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: ...

Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types

Docosahexaenoic acid: membrane properties of a unique fatty acid.

Area per Lipid and Acyl Length Distributions in Fluid Phosphatidylcholines Determined by 2H NMR Spectroscopy

Modulation of rhodopsin function by properties of the membrane bilayer

Molecular dynamics simulations of a fluid-phase dipalmitoyl phosphatidylcholine lipid bilayer in water and of neat hexadecane are reported and compared with nuclear magnetic resonance spin-lattice relaxation and quasi-elastic neutron scattering data. On the 100-picosecond time scale of the present simulations, there is effectively no difference in the reorientational dynamics of the carbons in the membrane interior and in pure hexadecane. Given that the calculated fast reorientational correlation times and the "microscopic" lateral diffusion of the lipids show excellent agreement with the experimental results, it is concluded that the apparently high viscosity of the membrane is more closely related to molecular interactions on the surface rather than in the interior.

https://science.sciencemag.org/content/sci/262/5131/223.full.pdf

Molecular dynamics simulations of a lipid bilayer and of hexadecane: an investigation of membrane fluidity

Natural abundance 13C spin-lattice (T1) relaxation time measurements are reported for unilamellar vesicles of 1,2-dipalmitoylphosphatidylcholine (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), in the liquid crystalline phase, at magnetic field strengths of 1.40, 1.87, 2.35, 4.23, 7.05, 8.45, and 11.7 tesla (resonance frequencies of 15.0, 20.0, 25.1, 45.3, 75.5, 90.5, and 126 MHz, respectively), and the results are compared to previous 2H T1 studies of multilamellar dispersions. For both the 13C and 2H T1 studies, a dramatic frequency dependence of the relaxation was observed. At superconducting magnetic field strengths (4.23-11.7 tesla), plots of the 13C T1(-1) relaxation rates as a function of acyl chain segment position clearly reveal the characteristic "plateau" signature of the liquid crystalline phase, as found previously from 2H NMR studies. The dependence of T1(1) on ordering, determined previously from 2H NMR, and the T1(-1) dependence on frequency, determined from both 13C and 2H NMR studies, suggest that a unified picture of the bilayer molecular dynamics can be provided by a simple relaxation law of the form T1(-1) approximately equal to A tau f + BS2C-H omega -1/2(0). In the above expression, A and B are constants, SC-H (= SC-D) is the bond segmental order parameter, and omega 0 is the nuclear Larmor frequency. The first (A) term includes contributions from fast, local segmental motions characterized by the effective correlation time tau f, whereas the second (B) term describes slower, collective fluctuations in the local ordering. The value of tau f approximately equal to 10(-11) sec, obtained by extrapolating T1(-1) to infinite frequency, suggests that the segmental microviscosity of the bilayer hydrocarbon region does not differ appreciably from that of the equivalent n-paraffinic liquids of similar chain length.

https://www.pnas.org/content/pnas/80/14/4325.full.pdf

New view of lipid bilayer dynamics from 2H and 13C NMR relaxation time measurements

The gain a better understanding of the biological roles of polyunsaturated phospholipids, deuterium (/sup 2/H) NMR studies have been conducted of 1-perdeuteriopalmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine, an asymmetric or mixed-chain saturated-polyunsaturated phospholipid, in the liquid crystalline (L/sub ..cap alpha../) phase. The palmitoyl (16:0) chain at the glycerol sn-1 position was labeled with /sup 2/H by perdeuteration, whereas the polyunsaturated, docosahexaenoyl (22:6 omega 3) chain at the sn-2 position was unlabeled, i.e., protiated. The /sup 2/H NMR results were compared to studies of 1,2-diperdeuteriopalmitoyl-sn-glycero-3-phosphocholine, in which both the sn-1 and sn-2 palmitoyl chains were perdeuterated, as well as 1-palmitoyl-2-perdeuteriopalmitoyl-sn-glycero-3-phosphocholine, in which only the sn-2 chain was perdeuterated. Multilamellar phospholipid dispersions containing 50 wt % H/sub 2/O were employed, and /sup 2/H NMR spectra were obtained using quadrupolar echo methods at a magnetic field strength of 8.5 T. The experimental /sup 2/H NMR spectra were numerically deconvoluted (de-Paked) to yield subspectra corresponding to the parallel bilayer orientation with respect to the main applied magnetic field. The increased resolution of the de-Paked subspectra enabled profiles of the segmental order parameters of the individual C-/sup 2/H bonds, denoted by absolute value of S/sub CD/(i), to be derived as a function of chain position. Significant differences in the /supmore » 2/H NMR spectra and derived absolute value of S/sub CD/(i) profiles of the per-/sup 2/H-16:0 chains of the polyunsaturated and saturated bilayers were found.« less

Configurational statistics of acyl chains in polyunsaturated lipid bilayers from deuterium nmr

1 I 0 0.3 06 0.9 1.2 Abstract: 2H NMR studies of a homologous series of 1,2-diacyl-sn-glycero-3-phosphocholines with perdeuterated saturated chains, ranging in length from C12:O to C16:0, have been performed with use of quadrupolar echo techniques at a resonance frequency of 55.4 MHz. Randomly oriented, multilamellar dispersions containing 50 wt % H20 in the liquid crystalline (La) phase have been employed. The 2H spin-lattice relaxation times (TI) and C-2H bond segmental order parameters (SCD) of each of the resolved quadrupolar splittings have been obtained from the powder-type spectra, corresponding to a random distribution of orientations, as well as from the 0 OC oriented subspectra obtained by numerical deconvolution (de-Pakeing). Evidence that the spin-lattice relaxation rate profiles as a function of chain position Tl-'(i) are related to the corresponding order profiles ScD(i) by a square-law functional dependence has been obtained, indicative of a contribution from relatively slow fluctuations in the local bilayer ordering to the relaxation. The results suggest that two broad classes of motions influence the 2H spin-lattice relaxation rates of lipid bilayers: rapid local motions, most likely due to bond rotational isomerizations and long-axis rotational diffusion of the lipid chains, as well as slower director fluctuations as found in other liquid crystalline mesophases.

Dependence of Deuterium Spin-Lattice Relaxation Rates of Multilamellar Phospholipid Dispersions on Orientational Order'

2H and 13C spin‐lattice (T1) relaxation time studies of 1,2‐dipalmitoyl‐sn‐glycero‐3‐phospho‐ choline (DPPC) in the lamellar, liquid crystalline (Lα) phase are discussed. It is shown that the T−11 results as a function of Larmor frequency ω0 are statistically better described by an ω−1/20 dependence than by an ω−10 or ω−20 dependence.

Gerald D. Williams

Papers

New view of lipid bilayer dynamics from 2H and 13C NMR relaxation time measurements

Configurational statistics of acyl chains in polyunsaturated lipid bilayers from deuterium nmr

Dependence of Deuterium Spin-Lattice Relaxation Rates of Multilamellar Phospholipid Dispersions on Orientational Order'

Frequency dependence of spin‐lattice relaxation times of lipid bilayers

Configurational Statistics of Acyl Chains in Polyunsaturated Lipid Bilayers from 2H NMR.