Article

Download article 		Title: Combining nuclear magnetic resonance with molecular dynamics simulations to address sumatriptan interaction with model membranes
Author: Wood, I.; Fabian L; Moglioni A; Cabeça, Luis Fernando; De Paula, Eneida; Pickholz, Monica
Year: 2019
Is part of: CHEMISTRY AND PHYSICS OF LIPIDS, v. 225, p. 104792 -
DOI: https://doi.org/10.1016/j.chemphyslip.2019.104792

Citation: Wood, I.; Fabian L; Moglioni A; Cabeça, Luis Fernando; De Paula, Eneida; Pickholz, Monica; Combining nuclear magnetic resonance with molecular dynamics simulations to address sumatriptan interaction with model membranes. CHEMISTRY AND PHYSICS OF LIPIDS, v.225, p. 104792-, 2019

Abstract: The goal of this work is to obtain a complete map on the interactions between sumatriptan, an amphiphilic ionizable anti-migraine drug, with lipid bilayers. To this end, we combined two physico-chemical techniques-nuclear magnetic resonance and molecular dynamics simulations - to obtain a detailed picture at different pH values. Both approaches were used considering the strength and constraints of each one. NMR experiments were performed at pH 7.4 where at least 95% of the drug molecules are in their protonated state. From NMR, sumatriptan shows partition on the interfacial region of model membranes (near the head groups and intercalating between adjacent lipids), inducing changes in chemical environment and affecting lipid dynamics of liposomes, in a dose dependent manner. Due to the experimental instability of lipid bilayers at high pH, we took advantage of the molecular dynamics power to emulate different pH values, to simulate sumatriptan in bilayers including at fully uncharged state. Simulations show that the neutral species have preferential orientation within the bilayer interface while the distribution of protonated drugs is independent on the initial conditions. In summary, several properties depicted the interfacial partition of the anti-migraine drug at the water-lipid interface at different conditions. Both techniques were found complementary to shed light on the structural and dynamics of sumatriptan-lipid bilayer interactions.

Keywords: molecular dynamics; nuclear magnetic resonance; sumatriptan;
Subjects: CIENCIAS_BIOLOGICAS; Biofísica de Processos e Sistemas;

Funding: The authors would like to acknowledge IQUIMEFA (CONICET-UBA) for NMR facility; LF for performing, processing and interpretation of NMR experiments; LAFEDAR for the donation of Sumatriptan Succinate; CONICET and Conselho Nacional Pesquisa (CNPq/Brazil, #1420869/2016-6) for the financial support. 		Financed by: