SKM 2023 – scientific programme
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BP: Fachverband Biologische Physik
BP 27: Computational Biophysics II
BP 27.4: Talk
Thursday, March 30, 2023, 15:45–16:00, BAR 0106
Structural Insights on Ionizable Dlin-MC3-DMA Lipids in DOPC Layers by Combining, Molecular Dynamics Simulations, and Neutron Reflectivity — •Ibrahim Mohd1,3, Jennifer Gilbert2, Marcel Heinz3, Tommy Nylander2, and Nadine Schwierz1,3 — 1University of Augsburg, 86159 Augsburg, Germany — 2Lund University, SE-22100 Lund, Sweden — 3Max-Planck-Institute of Biophysics, 60438 Frankfurt am Main, Germany
Dlin-MC3-DMA (MC3) is one the most promising ionisable lipid for designing lipid nanoparticles (LNPs), which are used as drug delivery agents. Here, we provide force field parameters for cationic and neutral MC3 compatible with the AMBER Lipid17 force field. Subsequently, we carefully assess the accuracy of the current and existing MC3 force fields by providing a direct comparison to neutron reflectivity experiments of mixed lipid bilayers consisting of MC3 and DOPC at different pH. At low pH (cationic MC3) and at high pH (neutral MC3) the newly developed MC3 parameters in combination with AMBER Lipid17 for DOPC give excellent agreement with the experiments compared to existing MC3 models. With the currently parametrized MC3 parameters we are able to simulate MC3 containing LNPs in atomistic details and gain insights into the effect of pH and RNA cargo on the LNP structure. Combining molecular dynamics simulations, neutron reflectivity experiments and other scattering techniques is therefore a valuable step to drive the advancement of accurate atomistic force fields and to unravel the detailed structure of LNPs.