TY - JOUR

T1 - Lipid Configurations from Molecular Dynamics Simulations

AU - Pezeshkian, Weria

AU - Khandelia, Himanshu

AU - Marsh, Derek

PY - 2018/4/24

Y1 - 2018/4/24

N2 - The extent to which current force fields faithfully reproduce conformational properties of lipids in bilayer membranes, and whether these reflect the structural principles established for phospholipids in bilayer crystals, are central to biomembrane simulations. We determine the distribution of dihedral angles in palmitoyl-oleoyl phosphatidylcholine from molecular dynamics simulations of hydrated fluid bilayer membranes. We compare results from the widely used lipid force field of Berger et al. with those from the most recent C36 release of the CHARMM force field for lipids. Only the CHARMM force field produces the chain inequivalence with sn-1 as leading chain that is characteristic of glycerolipid packing in fluid bilayers. The exposure and high partial charge of the backbone carbonyls in Berger lipids leads to artifactual binding of Na+ ions reported in the literature. Both force fields predict coupled, near-symmetrical distributions of headgroup dihedral angles, which is compatible with models of interconverting mirror-image conformations used originally to interpret NMR order parameters. The Berger force field produces rotamer populations that correspond to the headgroup conformation found in a phosphatidylcholine lipid bilayer crystal, whereas CHARMM36 rotamer populations are closer to the more relaxed crystal conformations of phosphatidylethanolamine and glycerophosphocholine. CHARMM36 alone predicts the correct relative signs of the timeaverage headgroup order parameters, and reasonably reproduces the full range of NMR data from the phosphate diester to the choline methyls. There is strong motivation to seek further experimental criteria for verifying predicted conformational distributions in the choline headgroup, including the P-31 chemical shift anisotropy and N-14 and CD3 NMR quadrupole splittings.

AB - The extent to which current force fields faithfully reproduce conformational properties of lipids in bilayer membranes, and whether these reflect the structural principles established for phospholipids in bilayer crystals, are central to biomembrane simulations. We determine the distribution of dihedral angles in palmitoyl-oleoyl phosphatidylcholine from molecular dynamics simulations of hydrated fluid bilayer membranes. We compare results from the widely used lipid force field of Berger et al. with those from the most recent C36 release of the CHARMM force field for lipids. Only the CHARMM force field produces the chain inequivalence with sn-1 as leading chain that is characteristic of glycerolipid packing in fluid bilayers. The exposure and high partial charge of the backbone carbonyls in Berger lipids leads to artifactual binding of Na+ ions reported in the literature. Both force fields predict coupled, near-symmetrical distributions of headgroup dihedral angles, which is compatible with models of interconverting mirror-image conformations used originally to interpret NMR order parameters. The Berger force field produces rotamer populations that correspond to the headgroup conformation found in a phosphatidylcholine lipid bilayer crystal, whereas CHARMM36 rotamer populations are closer to the more relaxed crystal conformations of phosphatidylethanolamine and glycerophosphocholine. CHARMM36 alone predicts the correct relative signs of the timeaverage headgroup order parameters, and reasonably reproduces the full range of NMR data from the phosphate diester to the choline methyls. There is strong motivation to seek further experimental criteria for verifying predicted conformational distributions in the choline headgroup, including the P-31 chemical shift anisotropy and N-14 and CD3 NMR quadrupole splittings.

KW - NUCLEAR-MAGNETIC-RESONANCE

KW - ELECTRON-SPIN-RESONANCE

KW - PARTICLE MESH EWALD

KW - CHOLINE HEAD GROUP

KW - FORCE-FIELD

KW - PHOSPHATIDYLCHOLINE HEADGROUP

KW - QUANTITATIVE-DETERMINATION

KW - PHOSPHOLIPID-BILAYERS

KW - SEGMENTAL ORDER

KW - NMR

U2 - 10.1016/j.bpj.2018.02.016

DO - 10.1016/j.bpj.2018.02.016

M3 - Journal article

VL - 114

SP - 1895

EP - 1907

JO - Biophysical Society. Annual Meeting. Abstracts

JF - Biophysical Society. Annual Meeting. Abstracts

SN - 0523-6800

IS - 8

ER -