title: CHARMM all-atom additive force field for sphingomyelin: elucidation of hydrogen bonding and of positive curvature.
abstract: The C36 CHARMM lipid force field has been extended to include sphingolipids, via a combination of high-level quantum mechanical calculations on small molecule fragments, and validation by extensive molecular dynamics simulations on N-palmitoyl and N-stearoyl sphingomyelin. NMR data on these two molecules from several studies in bilayers and micelles played a strong role in the development and testing of the force field parameters. Most previous force fields for sphingomyelins were developed before the availability of the detailed NMR data and relied on x-ray diffraction of bilayers alone for the validation; these are shown to be too dense in the bilayer plane based on published chain order parameter data from simulations and experiments. The present simulations reveal O-H:::O-P intralipid hydrogen bonding occurs 99% of the time, and interlipid N-H:::O=C (26-29%, depending on the lipid) and N-H:::O-H (17-19%). The interlipid hydrogen bonds are long lived, showing decay times of 50 ns, and forming strings of lipids, and leading to reorientational correlation time of nearly 100 ns. The spontaneous radius of curvature for pure N-palmitoyl sphingomyelin bilayers is estimated to be 43-100 Å, depending on the assumptions made in assigning a bending constant; this unusual positive curvature for a two-tailed neutral lipid is likely associated with hydrogen bond networks involving the NH of the sphingosine group.
authors.affiliation: Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Venable
authors.affiliation: Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Sodt
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland.
authors.forename: Brent
authors.initials: B
authors.lastname: Rogaski
authors.affiliation: Center for Bioinformatics and Department of Molecular Biosciences, The University of Kansas, Lawrence, Kansas.
authors.forename: Huan
authors.initials: H
authors.lastname: Rui
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hatcher
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland. Electronic address: alex@outerbanks.umaryland.edu.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: MacKerell
authors.affiliation: Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: pastorr@nhlbi.nih.gov.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Pastor
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland. Electronic address: jbklauda@umd.edu.
authors.forename: Jeffery B
authors.initials: JB
authors.lastname: Klauda
mesh_terms: D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D013109:Sphingomyelins / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D013109:Sphingomyelins; C033171:palmitoylsphingomyelin