MMTS presented two differential effects over the packing of DPPC hydrocarbonate chains atlow or at high molar ratios. An ordering effect was observed when a CGMMTS model was used. Finally, free diffusionMD and PMF decomposition for DMSO were used for comparison.