title: Derivation of original RESP atomic partial charges for MD simulations of the LDAO surfactant with AMBER: applications to a model of micelle and a fragment of the lipid kinase PI4KA.
abstract: In this paper, we describe the derivation and the validation of original RESP atomic partial charges for the N, N-dimethyl-dodecylamine oxide (LDAO) surfactant. These charges, designed to be fully compatible with all the AMBER force fields, are at first tested against molecular dynamics simulations of pure LDAO micelles and with a fragment of the lipid kinase PIK4A (DI) modeled with the QUARK molecular modeling server. To model the micelle, we used two distinct AMBER force fields (i.e. Amber99SB and Lipid14) and a variety of starting conditions. We find that the micelle structural properties (such as the shape, size, the LDAO headgroup hydration, and alkyl chain conformation) slightly depend on the force field but not on the starting conditions and more importantly are in good agreement with experiments and previous simulations. We also show that the Lipid14 force field should be used instead of the Amber99SB one to better reproduce the C(sp3)C(sp3)C(sp3)C(sp3) conformation in the surfactant alkyl chain. Concerning the simulations with LDAO-DI protein, we carried out different runs at two NaCl concentrations (i.e. 0 and 300 mM) to mimic, in the latter case, the experimental conditions. We notice a small dependence of the simulation results with the LDAO parameters and the salt concentration. However, we find that in the simulations, three out of four tryptophans of the DI protein are not accessible to water in agreement with our fluorescence spectroscopy experiments reported in the paper.
authors.affiliation: a Maison de la Simulation, USR 3441 , CEA - CNRS - INRIA - Univ. Paris-Sud - Univ. de Versailles , 91191 , Gif sur Yvette , France.|b Commissariat à l'Energie Atomique et aux Energies Alternatives, DRF/IBITECS/SB2SM/LBMS & CNRS UMR 9198 , Saclay , France.|c Institute for Integrative Biology of the Cell (I2BC), CEA , CNRS, Univ Paris Sud, Université Paris-Saclay , 91198 Gif sur Yvette , France.
authors.forename: Esra
authors.initials: E
authors.lastname: Karakas
authors.affiliation: c Institute for Integrative Biology of the Cell (I2BC), CEA , CNRS, Univ Paris Sud, Université Paris-Saclay , 91198 Gif sur Yvette , France.
authors.forename: Cyntia
authors.initials: C
authors.lastname: Taveneau
authors.affiliation: c Institute for Integrative Biology of the Cell (I2BC), CEA , CNRS, Univ Paris Sud, Université Paris-Saclay , 91198 Gif sur Yvette , France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bressanelli
authors.affiliation: b Commissariat à l'Energie Atomique et aux Energies Alternatives, DRF/IBITECS/SB2SM/LBMS & CNRS UMR 9198 , Saclay , France.|c Institute for Integrative Biology of the Cell (I2BC), CEA , CNRS, Univ Paris Sud, Université Paris-Saclay , 91198 Gif sur Yvette , France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Marchi
authors.affiliation: b Commissariat à l'Energie Atomique et aux Energies Alternatives, DRF/IBITECS/SB2SM/LBMS & CNRS UMR 9198 , Saclay , France.|c Institute for Integrative Biology of the Cell (I2BC), CEA , CNRS, Univ Paris Sud, Université Paris-Saclay , 91198 Gif sur Yvette , France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Robert
authors.affiliation: b Commissariat à l'Energie Atomique et aux Energies Alternatives, DRF/IBITECS/SB2SM/LBMS & CNRS UMR 9198 , Saclay , France.|c Institute for Integrative Biology of the Cell (I2BC), CEA , CNRS, Univ Paris Sud, Université Paris-Saclay , 91198 Gif sur Yvette , France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Abel
mesh_terms: D018647:Amber / Q000737:chemistry*; D004123:Dimethylamines / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008823:Micelles; D015778:Minor Histocompatibility Antigens / Q000737:chemistry; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D018647:Amber; D004123:Dimethylamines; D008055:Lipids; D008823:Micelles; D015778:Minor Histocompatibility Antigens; D011506:Proteins; D013501:Surface-Active Agents; C014518:dodecyldimethylamine oxide; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase
keywords: LDAO surfactant; MD simulation; fluorescence spectroscopy; lipid kinase PI4KA; micelle; molecular modeling