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Journal ArticleDOI: 10.1080/07391102.2020.1730971

Atomic-scale modeling of the effect of lipid peroxidation on the permeability of reactive species.

04 Mar 2021-Journal of Biomolecular Structure & Dynamics (Taylor & Francis)-Vol. 39, Iss: 4, pp 1284-1294
Abstract: Biomembranes and lipid systems are rich in unsaturated lipid components and are subject to photo-induced lipid peroxidation. The peroxidized lipid products in cellular systems are known to affect t...

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Topics: Lipid peroxidation (60%)

6 results found

Open accessJournal ArticleDOI: 10.3389/FCHEM.2020.00250
Abstract: Aquaporin-3 (AQP3) is one of the aquaglyceroporins, which is expressed in the basolateral layer of the skin membrane. Studies have reported that human skin squamous cell carcinoma overexpresses AQP3 and inhibition of its function may alleviate skin tumorigenesis. In the present study, we have applied a virtual screening method that encompasses filters for physicochemical properties and molecular docking to select potential hit compounds that bind to the Aquaporin-3 protein. Based on molecular docking results, the top 20 hit compounds were analyzed for stability in the binding pocket using unconstrained molecular dynamics simulations and further evaluated for binding free energy. Furthermore, examined the ligand-unbinding pathway of the inhibitor from its bound form to explore possible routes for inhibitor approach to the ligand-binding site. With a good docking score, stability in the binding pocket, and free energy of binding, these hit compounds can be developed as Aquaporin-3 inhibitors in the near future.

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Topics: Docking (molecular) (58%), Virtual screening (58%)

6 Citations

Journal ArticleDOI: 10.1016/J.COLSURFB.2020.111254
Abstract: Phospholipids are building blocks of biological membranes having a key role in cellular functionality. The presence of unsaturated fatty acids in their conformation makes them prompt to oxidation reactions, leading to dysfunctions of living cells or to instability of lipid containing food products. The aim of this review is to gather together the latest advances on the understanding on lipids' peroxidation, using liposomes as model systems, including the main available analytical methods to monitor peroxidation reactions, with special emphasis on Fourier Transform Infrared (FTIR) and Raman spectroscopies. Lipid peroxidation is the most widely studied free radical chain reaction, which occurs in three steps: initiation, propagation and termination, making difficult to determine peroxidation products. Using liposomes as model membrane systems provides a useful tool to investigate the effects of free radicals. Different analytical methods enable the determination of peroxidation primary or secondary products. In particular, FTIR and Raman spectroscopies allow the simultaneous determination of peroxidation products in a non-destructive and easy-to-use manner. A quick monitoring of both reagents and products provides a reliable method for the quality control of industrial products or even for diagnostics, thus underlying the strong potential of vibrational spectroscopic based techniques.

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Topics: Lipid peroxidation (52%)

6 Citations

Journal ArticleDOI: 10.1016/J.ABB.2020.108548
Abstract: Biological membranes are under constant attack of free radicals, which may lead to lipid nitro-oxidation, producing a complex mixture of nitro-oxidized lipids that are responsible for structural and dynamic changes on the membrane Despite the latter, nitro-oxidized lipids are also associated with several inflammatory and neurodegenerative diseases, the underlying mechanisms of which remain elusive We perform atomistic molecular dynamics simulations using several isomers of nitro-oxidized lipids to study their effect on the structure and permeability of the membrane, as well as the interaction between the mixture of these products in the phospholipid membrane environment Our results show that the stereo- and positional isomers have a stronger effect on the properties of the membrane composed of oxidized lipids compared to that containing nitrated lipids Nevertheless, nitrated lipids lead to three-fold increase in water permeability compared to oxidized lipids In addition, we show that in a membrane consisting of combined nitro-oxidized lipid products, the presence of oxidized lipids protects the membrane from transient pores Is well stablished that plasma application and photodynamic therapy produces a number of oxidative species used to kill cancer cells, through membrane damage induced by nitro-oxidative stress This study is important to elucidate the mechanisms and the molecular level properties involving the reactive species produced during that cancer therapies

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Topics: Biological membrane (59%), Membrane (55%), Phospholipid (55%)

4 Citations

Journal ArticleDOI: 10.1016/J.DYEPIG.2020.109131
01 Mar 2021-Dyes and Pigments
Abstract: Lipophilic photosensitizers able to photo-induce lipid oxidation in biomembranes are, in general, much more efficient than hydrophilic ones; acting through the formation of singlet oxygen (1O2), which oxidizes the fatty acid double bonds (type II mechanism). Here we investigate the binding and photosensitizing properties of 4-(decyloxy)pteridin-2-amine (O-decyl-Ptr) using unilamellar vesicles of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), a phospholipid with monounsaturated fatty acids. By means of molecular dynamic (MD) simulations, we showed that O-decyl-Ptr binds to the membrane in a localization that favors the direct reaction of the triplet excited state of O-decyl-Ptr with DOPC double bonds. As a consequence, although 1O2 is formed, O-decyl-Ptr acts mainly as a contact-dependent photosensitizer, meaning through radical formation (type I mechanism). Mass spectrometry analysis of vesicles irradiated in the presence of O-decyl-Ptr, demonstrated the generation of alcohols (LOH), ketones (LO) and hydroperoxides (LOOH). In agreement with the mechanistic hypothesis proposed, LOH and LO (type I photooxidation products) are formed faster than LOOH (type II photooxidation product). Interestingly, no short-chain oxidized products were detected. Accordingly, membrane fluctuations and formation of filaments and buds are observed during in-situ photo-activation of O-decyl-Ptr in giant unilamellar vesicles due to changes in membrane spontaneous curvature. Finally, we evaluated the effect of the photochemical processes studied at a cellular level and demonstrated in experiments of viability of mammalian cells that O-decyl-Ptr has important photodynamic properties. Similar experiments performed using the hydrophilic photosenstizer pterin (Ptr) show that alkylation leads to a striking increase in the efficiency of photosensitized lipid oxidation.

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Topics: Lipid oxidation (56%), Photosensitizer (55%), Vesicle (54%) ... read more

2 Citations

Journal ArticleDOI: 10.1080/07391102.2020.1833759
Abstract: Oxidative stress plays an essential role in the regulation of vital processes in living organisms. Reactive oxygen species can react chemically with the constituents of the cells leading to irrever...

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Topics: Lipid bilayer (52%), Oxidative stress (51%), Cell membrane (51%) ... read more

1 Citations


65 results found

Open accessJournal ArticleDOI: 10.1063/1.464397
Tom Darden1, Darrin M. York1, Lee G. Pedersen1Institutions (1)
Abstract: An N⋅log(N) method for evaluating electrostatic energies and forces of large periodic systems is presented. The method is based on interpolation of the reciprocal space Ewald sums and evaluation of the resulting convolutions using fast Fourier transforms. Timings and accuracies are presented for three large crystalline ionic systems.

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Topics: Ewald summation (69%), P3M (64%), Particle Mesh (51%)

20,639 Citations

Open accessJournal ArticleDOI: 10.1016/J.SOFTX.2015.06.001
Mark Abraham1, Teemu Murtola2, Roland Schulz3, Roland Schulz4  +6 moreInstitutions (4)
01 Sep 2015-SoftwareX
Abstract: GROMACS is one of the most widely used open-source and free software codes in chemistry, used primarily for dynamical simulations of biomolecules. It provides a rich set of calculation types, prepa ...

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8,050 Citations

Journal ArticleDOI: 10.1016/0021-9991(77)90121-8
G.M. Torrie1, John P. Valleau1Institutions (1)
Abstract: The free energy difference between a model system and some reference system can easily be written as an ensemble average, but the conventional Monte Carlo methods of obtaining such averages are inadequate for the free-energy case. That is because the Boltzmann-weighted sampling distribution ordinarily used is extremely inefficient for the purpose. This paper describes the use of arbitrary sampling distributions chosen to facilitate such estimates. The methods have been tested successfully on the Lennard-Jones system over a wide range of temperature and density, including the gas-liquid coexistence region, and are found to be extremely powerful and economical.

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Topics: Importance sampling (64%), Slice sampling (63%), Monte Carlo integration (62%) ... read more

4,439 Citations

Open accessJournal ArticleDOI: 10.1002/JCC.21224
Abstract: Adequate initial configurations for molecular dynamics simulations consist of arrangements of molecules distributed in space in such a way to approximately represent the system's overall structure. In order that the simulations are not disrupted by large van der Waals repulsive interactions, atoms from different molecules must keep safe pairwise distances. Obtaining such a molecular arrangement can be considered a packing problem: Each type molecule must satisfy spatial constraints related to the geometry of the system, and the distance between atoms of different molecules must be greater than some specified tolerance. We have developed a code able to pack millions of atoms, grouped in arbitrarily complex molecules, inside a variety of three-dimensional regions. The regions may be intersections of spheres, ellipses, cylinders, planes, or boxes. The user must provide only the structure of one molecule of each type and the geometrical constraints that each type of molecule must satisfy. Building complex mixtures, interfaces, solvating biomolecules in water, other solvents, or mixtures of solvents, is straightforward. In addition, different atoms belonging to the same molecule may also be restricted to different spatial regions, in such a way that more ordered molecular arrangements can be built, as micelles, lipid double-layers, etc. The packing time for state-of-the-art molecular dynamics systems varies from a few seconds to a few minutes in a personal computer. The input files are simple and currently compatible with PDB, Tinker, Molden, or Moldy coordinate files. The package is distributed as free software and can be downloaded from

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Topics: Personal computer (54%), Molecular dynamics (50%)

3,684 Citations

Journal ArticleDOI: 10.1002/JCC.20090
Abstract: Successive parameterizations of the GROMOS force field have been used successfully to simulate biomolecular systems over a long period of time. The continuing expansion of computational power with time makes it possible to compute ever more properties for an increasing variety of molecular systems with greater precision. This has led to recurrent parameterizations of the GROMOS force field all aimed at achieving better agreement with experimental data. Here we report the results of the latest, extensive reparameterization of the GROMOS force field. In contrast to the parameterization of other biomolecular force fields, this parameterization of the GROMOS force field is based primarily on reproducing the free enthalpies of hydration and apolar solvation for a range of compounds. This approach was chosen because the relative free enthalpy of solvation between polar and apolar environments is a key property in many biomolecular processes of interest, such as protein folding, biomolecular association, membrane formation, and transport over membranes. The newest parameter sets, 53A5 and 53A6, were optimized by first fitting to reproduce the thermodynamic properties of pure liquids of a range of small polar molecules and the solvation free enthalpies of amino acid analogs in cyclohexane (53A5). The partial charges were then adjusted to reproduce the hydration free enthalpies in water (53A6). Both parameter sets are fully documented, and the differences between these and previous parameter sets are discussed.

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Topics: Local Elevation (55%), Solvation (55%), Force field (chemistry) (52%)

3,063 Citations

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