scholarly journals Membrane Hydrophobicity Determines the Activation Free Energy of Passive Lipid Transport

2021 ◽  
Author(s):  
Julia R. Rogers ◽  
Gustavo Espinoza Garcia ◽  
Phillip L. Geissler
Keyword(s):  
Free Energy ◽  
Acyl Chain ◽  
Lipid Transport ◽  
Membrane Composition ◽  
Free Energies ◽  
Membrane Phase ◽  
Energy Barriers ◽  
Activation Free Energy ◽  
Acyl Chain Length ◽  
Lipid Dynamics

ABSTRACTThe collective behavior of lipids with diverse chemical and physical features determines a membrane’s thermodynamic properties. Yet, the influence of lipid physicochemical properties on lipid dynamics, in particular interbilayer transport, remains underexplored. Here, we systematically investigate how the activation free energy of passive lipid transport depends on lipid chemistry and membrane phase. Through all-atom molecular dynamics simulations of 11 chemically distinct glycerophospholipids, we determine how lipid acyl chain length, unsaturation, and headgroup influence the free energy barriers for two elementary steps of lipid transport, lipid desorption, which is rate-limiting, and lipid insertion into a membrane. Consistent with previous experimental measurements, we find that lipids with longer, saturated acyl chains have increased activation free energies compared to lipids with shorter, unsaturated chains. Lipids with different headgroups exhibit a range of activation free energies; however, no clear trend based solely on chemical structure can be identified, mirroring difficulties in the interpretation of previous experimental results. Compared to liquid-crystalline phase membranes, gel phase membranes exhibit substantially increased free energy barriers. Overall, we find that the activation free energy depends on a lipid’s local hydrophobic environment in a membrane and that the free energy barrier for lipid insertion depends on a membrane’s interfacial hydrophobicity. Both of these properties can be altered through changes in lipid acyl chain length, lipid headgroup, and membrane phase. Thus, the rate of lipid transport can be tuned through subtle changes in local membrane composition and order, suggesting an unappreciated role for nanoscale membrane domains in regulating cellular lipid dynamics.SIGNIFICANCECell homeostasis requires spatiotemporal regulation of heterogeneous membrane compositions, in part, through non-vesicular transport of individual lipids between membranes. By systematically investigating how the chemical diversity present in glycerophospholipidomes and variations in membrane order influence the free energy barriers for passive lipid transport, we discover a correlation between the activation free energy and membrane hydrophobicity. By demonstrating how membrane hydrophobicity is modulated by local changes in membrane composition and order, we solidify the link between membrane physicochemical properties and lipid transport rates. Our results suggest that variations in cell membrane hydrophobicity may be exploited to direct non-vesicular lipid traffic.

Thermodynamic studies in solution. Part IV. Solvent effect on the solvolysis of tert-butyl chloride. A new treatment of the experimental data

1979 ◽  
Vol 57 (5) ◽  
pp. 500-502 ◽  
Author(s):  
Joaquim Jose Moura Ramos ◽  
Jacques Reisse ◽  
M. H. Abraham
Keyword(s):  
Free Energy ◽  
Solvent Effect ◽  
Free Energies ◽  
Butyl Chloride ◽  
Activation Free Energy ◽  
Tert Butyl ◽  
New Treatment ◽  
The One ◽  
Activated Complex ◽  
Tert Butyl Chloride

A new treatment of the solvent effect on the solvolysis of tert-butyl chloride is proposed. This treatment is based on activation free energy measurements and on transfer free energy measurements of the reactant (R) on the one hand and of a model (M) of the activated complex (AC) on the other hand. Solute–solvent interaction free energies for the reactant, the activated complex and the model compound are estimated. This estimation involves the calculation of the free energy of cavity formation of these various solutes (R, AC, and M) in all the solvents. These cavity terms, which are a function of the cohesive properties of the solvent and of the surface of the cavity do not reflect the electronic structure of the solute whereas the interaction free energy term does. The method we propose can be described as a new 'experimental' approach for the study of the charge separation in an activated complex.

Article

1999 ◽  
Vol 77 (5-6) ◽  
pp. 934-942
Author(s):  
J Peter Guthrie
Keyword(s):  
Carbon Dioxide ◽  
Free Energy ◽  
Equilibrium Constants ◽  
Marcus Theory ◽  
Energy Of Activation ◽  
Free Energies ◽  
Orbital Theory ◽  
Activation Free Energy ◽  
Free Energy Of Activation ◽  
Rms Error

Rate constants for hydration of carbon dioxide and ketene can be calculated by applying No Barrier Theory, which needs only equilibrium constants and distortion energies, the latter calculated using molecular orbital theory. The calculated free energies of activation are in satisfactory agreement with experiment: the rms error in free energy of activation is 2.38 kcal/mol. These compounds can also be described using Marcus Theory or Multidimensional Marcus Theory using the transferable intrinsic barrier appropriate to simple carbonyl compounds; in this case the rms error in free energy of activation is 2.19 kcal/mol. The two methods agree on preferred mechanistic path except for uncatalyzed hydration of ketene where Multidimensional Marcus Theory leads to a lower activation free energy for addition to the C=O, while No Barrier Theory leads to a lower free energy of activation for addition to the C=CH2. A rate constant for hydroxide ion catalyzed hydration of ketene can be calculated and is in accord with preliminary experimental results.Key words: ketene, carbon dioxide, hydration, Marcus Theory, No Barrier Theory.

scholarly journals The effect of membrane composition and alcohols on the insulin-sensitive reconstituted monosaccharide-transport system of rat adipocyte plasma membranes

1983 ◽  
Vol 216 (1) ◽  
pp. 113-120 ◽  
Author(s):  
J E More ◽  
M N Jones
Keyword(s):  
Fatty Acids ◽  
Glucose Uptake ◽  
Plasma Membranes ◽  
Acyl Chain ◽  
Membrane Composition ◽  
Monosaccharide Transporter ◽  
Acyl Chain Length ◽  
Monosaccharide Transport ◽  
Phospholipid Acyl Chain ◽  
Adipocyte Plasma Membranes

The monosaccharide transporter from the plasma membranes of rat adipocytes and insulin-stimulated adipocytes has been reconstituted in sonicated liposomes. The stereospecific D-glucose uptake by liposomes made from a range of phospholipids and incorporating fatty acids has been investigated. D-Glucose uptake is correlated with an increase in lipid fluidity as a consequence of the addition of fluidizing fatty acids, changes in phospholipid acyl chain length and temperature. Benzyl alcohol and ethyl alcohol, which are generally considered to increase bilayer fluidity, decrease stereo-specific D-glucose uptake in both whole adipocytes and reconstituted liposomes. It is suggested that, although these alcohols may affect D-glucose transport by lipid-mediated fluidity changes, they also interact directly with the transporter resulting in inhibition of transport.

Theoretical and experimental barriers to internal rotation in 2,6-difluorobenzaldehyde and 2,4,6-trifluorobenzaldehyde. Relatively low barriers

1995 ◽  
Vol 73 (1) ◽  
pp. 106-112 ◽  
Author(s):  
Ted Schaefer ◽  
Craig S. Takeuchi ◽  
Guy M. Bernard ◽  
Frank E. Hruska
Keyword(s):  
Free Energy ◽  
Molecular Orbital ◽  
Parent Compound ◽  
Free Energies ◽  
Orbital Theory ◽  
Energy Barriers ◽  
Internal Barrier ◽  
Rotational Barriers ◽  
Linear Relationships ◽  
Internal Rotational Barriers

The free energies of activation at 110 K for rotation about the exocyclic C—C bonds in 2,6-difluorobenzaldehyde and 2,4,6-trifluorobenzaldehyde, in dimethyl ether solutions, are 18.8 ± 0.5 and 20.0 ± 0.5 kJ mol−1, respectively, as determined from 19F{1H} dynamic nuclear magnetic resonance measurements. For the parent compound ΔG≠ is 32.2 kJ mol−1 in the same solvent. These free energy barriers, the lowest available for benzaldehyde derivatives, are likely a result of steric and electrostatic repulsions between the C+—O− and C+—F− bonds. Computations of the spectroscopic barrier in the 2,6-difluoro compound at various levels of molecular orbital theory imply that the barrier is predominantly twofold, with a fourfold component of opposite sign, whose magnitude is about 10% of the twofold component. A correlation-gradient computation, MP2/6-31G*, finds a barrier height of 18.6 kJ mol−1 for this compound, lower by 3.0 kJ mol−1 than found with the 6-31G* basis and 2.9 kJ mol−1 with 6-31G**. Similar computations are compared for the parent compound and the 4-fluoro, 2,4,6-trifluoro, and 3,5-difluoro derivatives. Linear relationships exist between the computed spectroscopic barriers (ΔE values at absolute zero for the free molecules) and the free energy barriers for benzaldehyde and the four fluoro derivatives; the theoretical barriers utilize 6-31G** and correlation-gradient MP2/6-31G* procedures. For the 2,6-difluoro derivative, the computed frequencies of the torsional motions about the exocyclic C—C bond yield spectroscopic twofold barriers. These barriers are much lower than the computed energy differences between the planar and perpendicular conformers, perhaps because the negative fourfold components flatten the potential at its minimum. A rough estimate of the relationship between ΔG≠ and ΔE0 for the 2,6-difluorobenzaldehyde suggests that the solvent increases the internal barrier by only about 3 kJ mol−1. By way of contrast, the AM1 barriers, scaled by a factor of 1.9 (as previously recommended) range from 17.3 to 22.6 kJ mol−1, the ΔG≠ values from 18.8(5) to 34.4 kJ mol−1, and the MP2/6-31G* (correlation-gradient) barriers span 18.6 to 36.8 kJ mol−1 for benzaldehyde and the four fluorine derivatives. It seems likely that the internal barrier in benzaldehyde is considerably larger than that modeled on torsional frequencies. Keywords: Free energies of activation, internal rotational barriers in 2,6-difluoro- and 2,4,6-trifluorobenzaldehyde; molecular orbital computations, internal rotational barriers in 2,6-difluoro- and 2,4,6-trifluorobenzaldehyde; correlation gradient computations on internal barriers in benzaldehyde and four of its fluorine derivatives.

Glutathione radical: Intramolecular H abstraction by the thiyl radical

2001 ◽  
Vol 79 (4) ◽  
pp. 405-417 ◽  
Author(s):  
A Rauk ◽  
D A Armstrong ◽  
J Berges
Keyword(s):  
Free Energy ◽  
Gas Phase ◽  
Hydrogen Transfer ◽  
Single Point ◽  
Continuum Models ◽  
Thiyl Radical ◽  
Free Energies ◽  
Model Compounds ◽  
Activation Free Energy ◽  
Transition Structures

Ab initio computations (B3LYP/6-31G(D)) were used to predict transition structures and energies of activation for intramolecular H atom transfer to a thiyl radical (RS.) from the α-C—H bonds of glutathione (1) and from the model compounds, N-formylcysteinylglycine (2) and N-(2-thioethanyl)-γ-glutamine (3). For each compound, transition structures were located by in vacuo calculations on the neutral non-zwitterionic system. Thermodynamic functions derived at the same level and single point calculations at the B3LYP/6-311+G(3df,2p) level, were used to derive free energies of activation (ΔG[Formula: see text]) and reaction (ΔG°). For abstraction of the α-C—H (Gly) by the thiyl radical in the gas phase, ΔG[Formula: see text] = 134 kJ mol–1 if the amide link to Gly is in the more stable (Z)-configuration, and ΔG[Formula: see text] = 52 kJ mol–1 if it is in the less stable (E)-configuration. The isomerization of the amide group requires about 95 kJ mol–1. Previous studies had indicated that for intramolecular reaction of the thiyl radical at α-C—H (Cys), ΔG[Formula: see text] = 110 kJ mol–1. The lowest energy pathway for intramolecular H-transfer to the thiyl radical is from α-C—H (Gln), ΔG[Formula: see text] = 37–42 kJ mol–1, and corresponds rather well with experimental results in solution (ΔG[Formula: see text] = 43 kJ mol–1). The calculated free energy change for the equilibrium between thiyl and α-C forms of the glutathione radical is ΔG° = –54 kJ mol–1. The value estimated from experimental data is ΔG° = –37 kJ mol–1. The agreement between the energies from theory in the gas phase and experiment in solution suggests that the free energies of solvation of reactant thiyl radical, transition structures for H abstraction, and the product α-C-centred radical, are very similar. The effects of solution were estimated by two continuum models (SCIPCM and COSMO). The SCIPCM model yields results very similar to the gas phase, predicting a modest lowering of the activation free energy. The results from the COSMO method were inconclusive as to whether a rate enhancement or decrease could be expected.Key words: glutathione, thiyl radical, α-C-radical, hydrogen transfer.

SAMPL6 Octanol-Water Partition Coefficients from Alchemical Free Energy Calculations with MBIS Atomic Charges

2019 ◽  
Author(s):  
Maximiliano Riquelme ◽  
Esteban Vöhringer-Martinez
Keyword(s):  
Free Energy ◽  
Electron Density ◽  
Free Energy Calculations ◽  
Basis Set ◽  
Energetic Cost ◽  
Atomic Charges ◽  
Free Energies ◽  
Energy Calculations ◽  
Alchemical Free Energy ◽  
Alchemical Free Energy Calculations

In molecular modeling the description of the interactions between molecules forms the basis for a correct prediction of macroscopic observables. Here, we derive atomic charges from the implicitly polarized electron density of eleven molecules in the SAMPL6 challenge using the Hirshfeld-I and Minimal Basis Set Iterative Stockholder(MBIS) partitioning method. These atomic charges combined with other parameters in the GAFF force field and different water/octanol models were then used in alchemical free energy calculations to obtain hydration and solvation free energies, which after correction for the polarization cost, result in the blind prediction of the partition coefficient. From the tested partitioning methods and water models the S-MBIS atomic charges with the TIP3P water model presented the smallest deviation from the experiment. Conformational dependence of the free energies and the energetic cost associated with the polarization of the electron density are discussed.

Calculation of the free energy barriers in the oligomerisation of Ab

10.2741/3104 ◽  
2008 ◽  
Vol Volume (13) ◽  
pp. 5614 ◽  
Author(s):  
Mookyung Cheon
Keyword(s):  
Free Energy ◽  
Energy Barriers
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