Sphingomyelin is a major component of functional lipid domains in eukaryotic membranes. Here, the molecular structures of palmitoyl sphingomyelin (PSM) and stearoyl sphingomyelin (SSM) in the fluid phase were determined using a newly-developed scattering density profile (SDP) model that jointly analyzes small-angle neutron and X-ray scattering data. In addition, unconstrained all-atom molecular dynamics (MD) simulations using the C36 CHARMM force field were performed on PSM bilayers at 55 °C. The MD simulations determined an average area per lipid of 56 Å2, a value that is 10% lower than the one determined by SDP analysis (61.9 Å2). Interestingly, scattering form factors calculated from the unconstrained simulations were in poor agreement with experimental form factors, even though order parameter (SCD) profiles calculated from the simulations were in relatively good agreement with nuclear magnetic resonance (NMR) experiments. Conversely, constrained area simulations at 61.9 Å2 resulted in good agreement between the simulation and experimental scattering form factors, but not with the SCD profiles from NMR. Possible reasons for the discrepancies between the different experimental techniques – frequently used to validate MD force fields – will be presented.

Molecular structure of sphingomyelin using SANS, SAXS, and molecular dynamics

ACS Spring Meeting 2021

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