Structural characterization of ether lipids from the archaeon Sulfolobus islandicus by high‐resolution shotgun lipidomics

The molecular structures, biosynthetic pathways and physiological functions of membrane lipids produced by organisms in the domain Archaea are poorly characterized as compared with that of counterparts in Bacteria and Eukaryota. Here we report on the use of high‐resolution shotgun lipidomics to characterize, for the first time, the lipid complement of the archaeon Sulfolobus islandicus. To support the identification of lipids in S. islandicus, we first compiled a database of ether lipid species previously ascribed to Archaea. Next, we analyzed the lipid complement of S. islandicus by high‐resolution Fourier transform mass spectrometry using an ion trap‐orbitrap mass spectrometer. This analysis identified five clusters of molecular ions that matched ether lipids in the database with sub‐ppm mass accuracy. To structurally characterize and validate the identities of the potential lipid species, we performed structural analysis using multistage activation on the ion trap‐orbitrap instrument as well as tandem mass analysis using a quadrupole time‐of‐flight machine. Our analysis identified four ether lipid species previously reported in Archaea, and one ether lipid species that had not been described before. This uncharacterized lipid species features two head group structures composed of a trisaccharide residue carrying an uncommon sulfono group (?SO₃) and an inositol phosphate group. Both head groups are linked to a glycerol dialkyl glycerol tetraether core structure having isoprenoid chains with a total of 80 carbon atoms and 4 cyclopentane moieties. The shotgun lipidomics approach deployed here defines a novel workflow for exploratory lipid profiling of Archaea. Copyright © 2015 John Wiley & Sons, Ltd.     

CHARMM‐GUI Membrane Builder toward realistic biological membrane simulations

CHARMM‐GUI Membrane Builder, http://www.charmm‐gui.org/input/membrane , is a web‐based user interface designed to interactively build all‐atom protein/membrane or membrane‐only systems for molecular dynamics simulations through an automated optimized process. In this work, we describe the new features and major improvements in Membrane Builder that allow users to robustly build realistic biological membrane systems, including (1) addition of new lipid types, such as phosphoinositides, cardiolipin (CL), sphingolipids, bacterial lipids, and ergosterol, yielding more than 180 lipid types, (2) enhanced building procedure for lipid packing around protein, (3) reliable algorithm to detect lipid tail penetration to ring structures and protein surface, (4) distance‐based algorithm for faster initial ion displacement, (5) CHARMM inputs for P₂₁ image transformation, and (6) NAMD equilibration and production inputs. The robustness of these new features is illustrated by building and simulating a membrane model of the polar and septal regions of E. coli membrane, which contains five lipid types: CL lipids with two types of acyl chains and phosphatidylethanolamine lipids with three types of acyl chains. It is our hope that CHARMM‐GUI Membrane Builder becomes a useful tool for simulation studies to better understand the structure and dynamics of proteins and lipids in realistic biological membrane environments. © 2014 Wiley Periodicals, Inc.     

Stereoelective cationic polymerization of propenyl ether by asymmetric catalysts

In order to elucidate the possibility of stereoelective cationic polymerization (asymmetric selective polymerization) of olefinic monomers, racemic cis- and trans-1-methylpropyl propenyl ether and racemic 1-methylpropyl vinyl ether were polymerized by asymmetric alkoxyaluminum dichlorides. In the polymerization of racemic cis-1-methylpropyl propenyl ether with (?)-menthoxyaluminum dichloride in toluene at ?78°C, the polymer obtained showed a positive optical activity, and the residual monomers were converted by BF₃OEt₂ into a polymer having a negative optical activity. Thus, the stereoelective polymerization of racemic cis-1-methylpropyl propenyl ether was beyond any doubt attained in homogeneous cationic polymerization. In the polymerization of the trans isomer by the same catalyst, an optically active polymer was hardly formed. In the polymerization of racemic 1-methylpropyl vinyl ether which has no β-methyl group, stereoelectivity was not observed at all. The cis-1-methylpropyl propenyl ether did not produce an optical active polymer in the polymerization catalyzed by (S)-1-methylpropoxyaluminum dichloride or (S)-2-methylbutoxyaluminum dichloride under the same polymerization conditions.     

Stereoregularity of poly(vinyl ether)

α-Methylvinyl isobutyl and methyl ethers were polymerized cationically and the structure of the polymers was studied by NMR. Poly(α-methylvinyl methyl ether) polymerized with iodine or ferric chloride as catalyst was found to be almost atactic, whereas poly(α-methylvinyl isobutyl ether) polymerized in toluene with BF₃OEt₂ or AlEt₂Cl as catalyst was found to be isotactic. In both cases, the addition of polar solvent resulted in the increase of syndiotactic structure as is the case with polymerization of alkyl vinyl ether. tert-Butyl vinyl ether was polymerized, and the polymer was converted into poly(vinyl acetate), the structure of which was studied by NMR. A nearly linear relationship between the optical density ratio D₇₂₂/D₇₃₆ in poly(tert-butyl vinyl ether) and the isotacticity of the converted poly(vinyl acetate) was observed.     

Structural study on poly(ether ether ketone ketone)-poly(ether biphenyl ether ketone ketone) copolymers

Structures of poly(ether ether ketone ketone)-poly(ether biphenyl ether ketone ketone) copolymers were studied by using small angle X-ray scattering and the one-dimensional electron density correlation function method. The results revealed that structures of the aggregated state of the copolymers depend closely on the biphenyl content (n_b). When n_b = 0.35, invariant Q, long period L, average thickness of crystal lamellae d̄, electron density difference η_c − η_a and degree of crystallinity W_{c, x} assume minimum values.     

Glass transition and miscibility in blends of two semicrystalline polymers: Poly(aryl ether ketone) and poly(ether ether ketone)

Binary melt‐blended mixtures of two aryl ether ketone polymers (i.e., a new poly(aryl ether ketone) (code name PK99) and poly(ether ether ketone) (PEEK), have been studied. Polymer miscibility in glassy amorphous (or melt) domains has been demonstrated for the binary blend comprising of two aryl‐ether‐ketone‐type semicrystalline polymers. Composition‐dependent, single T_g was observed within full composition range in the PK99/PEEK blends, and the narrow T_g breadth also suggests that the scale of mixing was fine and uniform. To better resolve any possible overlapping T_g's, physical aging was imposed on a comparison set of blend samples for the purpose of improving detectability of overlapped multiple transitions if existing. The result still showed one single T_g. The relative sharp T_g and lack of cloud point transition suggest that the scale of molecular intermixing is good. Phase homogeneity was further confirmed using optical and scanning electron microscopy. The X‐ray diffractograms suggest that isomorphism does not exist in the PK99/PEEK blends and that the crystal forms of the respective polymers remain distinct and unchanged by the miscibility in the amorphous region. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 1485–1494, 1999     

Polyaniline decorated graphene oxide on sulfonated poly(ether ether ketone) membrane for direct methanol fuel cells application

In direct methanol fuel cells (DMFC), methanol crossover is a major issue which has reduced the performance of polymer electrolyte membrane (PEM) for energy generation. In this study, graphene oxide (GO) and conductive polyaniline decorated GO (PANI-GO) were used as additives in fabrication of sulfonated poly(ether ether ketone) (SPEEK) nanocomposite PEM membrane to reduce methanol crossover. PANI-GO was synthesized by in situ polymerization method and the formation of PANI coated GO nanostructures was confirmed by surface morphology and crystallinity analysis. The membrane morphology and topography analysis confirmed that GO and PANI-GO were well dispersed on the surface of SPEEK membrane. 0.1 wt% PANI-GO modified SPEEK nanocomposite membrane exhibited the highest water uptake and ion exchange capacity of 40% and 1.74 meq g^?1, respectively. The oxidative stability of the nanocomposite membranes also improved. Lower methanol permeability of 4.33 × 10^?7 cm^?2S^?1 was noticed for 0.1 wt% PANI-GO modified SPEEK membrane. PANI-GO modified SPEEK membrane enhanced the proton conductivity, which was due to the existence of acidic and hydrophilic group present in PANI and GO. PANI-GO modified SPEEK membrane held higher selectivity of 1.94 × 10⁴ S cm^?3 s^?1. Overall, these studies revealed that PANI-GO modified SPEEK membrane is a potential material for DMFC applications.     

Profiling changes triggered during maturation of dendritic cells: a lipidomic approach

Lipids are important in several biological processes because they act as signalling and regulating molecules, or, locally, as membrane components that modulate protein function. This paper reports the pattern of lipid composition of dendritic cells (DCs), a cell type of critical importance in inflammatory and immune responses. After activation by antigens, DCs undergo drastic phenotypical and functional transformations, in a process known as maturation. To better characterize this process, changes of lipid profile were evaluated by use of a lipidomic approach. As an experimental model of DCs, we used a foetal skin-derived dendritic cell line (FSDC) induced to mature by treatment with lipopolysaccharide (LPS). The results showed that LPS treatment increased ceramide (Cer) and phosphatidylcholine (PC) levels and reduced sphingomyelin (SM) and phosphatidylinositol (PI) content. Mass spectrometric analysis of a total lipid extract and of each class of lipids revealed that maturation promoted clear changes in ceramide profile. Quantitative analysis enabled identification of an increase in the total ceramide content and enhanced Cer at m/z 646.6, identified as Cer(d18:1/24:1), and at m/z 648.6, identified as Cer(d18:1/24:0). The pattern of change of these lipids give an extremely rich source of data for evaluating modulation of specific lipid species triggered during DC maturation.     

Structural and transport phenomena of urocanate-based proton carrier in sulfonated poly(ether ether ketone) membrane composite

Proton transport is one of crucial phenomena in electrolytic part highly considered to overcome a limit in fuel cell efficiency improvement. Proton conducting organic electrolyte was modeled and simulated at atomistic level of calculation by doping of butyl urocanate (C4U), a composite material with imidazole substructure, with sulfonated poly(ether ether ketone) (SPEEK) amorphous membrane at various working temperature. Molecular dynamics simulations were used to investigate structural and dynamics characteristic of C4U in the membrane comparing with the SPEEK-hydronium membrane model as a control. From simulations, thermal effect on water and proton carriers cluster surrounding the sulfonate groups was explored. At higher temperature, the more transport dynamics of C4U ions in SPEEK membranes were found than that of hydronium ions in the control system. Likewise, phase separation of hydrophobic and hydrophilic parts was taken into consideration here. A critical role of the enhancing proton conductivity by increasing the diffusion coefficient at temperature beyond C4U melting point in composite polymer membrane was emphasized. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 1625–1635     

Polymers derived from fluoroketones. III. Monomer synthesis,polymerization, and wetting properties of poly(allyl ether) and poly(vinyl ether)

The synthesis and polymerization of a series of perhaloalkyl allyl and vinyl ethers derived from perhaloketones is described. Data on the critical surface tension of wetting (γ_c) for high molecular weight polymers of heptafluoroisopropyl vinyl ether and low molecular weight poly(heptafluoroisopropyl allyl ether) is also presented. Preparation of the allyl ethers is a one-step, high-yield displacement reaction between the potassium fluoride–perhaloacetone adduct and an allyl halide, such as allyl bromide. The vinyl ethersare prepared by a two-step process which involves displacement of halide from a 1,2-dihaloethane with a KF–perhaloacetone adduct and dehydrohalogenation of the 1-halo-2-perhaloalkoxyethane to a vinyl ether. Low molecular weight polymers were obtained with heptafluoroisopropyl allyl ether by using a high concentration of a free-radical initiator. The low molecular weight poly(heptafluoroisopropyl allyl ether) had a γ_c of 21 dyne/cm. No polymer was obtained with tributylborane–oxygen or with VCl₃–AIR₃, with gamma radiation, or by exposure to ultraviolet light. High molecular weight polymers were obtained from heptafluoroisopropyl vinyl either by using either lauryl peroxide or ultraviolet light but not by exposure to BF₃–etherate. The γ_c for poly(heptafluoroisopropyl vinyl ether) ranged from 14.2 to 14.6 dyne/cm., and the significance of this value is discussed in relation to the γ_c for poly(heptafluoroisopropyl acrylate).     

Methoxy‐ether and crown‐ether ­derivatives of tetrahomodioxa‐ and octahomotetraoxacalix­[4]­arenes

Three methoxy­‐ether and one methoxy‐­ether/crown‐ether derivatives of p‐tert‐butyl­tetrahomodioxa‐ and p‐R‐octahomo­tetraoxacalix­[4]­arenes (R = methyl, tert‐butyl, H) have been investigated. The first three compounds, 7,15,21,27‐tetra‐tert‐butyl‐29,30,31,32‐tetra­methoxy‐3,11‐dioxapenta­cyclo­[23.3.­1.1^5,9.1^13,17.1^19,23]­ditriaconta‐1(29),5,7,­9(30),­13,15,‐17(31),­19,21,23(32),25,27‐dodecaene, C₅₀H₆₈O₆, 33,34,35,36‐tetra­methoxy‐7,15,23,31‐tetra­methyl‐3,11,19,27‐tetra­oxa­penta­cyclo[27.3.1.1^5,9.1^13,17.1^21,25]­hexa­tri­aconta‐1(33),5,7,9(34),13,15,­17(35),21,23,25(36),29,31‐dodecaene, C₄₀H₄₈O₈, and 7,23‐di‐tert‐butyl‐33,34,35,36‐tetra­methoxy‐3,11,19,27‐tetraoxapenta­cyclo­[27.3.1.1^5,9.1^13,17.1^21,25]­hexatriaconta‐1(33),5,7,9(34),13,15,­17(35),‐ 21,23,25(36),29,31‐dodecaene, C₄₄H₅₆O₈, in the partial‐cone or 1,2‐alternate conformations, present the common feature of methoxy‐­ether self‐inclusion, while the fourth, 42,43‐di­methoxy‐7,15,23,31‐tetra­methyl‐3,11,19,27,34,37,40‐heptaoxahexa­cyclo[15.15.9.1^5,9.1^21,25.0^13,41.0^29,33]­tritetra­conta‐5(42),6,8,13(41),­14,16,21(43),22,24,29(33),30,32‐dodecaene, C₄₂H₅₀O₉, adopts the 1,3‐alternate conformation owing to the presence of a 1,3‐polyether chain.     

Imide-aryl ether ketone block copolymers

Imide-aryl ether ketone block copolymers were prepared and their morphology and thermal and mechanical properties investigated. Two aryl ether ketone blocks were incorporated; the first was an amorphous block derived from bisphenol–A and the second block was a semi-crystalline poly(aryl ether ether ketone) prepared from a soluble and amorphous ketimine precursor. Bis(amino) aryl ether ketone and aryl ether ketimine oligomers were prepared via a nucleophilic aromaic substitution reaction with molecular weights ranging from 6,000 to 12,000 g/mol. The oligomers were co-reacted with 4,4′-oxydianiline (ODA) and pyromellitic dianhydride (PMDA) diethyl ester diacyl chloride in N-methyl–2-pyrrolidone (NMP) in the presence of N-methylmorpholine. The copolymer compositions, determined by H-NMR, of the resulting amic ester based copolymers ranged from 8 to 50 wt % aryl ether ketone or ketimine content. Prior to imide formation, the ketimine moiety of the aryl ether ketimine block was hydrolyzed (p-toluene sulfonic acid) to the ketone form producing the aryl ether ether ketone block. Compositions of this block were maintained low to retain solubility. Solutions of the copolymers were cast and cured to effect imidization, producing clear films with high moduli (ca. 2200 MPa) and elongations (33–100%). The copolymers displayed good thermal stability with decomposition temperatures in excess of 450°C. Multiphase morphologies were observed irrespective of the co-block type, block length or composition. © 1992 John Wiley & Sons, Inc.     

Synthesis of copolymers of poly(ether sulfone ether ketone ketone) and poly(ether ketone diphenyl ketone ether ketone ketone) by electrophilic Friedel–Crafts solution polycondensation

A new monomer, 4,4′‐bis(4‐phenoxybenzoyl)diphenyl(BPOBDP), was synthesized via a two‐step synthetic procedure. A series of novel poly(ether sulfone ether ketone ketone)/poly(ether ketone diphenyl ketone ether ketone ketone) copolymers were prepared by electrophilic Friedel–Crafts solution copolycondensation of isophthaloyl chloride (IPC) with a mixture of 4,4′‐diphenoxydiphenylsulfone (DPODPS) and 4,4′‐bis(4‐phenoxybenzoyl)diphenyl (BPOBDP), in the presence of anhydrous aluminum chloride and N‐methylpyrrolidone (NMP) in 1,2‐dichloroethane (DCE). The copolymers with 10–50 mol% DPODPS are semicrystalline and have remarkably increased T_gs over commercially available PEEK and PEKK. The copolymers with 40–50 mol% DPODPS had not only high T_gs of 170–172°C, but also moderate T_ms of 326–333°C, which are extremely suitable for melt processing. These copolymers have tensile strengths of 96.5–108.1 MPa, Young's moduli of 1.98–3.05 GPa, and elongations at break of 13–26% and exhibit excellent thermal stability and good resistance to acidity, alkali, and common organic solvents. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis of aromatic poly(ether amide amide ether ketone ketone)s by electrophilic Friedel–Crafts solution polycondensation

A new monomer, N,N′‐bis(4‐phenoxybenzoyl)‐p‐phenylenediamine (BPBPPD), was prepared by the condensation of p‐phenylenediamine with 4‐phenoxybenzoyl chloride in N,N‐dimethylacetamide (DMAc). Novel aromatic poly(ether amide amide ether ketone ketone)s (PEAAEKKs) were synthesized by electrophilic Friedel–Crafts solution copolycondensation of BPBPPD with a mixture of terephthaloyl chloride (TPC) and isophthaloyl chloride (IPC), over a wide range of TPC/IPC molar ratios, in the presence of anhydrous aluminum chloride and N‐methylpyrrolidone (NMP) in 1,2‐dichloroethane (DCE). The influences of reaction conditions on the preparation of polymers were examined. The polymers obtained were characterized by different physico–chemical techniques such as FT‐IR, Differential scanning calorimetry (DSC), Thermogravimetric analysis (TGA), and wide angle X‐ray diffraction (WAXD). The polymers with 70–100 mol% IPC are semicrystalline and have remarkably increased T_gs over commercially available poly(ether ether ketone) (PEEK) and poly(ether ketone ketone) (PEKK) due to the incorporation of amide groups in the main chain. The polymers with 70–80 mol% IPC had not only high T_gs of 209–213°C, but also moderate T_ms of 339–348°C, which are suitable for melt processing. The polymers with 70–80 mol% IPC had tensile strengths of 107.5–109.8 MPa, Young's moduli of 2.53–2.69 GPa, and elongations at break of 9–11% and exhibited high thermal stability and good resistance to organic solvents. Copyright © 2009 John Wiley & Sons, Ltd.     

Lipids from the Marine Alga <Emphasis Type="Italic">Gracilaria verrucosa</Emphasis>

The composition of lipids and fatty acids from the red alga Gracilaria verrucosa, for which a high content of 20:4n-6 acid is typical, was studied. The principal lipids were digalactosyldiacylglycerides, phosphatidylcholines (PC), monogalactosyldiacylglyderides (MGDG), and sulfoquinovosyldiacylglycerides, the fraction of each was approximately the same. Sphingophospholipids, inositephosphoceramides, were identified among the polar lipids. Each lipid class differed in the ratio of fatty acids (FA). The FA of all glycerolipids contained 20:4n-6 acid but its concentration was greatest in MGDG and PC, 67.2% and 56.5% of the acid mass.__________Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 230–232, May–June, 2005.     

Melting behavior of poly(ether ether ketone) in its blends with poly(ether imide)

We detail the melting behavior of poly(ether ether ketone) (PEEK) and investigate its melting behavior in miscible blends with poly(ether imide) (PEI). The determination of the equilibrium melting point (T_m⁰) of PEEK is discussed by considering its inhomogeneous morphology. T_m⁰ is obtained by a long extrapolation of a Hoffman–Weeks plot to 384°C. Hindrance of PEEK crystal reorganization induced by PEI during heating is observed over the blend composition investigated (20–75 wt % PEEK). This behavior is correlated with the incorporation of PEI in the interlamellar zones of PEEK crystals. The interaction parameter χ of PEEK/PEI blends is estimated by the equilibrium melting point depression. This gives the interaction density B = ?1.2 cal/cm³, and x = ?0.40 at 400°C. © 1993 John Wiley & Sons, Inc.     

Anionic polymerization of propylene oxide: Isomerization of allyl ether to propenyl ether end groups

The isomerization of allyl ether to propenyl ether end group in anionically-polymerized poly (propylene oxide) was monitored by ¹H NMR spectroscopy. It was confirmed that the reaction followed a simple second-order rate law: ?d[allyl]dt = k₂[allyl] [O^?]. Values of k₂ determined over the 90–130°C temperature range, indicated an activation energy of 116 kJ mol^?1. © 1994 John Wiley & Sons, Inc.     

Structure‐controlled synthesis of novel soluble and thermally stable poly (aryl ether nitrile ether ketone ketone)/poly (aryl ether nitrile ether ketone biphenyl ketone) copolymers by electrophilic polycondensation

One new synthesis route was first designed to synthesize the biphenyl acid chloride (BPACl), and then a series of novel poly (aryl ether nitrile ether ketone ketone) (PENEKK)/poly (aryl ether nitrile ether ketone biphenyl ketone) (PENEKBK) copolymers with different controlled structure compositions were synthesized by electrophilic polycondensation and varying the molar ratio of BPACl to terephthaloyl chloride (TPC). The obtained PENEKK/PENEKBK copolymers were characterized by different physical and chemical techniques. The results showed, the copolymers with 10–50% molar contents of biphenyl moities exhibited good thermal properties with glass transition temperatures (T_gs) of 184–196°C, decomposition temperatures (T_ds) of 498–515°C, and good solubility in organic solvents (N‐Methyl‐2‐pyrrolidone (NMP), N,N‐dimethylformamide (DMF), and DMSO), indicating that they would have good potential for solvent processing. The thin films of the polymers had tensile strengths of 93.6–101.5 MPa, Young's moduli of 3.03–3.32 GPa, elongations at break of 9–14%, indicating they were strong materials. The densities of the obtained polymers were 1.31–1.40 g/cm^?3, which were far lower than those of some main inorganic materials (such as Fe, nearly 7.8 g/cm^?3), indicating that they would have possible potential for substituting some inorganic materials used as high temperature materials in some areas due to the merits of lightweight. Thus, the copolymers with 10–50% molar contents of biphenyl moities were promising polymer materials. Copyright © 2010 John Wiley & Sons, Ltd.     

Mass spectral characteristics of poly(2,6-dimethyl-1,4-phenylene ether)

The mass spectral characteristics of poly(2,6-dimethyl-1,4-phenylene ether), its monomer (2,6-xylenol), and its dimer (3,5-dimethyl-4-hydroxyphenyl 2,6-xylyl ether) have been determined. The monomer and dimer show peaks for the molecular ions (122; 242 amu) and degradation patterns similar to those of o-methylaryl ethers. Loss of methyl and cleavage of the ether with transfer of an o-methyl hydrogen are observed. Metastable transitions are recorded corresponding to a loss of 15 from 122 and 56 from 107 amu (xylenol) and of 151 from 242 and 40 from 104 amu (ether). The polymer volatilizes readily at 380–400°C. (TGA shows rapid weight loss at 400°C) and gives sets of peaks at (N × 120) ± 14 up to 1080 (N = 9). The principal peak is at (N × 120) + 2, calibrated against PFA, and this is attributed to an ion of a volatilized oligomer. The oligomer is either present as such, is formed in a degradation process involving an ether redistribution, or is formed in a hydrogen transfer process in the ether cleavage reaction.     

G-Protein-Coupled Receptor–Membrane Interactions Depend on the Receptor Activation State

G-protein-coupled receptors (GPCRs) are the largest family of human membrane proteins and serve as primary targets of approximately one-third of currently marketed drugs. In particular, adenosine A₁ receptor (A₁AR) is an important therapeutic target for treating cardiac ischemia–reperfusion injuries, neuropathic pain, and renal diseases. As a prototypical GPCR, the A₁AR is located within a phospholipid membrane bilayer and transmits cellular signals by changing between different conformational states. It is important to elucidate the lipid–protein interactions in order to understand the functional mechanism of GPCRs. Here, all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method were performed on both the inactive (antagonist bound) and active (agonist and G-protein bound) A₁AR, which was embedded in a 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) lipid bilayer. In the GaMD simulations, the membrane lipids played a key role in stabilizing different conformational states of the A₁AR. Our simulations further identified important regions of the receptor that interacted distinctly with the lipids in highly correlated manner. Activation of the A₁AR led to differential dynamics in the upper and lower leaflets of the lipid bilayer. In summary, GaMD enhanced simulations have revealed strongly coupled dynamics of the GPCR and lipids that depend on the receptor activation state. © 2019 Wiley Periodicals, Inc.