Aggregation properties of the synthetic peptidic amphiphile OOCWW-palmitic acid studied by molecular dynamics simulations

DANIEL E. RODRIGUES; A. SERGIO GARAY

Ciudad Autónoma de Buenos Aires

Congreso; XLIX Reunión Anual SAB; 2021

Sociedad Argentina de Biofísica

The synthetic peptide basedamphiphile (PA), built by binding the aminoacid sequence OOCWW with apalmitic acid molecule, has been studied using molecular dynamicssimulations (MD). This molecule has an important biotecnologicalrelevance as a carrier that favours the DNA transfection in hostcells. These PA molecules can form dimeric complexes in aqueoussolutions at appropriate pH through the oxidation of their Cresidues, generating a gemini like amphiphile (PGA). Atomistic MD ofthese PA and PGA molecules, isolated and in lipid aggregates inaqueous solution, have been performed to provide a basis forinterpreting de fluorescence spectra at different pH. The mostpopulated structural conformations of the isolated PA and PGA insolution have been determined togheter with the interactions thatfavors such behavior and the solvent distribution in the environmentof the indole W moiety. The MD have shown that PA or PGA molecules,aggregate espontaneously in aqueous solution, building H-bonds amongtheir charged groups and lowering their solvent accesible surface.The simulations have also shown that miceles of 30 PA or of 10 PGAmolecules respectively, with their hidrocarbonated tails toward theircentre and the peptidic moiety exposed to the solvent, are stablethrough the reached simulation times. The gyration radius of thesemiceles, the stabilizing interactions and the solvent distribution inthe environment of the W residues have been determined and analyzed.A semi-classical calculation of the changes in the dipolar transitionenergy, due to the interaction of the W residues with the chargedgroups of the micelar and solvent environment, has been performed forall the studied cases along the simulated time. The environment ofthe W residues dynamics along the time, give rise to a dipolartransition energy distribution that can be used to correlate thefluorescent spectra features with the aggregation state of themolecules.p { line-height: 115%; margin-bottom: 0.1in; background: transparent }