Dataset Information

Hydrophobic mismatch and lipid sorting near OmpA in mixed bilayers: atomistic and coarse-grained simulations.

ABSTRACT: To understand the effects of lipid composition on membrane protein function in a mixture as complex as a biomembrane, one must know whether the lipid composition local to the protein differs from the mean lipid composition. In this study, we simulated the transmembrane domain of a ?-barrel protein, OmpA, in mixtures of lipids of different tail lengths under conditions of negative hydrophobic mismatch, i.e., local bilayer thinning. We modeled the influence of OmpA on the local lipid composition both at a coarse-grained (CG) resolution using conventional molecular dynamics, and at an atomistic resolution within the semi-grand canonical ensemble using mutation moves to rapidly approach an equilibrium lateral distribution of lipids. Moderate enrichment of the shorter tail component (either DDPC in DDPC/DMPC mixtures or DMPC in DMPC/DSPC mixtures) extending 2-3 nm away from the protein surface was observed with both the atomistic and CG models. The similarity in trends suggests that the more computationally economical CG models capture the essential features of lipid sorting induced by hydrophobic mismatch.

SUBMITTER: Yin F

PROVIDER: S-EPMC3353016 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Hydrophobic mismatch and lipid sorting near OmpA in mixed bilayers: atomistic and coarse-grained simulations.

Yin Fuchang F Kindt James T JT

Biophysical journal 20120515 10

To understand the effects of lipid composition on membrane protein function in a mixture as complex as a biomembrane, one must know whether the lipid composition local to the protein differs from the mean lipid composition. In this study, we simulated the transmembrane domain of a β-barrel protein, OmpA, in mixtures of lipids of different tail lengths under conditions of negative hydrophobic mismatch, i.e., local bilayer thinning. We modeled the influence of OmpA on the local lipid composition b ...[more]

PMID: 22677381

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Project description:Cholesterol trafficking, which is an essential function in mammalian cells, is intimately connected to molecular-scale interactions through cholesterol modulation of membrane structure and dynamics and interaction with membrane receptors. Since these effects of cholesterol occur on micro- to millisecond timescales, it is essential to develop accurate coarse-grained simulation models that can reach these timescales. Cholesterol has been shown experimentally to thicken the membrane and increase phospholipid tail order between 0-40% cholesterol, above which these effects plateau or slightly decrease. Here, we showed that the published MARTINI coarse-grained force-field for phospholipid (POPC) and cholesterol fails to capture these effects. Using reference atomistic simulations, we systematically modified POPC and cholesterol bonded parameters in MARTINI to improve its performance. We showed that the corrections to pseudo-bond angles between glycerol and the lipid tails and around the oleoyl double bond particle (the "angle-corrected model") slightly improves the agreement of MARTINI with experimentally measured thermal, elastic, and dynamic properties of POPC membranes. The angle-corrected model improves prediction of the thickening and ordering effects up to 40% cholesterol but overestimates these effects at higher cholesterol concentration. In accordance with prior work that showed the cholesterol rough face methyl groups are important for limiting cholesterol self-association, we revised the coarse-grained representation of these methyl groups to better match cholesterol-cholesterol radial distribution functions from atomistic simulations. In addition, by using a finer-grained representation of the branched cholesterol tail than MARTINI, we improved predictions of lipid tail order and bilayer thickness across a wide range of concentrations. Finally, transferability testing shows that a model incorporating our revised parameters into DOPC outperforms other CG models in a DOPC/cholesterol simulation series, which further argues for its efficacy and generalizability. These results argue for the importance of systematic optimization for coarse-graining biologically important molecules like cholesterol with complicated molecular structure.

Dataset Information

Hydrophobic mismatch and lipid sorting near OmpA in mixed bilayers: atomistic and coarse-grained simulations.

Publications

Hydrophobic mismatch and lipid sorting near OmpA in mixed bilayers: atomistic and coarse-grained simulations.

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