Toward Atomistic Resolution Structure of Phosphatidylcholine Headgroup and Glycerol Backbone at Different Ambient Conditions.
Phospholipids are essential building blocks of biological membranes. Despite a vast amount of very 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 simulations have the potential to resolve the structures, and to give an arrestingly intuitive interpretation of the experimental data, but only if the simulations reproduce the data within experimental accuracy. In the present work, we simulated phosphatidylcholine (PC) lipid bilayers with 13 different atomistic models, and compared simulations with NMR experiments in terms of the highly structurally sensitive C-H bond vector order parameters. Focusing on the glycerol backbone and choline headgroups, we showed that the order parameter comparison can be used to judge the atomistic resolution structural accuracy of the models. Accurate models, in turn, allow molecular dynamics simulations to be used as an interpretation tool that translates these NMR data into a dynamic three-dimensional representation of biomolecules in biologically relevant conditions. In addition to lipid bilayers in fully hydrated conditions, we reviewed previous experimental data for dehydrated bilayers and cholesterol-containing bilayers, and interpreted them with simulations. Although none of the existing models reached experimental accuracy, by critically comparing them we were able to distill relevant chemical information: (1) increase of choline order parameters indicates the P-N vector tilting more parallel to the membrane, and (2) cholesterol induces only minor changes to the PC (glycerol backbone) structure. This work has been done as a fully open collaboration, using nmrlipids.blogspot.fi as a communication platform; all the scientific contributions were made publicly on this blog. During the open research process, the repository holding our simulation trajectories and files ( https://zenodo.org/collection/user-nmrlipids ) has become the most extensive publicly available collection of molecular dynamics simulation trajectories of lipid bilayers.
Institut Lumière Matière, UMR5306 Université Lyon 1-CNRS, Université de Lyon , 69622 Villeurbanne, France.
Alexandru
A
Botan
Departamento de Física, Centro de Investigación y de Estudios Avanzados del IPN, Apartado , Postal 14-740, Mexico City, 07000 México D.F., México.
Fernando
F
Favela-Rosales
Institut Jacques Monod, UMR 7592 CNRS, Université Paris Diderot , Sorbonne, Paris Cité, F-75205 Paris, France.
Patrick F J
PF
Fuchs
Department of Physics, Tampere University of Technology , Tampere, 33101 Finland.
Matti
M
Javanainen
Fachbereich Physik, Freie Universität Berlin , Berlin, 14195 Germany.
Matej
M
Kanduč
Department of Physics, Tampere University of Technology , Tampere, 33101 Finland.
Waldemar
W
Kulig
Department of Chemical Engineering, Kyoto University , 615-8510 Kyoto, Japan.
Antti
A
Lamberg
Institut Lumière Matière, UMR5306 Université Lyon 1-CNRS, Université de Lyon , 69622 Villeurbanne, France.
Claire
C
Loison
Division of Physical Chemistry, Department of Materials and Environmental Chemistry, Stockholm University , S-106 91 Stockholm, Sweden.
Alexander
A
Lyubartsev
Fachbereich Physik, Freie Universität Berlin , Berlin, 14195 Germany.
Markus S
MS
Miettinen
Institut de Biologie et Chimie des Protéines (IBCP) , CNRS UMR 5086, Lyon 69 367, France.
Luca
L
Monticelli
Department of Chemistry, Aalto University , 00076 Aalto, Finland.
Jukka
J
Määttä
Department of Neuroscience and Biomedical Engineering, Aalto University , 00076 Aalto, Finland.
O H Samuli
OH
Ollila
Max Planck Institute for Chemical Energy Conversion , Stiftstr. 34-38, 45470 Mülheim an der Ruhr, Germany.
Marius
M
Retegan
Department of Physics, Tampere University of Technology , Tampere, 33101 Finland.
Tomasz
T
Róg
INSERM, UMR_S 1134, DSIMB , Paris 75739, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR_S 1134 , Paris, France.|Institut National de la Transfusion Sanguine (INTS) , Paris 75739, France.|Laboratoire d'Excellence GR-Ex , Paris 75015, France.
Hubert
H
Santuz
Department of Physics, Tampere University of Technology , Tampere, 33101 Finland.
Joona
J
Tynkkynen
D066241:Carbon-13 Magnetic Resonance Spectroscopy; D005990:Glycerol / Q000737:chemistry*; D015394:Molecular Structure; D010713:Phosphatidylcholines / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy
D010713:Phosphatidylcholines; D005990:Glycerol