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Description
In lungs, a lipid-protein surfactant layer enables breathing by reducing surface tension at the air-water interface. Lung surfactant function requires cycling of material between bilayer reservoirs and an active surfactant layer, presumably involving transient formation of highly curved lipid structures. Surfactant protein SP-B, a 79-residue protein that forms homodimers, is essential for lung function. To study how lipid-SP-B interactions might contribute to implied lipid assembly reorganization, GROMACS molecular dynamics simulations were used to study conformation and orientation of SP-B fragments SP-B$_{1-9}$ and SP-B$_{1-25}$ in DPPC/POPG (7:3) model lipid bilayers. SP-B$_{1-9}$ includes SP-B’s initial 7-residue insertion sequence. SP-B$_{1-25}$ also includes the first of SP-B’s four amphipathic helices. To obtain averages and test for protein-induced bilayer perturbation, each simulation involved multiple copies of each fragment (18 SP-B${1-9}$ or 9 SP-B$_{1-25}$ copies per bilayer leaflet). Simulations were also run with no peptide and with only one copy of SP-B$_{1-9}$ per leaflet. The simulation with multiple copies of SP-B$_{1-9}$ started with randomly oriented peptides inserted in the lipid bilayer and ran for 450 ns. SP-B1-25 simulations started with (i) randomly oriented peptides, (ii) peptides oriented along the bilayer surfaces, and (iii) peptides inserted across the bilayer (trans). On average, SP-B$_{1-9}$ was found to tilt only slightly into the bilayer with its N-terminal phenylalanine staying within about 0.75 nm of the bilayer phosphate layer. Comprising the insertion sequence plus first SP-B helix, SP-B$_{1-25}$, tended to remain in the trans-bilayer orientation when started in that orientation. If started roughly parallel to the bilayer surface, SP-B$_{1-25}$ tended to settle into non-trans orientations but with excursions toward the trans configuration. When starting from random peptide orientations, SP-B$_{1-25}$ largely settled into a mixture of trans and surface orientations. SP-B$_{1-25}$ is nearly the first third of the SP-B monomer. Its capacity to be accommodated in both trans-bilayer and single-leaflet environments may reflect SP-B’s role in promoting lipid assembly reorganization implied by the cycling between bilayer reservoir and surface-active layer structures. Supported by NSERC, ACENet, and Digital Research Alliance of Canada.
| Keyword-1 | Lipid-protein interaction |
|---|---|
| Keyword-2 | Lung surfactant |
| Keyword-3 | Molecular Dynamics Simulation |
