Interaction between different free fatty acids and the nicotinic acetylcholine receptor inserted in a lipid bilayer. A Molecular Dinamic approach.

OBIOL, D. ; AMUNDARAIN, M.J.; JAURE, O. ; ZAMARREÑO, F.; VISO, J.; ANTOLLINI, S.S.; COSTABEL, M.

La Plata

Congreso; XLVII Renión Annual de la Sociedad Argentina de Biofísica; 2018

Sociedad Argentina de Biofísica

The nicotinic acetylcholine receptor (nAChR) is blocked in a non-competitive wayby free fatty acids (FFAs) and the site of action might occur at the lipid-AChRinterface. The isomerism and position of the double bond are considered crucialfor this blocking mechanism. The objective of thiswork was to perform molecular dynamics (MD) for a system consisting of a nAChRmodel inserted into a lipid bilayer composed of cholesterol, palmitoyl oleoylphosphatidylamine and palmitoyl oleoyl phosphatidylcholine to evaluate theinfluence of different FFAs on the nAChR conformational changes. The parametersthat evaluate the quality of the model like molpdf, DOPE, GA341, QMEAN andZSCORE were maintained or improved with respect to the AChR from Torpedomarmorata (2BG9) published in the Protein Data Bank. To this minimized andbalanced system we made three replacements, in annular and non-annular sites ofthe receptor, with one of the following FFAs: cis-18:1 ω-6, cis-18:1 ω-9, cis-18:1ω-11, cis-18:1 ω-13 or trans-18:1 ω-9. We obtained a total of 10 systems, plus thecontrol system formed only by the model of the AChR included in the lipid bilayer.The results show the stability of the system along the entire MD trajectory by theroot-mean square deviation (RMSD), root-mean square fluctuation (RMSF), theradius of rotation of the protein, the electrostatic potential along the lipid bilayer,the thickness of the lipid bilayer and the area per lipid.These preliminary results show a good correlation with previouslypublished studies of our group, concurring with oleic acid (cis-18:1 ω-9)located near the TM4 segments and elaidic acid (trans-18:1 ω-9) positionednear the TM4 segments and confirming that the double bond and the isomerismof FFAs effectively influence AChR conformation.