Towards atomistic resolution structure of phosphatidylcholine glycerol backbone and choline headgroup at different ambient conditions

TL;DR

This study evaluates atomistic simulation models of phosphatidylcholine bilayers, revealing current limitations in structural accuracy and suggesting pathways for improvement to better interpret experimental data.

Contribution

It compares 14 models against experimental data, identifies the best performers, and discusses how to enhance model accuracy for resolving lipid structures.

Findings

Current models do not accurately resolve glycerol and choline structures.

Best models (CHARMM36, GAFFlipid, MacRog) show potential with improved dihedral sampling.

All models qualitatively capture dehydration response and lipid-cholesterol interactions.

Abstract

Phospholipids are essential building blocks of biological membranes. Despite of vast amount of accurate experimental data the atomistic resolution structures sampled by the glycerol backbone and choline headgroup in phoshatidylcholine bilayers are not known. Atomistic resolution molecular dynamics simulation model would automatically resolve the structures giving an interpretation of experimental results, if the model would reproduce the experimental data. In this work we compare the C-H bond vector order parameters for glycerol backbone and choline headgroup between 14 different atomistic resolution models and experiments in fully hydrated lipid bilayer. The current models are not accurately enough to resolve the structure. However, closer inspection of three best performing models (CHARMM36, GAFFlipid and MacRog) suggest that improvements in the sampled dihedral angle distributions would potentilly lead to the model which would resolve the structure. Despite of the inaccuracy in the fully hydrated structures, the response to the dehydration, i.e. P-N vector tilting more parallel to membrane normal, is qualitatively correct in all models. The CHARMM36 and MacRog models describe the interactions between lipids and cholesterol better than Berger/H\"oltje model. This work has been, and continues to be, progressed and discussed through the blog: nmrlipids.blogspot.fi. Everyone is invited to join the discussion and make contributions through the blog. The manuscript will be eventually submitted to an appropriate scientific journal. Everyone who has contributed to the work through the blog will be offered coauthorship. For more details see: nmrlipids.blogspot.fi.