Showing papers in "Journal of Physical Chemistry B in 2019"
TL;DR: Cl clustering analysis reveals that the menagerie of structures explored by IDPs is diverse, with the extent of heterogeneity being highly sequence-dependent, even though ensemble-averaged properties, such as the dependence of Rg on chain length, may suggest synthetic polymer-like behavior in a good solvent.
Abstract: Intrinsically disordered proteins (IDPs) lack well-defined three-dimensional structures, thus challenging the archetypal notion of structure-function relationships. Determining the ensemble of conformations that IDPs explore under physiological conditions is the first step toward understanding their diverse cellular functions. Here, we quantitatively characterize the structural features of IDPs as a function of sequence and length using coarse-grained simulations. For diverse IDP sequences, with the number of residues ( NT) ranging from 20 to 441, our simulations not only reproduce the radii of gyration ( Rg) obtained from experiments, but also predict the full scattering intensity profiles in excellent agreement with small-angle X-ray scattering experiments. The Rg values are well-described by the standard Flory scaling law, Rg = Rg0 NTν, with ν ≈ 0.588, making it tempting to assert that IDPs behave as polymers in a good solvent. However, clustering analysis reveals that the menagerie of structures explored by IDPs is diverse, with the extent of heterogeneity being highly sequence-dependent, even though ensemble-averaged properties, such as the dependence of Rg on chain length, may suggest synthetic polymer-like behavior in a good solvent. For example, we show that for the highly charged Prothymosin-α, a substantial fraction of conformations is highly compact. Even if the sequence compositions are similar, as is the case for α-Synuclein and a truncated construct from the Tau protein, there are substantial differences in the conformational heterogeneity. Taken together, these observations imply that metrics based on net charge or related quantities alone cannot be used to anticipate the phases of IDPs, either in isolation or in complex with partner IDPs or RNA. Our work sets the stage for probing the interactions of IDPs with each other, with folded protein domains, or with partner RNAs, which are critical for describing the structures of stress granules and biomolecular condensates with important cellular functions.
112 citations
TL;DR: An improved force field was developed for C/H/O/N chemistry based on the density functional theory data with a particular focus on N2 formation kinetics and its interactions with polymer-associated radicals formed during the carbonization process.
Abstract: During the carbonization process of raw polymer precursors, graphitic structures can evolve. The presence of these graphitic structures affects mechanical properties of the carbonized carbon fibers...
104 citations
TL;DR: The results clearly demonstrate that the membrane cholesterol alters the oligomeric status of the membrane-bound peptide and the effect of peptide-binding on the depth-dependent membrane organization and dynamics.
Abstract: The N-terminal fusion peptide (residues 770-788) of an S2 glycoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV), exposed upon receptor binding, is crucial for virus entry into the host cell. The fusion peptide alters the membrane organization and dynamics of the host membrane to facilitate membrane fusion. Generally, the effect of the fusion peptide on the membrane is sensitive to the lipid composition of target membranes. In the present work, we have utilized steady-state and time-resolved fluorescence spectroscopy in tandem with circular dichroism spectroscopy to elucidate the binding, oligomeric status, and secondary structure of the fusion peptide and its impact on the depth-dependent membrane organization and dynamics. We have used depth-dependent fluorescence probes, 1,6-diphenyl-1,3,5-hexatriene (DPH) and its trimethylammonium derivative (TMA-DPH), to evaluate the effect of the peptide binding along the bilayer normal. We have exploited the energy transfer efficiency of tryptophan between TMA-DPH and DPH to determine the relative location of the solitary tryptophan present in the membrane-bound fusion peptide. We have further evaluated the effect of membrane cholesterol on the binding and organization of the peptide and the impact of peptide binding on the depth-dependent physical properties of the membrane at various cholesterol concentrations. Our results clearly demonstrate that the membrane cholesterol alters the oligomeric status of the membrane-bound peptide and the effect of peptide binding on the depth-dependent membrane organization and dynamics. The role of cholesterol is important, as the eukaryotic host cells contain a good amount of cholesterol that might be important for the entry of pathogenic viruses.
89 citations
TL;DR: Findings indicate that Urethane linkages, which are straightforward to incorporate, impart dynamic character to polymer networks of diverse chemical composition, likely through a urethane reversion mechanism.
Abstract: Cross-linked polymers are used in many commercial products and are traditionally incapable of recycling via melt reprocessing. Recently, tough and reprocessable cross-linked polymers have been real...
84 citations
TL;DR: This paper focuses on a description of the most exciting contemporary developments in the field of halogen-bonded functional soft materials, assembled using the guiding principles of crystal engineering.
Abstract: Halogen bonding has recently gained well deserved attention in present-day research for its importance in many fields of supramolecular science and crystal engineering. Although generally overlooked in comprehensive studies in the past, halogen bonding has become an important tool also in the field of materials science. An increased number of scientific reports are published every year where halogen bonding is exploited in soft materials rather than in crystal engineering. Here, we focus on a description of the most exciting contemporary developments in the field of halogen-bonded functional soft materials, assembled using the guiding principles of crystal engineering. We give a particular emphasis to those published in the past few years.
83 citations
TL;DR: Detailed analysis of the atomic simulations showed that the specific AR-G protein coupling resulted from remarkably complementary residue interactions at the protein interface, involving mainly the receptor transmembrane 6 helix and the Gα α5 helixand α4-β6 loop.
Abstract: Coupling between G-protein-coupled receptors (GPCRs) and the G proteins is a key step in cellular signaling. Despite extensive experimental and computational studies, the mechanism of specific GPCR-G protein coupling remains poorly understood. This has greatly hindered effective drug design of GPCRs that are primary targets of ∼1/3 of currently marketed drugs. Here, we have employed all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method to decipher the mechanism of the GPCR-G protein interactions. Adenosine receptors (ARs) were used as model systems based on very recently determined cryo-EM structures of the A1AR and A2AAR coupled with the Gi and Gs proteins, respectively. Changing the Gi protein to the Gs led to increased fluctuations in the A1AR and agonist adenosine (ADO), while agonist 5'-N-ethylcarboxamidoadenosine (NECA) binding in the A2AAR could be still stabilized upon changing the Gs protein to the Gi. Free energy calculations identified one stable low-energy conformation for each of the A1AR-Gi and A2AAR-Gs complexes as in the cryo-EM structures, similarly for the A2AAR-Gi complex. In contrast, the ADO agonist and Gs protein sampled multiple conformations in the A1AR-Gs system. GaMD simulations thus indicated that the A1AR preferred to couple with the Gi protein to the Gs, while the A2AAR could couple with both the Gs and Gi proteins, being highly consistent with experimental findings of the ARs. More importantly, detailed analysis of the atomic simulations showed that the specific AR-G protein coupling resulted from remarkably complementary residue interactions at the protein interface, involving mainly the receptor transmembrane 6 helix and the Gα α5 helix and α4-β6 loop. In summary, the GaMD simulations have provided unprecedented insights into the dynamic mechanism of specific GPCR-G protein interactions at an atomistic level.
77 citations
TL;DR: This work demonstrates that two different scaling approaches to model the transport properties of fluids, separated by twenty-two years, can be connected through the use of a novel approach to scaling transport properties and an empirical bridging function.
Abstract: Rosenfeld proposed two different scaling approaches to model the transport properties of fluids, separated by 22 years, one valid in the dilute gas, and another in the liquid phase. In this work, we demonstrate that these two limiting cases can be connected through the use of a novel approach to scaling transport properties and a bridging function. This approach, which is empirical and not derived from theory, is used to generate reference correlations for the transport properties of the Lennard-Jones 12-6 fluid of viscosity, thermal conductivity, and self-diffusion. This approach, with a very simple functional form, allows for the reproduction of the most accurate simulation data to within nearly their statistical uncertainty. The correlations are used to confirm that for the Lennard-Jones fluid the appropriately scaled transport properties are nearly monovariate functions of the excess entropy from low-density gases into the supercooled phase and up to extreme temperatures. This study represents the most comprehensive metastudy of the transport properties of the Lennard-Jones fluid to date.
75 citations
TL;DR: A phenomenological model provides a consistent account of the timescale and surface concentration of free-droplet crystallization on drying for the different drying conditions studied, a necessary step in progress toward achieving control over rates of crystallization and the competitive formation of amorphous particles.
Abstract: Drying and crystallization of solution droplets is a problem of broad relevance, determining the microstructures of particles formed in spray-drying, the phase of particles delivered by, for example, aerosol formulations for inhalation therapies, and the impact of aerosols on radiative forcing and climate. The ephemeral nature of free droplets, particularly when considering the drying kinetics of droplets with highly volatile constituents, has often precluded the accurate measurement of transient properties such as droplet size and composition, preventing the robust assessment of predictive models of droplet-drying rates, nucleation, and crystallization. Here, we report novel measurements of the drying kinetics of individual aqueous sodium chloride solution droplets using an electrodynamic balance to isolate and trap single aerosol droplets (radius ≈ 25 μm). The initial solution droplet size and composition are shown to be highly reproducible in terms of drying rate and crystallization time when examined over hundreds of identical evaporating droplets. We introduce a numerical model that determines the concentration gradient across the radial profile of the droplet as it dries, considering both the surface recession because of evaporation and the diffusion of components within the droplet. Drying-induced crystallization is shown to be fully determined for this system, with nucleation and instantaneous crystallization occurring once a critical supersaturation level of 2.04 ± 0.02 is achieved at the surface of the evaporating droplet. This phenomenological model provides a consistent account of the timescale and surface concentration of free-droplet crystallization on drying for the different drying conditions studied, a necessary step in progress toward achieving control over rates of crystallization and the competitive formation of amorphous particles.
71 citations
TL;DR: An in-depth analysis of the arrangement and ordering of its components at molecular level is presented to understand the structural morphology of ethaline using optimum force-field parameters for EG recently proposed by the group.
Abstract: Atomistic molecular dynamics simulations have been performed to investigate the microscopic structure of ethaline deep eutectic solvent (DES), a mixture of choline chloride ([Ch][Cl]) and ethylene glycol (EG) in molar ratio of 1:2, respectively. As much as the structure of a DES is derived by the composition of the species present in it, the chemical nature of the hydrogen bond donor species involved also plays a crucial role in laying down the microscopic structure of DESs. By virtue of its inherent chemical structure, EG renders both intra- and intermolecular hydrogen bonds. Therefore, the molecular level structural landscape of DESs containing EG as hydrogen bond donor is reckoned to be a bit complex. In the present study, we aim to understand the structural morphology of ethaline using optimum force-field parameters for EG recently proposed by our group. After an initial assessment of the refined force-field parameters for ethaline DES, we have presented an in-depth analysis of the arrangement and ordering of its components at the molecular level. Simulated X-ray scattering structure function and its partial components reveal the presence of short-range as well as long-range interactions in ethaline. The role of hydrogen bonding interactions among all the three species [Ch]+, [Cl]-, and EG was predominantly observed through radial and radial-angular distribution functions and substantiated by spatial distribution functions. The observation of the competitive nature of [Ch]+ and EG to form a hydrogen bond with the anion is one of the major outcomes of the present study. Also, weaker intra- and intermolecular hydrogen bonding interactions between EG molecules were seen along with their simultaneous involvement with the ammonium group of the choline cation.
70 citations
TL;DR: It is shown that 600 ns molecular dynamics simulations of four G-protein-coupled receptors in their membrane environments generate ensembles of protein configurations that, collectively, are selected by 70-99% of the known ligands of these proteins.
Abstract: Ensemble docking in drug discovery or chemical biology uses dynamical simulations of target proteins to generate binding site conformations for docking campaigns. We show that 600 ns molecular dynamics simulations of four G-protein-coupled receptors in their membrane environments generate ensembles of protein configurations that, collectively, are selected by 70?99% of the known ligands of these proteins. Therefore, the process of ligand recognition by conformational selection can be reproduced by combining molecular dynamics and docking calculations. Clustering of the molecular dynamics trajectories, however, does not necessarily identify the protein conformations that are most often selected by the ligands.
65 citations
TL;DR: The molecular dynamics simulations are performed to obtain a better understanding of the relation between the microscopic structure, molecular interactions, and thermophysical properties of aqueous reline and ethaline solutions and show that viscosities decrease with temperature, while diffusivities and ionic conductivities increase.
Abstract: Deep eutectic solvents (DESs) are a new generation of green solvents, which are considered an environmentally friendly alternative to ionic liquids and volatile organic compounds. The addition of controlled amounts of water to DESs has a significant effect on their microscopic structure and thus on their thermodynamic and transport properties. In this way, DESs can be modified, leading to solvents with improved characteristics. In this work, molecular dynamics (MD) simulations are performed to obtain a better understanding of the relation between the microscopic structure, molecular interactions, and thermophysical properties of aqueous reline and ethaline solutions at temperatures ranging from 303.15 to 363.15 K. For both reline and ethaline solutions, the hydrogen bond (HB) networks disappear with increasing mass fraction of water, and the intensity of radial distribution function (RDF) peaks decreases. For a mass fraction of water of 40%, most of the HBs between the compounds of reline and ethaline are broken, and DESs are fully dissolved in water. Consequently, a monotonic decrease in viscosities and an increase in self-diffusion coefficients are observed. Ionic conductivities show a nonmonotonic behavior with increasing water content. Up to 60% water mass fraction, the ionic conductivities increase with increasing water content. A further increase in the mass fraction of water decreases conductivities. For all studied systems, the HB network and the peaks of RDFs show relatively small changes for water mass fractions below 5% and beyond 40%. The MD results show that viscosities decrease with temperature, while diffusivities and ionic conductivities increase. The effect of the temperature on the structure of DES-water mixtures is negligible.
TL;DR: It is found that pure solvent diffusivity, not polarity, is the most influential solvent property on mixture behavior, and the concentration dependence of ionic conductivity is explored, which can further guide the selection of solvents for electrochemical applications of RTILs.
Abstract: Room-temperature ionic liquids (RTILs) are a class of organic salts that are liquid at room temperature. Their physiochemical properties, including low vapor pressure and wide electrochemical stability window, have driven their use as electrolytes in many electrochemical applications; however, the slow transport properties of many RTILs have limited their utility in some applications. This issue is often mitigated by solvating ionic liquids in neutral organic solvents. To date, however, solvent interactions have only been explored for a small number of solvents, particularly acetonitrile and propylene carbonate, at only a few compositions. In this work, we use molecular dynamics simulations in the context of a computational screening approach to study mixtures of ionic liquids in many different solvents at a range of concentrations. Building on prior work, we again find that ionic liquid diffusivity increases monotonically with greater solvent concentration. In contrast to prior work, we find that pure so...
TL;DR: The results show that the solvation and transport properties of charge carriers in ILs can be modified via the presence of multiple ions with varying degree of coordination, which provides an approach to impact the performance in electrochemical processes.
Abstract: The structural and dynamical changes in the solvation shell surrounding Li+ in a multianion environment are studied by Raman spectroscopy and molecular dynamics (MD) simulations. The ternary electrolyte is composed of a mixture of two ionic liquids (ILs), n-methyl- n-propylpyrrolidinium bis(trifluoromethanesulfonyl)imide ([PYR13][TFSI]) and 1-ethyl-3-methylimidazolium dicyanamide ([EMIM][DCA]), and a lithium bis(trifluoromethanesulfonyl)imide ([Li][TFSI]) salt (0-1 M). A 1:9 volumetric mixture of [PYR13][TFSI]/[EMIM][DCA] formed an eutectic that exhibited a lower melting point than that of either parent IL. The local structure of Li+ in this eutectic is found to be heterogenous and preferentially solvated by [DCA], which is the smaller and more abundant anion. Whereas [TFSI] is able to bridge multiple Li+ at high salt concentrations and form both monodentate and bidentate conformations through its oxygen atoms, [DCA] is capable of forming only monodentate coordination with Li+ through either of its end nitrogen atoms. The Raman and MD analyses suggest a wide distribution of solvation structures in the form of [Li(TFSI) m(DCA) n]( m+ n-1)- where m = 0-1 and n = 3-4. The computations showed increased ion pair lifetime for Li+-[DCA] and decreased lifetimes for Li+-[TFSI] in the ternary mixture with the increase in the [Li][TFSI] concentration. These results show that the solvation and transport properties of charge carriers in ILs can be modified via the presence of multiple ions with varying degree of coordination, which provides an approach to impact the performance in electrochemical processes.
TL;DR: It is demonstrated that surface conductance generates a dynamical selectivity in ion transport, and this selectivity is controlled by so-called Dukhin, rather than Debye, overlap, suggesting the possibility of designing large-nanopore (10-100 nm), high-conductance membranes exhibiting significant ion selectivity.
Abstract: Traditionally, ion selectivity in nanopores and nanoporous membranes is understood to be a consequence of Debye overlap, in which the Debye screening length is comparable to the nanopore radius somewhere along the length of the nanopore(s). This criterion sets a significant limitation on the size of ion-selective nanopores, as the Debye length is on the order of 1-10 nm for typical ionic concentrations. However, the analytical results we present here demonstrate that surface conductance generates a dynamical selectivity in ion transport, and this selectivity is controlled by so-called Dukhin, rather than Debye, overlap. The Dukhin length, defined as the ratio of surface to bulk conductance, reaches values of hundreds of nanometers for typical surface charge densities and ionic concentrations, suggesting the possibility of designing large-nanopore (10-100 nm), high-conductance membranes exhibiting significant ion selectivity. Such membranes would have potentially dramatic implications for the efficiency of osmotic energy conversion and separation techniques. Furthermore, we demonstrate that this mechanism of dynamic selectivity leads ultimately to the rectification of ionic current, rationalizing previous studies, showing that Debye overlap is not a necessary condition for the occurrence of rectifying behavior in nanopores.
TL;DR: This work uses the selected force field to study in detail the variations of the self and collective diffusivities of all the species as well as the transport number of the lithium ion, and shows that correlation between ions and water play an important role over the whole concentration range.
Abstract: Water-in-salts are a new family of electrolytes that may allow the development of aqueous Li-ion batteries. They have a structure that is reminiscent of ionic liquids, and they are characterized by a high concentration of ionic species. In this work, we study their transport properties and how they evolve with concentration by using molecular dynamic simulations. We first focus on the choice of the force field. By comparing the simulated viscosities and self-diffusion coefficients with experimental measurements, we select a set of parameters that reproduces well the transport properties. We then use the selected force field to study in detail the variations of the self and collective diffusivities of all the species as well as the transport number of the lithium ion. We show that correlations between ions and water play an important role over the whole concentration range. In the water-in-salt regime, the anions form a percolating network that reduces the cation-anion correlations and leads to rather large values for the transport number compared to other standard electrolytes.
TL;DR: The utility of the fluorescence resonance energy transfer to probe dynamics of aggregates and assembled systems, mostly in water medium, which has a paramount importance in designing future biomaterials is highlighted.
Abstract: This Review Article highlights the utility of the fluorescence resonance energy transfer (FRET) to probe the dynamics and related issues in amphiphilic polymeric aggregates and supramolecular polymers. Amphiphilic polymers are more attractive compared to their small molecule analogues because they exhibit significantly lower critical aggregation concentration, relatively larger particle size (suitable for the enhanced permeation and retention effect), and a much slower dynamics of exchange between the unimer and the aggregate. Representative examples of exchange dynamics in amphiphilic polymer aggregates and their noncovalent encapsulation stability as a function of the structure of the macromolecule, cross-linking, environmental parameters, and biological conditions, as probed by FRET studies, have been included in this article. Further, related observations on the utility of FRET in studying the exchange dynamics in supramolecular polymers, particularly in aqueous medium, have been discussed at length, revealing a strong impact of chirality, side chain polarity, and other parameters. Overall, this Review Article brings out the strength of this technique to probe dynamics of aggregates and assembled systems, mostly in water medium, which has a paramount importance in designing future biomaterials.
TL;DR: P pH-responsive self-assembly and gelation of a highly biocompatible amphiphilic peptide PEP-1, an octa-peptide and double mutant of a naturally occurring β-strand peptide fragment of the protein Galectin-1 , available in bovine spleen is reported.
Abstract: Peptide-based hydrogels are highly promising for various biomedical applications owing to their precise self-assembly, biocompatibility, and sensitivity toward biologically relevant external stimuli. Herein, we report pH-responsive self-assembly and gelation of a highly biocompatible amphiphilic peptide PEP-1. This is an octa-peptide and double mutant of a naturally occurring β-strand peptide fragment of the protein Galectin-1, available in bovine spleen. PEP-1 was synthesized by using the Rink amide resin as the solid support in a homemade apparatus. At pH 7.4, it exhibits spontaneous gelation with very high yield stress of 88.0 Pa and gel-to-sol temperature of 84 °C at C = 2.0 wt %. Microscopy studies revealed entangled fibrillar morphology whereas circular dichroism, Fourier tranform IR, and Thioflavin T assay indicated formation of β-sheet rich secondary structure. The assembled state was found to be stable in neutral pH whereas either decrease or increase in the pH resulted in disassembly owing to the presence of the pH responsive Asp and Lys residues. The gel network showed ability to entrap water-soluble guest molecules such as Calcein which could be selectively released at acidic pH whereas under neutral condition the release was negligible. MTT assay revealed remarkable biocompatibility of the PEP-1 gel as almost 100% cells were alive after 48 h incubation in the presence of PEP-1 (2.0 mg/mL).
TL;DR: Broadband dielectric relaxation spectroscopy has been used to investigate aqueous solutions of MgCl2 and CaCl2 up to concentrations of about 1.8 mol L-1 over the frequency range and showed that both Mg2+ and Ca2+ are strongly solvated, each immobilizing ∼20 water molecules on the DRS timescale.
Abstract: Broadband dielectric relaxation spectroscopy (DRS) has been used to investigate aqueous solutions of MgCl2 and CaCl2 up to concentrations of about 1.8 mol L-1 at 25 °C over the frequency range 0.07 ≤ ν/GHz ≤ 89. Detailed analysis of the dominant solvent mode centered at ∼20 GHz showed that both Mg2+ and Ca2+ are strongly solvated, each immobilizing ∼20 water molecules on the DRS timescale. This is consistent with the formation of two well-defined hydration layers around both cations. The hydration shell of Ca2+(aq) was found to be slightly more labile compared with Mg2+(aq). Two or three low-intensity solute-related modes were observed at frequencies ≲10 GHz for MgCl2(aq) and CaCl2, respectively. Two of these modes were attributed to the formation of double-solvent-separated and solvent-shared 1:1 ion pairs. The third mode (observed at very low frequencies and only for some CaCl2 solutions) was thought to be due to an ion-cloud relaxation. No evidence was found for "slow" water or, consistent with the strong cation hydration, for contact ion pairs. The overall association constants for MgCl+(aq) and CaCl+(aq) calculated from the ion-pairing constants were very small but in good agreement with literature values obtained from other techniques.
TL;DR: Overall, this study supports the view that solution-like protein structures can be retained because of kinetic trapping on the time scale of typical ESI-IMS experiments.
Abstract: Experiments and molecular dynamics (MD) simulations in the literature indicate that gaseous proteins generated by electrospray ionization (ESI) can retain native-like structures. However, the exact...
TL;DR: Simulations show that these widely used force fields originating from the world of biomolecular simulations, are suitable candidates in the study of n-alkane properties, both in the pure and mixture states.
Abstract: The properties of higher n-alkanes and their mixtures is a topic of significant interest for the oil and chemical industry. However, the experimental data at high temperatures are scarce. The present study focuses on simulating n-dodecane, n-octacosane, their binary mixture at a n-dodecane mole fraction of 0.3, and a model mixture of the commercially available hydrocarbon wax SX-70 to evaluate the performance of several force fields on the reproduction of properties such as liquid densities, surface tension, and viscosities. Molecular dynamics simulations over a broad temperature range from 323.15 to 573.15 K were employed in examining a broad set of atomistic molecular models assessed for the reproduction of experimental data. The well-established united atom TraPPE (TraPPE-UA) was compared against the all atom optimized potentials for liquid simulations (OPLS) reparametrization for long n-alkanes, L-OPLS, as well as Lipid14 and MARTINI force fields. All models qualitatively reproduce the temperature dependence of the aforementioned properties, but TraPPE-UA was found to reproduce liquid densities most accurately and consistently over the entire temperature range. TraPPE-UA and MARTINI were very successful in reproducing surface tensions, and L-OPLS was found to be the most accurate in reproducing the measured viscosities as compared to the other models. Our simulations show that these widely used force fields originating from the world of biomolecular simulations are suitable candidates in the study of n-alkane properties, both in the pure and mixture states.
TL;DR: It is hypothesized that UBQLN2 450-624 regions previously identified to promote its oligomerization are the "stickers" that drive interchain interactions and phase separation, and systematically investigated how phase behavior is affected by all 19 possible single amino acid substitutions.
Abstract: UBQLN2 450-624 oligomerizes and undergoes temperature-responsive liquid-liquid phase transitions following a closed-loop temperature-concentration phase diagram. We recently showed that disease-linked mutations to UBQLN2 450-624 impart highly varying effects to its phase behavior, ranging from little change to significant decrease of saturation concentration and formation of gels and aggregates. However, how single mutations lead to these properties is unknown. Here, we use UBQLN2 450-624 as a model system to study the sequence determinants of phase separation. We hypothesized that UBQLN2 450-624 regions previously identified to promote its oligomerization are the "stickers" that drive interchain interactions and phase separation. We systematically investigated how phase behavior is affected by all 19 possible single amino acid substitutions at three sticker and two "spacer" (sequences separating stickers) positions. Overall, substitutions to stickers, but not spacers, substantially altered the shape of the phase diagram. Within the sticker regions, increasing hydrophobicity decreased saturation concentrations at low temperatures and enhanced oligomerization propensity and viscoelasticity of the dense phase. Conversely, substitutions to acidic residues at all positions greatly increased saturation concentrations. Our data demonstrate that single amino acid substitutions follow a molecular code to tune phase transition behavior of biopolymers.
TL;DR: It is argued that an examination of Laity resistance coefficients is more useful in any discussion of true association in molten salts and ionic liquids where known examples show negative like-ion resistance coefficients with NE deviation parameters close to unity.
Abstract: In this work, the Angell analysis of Walden plots of the conductivity of ionic liquids and other electrolytes against viscosity is used to examine simple molten salts at high temperatures, a test t...
TL;DR: It is argued that polarization systematically reduces charge oscillations by as much as ∼0.5-1 ion per radial shell, which is general to all room-temperature ILs as well as molten salts and emphasized universal similarities among ionic liquids and molten salts in the long-range ion ordering and the influence of electronic polarization.
Abstract: The properties of room-temperature ionic liquids (ILs) may be viewed as resulting from a balance of electrostatic interactions that can be tuned at short range but constrained to satisfy universal, asymptotic screening conditions. Short-range interactions and ion packing provide ample opportunity for chemical tunability, while asymptotic sum rules dictate that the long-range structure and charge oscillation be similar to those of molten alkali halide salts. In this work, we study the structure factors and long-range electrostatic interactions in six ILs. The cation in all cases is 1-butyl-3-methylimidazolium (BMIM+), and we study six anions, namely, tetrafluoroborate (BF4-), hexafluorophosphate (PF6-), nitrate (NO3-), triflate (CF3SO3-), bisfluorosulfonylimide [(FSO2)2N-], and bistriflimide [(CF3SO2)2N-]. To gain insight, we perform similar computer simulations of a primitive molten salt model with and without electronic polarization. We emphasize universal similarities among ionic liquids and molten salts in the long-range ion ordering and the influence of electronic polarization on the screening conditions while also characterizing important differences in the short-range electrostatic interactions. We show that polarization systematically reduces charge oscillations by as much as ∼0.5-1 ion per radial shell, which we argue is general to all room-temperature ILs as well as molten salts. We suggest that a fundamentally important distinction among BMIM-based ionic liquids (with different anions) is the nature of the midrange, ∼1 A-1 peak in the charge-correlation structure factor; while this correlation is straightforward to analyze in computer simulations, it may often be hidden in X-ray and/or neutron scattering structure factors.
TL;DR: It was established that addition of gold nanoparticles intensifies laser-induced water decomposition by almost 2 orders of magnitude, which was shown to be maximal at a nanoparticle concentration around 1010 NP/mL.
Abstract: This Article covers the influence of the concentration of gold nanoparticles on laser-induced water decomposition. It was established that addition of gold nanoparticles intensifies laser-induced water decomposition by almost 2 orders of magnitude. The water decomposition rate was shown to be maximal at a nanoparticle concentration around 1010 NP/mL, whereas a decrease or increase of nanoparticle concentration leads to a decrease of water decomposition rate. It was demonstrated that, if the concentration of nanoparticles in water-based colloid was less than 1010 NP/mL, laser irradiation of the colloid caused formation of molecular hydrogen, hydrogen peroxide, and molecular oxygen. If the concentration of nanoparticles exceeded 1011 NP/mL, only two products, molecular hydrogen and hydrogen peroxide, were formed. Correlations between the water decomposition rate and the main optical and acoustic parameters of optical breakdown-generated plasma were investigated. Variants of laser-induced decomposition of co...
TL;DR: Using extensive molecular dynamics simulations, this electrical double layer at the amorphous silica-aqueous electrolyte interface is studied as a function of salt concentration for a silica surface charge density of -0.82 e/nm2 (e = electron charge).
Abstract: The electrical double layer (EDL) at the amorphous silica-aqueous electrolyte interface is of long-standing scientific interest and current technological relevance. Using extensive molecular dynamics simulations, we have studied this EDL as a function of salt concentration for a silica surface charge density of -0.82e/nm2 (e = electron charge). The simulation results can be captured with a simple model by breaking the double-layer region into three zones: an inner region in which the Na+ counterion population is independent of [NaCl] and there are no Cl- co-ions, an intermediate region which hosts a population of nonexchangeable Na+ plus another group of Na+ and Cl- ions whose population is described by a Langmuir adsorption model, and an outer region where the ion distribution is well-described using the Poisson-Boltzmann theory. When the asymptotic [NaCl] >0.17 M, the adsorption of Na+ in the intermediate zone leads to an overcompensation of the negatively charged silica surface. Nonlinear spectroscopic experiments on the water-amorphous silica interface have been interpreted by others using the Gouy-Chapman model at low salt concentration and the constant capacitance model at high salt concentration. We discuss the applicability of these and other models and the implications for interpretation of the results of second harmonic and sum frequency generation experiments.
TL;DR: The co-monomer studies revealed that uniform, non-competitive binding of monomers around a target protein is favourable, which can be predicted using computation and represents a step towards the rational in silico design of more selective MIPs for proteins in the future.
Abstract: Molecularly imprinted polymers (MIPs) have potential as alternatives to antibodies in the diagnosis and treatment of disease. However, atomistic level knowledge of the prepolymerization process is limited that would facilitate rational design of more efficient MIPs. Accordingly, we have investigated using computation and experiment the protein-monomer binding interactions that may influence the desired specificity. Myoglobin was used as the target protein and five different acrylamide-based monomers considered. Protein binding sites were predicted using SiteMap and binding free energies of monomers at each site calculated using MM-GBSA. Statistical thermodynamic analysis and study of atomistic interactions facilitated rationalization of monomer performance in MIP rebinding studies (% rebind; imprinting factors). CD spectroscopy was used to determine monomer effects on myoglobin secondary structure, with all monomers except the smallest monomer (acrylamide) causing significant changes. A complex interplay between different protein-monomer binding effects and MIP efficacy was observed. Validation of hypotheses for key binding features was achieved by rational selection of two different co-monomer MIP combinations that produced experimental results in agreement with predictions. The co-monomer studies revealed that uniform, non-competitive binding of monomers around a target protein is favourable. This study represents a step towards future rational in silico design of MIPs for proteins.
TL;DR: In this study, the electronic properties of bioactive proteins were analyzed using an ab initio fragment molecular orbital (FMO) methodology in solution: coupling with an implicit solvent model based on the Poisson-Boltzmann surface area called as FMO-PBSA, which revealed solvent-screening mechanisms that affect local stability inside ubiquitin protein.
Abstract: In this study, the electronic properties of bioactive proteins were analyzed using an ab initio fragment molecular orbital (FMO) methodology in solution: coupling with an implicit solvent model based on the Poisson-Boltzmann surface area called as FMO-PBSA. We investigated the solvent effects on practical and heterogeneous targets with uneven exposure to solvents unlike deoxyribonucleic acid analyzed in our recent study. Interfragment interaction energy (IFIE) and its decomposition analyses by FMO-PBSA revealed solvent-screening mechanisms that affect local stability inside ubiquitin protein: the screening suppresses excessiveness in bare charge-charge interactions and enables an intuitive IFIE analysis. The electrostatic character and associated solvation free energy also give consistent results as a whole to previous studies on the explicit solvent model. Moreover, by using the estrogen receptor alpha (ERα) protein bound to ligands, we elucidated the importance of specific interactions that depend on the electric charge and activatability as agonism/antagonism of the ligand while estimating the influences of the implicit solvent on the ligand and helix-12 bindings. The predicted ligand-binding affinities of bioactive compounds to ERα also show a good correlation with their in vitro activities. The FMO-PBSA approach would thus be a promising tool both for biological and pharmaceutical research targeting proteins.
TL;DR: The 3D model, which consists of tetramer subunits, two distinct β-hairpin motifs and an asymmetric arrangement of eight antiparallel β-strands, is drastically destabilized for Aβ40 compared to its Aβ42 counterpart, which explains the higher deleterious property of A β42.
Abstract: The amyloid-β (Aβ) 42 oligomers are much more toxic than Aβ40 oligomers in Alzheimer's disease. Numerous experiments indicate that toxicity could involve the formation of pores in membranes, but experimental high-resolution structure determination of these pore-forming Aβ oligomers has been impeded by aggregate heterogeneity. Using extensive atomistic simulations, low-resolution data obtained in lipid bilayers, and other theoretical factors, we proposed atomic structures of Aβ40 and Aβ42 β-barrels in a bilayer mimicking a neuronal membrane. The 3D model, which consists of tetramer subunits, two distinct β-hairpin motifs and an asymmetric arrangement of eight antiparallel β-strands, is drastically destabilized for Aβ40 compared to its Aβ42 counterpart. Our computational modeling has several implications in Alzheimer's disease, sheds light on the amyloid pore hypothesis, and explains the higher deleterious property of Aβ42.
TL;DR: It is demonstrated that the size distributions of 'naked' gold nanoparticles produced by photochemical [AuCl4]- reduction can be effectively tuned by controlling the reaction kinetics.
Abstract: Laser-induced photochemical reduction of aqueous [AuCl4]− is a green synthesis approach requiring no chemical reducing agents or stabilizers; but size control over the resulting gold nanoparticles ...
TL;DR: The results show that by combining MD simulations and QSPR analysis the composition and structural effect on the properties of complex multicomponent glasses can be elucidated, thus suggesting that this is a promising approach for future glass research and new composition design.
Abstract: Quantitative structure–property relationship (QSPR) analysis is a promising approach to correlate structural features with properties of glass materials that lack long-range order and usually have ...