Modeling the Self-Assembly and Stability of DHPC Micelles Using Atomic Resolution and Coarse Grained MD Simulations

Abstract

Membrane mimics such as micelles and bicelles are widely used in experiments involving membrane proteins. With the aim of being able to carry out molecular dynamics simulations in environments comparable to experimental conditions, we set out to test the ability of both coarse grained and atomistic resolution force fields to model the experimentally observed behavior of the lipid 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), which is a widely used lipid for biophysical characterization of membrane proteins. It becomes clear from our results that a satisfactory modeling of DHPC aggregates in solution poses different demands to the force field than do the modeling of bilayers. First, the representation of the short tailed lipid DHPC in the coarse grained force field MARTINI is assessed with the intend of successfully self-assemble micelles with structural characteristics comparable to experimental data. Then, the use of the recently presented polarizable water model in MARTINI is shown to be essential for producing micelles that are structurally in accordance with experiments. For the atomistic representations of DHPC micelles in solution the GROMOS96 force field with lipid parameters by A. Kukol fails to maintain stable micelles, whereas the most recent CHARMM36 lipid parameters and GROMOS96 with the so-called Berger lipid parameters both succeed in this regard.

Interactions of Lipids and Detergents with a Viral Ion Channel Protein: Molecular Dynamics Simulation Studies

“…However, the choice of experimental method for determining micelle properties still causes greater deviation in calculated properties than the difference between experimental and computational results. 43 …”

Multiscale molecular dynamics simulations of sodium dodecyl sulfate micelles: from coarse-grained to all-atom resolution

“…However, the limitations of the method are related to the description of the molecule at each resolution (ideal bond lengths, angles, dihedrals, and partial charges distribution) [28] that usually remains based on general parameter sets covering wide areas of biochemistry [29] and therefore missing the specificity of the newly investigated systems. Moreover, multiscale simulations [30][31][32] are currently performed using parameters sets that differ according to the resolution. Indeed, while the charge is exclusively carried by the polar headgroup for the CG representation [16], the UA model displays a nonnegligible charge on the first methyl group (C1; Table 1; reference) of the hydrocarbon tail [20], and this charge is distributed along the whole molecule for the AA model [25].…”

Protobiotic Systems Chemistry Analyzed by Molecular Dynamics

“…and thus can be initially tested by utilizing already existing atomic models for certain amphiphilic molecules. Moreover, some of these molecules have already been proven to behave in accordance with experimental data even when featured in Coarse Grained Molecular Dynamics simulations, harnessing variations of the well-studied lipid-oriented MARTINI force field [81]. This could indicate a possibility for accurate simulations of the GARD model even in Coarse Grained resolution.…”

“…Thus, the simulation must be able to accurately recognize micellar assemblies and ascribe each molecule either to a micelle or to the surrounding simulated environment as a free monomer. This could be achieved by calculating local centers of mass [30] or more commonly, clustering molecular components together and assigning them to the same aggregate based on spatial distances, often by setting a limiting threshold [72,81]. By tracking these micelles along the experiment timeline, fission events could be discerned as described [77,82] and compositional vectors for each micellar state could be defined.…”