On the Calculation of Acyl Chain Order Parameters from Lipid Simulations

For molecular dynamics simulations of biological membrane systems
to live up to the potential of providing accurate atomic level detail
into membrane properties and functions, it is essential that the force
fields used to model such systems are as accurate as possible. One
membrane property that is often used to assess force field accuracy
is the carbon–hydrogen (or carbon–deuterium) order parameters
of the lipid tails, which can be accurately measured using experimental
NMR techniques. There are a variety of analysis tools available to
calculate these order parameters from simulations and it is essential
that these computational tools work correctly to ensure the accurate
assessment of the simulation force fields. In this work we compare
many of these computational tools for calculating the order parameters
of POPC membranes. While tools that work on all-atom systems and tools
that work on saturated lipid tails in general work extremely well,
we demonstrate that the majority of the tested tools that calculate
the order parameters for unsaturated united-atom lipid tails do so
incorrectly. We identify tools that do perform accurate calculations
and include one such program with this work, enabling rapid and accurate
calculation of united-atom lipid order parameters. Furthermore, we
discuss cases in which it is nontrivial to appropriately predict the
unsaturated carbon order parameters in united-atom systems. Finally,
we examine order parameter splitting for carbon 2 in sn-2 lipid chains, demonstrating substantial deviations from experimental
values in several all-atom and united-atom lipid force fields.