Comparative Molecular Dynamics Simulation Studies of Realistic Eukaryotic, Prokaryotic, and Archaeal Membranes

Abstract

We present a comparative all-atom molecular dynamics simulation study of 18 biomembrane systems with lipid compositions corresponding to eukaryotic, bacterial, and archaebacterial membranes together with three single-component lipid bilayers. A total of 105 lipid types used in this study include diverse sterols and glycerol-based lipids with acyl chains of various lengths, unsaturation degrees, and branched or cyclic moieties. Our comparative analysis provides deeper insight into the influences of sterols and lipid unsaturation on the structural and mechanical properties of these biomembranes, including water permeation into the membrane hydrocarbon core. For sterol-containing membranes, sterol fraction is correlated with the membrane thickness, the area compressibility modulus, and lipid order but anticorrelated with the area per lipid and sterol tilt angles. Similarly, for all 18 biomembranes, lipid order is correlated with the membrane thickness and area compressibility modulus. Sterols and lipid unsaturation produce opposite effects on membrane thickness, but only sterols influence water permeation into the membrane. All membrane systems are accessible for public use in CHARMM-GUI Archive. They can be used as templates to expedite future modeling of realistic cell membranes with transmembrane and peripheral membrane proteins to study their structure, dynamics, molecular interactions, and function in a nativelike membrane environment.

Unraveling membrane properties at the organelle-level with LipidDyn

“…4 C), suggesting a more disordered membrane. Recent all-atom MD simulations of a model system of ER with a complex lipid mixture [64] reported values of APL (average 0.62 nm 2 ) and thickness (average 4.02 nm) in broad agreement with our results. Our analyses shed light on the biophysical properties of ER bilayer, showing loose packing and low ordering of lipids that may reflect membrane dynamics involved in the functions of ER.…”

“…We used coarse-grained MD simulations to investigate if, with this approach, we can study the interaction of p24 with sphingomyelin, previously observed with all-atom MD simulations [63] , [64] , and observe effects associated with the presence of cholesterol ( Fig. 5 ).…”

In silico modelling human VPS13 proteins associated with donor and target membranes suggests lipid transfer mechanisms

“…Recent evidence showed the RBG protein superfamily can transfer phosphatidylcholines and phosphatidylethanolamines (Neuman et al, 2022; Toulmay et al, 2022). The ER is relatively enriched in those lipid species compared to endo-lysosomes (Escribá et al, 2015; Guo et al, 2009; Horvath and Daum, 2013; Pogozheva et al, 2022; Reglinski et al, 2020; Tauchi-Sato et al, 2002; van Meer and de Kroon, 2011; van Meer et al, 2008). Despite this, the levels of phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and sphingomyelin increase in the lysosome in VPS13C knockout clones (Hancock-Cerutti et al, 2022).…”

“…Finally, protein-lipid membrane components were assembled through the CHARMM-GUI Replacement Method. Lipid membranes compositions were based on previous predictions and biochemistry (Escribá et al, 2015; Guo et al, 2009; Horvath and Daum, 2013; Jo et al, 2008; Pogozheva et al, 2022; Reglinski et al, 2020; Tauchi-Sato et al, 2002; van Meer and de Kroon, 2011; van Meer et al, 2008). Protein-membrane orientations were based on previous experimental approaches (Baldwin et al, 2021; Koike et al, 2019; Kumar et al, 2018; Muñoz-Braceras et al, 2019; Seifert et al, 2011; Yeshaw et al, 2019).…”

From Molecular Dynamics to Supramolecular Organization: The Role of PIM Lipids in the Originality of theMycobacterialPlasma Membrane

“…Molecular dynamics (MD) simulations have been used to study lipid organization and the formation of domains on a large scale 22 as well as comparative studies of eukaryotic, prokaryotic, and archaeal membranes 23 . Despite this, at the time of writing, there are no complete models of the Mycobacterial plasma membrane that capture the asymmetry and the range of complex lipids 24 .…”