Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types.

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TitleUpdate of the CHARMM all-atom additive force field for lipids: validation on six lipid types.
Publication TypeJournal Article
Year of Publication2010
AuthorsKlauda, JB, Venable, RM, J Freites, A, O'Connor, JW, Tobias, DJ, Mondragon-Ramirez, C, Vorobyov, I, Mackerell, AD, Pastor, RW
JournalJ Phys Chem B
Date Published2010 Jun 17
Keywords1,2-Dipalmitoylphosphatidylcholine, Dimyristoylphosphatidylcholine, Lipid Bilayers, Lipids, Molecular Dynamics Simulation, Phosphatidylcholines, Phosphatidylethanolamines, Quantum Theory, Thermodynamics, X-Ray Diffraction

A significant modification to the additive all-atom CHARMM lipid force field (FF) is developed and applied to phospholipid bilayers with both choline and ethanolamine containing head groups and with both saturated and unsaturated aliphatic chains. Motivated by the current CHARMM lipid FF (C27 and C27r) systematically yielding values of the surface area per lipid that are smaller than experimental estimates and gel-like structures of bilayers well above the gel transition temperature, selected torsional, Lennard-Jones and partial atomic charge parameters were modified by targeting both quantum mechanical (QM) and experimental data. QM calculations ranging from high-level ab initio calculations on small molecules to semiempirical QM studies on a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer in combination with experimental thermodynamic data were used as target data for parameter optimization. These changes were tested with simulations of pure bilayers at high hydration of the following six lipids: DPPC, 1,2-dimyristoyl-sn-phosphatidylcholine (DMPC), 1,2-dilauroyl-sn-phosphatidylcholine (DLPC), 1-palmitoyl-2-oleoyl-sn-phosphatidylcholine (POPC), 1,2-dioleoyl-sn-phosphatidylcholine (DOPC), and 1-palmitoyl-2-oleoyl-sn-phosphatidylethanolamine (POPE); simulations of a low hydration DOPC bilayer were also performed. Agreement with experimental surface area is on average within 2%, and the density profiles agree well with neutron and X-ray diffraction experiments. NMR deuterium order parameters (S(CD)) are well predicted with the new FF, including proper splitting of the S(CD) for the aliphatic carbon adjacent to the carbonyl for DPPC, POPE, and POPC bilayers. The area compressibility modulus and frequency dependence of (13)C NMR relaxation rates of DPPC and the water distribution of low hydration DOPC bilayers also agree well with experiment. Accordingly, the presented lipid FF, referred to as C36, allows for molecular dynamics simulations to be run in the tensionless ensemble (NPT), and is anticipated to be of utility for simulations of pure lipid systems as well as heterogeneous systems including membrane proteins.

Alternate JournalJ Phys Chem B
PubMed ID20496934
PubMed Central IDPMC2922408
Grant ListR01 GM072558 / GM / NIGMS NIH HHS / United States
R01 GM070855 / GM / NIGMS NIH HHS / United States
R01 GM072558-06 / GM / NIGMS NIH HHS / United States
P01 GM086685 / GM / NIGMS NIH HHS / United States
GM 72558 / GM / NIGMS NIH HHS / United States
GM 86685 / GM / NIGMS NIH HHS / United States
15101 / / PHS HHS / United States
ZIA HL000340-04 / / Intramural NIH HHS / United States