After extensive discussion about correct parameters to run CHARMM36 simulations it was concluded that the results from Gromacs 5 are consistent with other simulation packages and literature. Thus, the results from CHARMM gui parameters simulated with Gromacs 5 are currently used in the manuscript. However, there might still be some issues with parameters given by CHARMM gui for systems with cholesterol.
Current comparison for acyl chain order parameters between different simulation models and experiments is shown in Fig. 1. The main conclusion is that cholesterol ordering effect is overestimated in Berger/Holtje and MacRog models, while slight overestimation is observed also in CHARMM36 and Slipid models. The significance of overestimation in CHARMM36 and Slipid is yet to be analyzed (see Things to do list below).
|FIG. 1: Order parameters from simulations and experiments for acyl chains of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) with and without cholesterol.|
Things to be done:
- We need to analyze if
overestimation of order parameters with cholesterol in CHARMM36 and
Slipids is significant. There are at least two issues to be clarified:
1) Is the quantitative accuracy of experimental order parameters same for acyl chains as for glycerol backbone and headgroup (0.02) discussed in NMRlipids I ?
2) Can the overestimation of order parameters in simulations be explained by missing undulations, as sometimes suggested?
- Lipid 14 results from model by Madej et al. should be somehow included.
- Comparison of form factors between simulations and experiments should be finished.