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1.
ACS Nano ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338519

RESUMO

Vesicles enriched in certain negatively charged lipids, such as phosphatidylserine and PIP2, are known to undergo fusion in the presence of calcium ions without assistance from protein assemblies. Other lipids do not exhibit this propensity, even if they are negatively charged. Using our recently developed methodology, we extract elastic properties of a representative set of lipids. This allows us to trace the origin of lipid-calcium selectivity in membrane fusion to the formation of lipid clusters with long-range correlations that induce negative curvature on the membrane surface. Furthermore, the clusters generate lateral tension in the headgroup region at the membrane surface, concomitantly also stabilizing negative Gaussian curvature. Finally, calcium binding also reduces the orientational polarization of water around the membrane head groups, potentially reducing the hydration force acting between membranes. Binding calcium only weakly increases membrane bending rigidity and tilt moduli, in agreement with experiments. We show how the combined effects of calcium binding to membranes lower the barriers along the fusion pathway that lead to the formation of the fusion stalk as well as the fusion pore.

2.
J Phys Chem Lett ; 12(32): 7659-7664, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34351767

RESUMO

From stem cell freeze-drying to organ storage, considerable recent efforts have been directed toward the development of new preservation technologies. A prominent protein stabilizing strategy involves vitrification in glassy matrices, most notably those formed of sugars such as the biologically relevant preservative trehalose. Here, we compare the folding thermodynamics of a model miniprotein in solution and in the glassy state of the sugars trehalose and glucose. Using synchrotron radiation circular dichroism (SRCD), we find that the same native structure persists in solution and glass. However, upon transition to the glass, a completely different, conformationally restricted unfolded state replaces the disordered denatured state found in solution, potentially inhibiting misfolding. Concomitantly, a large exothermic contribution is observed in glass, exposing the stabilizing effect of interactions with the sugar matrix on the native state. Our results shed light on the mechanism of protein stabilization in sugar glass and should aid in future preservation technologies.


Assuntos
Conformação Proteica/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Proteínas/metabolismo , Trealose/química , Sequência de Aminoácidos , Dobramento de Proteína/efeitos dos fármacos , Proteínas/química , Termodinâmica , Vitrificação
3.
J Chem Phys ; 154(22): 224505, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34241212

RESUMO

By complexing with hydrophobic compounds, cyclodextrins afford increased solubility and thermodynamic stability to hardly soluble compounds, thereby underlining their invaluable applications in pharmaceutical and other industries. However, common cyclodextrins such as ß-cyclodextrin, suffer from limited solubility in water, which often leads to precipitation and formation of unfavorable aggregates, driving the search for better solvents. Here, we study the solvation of cyclodextrin in deep eutectic solvents (DESs), environmentally friendly media that possess unique properties. We focus on reline, the DES formed from choline chloride and urea, and resolve the mechanism through which its constituents elevate ß-cyclodextrin solubility in hydrated solutions compared to pure water or dry reline. Combining experiments and simulations, we determine that the remarkable solubilization of ß-cyclodextrin in hydrated reline is mostly due to the inclusion of urea inside ß-cyclodextrin's cavity and at its exterior surfaces. The role of choline chloride in further increasing solvation is twofold. First, it increases urea's solubility beyond the saturation limit in water, ultimately leading to much higher ß-cyclodextrin solubility in hydrated reline in comparison to aqueous urea solutions. Second, choline chloride increases urea's accumulation in ß-cyclodextrin's vicinity. Specifically, we find that the accumulation of urea becomes stronger at high reline concentrations, as the solution transitions from reline-in-water to water-in-reline, where water alone cannot be regarded as the solvent. Simulations further suggest that in dry DES, the mechanism of ß-cyclodextrin solvation changes so that reline acts as a quasi-single component solvent that lacks preference for the accumulation of urea or choline chloride around ß-cyclodextrin.

4.
Biophys J ; 120(16): 3455-3469, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34087214

RESUMO

Protein aggregation is involved in a variety of diseases, including neurodegenerative diseases and cancer. The cellular environment is crowded by a plethora of cosolutes comprising small molecules and biomacromolecules at high concentrations, which may influence the aggregation of proteins in vivo. To account for the effect of cosolutes on cancer-related protein aggregation, we studied their effect on the aggregation of the cancer-related L106R mutant of the Axin protein. Axin is a key player in the Wnt signaling pathway, and the L106R mutation in its RGS domain results in a native molten globule that tends to form native-like aggregates. This results in uncontrolled activation of the Wnt signaling pathway, leading to cancer. We monitored the aggregation process of Axin RGS L106R in vitro in the presence of a wide ensemble of cosolutes including polyols, amino acids, betaine, and polyethylene glycol crowders. Except myo-inositol, all polyols decreased RGS L106R aggregation, with carbohydrates exerting the strongest inhibition. Conversely, betaine and polyethylene glycols enhanced aggregation. These results are consistent with the reported effects of osmolytes and crowders on the stability of molten globular proteins and with both amorphous and amyloid aggregation mechanisms. We suggest a model of Axin L106R aggregation in vivo, whereby molecularly small osmolytes keep the protein as a free soluble molecule but the increased crowding of the bound state by macromolecules induces its aggregation at the nanoscale. To our knowledge, this is the first systematic study on the effect of osmolytes and crowders on a process of native-like aggregation involved in pathology, as it sheds light on the contribution of cosolutes to the onset of cancer as a protein misfolding disease and on the relevance of aggregation in the molecular etiology of cancer.


Assuntos
Neoplasias , Polietilenoglicóis , Amiloide , Proteína Axina/genética , Mutação , Neoplasias/genética , Transdução de Sinais
5.
Langmuir ; 36(36): 10715-10724, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32787004

RESUMO

The interaction between lipid membranes and ions is associated with a range of key physiological processes. Most earlier studies have focused on the interaction of lipids with cations, while the specific effects of the anions have been largely overlooked. Owing to dissolved atmospheric carbon dioxide, bicarbonate is an important ubiquitous anion in aqueous media. In this paper, we report on the effect of bicarbonate anions on the interactions between dipolar lipid membranes in the presence of previously adsorbed calcium cations. Using a combination of solution X-ray scattering, osmotic stress, and molecular dynamics simulations, we followed the interactions between 1,2-didodecanoyl-sn-glycero-3-phosphocholine (DLPC) lipid membranes that were dialyzed against CaCl2 solutions in the presence and absence of bicarbonate anions. Calcium cations adsorbed onto DLPC membranes, charge them, and lead to their swelling. In the presence of bicarbonate anions, however, the calcium cations can tightly couple one dipolar DLPC membrane to the other and form a highly condensed and dehydrated lamellar phase with a repeat distance of 3.45 ± 0.02 nm. Similar tight condensation and dehydration has only been observed between charged membranes in the presence of multivalent counterions. Bridging between bilayers by calcium bicarbonate complexes induced this arrangement. Furthermore, in this condensed phase, lipid molecules and adsorbed ions were arranged in a two-dimensional oblique lattice.

6.
Angew Chem Int Ed Engl ; 59(36): 15575-15579, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32627307

RESUMO

Electrofreezing experiments of super-cooled water (SCW) with different ions, performed directly on the charged hemihedral faces of pyroelectric LiTaO3 and AgI crystals, in the presence and in the absence of pyroelectric charge are reported. It is demonstrated that bicarbonate (HCO3 - ) ions elevate the icing temperature near the positively charged faces. In contrast, the hydronium (H3 O+ ) slightly reduces the icing temperature. Molecular dynamics simulations suggest that the hydrated trigonal planar HCO3 - ions self-assemble with water molecules near the surface of the AgI crystal as clusters of slightly different configuration from those of the ice-like hexagons. These clusters, however, have a tendency to serve as embryonic nuclei for ice crystallization. Consequently, we predicted and experimentally confirmed that the trigonal planar ions of NO3 - and guanidinium (Gdm+ ), at appropriate concentrations, elevate the icing temperature near the positive and negative charged surfaces, respectively. On the other hand, the Cl- and SO4 2- ions of different configurations reduce the icing temperature.

7.
J Phys Chem B ; 124(33): 7166-7175, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32697588

RESUMO

Lipid nanodiscs are small synthetic lipid bilayer structures that are stabilized in solution by special circumscribing (or scaffolding) proteins or polymers. Because they create native-like environments for transmembrane proteins, lipid nanodiscs have become a powerful tool for structural determination of this class of systems when combined with cryo-electron microscopy or nuclear magnetic resonance. The elastic properties of lipid bilayers determine how the lipid environment responds to membrane protein perturbations, and how the lipid in turn modifies the conformational state of the embedded protein. However, despite the abundant use of nanodiscs in determining membrane protein structure, the elastic material properties of even pure lipid nanodiscs (i.e., without embedded proteins) have not yet been quantitatively investigated. A major hurdle is due to the inherently nonlocal treatment of the elastic properties of lipid systems implemented by most existing methods, both experimental and computational. In addition, these methods are best suited for very large "infinite" size lipidic assemblies, or ones that contain periodicity, in the case of simulations. We have previously described a computational analysis of molecular dynamics simulations designed to overcome these limitations, so it allows quantification of the bending rigidity (KC) and tilt modulus (κt) on a local scale even for finite, nonperiodic systems, such as lipid nanodiscs. Here we use this computational approach to extract values of KC and κt for a set of lipid nanodisc systems that vary in size and lipid composition. We find that the material properties of lipid nanodiscs are different from those of infinite bilayers of corresponding lipid composition, highlighting the effect of nanodisc confinement. Nanodiscs tend to show higher stiffness than their corresponding macroscopic bilayers, and moreover, their material properties vary spatially within them. For small-size MSP1 nanodiscs, the stiffness decreases radially, from a value that is larger in their center than the moduli of the corresponding bilayers by a factor of ∼2-3. The larger nanodiscs (MSP1E3D1 and MSP2N2) show milder spatial changes of moduli that are composition dependent and can be maximal in the center or at some distance from it. These trends in moduli correlate with spatially varying structural properties, including the area per lipid and the nanodisc thickness. Finally, as has previously been reported, nanodiscs tend to show deformations from perfectly flat circular geometries to varying degrees, depending on size and lipid composition. The modulations of lipid elastic properties that we find should be carefully considered when making structural and functional inferences concerning embedded proteins.


Assuntos
Bicamadas Lipídicas , Nanoestruturas , Microscopia Crioeletrônica , Proteínas de Membrana , Simulação de Dinâmica Molecular
8.
J Chem Theory Comput ; 16(5): 3335-3342, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32223260

RESUMO

Deep eutectic mixtures are a promising sustainable and diverse class of tunable solvents that hold great promise for various green chemical and technological processes. Many deep eutectic solvents (DES) are hygroscopic and find use in applications with varying extents of hydration, hence urging a profound understanding of changes in the nanostructure of DES with water content. Here, we report on molecular dynamics simulations of the quintessential choline chloride-urea mixture, using a newly parametrized force field with scaled charges to account for physical properties of hydrated DES mixtures. These simulations indicate that water changes the nanostructure of solution even at very low hydration. We present a novel approach that uses convex constrained analysis to dissect radial distribution functions into base components representing different modes of local association. Specifically, DES mixtures can be deconvoluted locally into two dominant competing nanostructures, whose relative prevalence (but not their salient structural features) change with added water over a wide concentration range, from dry up to ∼30 wt % hydration. Water is found to be associated strongly with several DES components but remarkably also forms linear bead-on-string clusters with chloride. At high water content (beyond ∼50 wt % of water), the solution changes into an aqueous electrolyte-like mixture. Finally, the structural evolution of the solution at the nanoscale with extent of hydration is echoed in the DES macroscopic material properties. These changes to structure, in turn, should prove important in the way DES acts as a solvent and to its interactions with additive components.

9.
J Chem Theory Comput ; 16(2): 1249-1262, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31917927

RESUMO

Trehalose is a naturally occurring disaccharide known to remarkably stabilize biomacromolecules in the biologically active state. The stabilizing effect is typically observed over a large concentration range and affects many macromolecules including proteins, lipids, and DNA. Of special interest is the transition from aqueous solution to the dense and highly concentrated glassy state of trehalose that has been implicated in bioadaptation of different organisms toward desiccation stress. Although several mechanisms have been suggested to link the structure of the low water content glass with its action as an exceptional stabilizer, studies are ongoing to resolve which are most pertinent. Specifically, the role that hydrogen bonding plays in the formation of the glass is not well resolved. Here we model aqueous trehalose mixtures over a wide concentration range, using molecular dynamics simulations with two available force fields. Both force fields indicate glass transition temperatures and osmotic pressures that are close to experimental values, particularly at high trehalose contents. We develop and employ a methodology that allows us to analyze the thermodynamics of hydrogen bonds in simulations at different water contents and temperatures. Remarkably, this analysis is able to link the liquid to glass transition with changes in hydrogen bond characteristics. Most notably, the onset of the glassy state can be quantitatively related to the transition from weakly to strongly correlated hydrogen bonds. Our findings should help resolve the properties of the glass and the mechanisms of its formation in the presence of added macromolecules.

10.
J Am Chem Soc ; 141(45): 18056-18063, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31619038

RESUMO

The aggregation of drugs and nutraceuticals in aqueous media is an outstanding problem for their efficacy and bioavailability. A common solution is to add excipients or hydrotropes that increase solubility and limit aggregation. Here we study caffeine, a widely consumed drug that undergoes oligomerization and aggregation in aqueous solutions. Combining partition and solubility experiments with molecular dynamics simulations, we determined the effect of sugars (mono- and disaccharides) on caffeine self-association and solubility. We find that sugars selectively increase the concentration of caffeine in its monomeric state, but decrease its solubility in all oligomeric forms. Thus, we determine that, in contrast to common hydrotropes, sugars act as selective hydrotropes toward caffeine, since they differentially act on specific solvated forms of the drug. We furthermore unravel the molecular mechanism for this selectivity, and comment on the general design principles that should help develop targeted excipients for bioavailability and taste modification in drugs and foods.


Assuntos
Cafeína/química , Açúcares/química , Simulação de Dinâmica Molecular , Solubilidade
11.
Food Chem ; 255: 165-173, 2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-29571463

RESUMO

Dramatic increase in NaCl consumption lead to sodium intake beyond health guidelines. KCl substitution helps reduce sodium intake but results in a bitter-metallic off-taste. Two disaccharides, trehalose and sucrose, were tested in order to untangle the chemical (increase in effective concentration of KCl due to sugar addition) from the sensory effects. The bitter-metallic taste of KCl was reduced by these sugars, while saltiness was enhanced or unaltered. The perceived sweetness of sugar, regardless of its type and concentration, was an important factor in KCl taste modulation. Though KCl was previously shown to increase the chemical activity of trehalose but not of sucrose, we found that it suppressed the perceived sweetness of both sugars. Therefore, sensory integration was the dominant factor in the tested KCl-sugar combinations.


Assuntos
Cloreto de Potássio/farmacologia , Sacarose/farmacologia , Paladar/fisiologia , Trealose/farmacologia , Adulto , Feminino , Humanos , Masculino , Cloreto de Potássio/administração & dosagem , Cloreto de Sódio/farmacologia , Paladar/efeitos dos fármacos
12.
Phys Chem Chem Phys ; 19(44): 29862-29871, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29110014

RESUMO

Under environmental duress, many organisms accumulate large amounts of osmolytes - molecularly small organic solutes. Osmolytes are known to counteract stress, driving proteins to their compact native states by their exclusion from protein surfaces. In contrast, the effect of osmolytes on lipid membranes is poorly understood and widely debated. Many fully membrane-permeable osmolytes exert an apparent attractive force between lipid membranes, yet all proposed models fail to fully account for the origin of this force. We follow the quintessential osmolyte trimethylamine N-oxide (TMAO) and its interaction with dimyristoyl phosphatidylcholine (DMPC) membranes in aqueous solution. We find that by partitioning away from the inter-bilayer space, TMAO pushes adjacent membranes closer together. Experiments and simulations further show that the partitioning of TMAO away from the volume between bilayers stems from its exclusion from the lipid-water interface, similar to the mechanism of protein stabilization by osmolytes. We extend our analysis to show that the preferential interaction of other physiologically relevant solutes (including sugars and DMSO) also correlates with their effect on membrane bilayer interactions. Our study resolves a long-standing puzzle, explaining how osmolytes can increase membrane-membrane attraction or repulsion depending on their preferential interactions with lipids.


Assuntos
Lipídeos de Membrana , Metilaminas/farmacologia , Bicamadas Lipídicas , Proteínas/química , Soluções , Água
13.
Food Chem ; 237: 1209-1215, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28763971

RESUMO

Trehalose is revered for its multiple unique impacts on solution properties, including the ability to modulate the salty and bitter tastes of sodium and potassium salts. However, the molecular mechanisms underlying trehalose's effect on taste perception are unknown. Here we focus on the physico-chemical effect of trehalose to alter the activity of monovalent salts in aqueous solution. Using a modified isopiestic methodology that relies on contemporary vapor pressure osmometry, we elucidate how trehalose modifies the thermodynamic chemical activity of sodium and potassium chloride, as well as the effect of the salts on the sugar's activity. We find that trehalose has a specific impact on potassium chloride that is unlike that of other sugars or polyols. Remarkably, especially at low salt concentrations, trehalose considerably elevates the activity (or chemical potential) of KCl, raising the salt activity coefficient as high as ∼1.5 its value in the absence of the sugar. Moreover, in contrast to their action on other known carbohydrates, both KCl and NaCl act as salting-out agents towards trehalose, as seen in the elevated activity coefficient compared with its value in pure water (up to ∼1.5 higher at low sugar and salt concentrations). We discuss the possible relevance of our findings to the mechanism of trehalose taste perception modification, and point to necessary future directed sensory experiments needed to resolve the possible link between our findings and the emerging biochemical or physiological mechanisms involved.


Assuntos
Trealose/química , Cloreto de Potássio , Cloreto de Sódio , Paladar
14.
J Chem Theory Comput ; 13(6): 2851-2857, 2017 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28489952

RESUMO

In processes involving aqueous solutions and in almost every biomolecular interaction, hydrogen bonds play important roles. Though weak compared to the covalent bond, hydrogen bonds modify the stability and conformation of numerous small and large molecules and modulate their intermolecular interactions. We propose a simple methodology for extracting hydrogen bond strength from atomistic level simulations. The free energy associated with hydrogen bond formation is conveniently calculated as the reversible work required to reshape a completely random pair probability distribution reference state into the one found in simulations where hydrogen bonds are formed. Requiring only the probability density distribution of donor-acceptor pairs in the first solvation shell of an electronegative atom, the method uniquely defines the free energy, entropy, and enthalpy of the hydrogen bond. The method can be easily extended to molecules other than water and to multiple component mixtures. We demonstrate and apply this methodology to hydrogen bonds that form in molecular dynamics simulations between water molecules in pure water, as well as to bonds formed between different molecules in a binary mixture of a sugar (trehalose) and water. Finally, we comment on how the method should be useful in assessing the role of hydrogen bonds in different molecular mechanisms.

15.
J Am Chem Soc ; 138(49): 16112-16119, 2016 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-27960351

RESUMO

We present the assembly of asymmetric two-layer hybrid DNA-based hydrogels revealing stimuli-triggered reversibly modulated shape transitions. Asymmetric, linear hydrogels that include layer-selective switchable stimuli-responsive elements that control the hydrogel stiffness are designed. Trigger-induced stress in one of the layers results in the bending of the linear hybrid structure, thereby minimizing the elastic free energy of the systems. The removal of the stress by a counter-trigger restores the original linear bilayer hydrogel. The stiffness of the DNA hydrogel layers is controlled by thermal, pH (i-motif), K+ ion/crown ether (G-quadruplexes), chemical (pH-doped polyaniline), or biocatalytic (glucose oxidase/urease) triggers. A theoretical model relating the experimental bending radius of curvatures of the hydrogels with the Young's moduli and geometrical parameters of the hydrogels is provided. Promising applications of shape-regulated stimuli-responsive asymmetric hydrogels include their use as valves, actuators, sensors, and drug delivery devices.


Assuntos
DNA/química , Hidrogéis/química , Compostos de Anilina/química , Éteres de Coroa/química , Quadruplex G , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Concentração de Íons de Hidrogênio , Modelos Moleculares , Potássio/química , Estresse Mecânico , Termodinâmica , Urease/química , Urease/metabolismo
16.
J Am Chem Soc ; 138(44): 14756-14763, 2016 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-27779856

RESUMO

The riddle of anomalous polar behavior of the centrosymmetric crystal of α-glycine is resolved by the discovery of a polar, several hundred nanometer thick hydrated layer, created at the {010} faces during crystal growth. This layer was detected by two independent pyroelectric analytical methods: (i) periodic temperature change technique (Chynoweth) at ambient conditions and (ii) contactless X-ray photoelectron spectroscopy under ultrahigh vacuum. The total polarization of the surface layer is extremely large, yielding ≈1 µC·cm-2, and is preserved in ultrahigh vacuum, but disappears upon heating to 100 °C. Molecular dynamics simulations corroborate the formation of polar hydrated layers at the sub-microsecond time scale, however with a thickness of only several nanometers, not several hundred. This inconsistency might be reconciled by invoking a three-step nonclassical crystal growth mechanism comprising (i) docking of clusters from the supersaturated solution onto the evolving crystal, (ii) surface recognition and polar induction, and (iii) annealing and dehydration, followed by site-selective recrystallization.


Assuntos
Glicina/química , Simulação de Dinâmica Molecular , Cristalização , Microscopia de Força Atômica , Água/química
17.
Phys Chem Chem Phys ; 18(32): 22516-25, 2016 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-27468431

RESUMO

Kappa-casein (κCN) and beta-casein (ßCN) are disordered proteins present in mammalian milk. In vitro, ßCN self-assembles into core-shell micelles. κCN self assembles into similar micelles, as well as into amyloid-like fibrils. Recent studies indicate that fibrillization can be suppressed by mixing ßCN and κCN, but the mechanism of fibril inhibition has not been identified. Examining the interactions of native and reduced kappa-caseins (N-κCN and R-κCN) with ßCN, we expose a competition between two different self-assembly processes: micellization and fibrillization. Quite surprisingly, however, we find significant qualitative and quantitative differences in the self-assembly between the native and reduced κCN forms. Specifically, thermodynamic analysis reveals exothermic demicellization for ßCN and its mixtures with R-κCN, as opposed to endothermic demicellization of N-κCN and its mixtures with ßCN at the same temperature. Furthermore, with time, R-κCN/ßCN mixtures undergo phase separation into pure ßCN micelles and R-κCN fibrils, while in the N-κCN/ßCN mixtures fibril formation is considerably delayed and mixed micelles persist for longer periods of time. Fibrils formed in N-κCN/ßCN mixtures are shorter and more flexible than those formed in R-κCN/ßCN systems. Interestingly, in the N-κCN/ßCN mixtures, the sugar moieties of N-κCN oligomers seem to organize on the mixed micelles surface in a manner similar to the organization of κCN in milk casein micelles.


Assuntos
Caseínas/química , Micelas , Leite/química , Amiloide/metabolismo , Animais , Caseínas/metabolismo , Temperatura , Termodinâmica
19.
BMC Bioinformatics ; 17: 161, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-27071656

RESUMO

BACKGROUND: The importance of the material properties of membranes for diverse cellular processes is well established. Notably, the elastic properties of the membrane, which depend on its composition, can directly influence membrane reshaping and fusion processes as well as the organisation and function of membrane proteins. Determining these properties is therefore key for a mechanistic understanding of how the cell functions. RESULTS: We have developed a method to determine the bending rigidity and tilt modulus, for lipidic assemblies of arbitrary lipid composition and shape, from molecular dynamics simulations. The method extracts the elastic moduli from the distributions of microscopic tilts and splays of the lipid components. We present here an open source implementation of the method as a set of Python modules using the computational framework OpenStructure. These modules offer diverse algorithms typically used in the calculatation the elastic moduli, including routines to align MD trajectories of complex lipidic systems, to determine the water/lipid interface, to calculate lipid tilts and splays, as well as to fit the corresponding distributions to extract the elastic properties. We detail the implementation of the method and give several examples of how to use the modules in specific cases. CONCLUSIONS: The method presented here is, to our knowledge, the only available computational approach allowing to quantify the elastic properties of lipidic assemblies of arbitrary shape and composition (including lipid mixtures). The implementation as python modules offers flexibility, which has already allowed the method to be applied to diverse lipid assembly types, ranging from bilayers in the liquid ordered and disordered phases to a study of the inverted-hexagonal phase, and with different force-fields (both all-atom and coarse grained representations). The modules are freely available through GitHub at https://github.com/njohner/ost_pymodules/ while OpenStructure can be obtained at http://www.openstructure.org .


Assuntos
Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Algoritmos , Proteínas de Membrana/química , Modelos Teóricos , Software , Água
20.
J Phys Chem A ; 120(19): 3253-9, 2016 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-26963367

RESUMO

Deep eutectic solvents (DES) are mixtures of two or more components with high melting temperatures, which form a liquid at room temperature. These DES hold great promise as green solvents for chemical processes, as they are inexpensive and environmentally friendly. Specifically, they present a unique solvating environment to polymers that is different from water. Here, we use small angle neutron scattering to study the polymer properties of the common, water-soluble, polyvinylpyrrolidone (PVP) in the prominent DES formed by a 1:2 molar mixture of choline chloride and urea. We find that the polymer adopts a slightly different structure in DES than in water, so that at higher concentrations the polymer favors a more expanded conformation compared to the same concentration in water. Yet, the osmotic pressure of PVP solutions in DES is very similar to that in water, indicating that both solvents are of comparable quality and that the DES components interact favorably with PVP. The osmotic pressure measurements within this novel class of promising solvents should be of value toward future technological applications as well as for osmotic stress experiments in nonaqueous environments.

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