CHARMM all-atom additive force field for sphingomyelin: elucidation of hydrogen bonding and of positive curvature.

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TitleCHARMM all-atom additive force field for sphingomyelin: elucidation of hydrogen bonding and of positive curvature.
Publication TypeJournal Article
Year of Publication2014
AuthorsVenable, RM, Sodt, AJ, Rogaski, B, Rui, H, Hatcher, E, Mackerell, AD, Pastor, RW, Klauda, JB
JournalBiophys J
Volume107
Issue1
Pagination134-45
Date Published2014 Jul 01
ISSN1542-0086
KeywordsHydrogen Bonding, Lipid Bilayers, Molecular Dynamics Simulation, Sphingomyelins
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.

DOI10.1016/j.bpj.2014.05.034
Alternate JournalBiophys. J.
PubMed ID24988348
PubMed Central IDPMC4119286
Grant ListR01 GM072558 / GM / NIGMS NIH HHS / United States
R01 GM070855 / GM / NIGMS NIH HHS / United States
/ / Intramural NIH HHS / United States
GM070855 / GM / NIGMS NIH HHS / United States
P41 GM103712 / GM / NIGMS NIH HHS / United States
P41GM103712-S1 / GM / NIGMS NIH HHS / United States
GM072558 / GM / NIGMS NIH HHS / United States