Virtual screening of mandelate racemase mutants with enhanced activity based on binding energy in the transition state.

PubMed

Gu, Jiali; Liu, Min; Guo, Fei; Xie, Wenping; Lu, Wenqiang; Ye, Lidan; Chen, Zhirong; Yuan, Shenfeng; Yu, Hongwei

2014-02-05

Mandelate racemase (MR) is a promising candidate for the dynamic kinetic resolution of racemates. However, the poor activity of MR towards most of its non-natural substrates limits its widespread application. In this work, a virtual screening method based on the binding energy in the transition state was established to assist in the screening of MR mutants with enhanced catalytic efficiency. Using R-3-chloromandelic acid as a model substrate, a total of 53 mutants were constructed based on rational design in the two rounds of screening. The number of mutants for experimental validation was brought down to 17 by the virtual screening method, among which 14 variants turned out to possess improved catalytic efficiency. The variant V26I/Y54V showed 5.2-fold higher catalytic efficiency (k(cat)/K(m)) towards R-3-chloromandelic acid than that observed for the wild-type enzyme. Using this strategy, mutants were successfully obtained for two other substrates, R-mandelamide and R-2-naphthylglycolate (V26I and V29L, respectively), both with a 2-fold improvement in catalytic efficiency. These results demonstrated that this method could effectively predict the trend of mutational effects on catalysis. Analysis from the energetic and structural assays indicated that the enhanced interactions between the active sites and the substrate in the transition state led to improved catalytic efficiency. It was concluded that this virtual screening method based on the binding energy in the transition state was beneficial in enzyme rational redesign and helped to better understand the catalytic properties of the enzyme. Copyright © 2013 Elsevier Inc. All rights reserved.

The Catalytic Function of Enzymes.

ERIC Educational Resources Information Center

Splittgerber, Allan G.

1985-01-01

Discusses: structure of the enzyme molecule; active site; reaction mechanism; transition state; factors affecting enzyme reaction rates, concentration of enzyme; concentration of substrate; product concentration; temperature effects and pH effects; factors causing a lowering of activation energy; proximity and orientation effects; substrate strain…

Structures and fabrication techniques for solid state electrochemical devices

DOEpatents

Visco, Steven J.; Jacobson, Craig P.; DeJonghe, Lutgard C.

2006-10-10

Low-cost, mechanically strong, highly electronically conductive porous substrates and associated structures for solid-state electrochemical devices, techniques for forming these structures, and devices incorporating the structures provide solid state electrochemical device substrates of novel composition and techniques for forming thin electrode/membrane/electrolyte coatings on the novel or more conventional substrates. In particular, in one aspect the invention provides techniques for co-firing of device substrate (often an electrode) with an electrolyte or membrane layer to form densified electrolyte/membrane films 5 to 20 microns thick. In another aspect, densified electrolyte/membrane films 5 to 20 microns thick may be formed on a pre-sintered substrate by a constrained sintering process. In some cases, the substrate may be a porous metal, alloy, or non-nickel cermet incorporating one or more of the transition metals Cr, Fe and Cu, or alloys thereof.

Effect of strain on structure and charge order transitions in epitaxial Bi0.4Ca0.6MnO3 films on perovskite (001) and (011) substrates

NASA Astrophysics Data System (ADS)

Kim, Dae Ho; Christen, Hans M.; Varela, Maria; Lee, Ho Nyung; Lowndes, Douglas H.

2006-05-01

The effect of epitaxial strain on the charge order (CO) transition in Bi0.4Ca0.6MnO3 films was studied by varying the strain's strength and symmetry via the use of SrTiO3 and LaAlO3 substrates having different crystallographic orientations. The film on pseudocubic (001) LaAlO3, under symmetric compressive strain, exhibits a clear CO transition. In the film on a (001) SrTiO3 substrate, under symmetric tensile strain, highly segregated line-shaped features in the Bi distribution are seen in Z-contrast scanning transmission microscopy, accompanied by a strongly broadened CO transition. The asymmetric tensile stress on (011) SrTiO3 results in an apparent compressive strain state with a deviation from tetragonality (i.e., γ ≠90°), accompanied by the sharpest CO transition. These comparisons illustrate the importance of considering both the strength and symmetry of epitaxial strain.

Quantum mechanical hydrogen tunneling in bacterial copper amine oxidase reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murakawa, Takeshi; Okajima, Toshihide; Kuroda, Shun'ichi

A key step decisively affecting the catalytic efficiency of copper amine oxidase is stereospecific abstraction of substrate {alpha}-proton by a conserved Asp residue. We analyzed this step by pre-steady-state kinetics using a bacterial enzyme and stereospecifically deuterium-labeled substrates, 2-phenylethylamine and tyramine. A small and temperature-dependent kinetic isotope effect (KIE) was observed with 2-phenylethylamine, whereas a large and temperature-independent KIE was observed with tyramine in the {alpha}-proton abstraction step, showing that this step is driven by quantum mechanical hydrogen tunneling rather than the classical transition-state mechanism. Furthermore, an Arrhenius-type preexponential factor ratio approaching a transition-state value was obtained in the reactionmore » of a mutant enzyme lacking the critical Asp. These results provide strong evidence for enzyme-enhanced hydrogen tunneling. X-ray crystallographic structures of the reaction intermediates revealed a small difference in the binding mode of distal parts of substrates, which would modulate hydrogen tunneling proceeding through either active or passive dynamics.« less

Mapping specificity landscapes of RNA-protein interactions by high throughput sequencing.

PubMed

Jankowsky, Eckhard; Harris, Michael E

2017-04-15

To function in a biological setting, RNA binding proteins (RBPs) have to discriminate between alternative binding sites in RNAs. This discrimination can occur in the ground state of an RNA-protein binding reaction, in its transition state, or in both. The extent by which RBPs discriminate at these reaction states defines RBP specificity landscapes. Here, we describe the HiTS-Kin and HiTS-EQ techniques, which combine kinetic and equilibrium binding experiments with high throughput sequencing to quantitatively assess substrate discrimination for large numbers of substrate variants at ground and transition states of RNA-protein binding reactions. We discuss experimental design, practical considerations and data analysis and outline how a combination of HiTS-Kin and HiTS-EQ allows the mapping of RBP specificity landscapes. Copyright © 2017 Elsevier Inc. All rights reserved.

Structures And Fabrication Techniques For Solid State Electrochemical Devices

DOEpatents

Visco, Steven J.; Jacobson, Craig P.; DeJonghe, Lutgard C.

2005-12-27

Provided are low-cost, mechanically strong, highly electronically conductive porous substrates and associated structures for solid-state electrochemical devices, techniques for forming these structures, and devices incorporating the structures. The invention provides solid state electrochemical device substrates of novel composition and techniques for forming thin electrode/membrane/electrolyte coatings on the novel or more conventional substrates. In particular, in one embodiment the invention provides techniques for co-firing of device substrate (often an electrode) with an electrolyte or membrane layer to form densified electrolyte/membrane films 5 to 20 microns thick. In another embodiment, densified electrolyte/membrane films 5 to 20 microns thick may be formed on a pre-sintered substrate by a constrained sintering process. In some cases, the substrate may be a porous metal, alloy, or non-nickel cermet incorporating one or more of the transition metals Cr, Fe, Cu and Ag, or alloys thereof.

Structures and fabrication techniques for solid state electrochemical devices

DOEpatents

Visco, Steven J.; Jacobson, Craig P.; DeJonghe, Lutgard C.

2003-08-12

Provided are low-cost, mechanically strong, highly electronically conductive porous substrates and associated structures for solid-state electrochemical devices, techniques for forming these structures, and devices incorporating the structures. The invention provides solid state electrochemical device substrates of novel composition and techniques for forming thin electrode/membrane/electrolyte coatings on the novel or more conventional substrates. In particular, in one embodiment the invention provides techniques for co-firing of device substrate (often an electrode) with an electrolyte or membrane layer to form densified electrolyte/membrane films 5 to 20 microns thick. In another embodiment, densified electrolyte/membrane films 5 to 20 microns thick may be formed on a pre-sintered substrate by a constrained sintering process. In some cases, the substrate may be a porous metal, alloy, or non-nickel cermet incorporating one or more of the transition metals Cr, Fe, Cu and Ag, or alloys thereof.

Collective transport for active matter run-and-tumble disk systems on a traveling-wave substrate

DOE PAGES

Sándor, Csand; Libál, Andras; Reichhardt, Charles; ...

2017-01-17

Here, we examine numerically the transport of an assembly of active run-and-tumble disks interacting with a traveling-wave substrate. We show that as a function of substrate strength, wave speed, disk activity, and disk density, a variety of dynamical phases arise that are correlated with the structure and net flux of disks. We find that there is a sharp transition into a state in which the disks are only partially coupled to the substrate and form a phase-separated cluster state. This transition is associated with a drop in the net disk flux, and it can occur as a function of themore » substrate speed, maximum substrate force, disk run time, and disk density. Since variation of the disk activity parameters produces different disk drift rates for a fixed traveling-wave speed on the substrate, the system we consider could be used as an efficient method for active matter species separation. Within the cluster phase, we find that in some regimes the motion of the cluster center of mass is in the opposite direction to that of the traveling wave, while when the maximum substrate force is increased, the cluster drifts in the direction of the traveling wave. This suggests that swarming or clustering motion can serve as a method by which an active system can collectively move against an external drift.« less

Collective transport for active matter run-and-tumble disk systems on a traveling-wave substrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sándor, Csand; Libál, Andras; Reichhardt, Charles

Here, we examine numerically the transport of an assembly of active run-and-tumble disks interacting with a traveling-wave substrate. We show that as a function of substrate strength, wave speed, disk activity, and disk density, a variety of dynamical phases arise that are correlated with the structure and net flux of disks. We find that there is a sharp transition into a state in which the disks are only partially coupled to the substrate and form a phase-separated cluster state. This transition is associated with a drop in the net disk flux, and it can occur as a function of themore » substrate speed, maximum substrate force, disk run time, and disk density. Since variation of the disk activity parameters produces different disk drift rates for a fixed traveling-wave speed on the substrate, the system we consider could be used as an efficient method for active matter species separation. Within the cluster phase, we find that in some regimes the motion of the cluster center of mass is in the opposite direction to that of the traveling wave, while when the maximum substrate force is increased, the cluster drifts in the direction of the traveling wave. This suggests that swarming or clustering motion can serve as a method by which an active system can collectively move against an external drift.« less

Process for making dense thin films

DOEpatents

Jacobson, Craig P.; Visco, Steven J.; DeJonghe, Lutgard C.

2005-07-26

Provided are low-cost, mechanically strong, highly electronically conductive porous substrates and associated structures for solid-state electrochemical devices, techniques for forming these structures, and devices incorporating the structures. The invention provides solid state electrochemical device substrates of novel composition and techniques for forming thin electrode/membrane/electrolyte coatings on the novel or more conventional substrates. In particular, in one embodiment the invention provides techniques for firing of device substrate to form densified electrolyte/membrane films 5 to 20 microns thick. In another embodiment, densified electrolyte/membrane films 5 to 20 microns thick may be formed on a pre-sintered substrate by a constrained sintering process. In some cases, the substrate may be a porous metal, alloy, or non-nickel cermet incorporating one or more of the transition metals Cr, Fe, Cu and Ag, or alloys thereof.

Direct Observation on Spin-Coating Process of PS- b -P2VP Thin Films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, Hiroki; Takenaka, Mikihito; Miyazaki, Tsukasa

We studied the structural development of symmetric poly(styrene-b-2-vinylpyridine) (PS-b-P2VP) block copolymers during spin-coating using in situ grazing incidence small angle X-ray scattering (GISAXS) measurements. During the spin-coating process, after the formation of the micelles in dilute solution, the selective solvent induced two kinds of the morphological transition. Firstly, the disordered spherical micelles were transformed into a BCC lattice of spheres of which the (110) plane was oriented perpendicularly to the substrate surface. Secondly, further evaporation induced a transition from spheres on the BCC lattice into cylindrical structures. The orientation of the cylinders perpendicular to the substrate surface was induced bymore » solvent convection perpendicular to the substrate, which occurs during rapid solvent evaporation. After this transition, vitrification of PS and P2VP prevented any further transition from cylinders to the more thermodynamically stable lamellar structures, as are generally observed as the bulk equilibrium state.« less

A study of substrate-liquid crystal interaction

NASA Astrophysics Data System (ADS)

Zhang, Baoshe

This thesis concerns the study of substrate-liquid crystal interaction from two different angles. In one approach, we used the IPS (in-plane switching) technique to investigate the liquid crystal alignment by rubbed polyimide films. The IPS mode of liquid crystal cell operation is facilitated through comb electrodes capable of producing planar electric field. We have fabricated comb electrodes with a periodicity of 2 mum in order to confine the planar electric field close to the liquid crystal-substrate interface. Through optical transmittance measurements and comparison with theoretical predictions based on the Ladau-de Gennes formalism, we found the experimental data to be consistent with the physical picture of soft anchoring, in which the liquid crystal director at the substrate interface is rotated azimuthally under the planar electric field. As a result, we were able to obtain the azimuthal anchoring strength as a fitting parameter of the theory. This part of the thesis thus presents evidence(s) for director switching at the liquid crystal-substrate interface, as well as a method for measuring the azimuthal anchoring strength through optical means. In the second approach, we used nano-lithographic technique to fabricate textured two dimensional periodic patterns on silicon wafers, and examined the resulting liquid crystal alignment effect of such textured substrates. It was found that with decreasing periodicity, there exists an orientational transition from a state in which the liquid crystal alignment copies the substrate pattern at larger periodicity, to a state of uniform alignment at smaller periodicity. In our system, this transition occurs at a periodicity between 0.4 mum and 0.8 mum. Through theoretical simulations based on the model of competition between the elastic distortion energy and the interfacial anchoring potential, it was found that there is indeed a first-order abrupt transition when the periodicity is decreased. This is due to the fact that the elastic distortion energy scales as the inverse of the periodicity squared. Hence when the periodicity is decreased, the elastic distortion energy increases rapidly. At the critical periodicity the elastic distortion energy crosses the interfacial anchoring potential, below which the uniform alignment becomes the lower energy state. The uniform-aligned state was confirmed by the excellent theory-experiment agreement on spectral measurements, in conjunction with the optical microscope observations. In the uniform-aligned state, a large pretilt angle (35°) was obtained.

Wetting transition on patterned surfaces: transition states and energy barriers.

PubMed

Ren, Weiqing

2014-03-18

We study the wetting transition on microstructured hydrophobic surfaces. We use the string method [J. Chem. Phys. 2007, 126, 164103; J. Chem. Phys. 2013, 138, 134105] to accurately compute the transition states, the energy barriers, and the minimum energy paths for the wetting transition from the Cassie-Baxter state to the Wenzel state. Numerical results are obtained for the wetting of a hydrophobic surface textured with a square lattice of pillars. It is found that the wetting of the solid substrate occurs via infiltration of the liquid in a single groove, followed by lateral propagation of the liquid front. The propagation of the liquid front proceeds in a stepwise manner, and a zipping mechanism is observed during the infiltration of each layer. The minimum energy path for the wetting transition goes through a sequence of intermediate metastable states, whose wetted areas reflect the microstructure of the patterned surface. We also study the dependence of the energy barrier on the drop size and the gap between the pillars.

Role of Loop-Clamping Side Chains in Catalysis by Triosephosphate Isomerase.

PubMed

Zhai, Xiang; Amyes, Tina L; Richard, John P

2015-12-09

The side chains of Y208 and S211 from loop 7 of triosephosphate isomerase (TIM) form hydrogen bonds to backbone amides and carbonyls from loop 6 to stabilize the caged enzyme-substrate complex. The effect of seven mutations [Y208T, Y208S, Y208A, Y208F, S211G, S211A, Y208T/S211G] on the kinetic parameters for TIM catalyzed reactions of the whole substrates dihydroxyacetone phosphate and d-glyceraldehyde 3-phosphate [(k(cat)/K(m))(GAP) and (k(cat)/K(m))DHAP] and of the substrate pieces glycolaldehyde and phosphite dianion (k(cat)/K(HPi)K(GA)) are reported. The linear logarithmic correlation between these kinetic parameters, with slope of 1.04 ± 0.03, shows that most mutations of TIM result in an identical change in the activation barriers for the catalyzed reactions of whole substrate and substrate pieces, so that the transition states for these reactions are stabilized by similar interactions with the protein catalyst. The second linear logarithmic correlation [slope = 0.53 ± 0.16] between k(cat) for isomerization of GAP and K(d)(⧧) for phosphite dianion binding to the transition state for wildtype and many mutant TIM-catalyzed reactions of substrate pieces shows that ca. 50% of the wildtype TIM dianion binding energy, eliminated by these mutations, is expressed at the wildtype Michaelis complex, and ca. 50% is only expressed at the wildtype transition state. Negative deviations from this correlation are observed when the mutation results in a decrease in enzyme reactivity at the catalytic site. The main effect of Y208T, Y208S, and Y208A mutations is to cause a reduction in the total intrinsic dianion binding energy, but the effect of Y208F extends to the catalytic site.

Evidence That Nucleophile Deprotonation Exceeds Bond Formation in the HDV Ribozyme Transition State.

PubMed

Lu, Jun; Koo, Selene C; Weissman, Benjamin P; Harris, Michael E; Li, Nan-Sheng; Piccirilli, Joseph A

2018-06-26

Steric constraints imposed by the active sites of protein and RNA enzymes pose major challenges to the investigation of structure-function relationships within these systems. As a strategy to circumvent such constraints in the HDV ribozyme, we have synthesized phosphoramidites from propanediol derivatives and incorporated them at the 5'-termini of RNA and DNA oligonucleotides to generate a series of novel substrates with nucleophiles perturbed electronically through geminal fluorination. In nonenzymatic, hydroxide-catalyzed intramolecular transphosphorylation of the DNA substrates, pH-rate profiles revealed that fluorine substitution reduces the maximal rate and the kinetic p K a , consistent with the expected electron-withdrawing effect. In HDV ribozyme reactions, we observed that the RNA substrates undergo transphosphorylation relatively efficiently, suggesting that the conformational constraints imposed by a ribofuranose ring are not strictly required for ribozyme catalysis. In contrast to the nonenzymatic reactions, however, substrate fluorination modestly increases the ribozyme reaction rate, consistent with a mechanism in which (1) the 2'-hydroxyl nucleophile exists predominantly in its neutral, protonated form in the ground state and (2) the 2'-hydroxyl bears some negative charge in the rate-determining step, consistent with a transition state in which the extent of 2'-OH deprotonation exceeds the extent of P-O bond formation.

Molecular Dynamics Study of the Opening Mechanism for DNA Polymerase I

PubMed Central

Miller, Bill R.; Parish, Carol A.; Wu, Eugene Y.

2014-01-01

During DNA replication, DNA polymerases follow an induced fit mechanism in order to rapidly distinguish between correct and incorrect dNTP substrates. The dynamics of this process are crucial to the overall effectiveness of catalysis. Although X-ray crystal structures of DNA polymerase I with substrate dNTPs have revealed key structural states along the catalytic pathway, solution fluorescence studies indicate that those key states are populated in the absence of substrate. Herein, we report the first atomistic simulations showing the conformational changes between the closed, open, and ajar conformations of DNA polymerase I in the binary (enzyme∶DNA) state to better understand its dynamics. We have applied long time-scale, unbiased molecular dynamics to investigate the opening process of the fingers domain in the absence of substrate for B. stearothermophilis DNA polymerase in silico. These simulations are biologically and/or physiologically relevant as they shed light on the transitions between states in this important enzyme. All closed and ajar simulations successfully transitioned into the fully open conformation, which is known to be the dominant binary enzyme-DNA conformation from solution and crystallographic studies. Furthermore, we have detailed the key stages in the opening process starting from the open and ajar crystal structures, including the observation of a previously unknown key intermediate structure. Four backbone dihedrals were identified as important during the opening process, and their movements provide insight into the recognition of dNTP substrate molecules by the polymerase binary state. In addition to revealing the opening mechanism, this study also demonstrates our ability to study biological events of DNA polymerase using current computational methods without biasing the dynamics. PMID:25474643

Thickness-dependent phase transition in graphite under high magnetic field

NASA Astrophysics Data System (ADS)

Taen, Toshihiro; Uchida, Kazuhito; Osada, Toshihito

2018-03-01

Various electronic phases emerge when applying high magnetic fields in graphite. However, the origin of a semimetal-insulator transition at B ≃30 T is still not clear, while an exotic density-wave state is theoretically proposed. In order to identify the electronic state of the insulator phase, we investigate the phase transition in thin-film graphite samples that were fabricated on silicon substrate by a mechanical exfoliation method. The critical magnetic fields of the semimetal-insulator transition in thin-film graphite shift to higher magnetic fields, accompanied by a reduction in temperature dependence. These results can be qualitatively reproduced by a density-wave model by introducing a quantum size effect. Our findings establish the electronic state of the insulator phase as a density-wave state standing along the out-of-plane direction, and help determine the electronic states in other high-magnetic-field phases.

Dissecting the total transition state stabilization provided by amino acid side chains at orotidine 5'-monophosphate decarboxylase: a two-part substrate approach.

PubMed

Barnett, Shonoi A; Amyes, Tina L; Wood, Bryant M; Gerlt, John A; Richard, John P

2008-07-29

Kinetic analysis of decarboxylation catalyzed by S154A, Q215A, and S154A/Q215A mutant yeast orotidine 5'-monophosphate decarboxylases with orotidine 5'-monophosphate (OMP) and with a truncated nucleoside substrate (EO) activated by phosphite dianion shows (1) the side chain of Ser-154 stabilizes the transition state through interactions with the pyrimidine rings of OMP or EO, (2) the side chain of Gln-215 interacts with the phosphodianion group of OMP or with phosphite dianion, and (3) the interloop hydrogen bond between the side chains of Ser-154 and Gln-215 orients the amide side chain of Gln-215 to interact with the phosphodianion group of OMP or with phosphite dianion.

Hydrophobic properties of a wavy rough substrate.

PubMed

Carbone, G; Mangialardi, L

2005-01-01

The wetting/non-wetting properties of a liquid drop in contact with a chemically hydrophobic rough surface (thermodynamic contact angle theta(e)>pi/2) are studied for the case of an extremely idealized rough profile: the liquid drop is considered to lie on a simple sinusoidal profile. Depending on surface geometry and pressure values, it is found that the Cassie and Wenzel states can coexist. But if the amplitude h of the substrate is sufficiently large the only possible stable state is the Cassie one, whereas if h is below a certain critical value hcr a transition to the Wenzel state occurs. Since in many potential applications of such super-hydrophobic surfaces, liquid drops often collide with the substrate (e.g. vehicle windscreens), in the paper the critical drop pressure pW is calculated at which the Cassie state is no longer stable and the liquid jumps into full contact with the substrate (Wenzel state). By analyzing the asymptotic behavior of the systems in the limiting case of a large substrate corrugation, a simple criterion is also proposed to calculate the minimum height asperity h necessary to prevent the Wenzel state from being formed, to preserve the super-hydrophobic properties of the substrate, and, hence, to design a robust super-hydrophobic surface.

Kinetic isotope effects reveal early transition state of protein lysine methyltransferase SET8

PubMed Central

Linscott, Joshua A.; Kapilashrami, Kanishk; Wang, Zhen; Senevirathne, Chamara; Bothwell, Ian R.; Blum, Gil; Luo, Minkui

2016-01-01

Protein lysine methyltransferases (PKMTs) catalyze the methylation of protein substrates, and their dysregulation has been linked to many diseases, including cancer. Accumulated evidence suggests that the reaction path of PKMT-catalyzed methylation consists of the formation of a cofactor(cosubstrate)–PKMT–substrate complex, lysine deprotonation through dynamic water channels, and a nucleophilic substitution (SN2) transition state for transmethylation. However, the molecular characters of the proposed process remain to be elucidated experimentally. Here we developed a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) method and corresponding mathematic matrix to determine precisely the ratios of isotopically methylated peptides. This approach may be generally applicable for examining the kinetic isotope effects (KIEs) of posttranslational modifying enzymes. Protein lysine methyltransferase SET8 is the sole PKMT to monomethylate histone 4 lysine 20 (H4K20) and its function has been implicated in normal cell cycle progression and cancer metastasis. We therefore implemented the MS-based method to measure KIEs and binding isotope effects (BIEs) of the cofactor S-adenosyl-l-methionine (SAM) for SET8-catalyzed H4K20 monomethylation. A primary intrinsic 13C KIE of 1.04, an inverse intrinsic α-secondary CD3 KIE of 0.90, and a small but statistically significant inverse CD3 BIE of 0.96, in combination with computational modeling, revealed that SET8-catalyzed methylation proceeds through an early, asymmetrical SN2 transition state with the C-N and C-S distances of 2.35–2.40 Å and 2.00–2.05 Å, respectively. This transition state is further supported by the KIEs, BIEs, and steady-state kinetics with the SAM analog Se-adenosyl-l-selenomethionine (SeAM) as a cofactor surrogate. The distinct transition states between protein methyltransferases present the opportunity to design selective transition-state analog inhibitors. PMID:27940912

Occupancy of the Zinc-binding Site by Transition Metals Decreases the Substrate Affinity of the Human Dopamine Transporter by an Allosteric Mechanism*

PubMed Central

Li, Yang; Mayer, Felix P.; Hasenhuetl, Peter S.; Burtscher, Verena; Schicker, Klaus; Sitte, Harald H.; Freissmuth, Michael; Sandtner, Walter

2017-01-01

The human dopamine transporter (DAT) has a tetrahedral Zn2+-binding site. Zn2+-binding sites are also recognized by other first-row transition metals. Excessive accumulation of manganese or of copper can lead to parkinsonism because of dopamine deficiency. Accordingly, we examined the effect of Mn2+, Co2+, Ni2+, and Cu2+ on transport-associated currents through DAT and DAT-H193K, a mutant with a disrupted Zn2+-binding site. All transition metals except Mn2+ modulated the transport cycle of wild-type DAT with affinities in the low micromolar range. In this concentration range, they were devoid of any action on DAT-H193K. The active transition metals reduced the affinity of DAT for dopamine. The affinity shift was most pronounced for Cu2+, followed by Ni2+ and Zn2+ (= Co2+). The extent of the affinity shift and the reciprocal effect of substrate on metal affinity accounted for the different modes of action: Ni2+ and Cu2+ uniformly stimulated and inhibited, respectively, the substrate-induced steady-state currents through DAT. In contrast, Zn2+ elicited biphasic effects on transport, i.e. stimulation at 1 μm and inhibition at 10 μm. A kinetic model that posited preferential binding of transition metal ions to the outward-facing apo state of DAT and a reciprocal interaction of dopamine and transition metals recapitulated all experimental findings. Allosteric activation of DAT via the Zn2+-binding site may be of interest to restore transport in loss-of-function mutants. PMID:28096460

Catalysis by orotidine 5'-monophosphate decarboxylase: effect of 5-fluoro and 4'-substituents on the decarboxylation of two-part substrates.

PubMed

Goryanova, Bogdana; Spong, Krisztina; Amyes, Tina L; Richard, John P

2013-01-22

The syntheses of two novel truncated analogs of the natural substrate orotidine 5'-monophosphate (OMP) for orotidine 5'-monophosphate decarboxylase (OMPDC) with enhanced reactivity toward decarboxylation are reported: 1-(β-d-erythrofuranosyl)-5-fluoroorotic acid (FEO) and 5'-deoxy-5-fluoroorotidine (5'-dFO). A comparison of the second-order rate constants for the OMPDC-catalyzed decarboxylations of FEO (10 M⁻¹ s⁻¹) and 1-(β-d-erythrofuranosyl)orotic acid (EO, 0.026 M⁻¹ s⁻¹) shows that the vinyl carbanion-like transition state is stabilized by 3.5 kcal/mol by interactions with the 5-F substituent of FEO. The OMPDC-catalyzed decarboxylations of FEO and EO are both activated by exogenous phosphite dianion (HPO₃²⁻), but the 5-F substituent results in only a 0.8 kcal stabilization of the transition state for the phosphite-activated reaction of FEO. This provides strong evidence that the phosphite-activated OMPDC-catalyzed reaction of FEO is not limited by the chemical step of decarboxylation of the enzyme-bound substrate. Evidence is presented that there is a change in the rate-limiting step from the chemical step of decarboxylation for the phosphite-activated reaction of EO, to closure of the phosphate gripper loop and an enzyme conformational change at the ternary E•FEO•HPO₃²⁻ complex for the reaction of FEO. The 4'-CH₃ and 4'-CH₂OH groups of 5'-dFO and orotidine, respectively, result in identical destabilizations of the transition state for the unactivated decarboxylation of 2.9 kcal/mol. By contrast, the 4'-CH₃ group of 5'-dFO and the 4'-CH₂OH group of orotidine result in very different 4.7 and 8.3 kcal/mol destabilizations of the transition state for the phosphite-activated decarboxylation. Here, the destabilizing effect of the 4'-CH₃ substituent at 5'-dFO is masked by the rate-limiting conformational change that depresses the third-order rate constant for the phosphite-activated reaction of the parent substrate FEO.

Low energy electron catalyst: the electronic origin of catalytic strategies.

PubMed

Davis, Daly; Sajeev, Y

2016-10-12

Using a low energy electron (LEE) as a catalyst, the electronic origin of the catalytic strategies corresponding to substrate selectivity, reaction specificity and reaction rate enhancement is investigated for a reversible unimolecular elementary reaction. An electronic energy complementarity between the catalyst and the substrate molecule is the origin of substrate selectivity and reaction specificity. The electronic energy complementarity is induced by tuning the electronic energy of the catalyst. The energy complementarity maximizes the binding forces between the catalyst and the molecule. Consequently, a new electronically metastable high-energy reactant state and a corresponding new low barrier reaction path are resonantly created for a specific reaction of the substrate through the formation of a catalyst-substrate transient adduct. The LEE catalysis also reveals a fundamental structure-energy correspondence in the formation of the catalyst-substrate transient adduct. Since the energy complementarities corresponding to the substrate molecules of the forward and the backward steps of the reversible reactions are not the same due to their structural differences, the LEE catalyst exhibits a unique one-way catalytic strategy, i.e., the LEE catalyst favors the reversible reaction more effectively in one direction. A characteristic stronger binding of the catalyst to the transition state of the reaction than in the initial reactant state and the final product state is the molecular origin of barrier lowering.

Transition States and transition state analogue interactions with enzymes.

PubMed

Schramm, Vern L

2015-04-21

Enzymatic transition states have lifetimes of a few femtoseconds (fs). Computational analysis of enzyme motions leading to transition state formation suggests that local catalytic site motions on the fs time scale provide the mechanism to locate transition states. An experimental test of protein fs motion and its relation to transition state formation can be provided by isotopically heavy proteins. Heavy enzymes have predictable mass-altered bond vibration states without altered electrostatic properties, according to the Born-Oppenheimer approximation. On-enzyme chemistry is slowed in most heavy proteins, consistent with altered protein bond frequencies slowing the search for the transition state. In other heavy enzymes, structural changes involved in reactant binding and release are also influenced. Slow protein motions associated with substrate binding and catalytic site preorganization are essential to allow the subsequent fs motions to locate the transition state and to facilitate the efficient release of products. In the catalytically competent geometry, local groups move in stochastic atomic motion on the fs time scale, within transition state-accessible conformations created by slower protein motions. The fs time scale for the transition state motions does not permit thermodynamic equilibrium between the transition state and stable enzyme states. Isotopically heavy enzymes provide a diagnostic tool for fast coupled protein motions to transition state formation and mass-dependent conformational changes. The binding of transition state analogue inhibitors is the opposite in catalytic time scale to formation of the transition state but is related by similar geometries of the enzyme-transition state and enzyme-inhibitor interactions. While enzymatic transition states have lifetimes as short as 10(-15) s, transition state analogues can bind tightly to enzymes with release rates greater than 10(3) s. Tight-binding transition state analogues stabilize the rare but evolved enzymatic geometry to form the transition state. Evolution to efficient catalysis optimized this geometry and its stabilization by a transition state mimic results in tight binding. Release rates of transition state analogues are orders of magnitude slower than product release in normal catalytic function. During catalysis, product release is facilitated by altered chemistry. Compared to the weak associations found in Michaelis complexes, transition state analogues involve strong interactions related to those in the transition state. Optimum binding of transition state analogues occurs when the complex retains the system motions intrinsic to transition state formation. Conserved dynamic motion retains the entropic components of inhibitor complexes, improving the thermodynamics of analogue binding.

Dynamic phases of active matter systems with quenched disorder

DOE PAGES

Sandor, Csand; Libal, Andras; Reichhardt, Charles; ...

2017-03-16

Depinning and nonequilibrium transitions within sliding states in systems driven over quenched disorder arise across a wide spectrum of size scales ranging from atomic friction at the nanoscale, flux motion in type II superconductors at the mesoscale, colloidal motion in disordered media at the microscale, and plate tectonics at geological length scales. Here we show that active matter or self-propelled particles interacting with quenched disorder under an external drive represents a class of system that can also exhibit pinning-depinning phenomena, plastic flow phases, and nonequilibrium sliding transitions that are correlated with distinct morphologies and velocity-force curve signatures. When interactions withmore » the substrate are strong, a homogeneous pinned liquid phase forms that depins plastically into a uniform disordered phase and then dynamically transitions first into a moving stripe coexisting with a pinned liquid and then into a moving phase-separated state at higher drives. We numerically map the resulting dynamical phase diagrams as a function of external drive, substrate interaction strength, and self-propulsion correlation length. These phases can be observed for active matter moving through random disorder. Lastly, our results indicate that intrinsically nonequilibrium systems can exhibit additional nonequilibrium transitions when subjected to an external drive.« less

Dynamic phases of active matter systems with quenched disorder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandor, Csand; Libal, Andras; Reichhardt, Charles

Depinning and nonequilibrium transitions within sliding states in systems driven over quenched disorder arise across a wide spectrum of size scales ranging from atomic friction at the nanoscale, flux motion in type II superconductors at the mesoscale, colloidal motion in disordered media at the microscale, and plate tectonics at geological length scales. Here we show that active matter or self-propelled particles interacting with quenched disorder under an external drive represents a class of system that can also exhibit pinning-depinning phenomena, plastic flow phases, and nonequilibrium sliding transitions that are correlated with distinct morphologies and velocity-force curve signatures. When interactions withmore » the substrate are strong, a homogeneous pinned liquid phase forms that depins plastically into a uniform disordered phase and then dynamically transitions first into a moving stripe coexisting with a pinned liquid and then into a moving phase-separated state at higher drives. We numerically map the resulting dynamical phase diagrams as a function of external drive, substrate interaction strength, and self-propulsion correlation length. These phases can be observed for active matter moving through random disorder. Lastly, our results indicate that intrinsically nonequilibrium systems can exhibit additional nonequilibrium transitions when subjected to an external drive.« less

Leaving Group Ability Observably Affects Transition State Structure in a Single Enzyme Active Site.

PubMed

Roston, Daniel; Demapan, Darren; Cui, Qiang

2016-06-15

A reaction's transition state (TS) structure plays a critical role in determining reactivity and has important implications for the design of catalysts, drugs, and other applications. Here, we explore TS structure in the enzyme alkaline phosphatase using hybrid Quantum Mechanics/Molecular Mechanics simulations. We find that minor perturbations to the substrate have major effects on TS structure and the way the enzyme stabilizes the TS. Substrates with good leaving groups (LGs) have little cleavage of the phosphorus-LG bond at the TS, while substrates with poor LGs have substantial cleavage of that bond. The results predict nonlinear free energy relationships for a single rate-determining step, and substantial differences in kinetic isotope effects for different substrates; both trends were observed in previous experimental studies, although the original interpretations differed from the present model. Moreover, due to different degrees of phosphorus-LG bond cleavage at the TS for different substrates, the LG is stabilized by different interactions at the TS: while a poor LG is directly stabilized by an active site zinc ion, a good LG is mainly stabilized by active site water molecules. Our results demonstrate the considerable plasticity of TS structure and stabilization in enzymes. Furthermore, perturbations to reactivity that probe TS structure experimentally (i.e., substituent effects) may substantially perturb the TS they aim to probe, and thus classical experimental approaches such as free energy relations should be interpreted with care.

Substrate-induced ubiquitylation and endocytosis of yeast amino acid permeases.

PubMed

Ghaddar, Kassem; Merhi, Ahmad; Saliba, Elie; Krammer, Eva-Maria; Prévost, Martine; André, Bruno

2014-12-01

Many plasma membrane transporters are downregulated by ubiquitylation, endocytosis, and delivery to the lysosome in response to various stimuli. We report here that two amino acid transporters of Saccharomyces cerevisiae, the general amino acid permease (Gap1) and the arginine-specific permease (Can1), undergo ubiquitin-dependent downregulation in response to their substrates and that this downregulation is not due to intracellular accumulation of the transported amino acids but to transport catalysis itself. Following an approach based on permease structural modeling, mutagenesis, and kinetic parameter analysis, we obtained evidence that substrate-induced endocytosis requires transition of the permease to a conformational state preceding substrate release into the cell. Furthermore, this transient conformation must be stable enough, and thus sufficiently populated, for the permease to undergo efficient downregulation. Additional observations, including the constitutive downregulation of two active Gap1 mutants altered in cytosolic regions, support the model that the substrate-induced conformational transition inducing endocytosis involves remodeling of cytosolic regions of the permeases, thereby promoting their recognition by arrestin-like adaptors of the Rsp5 ubiquitin ligase. Similar mechanisms might control many other plasma membrane transporters according to the external concentrations of their substrates. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Allosteric Inhibition via R-state Destabilization in ATP Sulfurylase from Penicillium chrysogenum

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacRae, I. J.

2002-01-01

The structure of the cooperative hexameric enzyme ATP sulfurylase from Penicillium chrysogenum bound to its allosteric inhibitor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS), was determined to 2.6 {angstrom} resolution. This structure represents the low substrate-affinity T-state conformation of the enzyme. Comparison with the high substrate-affinity R-state structure reveals that a large rotational rearrangement of domains occurs as a result of the R-to-T transition. The rearrangement is accompanied by the 17 {angstrom} movement of a 10-residue loop out of the active site region, resulting in an open, product release-like structure of the catalytic domain. Binding of PAPS is proposed to induce the allosteric transition bymore » destabilizing an R-state-specific salt linkage between Asp 111 in an N-terminal domain of one subunit and Arg 515 in the allosteric domain of a trans-triad subunit. Disrupting this salt linkage by site-directed mutagenesis induces cooperative inhibition behavior in the absence of an allosteric effector, confirming the role of these two residues.« less

Evolution of optical properties and band structure from amorphous to crystalline Ga2O3 films

NASA Astrophysics Data System (ADS)

Zhang, Fabi; Li, Haiou; Cui, Yi-Tao; Li, Guo-Ling; Guo, Qixin

2018-04-01

The optical properties and band structure evolution from amorphous to crystalline Ga2O3 films was investigated in this work. Amorphous and crystalline Ga2O3 films were obtained by changing the growth substrate temperatures of pulsed laser deposition and the crystallinity increase with the rising of substrate temperature. The bandgap value and ultraviolet emission intensity of the films increase with the rising of crystallinity as observed by means of spectrophotometer and cathodoluminescence spectroscopy. Abrupt bandgap value and CL emission variations were observed when amorphous to crystalline transition took place. X-ray photoelectron spectroscopy core level spectra reveal that more oxygen vacancies and disorders exist in amorphous Ga2O3 film grown at lower substrate temperature. The valence band spectra of hard X-ray photoelectron spectroscopy present the main contribution from Ga 4sp for crystalline film deposited at substrate temperature of 500 oC, while extra subgap states has been observed in amorphous film deposited at 300 oC. The oxygen vacancy and the extra subgap density of states are suggested to be the parts of origin of bandgap and CL spectra variations. The experimental data above yields a realistic picture of optical properties and band structure variation for the amorphous to crystalline transition of Ga2O3 films.

Active site dynamics of ribonuclease.

PubMed Central

Brünger, A T; Brooks, C L; Karplus, M

1985-01-01

The stochastic boundary molecular dynamics method is used to study the structure, dynamics, and energetics of the solvated active site of bovine pancreatic ribonuclease A. Simulations of the native enzyme and of the enzyme complexed with the dinucleotide substrate CpA and the transition-state analog uridine vanadate are compared. Structural features and dynamical couplings for ribonuclease residues found in the simulation are consistent with experimental data. Water molecules, most of which are not observed in crystallographic studies, are shown to play an important role in the active site. Hydrogen bonding of residues with water molecules in the free enzyme is found to mimic the substrate-enzyme interactions of residues involved in binding. Networks of water stabilize the cluster of positively charged active site residues. Correlated fluctuations between the uridine vanadate complex and the distant lysine residues are mediated through water and may indicate a possible role for these residues in stabilizing the transition state. Images PMID:3866234

Strain driven sequential magnetic transitions in strained GdTiO3 on compressive substrates: a first-principles study.

PubMed

Yang, Li-Juan; Weng, Ya-Kui; Zhang, Hui-Min; Dong, Shuai

2014-11-26

The compressive strain effect on the magnetic ground state and electronic structure of strained GdTiO3 has been studied using the first-principles method. Unlike the cases of congeneric YTiO3 and LaTiO3, both of which become the A-type antiferromagnetism on the (0 0 1) LaAlO3 substrate despite their contrastive magnetism, the ground state of strained GdTiO3 on the LaAlO3 substrate changes from the original ferromagnetism to a G-type antiferromagnetim, instead of the A-type one although Gd(3+) is between Y(3+) and La(3+). It is only when the in-plane compressive strain is large enough, e.g. on the (0 0 1) YAlO3 substrate, that the ground state finally becomes the A-type. The band structure calculation shows that the compressive strained GdTiO3 remains insulating, although the band gap changes a little in the strained GdTiO3.

Structure-based analysis of catalysis and substrate definition in the HIT protein family.

PubMed

Lima, C D; Klein, M G; Hendrickson, W A

1997-10-10

The histidine triad (HIT) protein family is among the most ubiquitous and highly conserved in nature, but a biological activity has not yet been identified for any member of the HIT family. Fragile histidine triad protein (FHIT) and protein kinase C interacting protein (PKCI) were used in a structure-based approach to elucidate characteristics of in vivo ligands and reactions. Crystallographic structures of apo, substrate analog, pentacovalent transition-state analog, and product states of both enzymes reveal a catalytic mechanism and define substrate characteristics required for catalysis, thus unifying the HIT family as nucleotidyl hydrolases, transferases, or both. The approach described here may be useful in identifying structure-function relations between protein families identified through genomics.

Enhanced electrodes for solid state gas sensors

DOEpatents

Garzon, Fernando H.; Brosha, Eric L.

2001-01-01

A solid state gas sensor generates an electrical potential between an equilibrium electrode and a second electrode indicative of a gas to be sensed. A solid electrolyte substrate has the second electrode mounted on a first portion of the electrolyte substrate and a composite equilibrium electrode including conterminous transition metal oxide and Pt components mounted on a second portion of the electrolyte substrate. The composite equilibrium electrode and the second electrode are electrically connected to generate an electrical potential indicative of the gas that is being sensed. In a particular embodiment of the present invention, the second electrode is a reference electrode that is exposed to a reference oxygen gas mixture so that the electrical potential is indicative of the oxygen in a gas stream.

Band structure dynamics in indium wires

NASA Astrophysics Data System (ADS)

Chávez-Cervantes, M.; Krause, R.; Aeschlimann, S.; Gierz, I.

2018-05-01

One-dimensional indium wires grown on Si(111) substrates, which are metallic at high temperatures, become insulating below ˜100 K due to the formation of a charge density wave (CDW). The physics of this transition is not conventional and involves a multiband Peierls instability with strong interband coupling. This CDW ground state is readily destroyed with femtosecond laser pulses resulting in a light-induced insulator-to-metal phase transition. The current understanding of this transition remains incomplete, requiring measurements of the transient electronic structure to complement previous investigations of the lattice dynamics. Time- and angle-resolved photoemission spectroscopy with extreme ultraviolet radiation is applied to this end. We find that the transition from the insulating to the metallic band structure occurs within ˜660 fs, which is a fraction of the amplitude mode period. The long lifetime of the transient state (>100 ps) is attributed to trapping in a metastable state in accordance with previous work.

Epitaxy, strain, and composition effects on metal-insulator transition characteristics of SmNiO{sub 3} thin films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aydogdu, Gulgun H.; Ha, Sieu D.; Viswanath, B.

SmNiO{sub 3} (SNO) thin films were deposited on LaAlO{sub 3} (LAO), SrTiO{sub 3}, SrLaAlO{sub 4}, Si, and Al{sub 2}O{sub 3} (sapphire) substrates by RF magnetron sputtering and studies were conducted to understand how film structure and composition influence the insulator-metal transition properties. It is observed that the compressive strain induces the insulator to metal transition (MIT), while tensile strain suppresses it. In the case of non-epitaxial films, semiconducting behavior is obtained on sapphire over a broad temperature range, while on heavily-doped Si substrate; an MIT is seen in out-of-plane resistance measurement. In addition, thickness dependence on the resistance behavior andmore » nickel oxidation state has been examined for epitaxial SNO films on LAO substrates. Fine control of the MIT by modifications to the mismatch strain and thickness provides insights to enhance the performance and the functionality of these films for emerging electron devices.« less

δ-Deuterium Isotope Effects as Probes for Transition-State Structures of Isoprenoid Substrates

PubMed Central

2015-01-01

The biosynthetic pathways to isoprenoid compounds involve transfer of the prenyl moiety in allylic diphosphates to electron-rich (nucleophilic) acceptors. The acceptors can be many types of nucleophiles, while the allylic diphosphates only differ in the number of isoprene units and stereochemistry of the double bonds in the hydrocarbon moieties. Because of the wide range of nucleophilicities of naturally occurring acceptors, the mechanism for prenyltransfer reactions may be dissociative or associative with early to late transition states. We have measured δ-secondary kinetic isotope effects operating through four bonds for substitution reactions with dimethylallyl derivatives bearing deuterated methyl groups at the distal (C3) carbon atom in the double bond under dissociative and associative conditions. Computational studies with density functional theory indicate that the magnitudes of the isotope effects correlate with the extent of bond formation between the allylic moiety and the electron-rich acceptor in the transition state for alkylation and provide insights into the structures of the transition states for associative and dissociative alkylation reactions. PMID:24665882

Structural basis of the broad substrate tolerance of the antibody 7B9-catalyzed hydrolysis of p-nitrobenzyl esters.

PubMed

Miyamoto, Naoki; Yoshimura, Miho; Okubo, Yuji; Suzuki-Nagata, Kayo; Tsumuraya, Takeshi; Ito, Nobutoshi; Fujii, Ikuo

2018-05-01

Catalytic antibody 7B9, which was elicited against p-nitrobenzyl phosphonate transition-state analogue (TSA) 1, hydrolyzes a wide range of p-nitrobenzyl monoesters and thus shows broad substrate tolerance. To reveal the molecular basis of this substrate tolerance, the 7B9 Fab fragment complexed with p-nitrobenzyl ethylphosphonate 2 was crystallized and the three-dimensional structure was determined. The crystal structure showed that the strongly antigenic p-nitrobenzyl moiety occupied a relatively shallow antigen-combining site and therefore the alkyl moiety was located outside the pocket. These results support the observed broad substrate tolerance of 7B9 and help rationalize how 7B9 can catalyze various p-nitrobenzyl ester derivatives. The crystal structure also showed that three amino acid residues (Asn H33 , Ser H95 , and Arg L96 ) were placed in key positions to form hydrogen bonds with the phosphonate oxygens of the transitions-state analogue. In addition, the role of these amino acid residues was examined by site-directed mutagenesis to alanine: all mutants (Asn H33 Ala, Ser H95 Ala, and Arg L96 Ala) showed no detectable catalytic activity. Coupling the findings from our structural studies with these mutagenesis results clarified the structural basis of the observed broad substrate tolerance of antibody 7B9-catalyzed hydrolyses. Our findings provide new strategies for the generation of catalytic antibodies that accept a broad range of substrates, aiding their practical application in synthetic organic chemistry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Entropically Driven Layering Near a Substrate: A Fluids DFT Study

NASA Astrophysics Data System (ADS)

McGarrity, Erin; Frischknecht, Amalie; Mackay, Michael

2008-03-01

We employ a fluids density functional theory to study the phase behavior of athermal polymer/nanoparticle blends near a hard substrate. These blends exhibit two types of first order, entropically driven layering transitions. In the first type of transition, the nanoparticles order to form a layer which is a fixed distance from the surface. The structure and location of this layer depends on nanoparticle radius. In the second type of transition, which occurs at melt-like densities, the nanoparticles and polymers form laminar structures which resemble colloidal crystals. We examine the effects of packing density, chain length and nanoparticle radius on the system and show that the transitions are first order. In addition we show that the crystalline phase is nucleated by the presence of the surface. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

A metal-insulator transition study of VO 2 thin films grown on sapphire substrates

DOE PAGES

Yu, Shifeng; Wang, Shuyu; Lu, Ming; ...

2017-12-15

In this paper, vanadium thin films were deposited on sapphire substrates by DC magnetron sputtering and then oxidized in a tube furnace filled with oxygen under different temperatures and oxygen flow rates. The significant influence of the oxygen flow rate and oxidation temperature on the electrical and structural properties of the vanadium oxide thin films were investigated systematically. It shows the pure vanadium dioxide (VO 2) state can only be obtained in a very narrow temperature and oxygen flow rate range. The resistivity change during the metal-insulator transition varies from 0.2 to 4 orders of magnitude depending on the oxidationmore » condition. Large thermal hysteresis during the metal-insulator phase transition was observed during the transition compared to the results in literature. Proper oxidation conditions can significantly reduce the thermal hysteresis. Finally, the fabricated VO 2 thin films showed the potential to be applied in the development of electrical sensors and other smart devices.« less

Heterogeneous nucleation and growth dynamics in the light-induced phase transition in vanadium dioxide

DOE PAGES

Brady, Nathaniel F.; Appavoo, Kannatassen; Seo, Minah; ...

2016-03-02

Here we report on ultrafast optical investigations of the light-induced insulator-to-metal phase transition in vanadium dioxide with controlled disorder generated by substrate mismatch. These results reveal common dynamics of this optically-induced phase transition that are independent of this disorder. Lastly, above the fluence threshold for completing the transition to the rutile crystalline phase, we find a common time scale, independent of sample morphology, of 40.5 ± 2 ps that is consistent with nucleation and growth dynamics of the R phase from the parent M1 ground state.

Molecular Dynamics Simulation of the Allosteric Regulation of eIF4A Protein from the Open to Closed State, Induced by ATP and RNA Substrates

PubMed Central

Meng, Hongqing; Li, Chaoqun; Wang, Yan; Chen, Guangju

2014-01-01

Background Eukaryotic initiation factor 4A (eIF4A) plays a key role in the process of protein translation initiation by facilitating the melting of the 5′ proximal secondary structure of eukaryotic mRNA for ribosomal subunit attachment. It was experimentally postulated that the closed conformation of the eIF4A protein bound by the ATP and RNA substrates is coupled to RNA duplex unwinding to promote protein translation initiation, rather than an open conformation in the absence of ATP and RNA substrates. However, the allosteric process of eIF4A from the open to closed state induced by the ATP and RNA substrates are not yet fully understood. Methodology In the present work, we constructed a series of diplex and ternary models of the eIF4A protein bound by the ATP and RNA substrates to carry out molecular dynamics simulations, free energy calculations and conformation analysis and explore the allosteric properties of eIF4A. Results The results showed that the eIF4A protein completes the conformational transition from the open to closed state via two allosteric processes of ATP binding followed by RNA and vice versa. Based on cooperative allosteric network analysis, the ATP binding to the eIF4A protein mainly caused the relative rotation of two domains, while the RNA binding caused the proximity of two domains via the migration of RNA bases in the presence of ATP. The cooperative binding of ATP and RNA for the eIF4A protein plays a key role in the allosteric transition. PMID:24465900

Deduced catalytic mechanism of d-amino acid amidase from Ochrobactrum anthropi SV3

PubMed Central

Okazaki, Seiji; Suzuki, Atsuo; Komeda, Hidenobu; Asano, Yasuhisa; Yamane, Takashi

2008-01-01

d-Amino acid amidase (DAA) from Ochrobactrum anthropi SV3 catalyzes d-stereospecific hydrolysis of amino acid amides. DAA has attracted attention as a catalyst for the stereospecific production of d-amino acids, although the mechanism that drives the reaction has not been clear. Previously, the structure of DAA was classified into two types, a substrate-bound state with an ordered Ω loop, and a ground state with a disordered Ω loop. Because the binding of the substrate facilitates ordering, this transition was regarded to be induced fit motion. The angles and distances of hydrogen bonds at Tyr149 Oη, Ser60 Oγ and Lys63 Nζ revealed that Tyr149 Oη donates an H atom to a water molecule in the substrate-bound state, and that Tyr149 Oη donates an H atom to Ser60 Oγ or Lys63 Nζ in the ground state. Taking into consideration the locations of the H atoms of Tyr149 Oη, Ser60 Oγ and Lys63 Nζ, a catalytic mechanism of DAA activity is presented, wherein a shift of an H atom at Tyr149 Oη in the substrate-bound versus the ground state plays a significant role in the reaction. This mechanism explains well why acylation proceeds and deacylation does not proceed in the substrate-bound state. PMID:18421151

Lateral epitaxy of atomically sharp WSe 2/WS 2 heterojunctions on silicon dioxide substrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Jianyi; Zhou, Wu; Tang, Wei

Here, in recent years, 2-D transition-metal dichalcogenides (TMDCs) have received great interests because of the broader possibilities offered by their tunable band gaps, as opposed to gapless graphene which precludes application in digital electronics. TMDCs exhibit an indirect-to-direct band gap transition at the single atomic sheet state as well as optically accessible spin degree of freedom in valleytronics.

Lateral epitaxy of atomically sharp WSe 2/WS 2 heterojunctions on silicon dioxide substrates

DOE PAGES

Chen, Jianyi; Zhou, Wu; Tang, Wei; ...

2016-09-30

Here, in recent years, 2-D transition-metal dichalcogenides (TMDCs) have received great interests because of the broader possibilities offered by their tunable band gaps, as opposed to gapless graphene which precludes application in digital electronics. TMDCs exhibit an indirect-to-direct band gap transition at the single atomic sheet state as well as optically accessible spin degree of freedom in valleytronics.

Probing the importance of hydrogen bonds in the active site of the subtilisin nattokinase by site-directed mutagenesis and molecular dynamics simulation

PubMed Central

Zheng, Zhong-liang; Ye, Mao-qing; Zuo, Zhen-yu; Liu, Zhi-gang; Tai, Keng-chang; Zou, Guo-lin

2006-01-01

Hydrogen bonds occurring in the catalytic triad (Asp32, His64 and Ser221) and the oxyanion hole (Asn155) are very important to the catalysis of peptide bond hydrolysis by serine proteases. For the subtilisin NK (nattokinase), a bacterial serine protease, construction and analysis of a three-dimensional structural model suggested that several hydrogen bonds formed by four residues function to stabilize the transition state of the hydrolysis reaction. These four residues are Ser33, Asp60, Ser62 and Thr220. In order to remove the effect of these hydrogen bonds, four mutants (Ser33→Ala33, Asp60→Ala60, Ser62→Ala62, and Thr220→Ala220) were constructed by site-directed mutagenesis. The results of enzyme kinetics indicated that removal of these hydrogen bonds increases the free-energy of the transition state (ΔΔGT). We concluded that these hydrogen bonds are more important for catalysis than for binding the substrate, because removal of these bonds mainly affects the kcat but not the Km values. A substrate, SUB1 (succinyl-Ala-Ala-Pro-Phe-p-nitroanilide), was used during enzyme kinetics experiments. In the present study we have also shown the results of FEP (free-energy perturbation) calculations with regard to the binding and catalysis reactions for these mutant subtilisins. The calculated difference in FEP also suggested that these four residues are more important for catalysis than binding of the substrate, and the simulated values compared well with the experimental values from enzyme kinetics. The results of MD (molecular dynamics) simulations further demonstrated that removal of these hydrogen bonds partially releases Asp32, His64 and Asn155 so that the stability of the transition state decreases. Another substrate, SUB2 (H-D-Val-Leu-Lys-p-nitroanilide), was used for FEP calculations and MD simulations. PMID:16411898

Probing the importance of hydrogen bonds in the active site of the subtilisin nattokinase by site-directed mutagenesis and molecular dynamics simulation.

PubMed

Zheng, Zhong-liang; Ye, Mao-qing; Zuo, Zhen-yu; Liu, Zhi-gang; Tai, Keng-chang; Zou, Guo-lin

2006-05-01

Hydrogen bonds occurring in the catalytic triad (Asp32, His64 and Ser221) and the oxyanion hole (Asn155) are very important to the catalysis of peptide bond hydrolysis by serine proteases. For the subtilisin NK (nattokinase), a bacterial serine protease, construction and analysis of a three-dimensional structural model suggested that several hydrogen bonds formed by four residues function to stabilize the transition state of the hydrolysis reaction. These four residues are Ser33, Asp60, Ser62 and Thr220. In order to remove the effect of these hydrogen bonds, four mutants (Ser33-->Ala33, Asp60-->Ala60, Ser62-->Ala62, and Thr220-->Ala220) were constructed by site-directed mutagenesis. The results of enzyme kinetics indicated that removal of these hydrogen bonds increases the free-energy of the transition state (DeltaDeltaG(T)). We concluded that these hydrogen bonds are more important for catalysis than for binding the substrate, because removal of these bonds mainly affects the kcat but not the K(m) values. A substrate, SUB1 (succinyl-Ala-Ala-Pro-Phe-p-nitroanilide), was used during enzyme kinetics experiments. In the present study we have also shown the results of FEP (free-energy perturbation) calculations with regard to the binding and catalysis reactions for these mutant subtilisins. The calculated difference in FEP also suggested that these four residues are more important for catalysis than binding of the substrate, and the simulated values compared well with the experimental values from enzyme kinetics. The results of MD (molecular dynamics) simulations further demonstrated that removal of these hydrogen bonds partially releases Asp32, His64 and Asn155 so that the stability of the transition state decreases. Another substrate, SUB2 (H-D-Val-Leu-Lys-p-nitroanilide), was used for FEP calculations and MD simulations.

Metal-insulator transition characteristics of VO2 thin films grown on Ge(100) single crystals

NASA Astrophysics Data System (ADS)

Yang, Z.; Ko, C.; Ramanathan, S.

2010-10-01

Phase transitions exhibited by correlated oxides could be of potential relevance to the emerging field of oxide electronics. We report on the synthesis of high-quality VO2 thin films grown on single crystal Ge(100) substrates by physical vapor deposition and their metal-insulator transition (MIT) properties. Thermally triggered MIT is demonstrated with nearly three orders of magnitude resistance change across the MIT with transition temperatures of 67 °C (heating) and 61 °C (cooling). Voltage-triggered hysteretic MIT is observed at room temperature at threshold voltage of ˜2.1 V for ˜100 nm thickness VO2 films. Activation energies for electron transport in the insulating and conducting states are obtained from variable temperature resistance measurements. We further compare the properties of VO2 thin films grown under identical conditions on Si(100) single crystals. The VO2 thin films grown on Ge substrate show higher degree of crystallinity, slightly reduced compressive strain, larger resistance change across MIT compared to those grown on Si. Depth-dependent x-ray photoelectron spectroscopy measurements were performed to provide information on compositional variation trends in the two cases. These results suggest Ge could be a suitable substrate for further explorations of switching phenomena and devices for thin film functional oxides.

Transition State Gauche Effects Control the Torquoselectivities of the Electrocyclizations of Chiral 1-Azatrienes.

PubMed

Patel, Ashay; Vella, Joseph R; Ma, Zhi-Xiong; Hsung, R P; Houk, K N

2015-12-04

Hsung et al. have reported a series of torquoselective electrocyclizations of chiral 1-azahexa-1E,3Z,5E-trienes that yield functionalized dihydropyridines. To understand the origins of the torquoselectivities of these azaelectrocyclizations, we modeled these electrocyclic ring closures using the M06-2X density functional. A new stereochemical model that rationalizes the observed 1,2 stereoinduction emerges from these computations. This model is an improvement and generalization of the "inside-alkoxy" model used to rationalize stereoselectivities of the 1,3-dipolar cycloaddition of chiral allyl ethers and emphasizes a stabilizing hyperconjugative effect, which we have termed a transition state gauche effect. This stereoelectronic effect controls the conformational preferences at the electrocyclization transition states, and only in one of the allowed disrotatory electrocyclization transition states is the ideal stereoelectronic arrangement achieved without the introduction of a steric clash. Computational experiments confirm the role of this effect as a stereodeterminant since substrates with electropositive groups and electronegative groups have different conformational preferences at the transition state and undergo ring closure with divergent stereochemical outcomes. This predicted reversal of stereoselectivity for the ring closures of several silyl substituted azatrienes have been demonstrated experimentally.

Basic Residues R260 and K357 Affect the Conformational Dynamics of the Major Facilitator Superfamily Multidrug Transporter LmrP

PubMed Central

Wang, Wei; van Veen, Hendrik W.

2012-01-01

Secondary-active multidrug transporters can confer resistance on cells to pharmaceuticals by mediating their extrusion away from intracellular targets via substrate/H+(Na+) antiport. While the interactions of catalytic carboxylates in these transporters with coupling ions and substrates (drugs) have been studied in some detail, the functional importance of basic residues has received much less attention. The only two basic residues R260 and K357 in transmembrane helices in the Major Facilitator Superfamily transporter LmrP from Lactococcus lactis are present on the outer surface of the protein, where they are exposed to the phospholipid head group region of the outer leaflet (R260) and inner leaflet (K357) of the cytoplasmic membrane. Although our observations on the proton-motive force dependence and kinetics of substrate transport, and substrate-dependent proton transport demonstrate that K357A and R260A mutants are affected in ethidium-proton and benzalkonium-proton antiport compared to wildtype LmrP, our findings suggest that R260 and K357 are not directly involved in the binding of substrates or the translocation of protons. Secondary-active multidrug transporters are thought to operate by a mechanism in which binding sites for substrates are alternately exposed to each face of the membrane. Disulfide crosslinking experiments were performed with a double cysteine mutant of LmrP that reports the substrate-stimulated transition from the outward-facing state to the inward-facing state with high substrate-binding affinity. In the experiments, the R260A and K357A mutations were found to influence the dynamics of these major protein conformations in the transport cycle, potentially by removing the interactions of R260 and K357 with phospholipids and/or other residues in LmrP. The R260A and K357A mutations therefore modify the maximum rate at which the transport cycle can operate and, as the transitions between conformational states are differently affected by components of the proton-motive force, the mutations also influence the energetics of transport. PMID:22761697

Mid-infrared intersubband absorption from p-Ge quantum wells grown on Si substrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gallacher, K.; Millar, R. W.; Paul, D. J., E-mail: Douglas.Paul@glasgow.ac.uk

2016-02-29

Mid-infrared intersubband absorption from p-Ge quantum wells with Si{sub 0.5}Ge{sub 0.5} barriers grown on a Si substrate is demonstrated from 6 to 9 μm wavelength at room temperature and can be tuned by adjusting the quantum well thickness. Fourier transform infra-red transmission and photoluminescence measurements demonstrate clear absorption peaks corresponding to intersubband transitions among confined hole states. The work indicates an approach that will allow quantum well intersubband photodetectors to be realized on Si substrates in the important atmospheric transmission window of 8–13 μm.

Pattern-induced anchoring transitions in nematic liquid crystals

NASA Astrophysics Data System (ADS)

Rojas-Gómez, Óscar A.; Romero-Enrique, José M.; Silvestre, Nuno M.; Telo da Gama, Margarida M.

2017-02-01

In this paper we revisit the problem of a nematic liquid crystal in contact with patterned substrates. The substrate is modelled as a periodic array of parallel infinite grooves of well-defined cross-section sculpted on a chemically homogeneous substrate which favours local homeotropic anchoring of the nematic. We consider three cases: a sawtooth, a crenellated and a sinusoidal substrate. We analyse this problem within the modified Frank-Oseen formalism. We argue that, for substrate periodicities much larger than the extrapolation length, the existence of different nematic textures with distinct far-field orientations, as well as the anchoring transitions between them, are associated with the presence of topological defects either on or close to the substrate. For the sawtooth and sinusoidal cases, we observe a homeotropic to planar anchoring transition as the substrate roughness increases. On the other hand, a homeotropic to oblique anchoring transition is observed for crenellated substrates. In this case, the anchoring phase diagram shows a complex dependence on the substrate roughness and substrate anchoring strength.

Magnus-induced dynamics of driven skyrmions on a quasi-one-dimensional periodic substrate

DOE PAGES

Reichhardt, Charles; Reichhardt, Cynthia Jane

2016-09-13

Here we numerically examine driven skyrmions interacting with a periodic quasi-one-dimensional substrate where the driving force is applied either parallel or perpendicular to the substrate periodicity direction. For perpendicular driving, the particles in a purely overdamped system simply slide along the substrate minima; however, for skyrmions where the Magnus force is relevant, we find that a rich variety of dynamics can arise. In the single skyrmion limit, the skyrmion motion is locked along the driving or longitudinal direction for low drives, while at higher drives a transition occurs to a state in which the skyrmion moves both transverse and longitudinalmore » to the driving direction. Within the longitudinally locked phase we find a pronounced speedup effect that occurs when the Magnus force aligns with the external driving force, while at the transition to transverse and longitudinal motion, the skyrmion velocity drops, producing negative differential conductivity. For collectively interacting skyrmion assemblies, the speedup effect is still present and we observe a number of distinct dynamical phases, including a sliding smectic phase, a disordered or moving liquid phase, a moving hexatic phase, and a moving crystal phase. The transitions between the dynamic phases produce distinct features in the structure of the skyrmion lattice and in the velocity-force curves. Lastly, we map these different phases as a function of the ratio of the Magnus term to the dissipative term, the substrate strength, the commensurability ratio, and the magnitude of the driving force.« less

Magnus-induced dynamics of driven skyrmions on a quasi-one-dimensional periodic substrate

NASA Astrophysics Data System (ADS)

Reichhardt, C.; Reichhardt, C. J. Olson

2016-09-01

We numerically examine driven skyrmions interacting with a periodic quasi-one-dimensional substrate where the driving force is applied either parallel or perpendicular to the substrate periodicity direction. For perpendicular driving, the particles in a purely overdamped system simply slide along the substrate minima; however, for skyrmions where the Magnus force is relevant, we find that a rich variety of dynamics can arise. In the single skyrmion limit, the skyrmion motion is locked along the driving or longitudinal direction for low drives, while at higher drives a transition occurs to a state in which the skyrmion moves both transverse and longitudinal to the driving direction. Within the longitudinally locked phase we find a pronounced speedup effect that occurs when the Magnus force aligns with the external driving force, while at the transition to transverse and longitudinal motion, the skyrmion velocity drops, producing negative differential conductivity. For collectively interacting skyrmion assemblies, the speedup effect is still present and we observe a number of distinct dynamical phases, including a sliding smectic phase, a disordered or moving liquid phase, a moving hexatic phase, and a moving crystal phase. The transitions between the dynamic phases produce distinct features in the structure of the skyrmion lattice and in the velocity-force curves. We map these different phases as a function of the ratio of the Magnus term to the dissipative term, the substrate strength, the commensurability ratio, and the magnitude of the driving force.

Enzymatic hydrolysis of short-chain lecithin/long-chain phospholipid unilamellar vesicles: sensitivity of phospholipases to matrix phase state.

PubMed

Gabriel, N E; Agman, N V; Roberts, M F

1987-11-17

Short-chain lecithin/long-chain phospholipid unilamellar vesicles (SLUVs), unlike pure long-chain lecithin vesicles, are excellent substrates for water-soluble phospholipases. Hemolysis assays show that greater than 99.5% of the short-chain lecithin is partitioned in the bilayer. In these binary component vesicles, the short-chain species is the preferred substrate, while the long-chain phospholipid can be treated as an inhibitor (phospholipase C) or poor substrate (phospholipase A2). For phospholipase C Bacillus cereus, apparent Km and Vmax values show that bilayer-solubilized diheptanoylphosphatidylcholine (diheptanoyl-PC) is nearly as good a substrate as pure micellar diheptanoyl-PC, although the extent of short-chain lecithin hydrolysis depends on the phase state of the long-chain lipid. For phospholipase A2 Naja naja naja, both Km and Vmax values show a greater range: in a gel-state matrix, diheptanoyl-PC is hydrolyzed with micellelike kinetic parameters; in a liquid-crystalline matrix, the short-chain lecithin becomes comparable to the long-chain component. Both enzymes also show an anomalous increase in specific activity toward diheptanoyl-PC around the phase transition temperature of the long-chain phospholipid. Since the short-chain lecithin does not exhibit a phase transition, this must reflect fluctuations in head-group area or vertical motions of the short-chain lecithin caused by surrounding long-chain lecithin molecules. These results are discussed in terms of a specific model for SLUV hydrolysis and a general explanation for the "interfacial activation" observed with water-soluble phospholipases.

Method of preparing an electrochemical cell in uncharged state

DOEpatents

Shimotake, Hiroshi; Bartholme, Louis G.; Arntzen, John D.

1977-02-01

A secondary electrochemical cell is assembled in an uncharged state for the preparation of a lithium alloy-transition metal sulfide cell. The negative electrode includes a material such as aluminum or silicon for alloying with lithium as the cell is charged. The positive electrode is prepared by blending particulate lithium sulfide, transition metal powder and electrolytic salt in solid phase. The mixture is simultaneously heated to a temperature in excess of the melting point of the electrolyte and pressed onto an electrically conductive substrate to form a plaque. The plaque is assembled as a positive electrode within the cell. During the first charge cycle lithium alloy is formed within the negative electrode and transition metal sulfide such as iron sulfide is produced within the positive electrode.

Orotidine 5'-Monophosphate Decarboxylase: Probing the Limits of the Possible for Enzyme Catalysis.

PubMed

Richard, John P; Amyes, Tina L; Reyes, Archie C

2018-04-17

The mystery associated with catalysis by what were once regarded as protein black boxes, diminished with the X-ray crystallographic determination of the three-dimensional structures of enzyme-substrate complexes. The report that several high-resolution X-ray crystal structures of orotidine 5'-monophosphate decarboxylase (OMPDC) failed to provide a consensus mechanism for enzyme-catalyzed decarboxylation of OMP to form uridine 5'-monophosphate, therefore, provoked a flurry of controversy. This controversy was fueled by the enormous 10 23 -fold rate acceleration for this enzyme, which had " jolted many biochemists' assumptions about the catalytic potential of enzymes." Our studies on the mechanism of action of OMPDC provide strong evidence that catalysis by this enzyme is not fundamentally different from less proficient catalysts, while highlighting important architectural elements that enable a peak level of performance. Many enzymes undergo substrate-induced protein conformational changes that trap their substrates in solvent occluded protein cages, but the conformational change induced by ligand binding to OMPDC is incredibly complex, as required to enable the development of 22 kcal/mol of stabilizing binding interactions with the phosphodianion and ribosyl substrate fragments of OMP. The binding energy from these fragments is utilized to activate OMPDC for catalysis of decarboxylation at the orotate fragment of OMP, through the creation of a tight, catalytically active, protein cage from the floppy, open, unliganded form of OMPDC. Such utilization of binding energy for ligand-driven conformational changes provides a general mechanism to obtain specificity in transition state binding. The rate enhancement that results from the binding of carbon acid substrates to enzymes is partly due to a reduction in the carbon acid p K a that is associated with ligand binding. The binding of UMP to OMPDC results in an unusually large >12 unit decrease in the p K a = 29 for abstraction of the C-6 substrate hydrogen, due to stabilization of an enzyme-bound vinyl carbanion, which is also an intermediate of OMPDC-catalyzed decarboxylation. The protein-ligand interactions operate to stabilize the vinyl carbanion at the enzyme active site compared to aqueous solution, rather than to stabilize the transition state for the concerted electrophilic displacement of CO 2 by H + that avoids formation of this reaction intermediate. There is evidence that OMPDC induces strain into the bound substrate. The interaction between the amide side chain of Gln-215 from the phosphodianion gripper loop and the hydroxymethylene side chain of Ser-154 from the pyrimidine umbrella of ScOMPDC position the amide side chain to interact with the phosphodianion of OMP. There are no direct stabilizing interactions between dianion gripper protein side chains Gln-215, Tyr-217, and Arg-235 and the pyrimidine ring at the decarboxylation transition state. Rather these side chains function solely to hold OMPDC in the catalytically active closed conformation. The hydrophobic side chains that line the active site of OMPDC in the region of the departing CO 2 product may function to stabilize the decarboxylation transition state by providing hydrophobic solvation of this product.

Substrate Control in Stereoselective Lanthionine Biosynthesis

PubMed Central

Tang, Weixin; Jiménez-Osés, Gonzalo; Houk, K. N.; van der Donk, Wilfred A.

2014-01-01

Enzymes are typically highly stereoselective catalysts that enforce a reactive conformation on their native substrates. We report here a rare example where the substrate controls the stereoselectivity of an enzyme-catalyzed Michael-type addition during the biosynthesis of lanthipeptides. These natural products contain thioether crosslinks formed by cysteine attack on dehydrated Ser and Thr residues. We demonstrate that several lanthionine synthetases catalyze highly selective anti additions in which the substrate (and not the enzyme) determines whether the addition occurs from the Re or Si face. A single point mutation in the peptide substrate completely inverted the stereochemical outcome of the enzymatic modification. Quantum mechanical calculations reproduced the experimentally observed selectivity and suggest that conformational restraints imposed by the amino acid sequence on the transition states determine the face selectivity of the Michael-type cyclization. PMID:25515891

Strain driven sequential magnetic transitions in strained GdTiO3 on compressive substrates: a first-principles study

NASA Astrophysics Data System (ADS)

Yang, Li-Juan; Weng, Ya-Kui; Zhang, Hui-Min; Dong, Shuai

2014-11-01

The compressive strain effect on the magnetic ground state and electronic structure of strained GdTiO3 has been studied using the first-principles method. Unlike the cases of congeneric YTiO3 and LaTiO3, both of which become the A-type antiferromagnetism on the (0 0 1) LaAlO3 substrate despite their contrastive magnetism, the ground state of strained GdTiO3 on the LaAlO3 substrate changes from the original ferromagnetism to a G-type antiferromagnetim, instead of the A-type one although Gd3+ is between Y3+ and La3+. It is only when the in-plane compressive strain is large enough, e.g. on the (0 0 1) YAlO3 substrate, that the ground state finally becomes the A-type. The band structure calculation shows that the compressive strained GdTiO3 remains insulating, although the band gap changes a little in the strained GdTiO3.

QM/MM Investigation of Substrate and Product Specificities of Suv4-20h2: How Does This Enzyme Generate Dimethylated H4K20 from Monomethylated Substrate?

PubMed

Qian, Ping; Guo, Haobo; Wang, Liang; Guo, Hong

2017-06-13

Protein lysine methyltransferases (PKMTs) catalyze the methylation of lysine residues on histone proteins in the regulation of chromatin structure and gene expression. In contrast to many other PKMTs for which unmodified lysine is the methylation target, the enzymes in the Suv4-20 family are able to generate dimethylated product (H4K20me2) based exclusively on the monomethylated H4K20 substrate (H4K20me1). The origin of such substrate/product specificity is still not clear. Here, molecular dynamics (MD) and free energy (potential of mean force) simulations are undertaken using quantum mechanical/molecular mechanical (QM/MM) potentials to understand the substrate/product specificities of Suv4-20h2, a member of the Suv4-20 family. The free energy barriers for mono-, di-, and trimethylation in Suv4-20h2 obtained from the simulations are found to be well correlated with the specificities observed experimentally with the allowed dimethylation based on the H4K20me1 substrate and prohibited monomethylation and trimethylation based on H4K20 and H4K20me2, respectively. It is demonstrated that the reason for the relatively efficient dimethylation is an effective transition state (TS) stabilization through strengthening the CH···O interactions as well as the presence of a cation-π interaction at the transition state. The simulations also show that the failures of Suv4-20h2 to catalyze monomethylation and trimethylation are due, respectively, to a less effective TS stabilization and inability of the reactant complex containing H4K20me2 to adopt a reactive (near attack) configuration for methyl transfer. The results suggest that care must be exercised in the prediction of the substrate specificity based only on the existence of near attack configurations in substrate complexes.

Catalysis by Orotidine 5′-Monophosphate Decarboxylase: Effect of 5-Fluoro and 4′-Substituents on the Decarboxylation of Two-Part Substrates†

PubMed Central

Goryanova, Bogdana; Spong, Krisztina; Amyes, Tina L.; Richard, John P.

2013-01-01

The syntheses of two novel truncated analogs of the natural substrate orotidine 5′-monophosphate (OMP) for orotidine 5′-monophosphate decarboxylase (OMPDC) with enhanced reactivity towards decarboxylation are reported: 1-(β-D-erythrofuranosyl)-5-fluoroorotic acid (FEO) and 5′-deoxy-5-fluoroorotidine (5′-dFO). A comparison of the second-order rate constants for the OMPDC-catalyzed decarboxylations of FEO (10 M−1 s−1) and 1-(β-D-erythrofuranosyl)orotic acid (EO, 0.026 M−1 s−1) shows that the vinyl carbanion-like transition state is stabilized by 3.5 kcal/mol by interactions with the 5-F substituent of FEO. The OMPDC-catalyzed decarboxylations of FEO and EO are both activated by exogenous phosphite dianion (HPO32−), but the 5-F substituent results in only a 0.8 kcal stabilization of the transition state for the phosphite-activated reaction of FEO. This provides strong evidence that the phosphite-activated OMPDC-catalyzed reaction of FEO is not limited by the chemical step of decarboxylation of the enzyme-bound substrate. Evidence is presented that there is a change in rate-limiting step from the chemical step of decarboxylation for the phosphite-activated reaction of EO, to closure of the phosphate gripper loop and an enzyme conformational change at the ternary E·FEO·HPO32− complex for the reaction of FEO. The 4′-CH3 and 4′-CH2OH groups of 5′-dFO and orotidine, respectively, result in identical destabilizations of the transition state for the unactivated decarboxylation of 2.9 kcal/mol. By contrast, the 4′-CH3 group of 5′-dFO and the 4′-CH2OH group of orotidine result in very different 4.7 and 8.3 kcal/mol destabilizations of the transition state for the phosphite-activated decarboxylation. Here, the destabilizing effect of the 4′-CH3 substituent at 5′-dFO is masked by the rate-limiting conformational change that depresses the third-order rate constant for the phosphite-activated reaction of the parent substrate FEO. PMID:23276261

RICIN-inhibitor design. Final report, 15 April 1993-14 April 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schramm, V.L.

1996-05-01

The purpose of this proposal was to provide information which will permit the design of transition state inhibitors for ricin A-chain. The original goals were to solve the transition state structure based on kinetic isotope effects. Substrates were synthesized and the conditions for assays optimized to provide catalytic rates at least 1000 fold greater than those published prior to this work. Reliable assay methods have been established to permit routine assays for ricin A-chain. Substrate analogues for N-ribohydrolase reactions have been designed to establish whether the reaction involves leaving-group activation or oxycarbonium ion formation. Based on these results, leaving groupmore » activation is a major contributor and oxycarbonium-ion formation is a secondary contribution in the mechanism of catalysis by ricin A-chain. Using this information, the first submicromolar inhibitor of ricin A-chain has been synthesized, tested and kinetically characterized. The development of powerful inhibitors will be a direct extrapolation of these results.« less

Metal-semiconductor phase transition of order arrays of VO2 nanocrystals

NASA Astrophysics Data System (ADS)

Lopez, Rene; Suh, Jae; Feldman, Leonard; Haglund, Richard

2004-03-01

The study of solid-state phase transitions at nanometer length scales provides new insights into the effects of material size on the mechanisms of structural transformations. Such research also opens the door to new applications, either because materials properties are modified as a function of particle size, or because the nanoparticles interact with a surrounding matrix material, or with each other. In this paper, we describe the formation of vanadium dioxide nanoparticles in silicon substrates by pulsed laser deposition of ion beam lithographically selected sites and thermal processing. We observe the collective behavior of 50 nm diameter VO2 oblate nanoparticles, 10 nm high, and ordered in square arrays with arbitrary lattice constant. The metal-semiconductor-transition of the VO2 precipitates shows different features in each lattice spacing substrate. The materials are characterized by electron microscopy, x-ray diffraction, Rutherford backscattering. The features of the phase transition are studied via infrared optical spectroscopy. Of particular interest are the enhanced scattering and the surface plasmon resonance when the particles reach the metallic state. This resonance amplifies the optical contrast in the range of near-infrared optical communication wavelengths and it is altered by the particle-particle coupling as in the case of noble metals. In addition the VO2 nanoparticles exhibit sharp transitions with up to 50 K of hysteresis, one of the largest values ever reported for this transition. The optical properties of the VO2 nanoarrays are correlated with the size of the precipitates and their inter-particle distance. Nonlinear and ultra fast optical measurements have shown that the transition is the fastest known solid-solid transformation. The VO2 nanoparticles show the same bulk property, transforming in times shorter than 150 fs. This makes them remarkable candidates for ultrafast optical and electronic switching applications.

Ring-Shaped Microlanes and Chemical Barriers as a Platform for Probing Single-Cell Migration.

PubMed

Schreiber, Christoph; Segerer, Felix J; Wagner, Ernst; Roidl, Andreas; Rädler, Joachim O

2016-05-31

Quantification and discrimination of pharmaceutical and disease-related effects on cell migration requires detailed characterization of single-cell motility. In this context, micropatterned substrates that constrain cells within defined geometries facilitate quantitative readout of locomotion. Here, we study quasi-one-dimensional cell migration in ring-shaped microlanes. We observe bimodal behavior in form of alternating states of directional migration (run state) and reorientation (rest state). Both states show exponential lifetime distributions with characteristic persistence times, which, together with the cell velocity in the run state, provide a set of parameters that succinctly describe cell motion. By introducing PEGylated barriers of different widths into the lane, we extend this description by quantifying the effects of abrupt changes in substrate chemistry on migrating cells. The transit probability decreases exponentially as a function of barrier width, thus specifying a characteristic penetration depth of the leading lamellipodia. Applying this fingerprint-like characterization of cell motion, we compare different cell lines, and demonstrate that the cancer drug candidate salinomycin affects transit probability and resting time, but not run time or run velocity. Hence, the presented assay allows to assess multiple migration-related parameters, permits detailed characterization of cell motility, and has potential applications in cell biology and advanced drug screening.

On the shedding of impaled droplets: The role of transient intervening layers

NASA Astrophysics Data System (ADS)

Stamatopoulos, Christos; Schutzius, Thomas M.; Köppl, Christian J.; Hayek, Nicolas El; Maitra, Tanmoy; Hemrle, Jaroslav; Poulikakos, Dimos

2016-01-01

Maintaining the non-wetting property of textured hydrophobic surfaces is directly related to the preservation of an intervening fluid layer (gaseous or immiscible liquid) between the droplet and substrate; once displaced, it cannot be recovered spontaneously as the fully penetrated Wenzel wetting state is energetically favorable. Here, we identify pathways for the “lifting” of droplets from the surface texture, enabling a complete Wenzel-to-Cassie-Baxter wetting state transition. This is accomplished by the hemiwicking of a transient (limited lifetime due to evaporation) low surface tension (LST) liquid, which is capable of self-assembling as an intervening underlayer, lifting the droplet from its impaled state and facilitating a skating-like behavior. In the skating phase, a critical substrate tilting angle is identified, up to which underlayer and droplet remain coupled exhibiting a pseudo-Cassie-Baxter state. For greater titling angles, the droplet, driven by inertia, detaches itself from the liquid intervening layer and transitions to a traditional Cassie-Baxter wetting state, thereby accelerating and leaving the underlayer behind. A model is also presented that elucidates the mechanism of mobility recovery. Ultimately, this work provides a better understanding of multiphase mass transfer of immiscible LST liquid-water mixtures with respect to establishing facile methods towards retaining intervening layers.

On the shedding of impaled droplets: The role of transient intervening layers

PubMed Central

Stamatopoulos, Christos; Schutzius, Thomas M.; Köppl, Christian J.; Hayek, Nicolas El; Maitra, Tanmoy; Hemrle, Jaroslav; Poulikakos, Dimos

2016-01-01

Maintaining the non-wetting property of textured hydrophobic surfaces is directly related to the preservation of an intervening fluid layer (gaseous or immiscible liquid) between the droplet and substrate; once displaced, it cannot be recovered spontaneously as the fully penetrated Wenzel wetting state is energetically favorable. Here, we identify pathways for the “lifting” of droplets from the surface texture, enabling a complete Wenzel-to-Cassie-Baxter wetting state transition. This is accomplished by the hemiwicking of a transient (limited lifetime due to evaporation) low surface tension (LST) liquid, which is capable of self-assembling as an intervening underlayer, lifting the droplet from its impaled state and facilitating a skating-like behavior. In the skating phase, a critical substrate tilting angle is identified, up to which underlayer and droplet remain coupled exhibiting a pseudo-Cassie-Baxter state. For greater titling angles, the droplet, driven by inertia, detaches itself from the liquid intervening layer and transitions to a traditional Cassie-Baxter wetting state, thereby accelerating and leaving the underlayer behind. A model is also presented that elucidates the mechanism of mobility recovery. Ultimately, this work provides a better understanding of multiphase mass transfer of immiscible LST liquid-water mixtures with respect to establishing facile methods towards retaining intervening layers. PMID:26743806

Combined strain and composition-induced effects in the metal-insulator transition of epitaxial VO2 films

NASA Astrophysics Data System (ADS)

Théry, V.; Boulle, A.; Crunteanu, A.; Orlianges, J. C.

2017-12-01

The role of epitaxial strain, thermal strain, and bulk (strain-free) lattice parameters in the metal-insulator transition (MIT) and the structural phase transition (SPT) of VO2 is investigated for the case of epitaxial films grown on (001)-oriented TiO2 substrates. Temperature-resolved X-ray reciprocal space mapping has been used to determine the absolute state of strain as well as the bulk lattice parameters of VO2 at 100 °C. For the thinnest film (15 nm), the state of strain is dominated by the film/substrate lattice mismatch yielding an in-plane tensile strain which, in turn, shifts both the MIT and the SPT towards lower temperatures. Conversely, for the thickest film (100 nm), the epitaxial strain is relaxed, so that the state of strain is dominated by the VO2/TiO2 thermal expansion mismatch which is responsible for a compressive in-plane strain. In all cases, a swelling of the strain-free VO2 unit-cell is observed which indicates the presence of interfacial oxygen vacancies and/or Ti diffusion into the VO2 films. The presence of oxygen vacancies stabilizes the metallic rutile phase and counterbalances the action of thermal strain on the MIT and the SPT and degrades the electric properties for the thinnest film. For the thickest film, the resistivity ratio is 6.4 × 104.

Excavated substrate modulates growth instability during nest building in ants

PubMed Central

Toffin, Etienne; Kindekens, Jonathan; Deneubourg, Jean-Louis

2010-01-01

In social insects, the nests of the same species can show a large difference in size and shape. Despite these large variations, the nests share the same substructures, some appearing during nest growth. In ants, the interplay between nest size and digging activity leads to two successive morphological transitions from circular to branched shapes (budding along the perimeter of the circular cavity and tunnelling of the galleries). Like several other self-organized collective behaviours, this phenomenon, as well as the entire nest-digging process, is thought to be modulated by environmental properties. The present study investigates the effect of excavated substrate on the nest morphogenesis and the morphological transitions by using two materials with different cohesions. Here, we show that the two morphological transitions occur more frequently with a cohesive substrate than with a granular one: 96 per cent of cohesive experiments showed both transitions, whereas only 50 per cent did in granular experiments. We found that transitions and excavation cessation follow area–response thresholds: the shape transitions take place and the digging activity stops when the dug area reaches the corresponding threshold values. The shape transition thresholds are lower with the cohesive substrate and that of stopping digging is independent of nest shape and material. According to simulations, the experimental frequencies of transitions found their origin in the competition between transitions and activity cessation and in the difference between the transition threshold values of each substrate. Our results demonstrate how the substrate properties modulate the collective response and lead to various patterns. Considering the non-specific mechanisms at work, such effects of substrate coarseness have their counterparts in various collective behaviours, generating alternative patterns to colonize and exploit the environment. PMID:20410036

Substrate-modulated unwinding of transmembrane helices in the NSS transporter LeuT.

PubMed

Merkle, Patrick S; Gotfryd, Kamil; Cuendet, Michel A; Leth-Espensen, Katrine Z; Gether, Ulrik; Loland, Claus J; Rand, Kasper D

2018-05-01

LeuT, a prokaryotic member of the neurotransmitter:sodium symporter (NSS) family, is an established structural model for mammalian NSS counterparts. We investigate the substrate translocation mechanism of LeuT by measuring the solution-phase structural dynamics of the transporter in distinct functional states by hydrogen/deuterium exchange mass spectrometry (HDX-MS). Our HDX-MS data pinpoint LeuT segments involved in substrate transport and reveal for the first time a comprehensive and detailed view of the dynamics associated with transition of the transporter between outward- and inward-facing configurations in a Na + - and K + -dependent manner. The results suggest that partial unwinding of transmembrane helices 1/5/6/7 drives LeuT from a substrate-bound, outward-facing occluded conformation toward an inward-facing open state. These hitherto unknown, large-scale conformational changes in functionally important transmembrane segments, observed for LeuT in detergent-solubilized form and when embedded in a native-like phospholipid bilayer, could be of physiological relevance for the translocation process.

Epitaxial Ni-Mn-Ga-Co thin films on PMN-PT substrates for multicaloric applications

NASA Astrophysics Data System (ADS)

Schleicher, B.; Niemann, R.; Diestel, A.; Hühne, R.; Schultz, L.; Fähler, S.

2015-08-01

Multicaloric stacks consisting of a magnetocaloric film on a piezoelectric substrate promise improved caloric properties as the transition temperature can be controlled by both magnetic and electric fields. We present epitaxially grown magnetocaloric Ni-Mn-Ga-Co thin films on ferroelectric Pb(Mg1/3Nb2/3)0.72Ti0.28O3 substrates. Structure and microstructure of two samples, being in the austenitic and martensitic state at room temperature, are investigated by X-ray diffraction in two- and four-circle geometry and by atomic force microscopy. In addition, high temperature magnetometry was performed on the latter sample. The combination of these methods allows separating the influence of epitaxial growth and martensitic transformation. A preferential alignment of twin boundaries is observed already in the as-deposited state, which indicates the presence of prestress, without applying an electric field to the substrate. A temperature-magnetic field phase diagram is presented, which demonstrates the inverse magnetocaloric effect of the epitaxial Ni-Mn-Ga-Co film.

Geometric confinement effects on the metal-insulator transition temperature and stress relaxation in VO2 thin films grown on silicon

NASA Astrophysics Data System (ADS)

Viswanath, Changhyun Ko, B.; Yang, Zheng; Ramanathan, Shriram

2011-03-01

VO2 undergoes a sharp metal-insulator transition at ˜67 °C with several orders of change in conductivity and optical transmittance. Understanding and control of the properties of vanadium oxide layers grown on technologically relevant substrates such as Si (100) single crystals is therefore of great interest. In this work, we show tunability of metal-insulator transition temperature as well as recoverable stress in VO2 thin films grown on Si substrate by introducing nanoscale atomic layer deposited HfO2 interfacial layers with no degradation in the resistance ratio. For a confined VO2 film, the metal-insulator transition temperature is suppressed by ˜16 °C and the recoverable stress is 150 MPa, compared to 400 MPa for a bare film. These observations are further correlated with in situ variable temperature measurement of stress changes occurring during the phase transition. Structural and microstructural studies on the various samples have been carried out by x ray diffraction and cross-sectional transmission electron microscopy. The strategy of tuning the metal-insulator transition characteristics by nanoscale interfacial dielectrics is of broader relevance in design of programmable materials and integration into solid state devices for electronics.

Mobility restrictions and glass transition behaviour of an epoxy resin under confinement.

PubMed

Djemour, A; Sanctuary, R; Baller, J

2015-04-07

Confinement can have a big influence on the dynamics of glass formers in the vicinity of the glass transition. Already 40 to 50 K above the glass transition temperature, thermal equilibration of glass formers can be strongly influenced by the confining substrate. We investigate the linear thermal expansion and the specific heat capacity cp of an epoxy resin (diglycidyl ether of bisphenol A, DGEBA) in a temperature interval of 120 K around the glass transition temperature. The epoxy resin is filled into controlled pore glasses with pore diameters between 4 and 111 nm. Since DGEBA can form H-bonds with silica surfaces, we also investigate the influence of surface silanization of the porous substrates. In untreated substrates a core/shell structure of the epoxy resin can be identified. The glass transition behaviours of the bulk phase and that of the shell phase are different. In silanized substrates, the shell phase disappears. At a temperature well above the glass transition, a second transition is found for the bulk phase - both in the linear expansion data as well as in the specific heat capacity. The cp data do not allow excluding the glass transition of a third phase as being the cause for this transition, whereas the linear expansion data do so. The additional transition temperature is interpreted as a separation between two regimes: above this temperature, macroscopic flow of the bulk phase inside the porous structure is possible to balance the mismatch of thermal expansion coefficients between DGEBA and the substrate. Below the transition temperature, this degree of freedom is hindered by geometrical constraints of the porous substrates. Moreover, this second transition could also be found in the linear expansion data of the shell phase.

Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study

PubMed Central

Raza, Sami; Fransson, Linda; Hult, Karl

2001-01-01

A major problem in predicting the enantioselectivity of an enzyme toward substrate molecules is that even high selectivity toward one substrate enantiomer over the other corresponds to a very small difference in free energy. However, total free energies in enzyme-substrate systems are very large and fluctuate significantly because of general protein motion. Candida antarctica lipase B (CALB), a serine hydrolase, displays enantioselectivity toward secondary alcohols. Here, we present a modeling study where the aim has been to develop a molecular dynamics-based methodology for the prediction of enantioselectivity in CALB. The substrates modeled (seven in total) were 3-methyl-2-butanol with various aliphatic carboxylic acids and also 2-butanol, as well as 3,3-dimethyl-2-butanol with octanoic acid. The tetrahedral reaction intermediate was used as a model of the transition state. Investigative analyses were performed on ensembles of nonminimized structures and focused on the potential energies of a number of subsets within the modeled systems to determine which specific regions are important for the prediction of enantioselectivity. One category of subset was based on atoms that make up the core structural elements of the transition state. We considered that a more favorable energetic conformation of such a subset should relate to a greater likelihood for catalysis to occur, thus reflecting higher selectivity. The results of this study conveyed that the use of this type of subset was viable for the analysis of structural ensembles and yielded good predictions of enantioselectivity. PMID:11266619

Conformational Dynamics of a Y-Family DNA Polymerase during Substrate Binding and Catalysis As Revealed by Interdomain Förster Resonance Energy Transfer

PubMed Central

2015-01-01

Numerous kinetic, structural, and theoretical studies have established that DNA polymerases adjust their domain structures to enclose nucleotides in their active sites and then rearrange critical active site residues and substrates for catalysis, with the latter conformational change acting to kinetically limit the correct nucleotide incorporation rate. Additionally, structural studies have revealed a large conformational change between the apoprotein and the DNA–protein binary state for Y-family DNA polymerases. In previous studies [Xu, C., Maxwell, B. A., Brown, J. A., Zhang, L., and Suo, Z. (2009) PLoS Biol.7, e1000225], a real-time Förster resonance energy transfer (FRET) method was developed to monitor the global conformational transitions of DNA polymerase IV from Sulfolobus solfataricus (Dpo4), a prototype Y-family enzyme, during nucleotide binding and incorporation by measuring changes in distance between locations on the enzyme and the DNA substrate. To elucidate further details of the conformational transitions of Dpo4 during substrate binding and catalysis, in this study, the real-time FRET technique was used to monitor changes in distance between various pairs of locations in the protein itself. In addition to providing new insight into the conformational changes as revealed in previous studies, the results here show that the previously described conformational change between the apo and DNA-bound states of Dpo4 occurs in a mechanistic step distinct from initial formation or dissociation of the binary complex of Dpo4 and DNA. PMID:24568554

Substrate Binding Drives Active-Site Closing of Human Blood Group B Galactosyltransferase as Revealed by Hot-Spot Labeling and NMR Spectroscopy Experiments.

PubMed

Weissbach, Sophie; Flügge, Friedemann; Peters, Thomas

2018-05-04

Crystallography has shown that human blood group A (GTA) and B (GTB) glycosyltransferases undergo transitions between "open", "semiclosed", and "closed" conformations upon substrate binding. However, the timescales of the corresponding conformational reorientations are unknown. Crystal structures show that the Trp and Met residues are located at "conformational hot spots" of the enzymes. Therefore, we utilized 15 N side-chain labeling of Trp residues and 13 C-methyl labeling of Met residues to study substrate-induced conformational transitions of GTB. Chemical-shift perturbations (CSPs) of Met and Trp residues in direct contact with substrate ligands reflect binding kinetics, whereas the CSPs of Met and Trp residues at remote sites reflect conformational changes of the enzyme upon substrate binding. Acceptor binding is fast on the chemical-shift timescale with rather small CSPs in the range of less than approximately 20 Hz. Donor binding matches the intermediate exchange regime to yield an estimate for exchange rate constants of approximately 200-300 Hz. Donor or acceptor binding to GTB saturated with acceptor or donor substrate, respectively, is slow (<10 Hz), as are coupled protein motions, reflecting mutual allosteric control of donor and acceptor binding. Remote CSPs suggest that substrate binding drives the enzyme into the closed state required for catalysis. These findings should contribute to better understanding of the mechanism of glycosyl transfer of GTA and GTB. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Resonant electronic Raman scattering of below-gap states in molecular-beam epitaxy grown and liquid-encapsulated Czochralski grown GaAs

NASA Astrophysics Data System (ADS)

Fluegel, B.; Rice, A. D.; Mascarenhas, A.

2018-05-01

Resonant electronic Raman (ER) scattering is used to compare the below-gap excitations in molecular-beam epitaxially grown GaAs and in undoped semi-insulating GaAs substrates. The measurement geometry was designed to eliminate common measurement artifacts caused by the high optical transmission below the fundamental absorption edge. In epitaxial GaAs, ER is a clear Raman signal from the two-electron transitions of donors, eliminating an ambiguity encountered in previous results. In semi-insulating GaAs, ER occurs in a much broader dispersive band well below the bound exciton energies. The difference in the two materials may be due to the occupation of the substrate acceptor states in the presence of the midgap state EL2.

A theoretical study of the structure and stability of borohydride on 3d transition metals

NASA Astrophysics Data System (ADS)

Arevalo, Ryan Lacdao; Escaño, Mary Clare Sison; Gyenge, Elod; Kasai, Hideaki

2012-12-01

The adsorption of borohydride on 3d transition metals (Cr, Mn, Fe, Co, Ni and Cu) was studied using first principles calculations within spin-polarized density functional theory. Magnetic effect on the stability of borohydride is noted. Molecular adsorption is favorable on Co, Ni and Cu, which is characterized by the strong s-dzz hybridization of the adsorbate-substrate states. Dissociated adsorption structure yielding one or two H adatom fragments on the surface is observed for Cr, Mn and Fe.

Structural and phase transitions of one and two polymer mushrooms in poor solvent

NASA Astrophysics Data System (ADS)

Yang, Delian; Wang, Qiang

2014-05-01

Using the recently proposed fast lattice Monte Carlo (FLMC) simulations and the corresponding lattice self-consistent field (LSCF) calculations based on the same model system, where multiple occupancy of lattice sites is allowed [Q. Wang, Soft Matter 5, 4564 (2009); Q. Wang, Soft Matter 5, 6206 (2010)], we studied the coil-globule transition (CGT) of one-mushroom systems and the fused-separated transition (FST) of two-mushroom systems, where a polymer mushroom is formed by a group of n homopolymer chains each of N segments end-grafted at the same point onto a flat substrate and immersed in a poor solvent. With our soft potential that allows complete particle overlapping, LSCF theory neglecting the system fluctuations/correlations becomes exact in the limit of n → ∞, and FLMC results approach LSCF predictions with increasing n. Using LSCF calculations, we systematically constructed the phase diagrams of one- and two-mushroom systems. A second-order symmetric-asymmetric transition (SAT) was found in the globule state of one-mushroom systems, where the rotational symmetry around the substrate normal passing through the grafting point is broken in each individual configuration but preserved by the degeneracy of different orientations of these asymmetric configurations. Three different states were also found in two-mushroom systems: separated coils, separated globules, and fused globule. We further studied the coupling between FST in two-mushroom systems and CGT and SAT of each mushroom. Finally, direct comparisons between our simulation and theoretical results, without any parameter-fitting, unambiguously and quantitatively revealed the fluctuation/correlation effects on these phase transitions.

Methods of making composite optical devices employing polymer liquid crystal

DOEpatents

Jacobs, Stephen D.; Marshall, Kenneth L.; Cerqua, Kathleen A.

1991-01-01

Composite optical devices using polymer liquid crystal materials both as optical and adhesive elements. The devices are made by assembling a heated polymer liquid crystal compound, while in a low viscosity form between optically transparent substrates. The molecules of the polymer are oriented, while in the liquid crystalline state and while above the glass transition temperature (T.sub.g) of the polymer, to provide the desired optical effects, such as polarization, and selective reflection. The liquid crystal polymer cements the substrates together to form an assembly providing the composite optical device.

Arginine Kinase. Joint Crystallographic & NMR RDC Analyses link Substrate-Associated Motions to Intrinsic Flexibility

PubMed Central

Niu, Xiaogang; Brüschweiler-Li, Lei; Davulcu, Omar; Skalicky, Jack J.; Brüschweiler, Rafael; Chapman, Michael S.

2010-01-01

The phosphagen kinase family, including creatine and arginine kinases, catalyze the reversible transfer of a “high energy” phosphate between ATP and a phospho-guanidino substrate. They have become a model for the study of both substrate-induced conformational change and intrinsic protein dynamics. Prior crystallographic studies indicated large substrate-induced domain rotations, but differences among a recent set of arginine kinase structures was interpreted as a plastic deformation. Here, the structure of Limulus substrate-free arginine kinase is refined against high resolution crystallographic data and compared quantitatively with NMR chemical shifts and residual dipolar couplings (RDCs). This demonstrates the feasibility of this type of RDC analysis of proteins that are large by NMR standards (42 kDa), and illuminates the solution structure, free from crystal-packing constraints. Detailed comparison of the 1.7 Å resolution substrate-free crystal structure against the 1.2 Å transition state analog complex shows large substrate-induced domain motions which can be broken down into movements of smaller quasi-rigid bodies. The solution state structure of substrate-free arginine kinase is most consistent with an equilibrium of substrate-free and –bound structures, with the substrate-free form dominating, but with varying displacements of the quasi-rigid groups. Rigid-group rotations evident from the crystal structures are about axes previously associated with intrinsic millisecond dynamics using NMR relaxation dispersion. Thus, “substrate-induced” motions are along modes that are intrinsically flexible in the substrate-free enzyme, and likely involve some degree of conformational selection. PMID:21075117

Contactless electroreflectance study of strained Zn0.79Cd0.21Se/ZnSe double quantum wells

NASA Astrophysics Data System (ADS)

Tu, R. C.; Su, Y. K.; Lin, D. Y.; Li, C. F.; Huang, Y. S.; Lan, W. H.; Tu, S. L.; Chang, S. J.; Chou, S. C.; Chou, W. C.

1998-01-01

We have studied various excitonic transitions of strained Zn0.79Cd0.21Se/ZnSe double quantum wells, grown by molecular beam epitaxy on (100) GaAs substrates, using contactless electroreflectance (CER) at 15 and 300 K. A number of intersub-band transitions in the CER spectra from the sample have been observed. An analysis of the CER spectra has led to the identification of various excitonic transitions, mnH(L), between the mth conduction band state and the nth heavy (light)-hole band state. The conduction-band offset Qc is used as an adjustable parameter to study the band offset in the strained Zn0.79Cd0.21Se/ZnSe system. The value of Qc is determined to be 0.67±0.03.

State transitions and feedback mechanisms control hydrology in the constructed catchment ´Chicken Creeḱ

NASA Astrophysics Data System (ADS)

Schaaf, Wolfgang; Gerwin, Werner; Hinz, Christoph; Zaplata, Markus

2016-04-01

Landscapes and ecosystems are complex systems with many feedback mechanisms acting between the various abiotic and biotic components. The knowledge about these interacting processes is mainly derived from mature ecosystems. The initial development of ecosystem complexity may involve state transitions following catastrophic shifts, disturbances or transgression of thresholds. The Chicken Creek catchment was constructed in 2005 in the mining area of Lusatia/Germany to study processes and feedback mechanisms during ecosystem evolution. The hillslope-shaped 6 ha site has defined boundary conditions and well-documented inner structures. The dominating substrate above the underlying clay layer is Pleistocene sandy material representing mainly the lower C horizon of the former landscape. Since 2005, the unrestricted, unmanaged development of the catchment was intensively monitored. During the ten years since then, we observed characteristic state transitions in catchment functioning driven by feedbacks between original substrate properties, surface structures, soil development and vegetation succession. Whereas surface runoff induced by surface crusting and infiltration dominated catchment hydrology in the first years, the impact of vegetation on hydrological pathways and groundwater levels became more and more evident during the last years. Discharge from the catchment changed from episodic events driven by precipitation and surface runoff to groundwater driven. This general picture is overlain by spatial patterns and single episodic events of external drivers. The scientific value of the Chicken Creek site with known boundary conditions and structure information could help in disentangling general feedback mechanisms between hydrologic, pedogenic, biological and geomorphological processes as well as a in gaining a more integrative view of succession and its drivers during the transition from initial, less complex systems to more mature ecosystems. Long-term time series of data are a key for a better understanding of these processes and the effects on ecosystem resilience and self-organization.

Oak woodland vegetation dynamics: a state and transition approach

Treesearch

Melvin R. George; Maximo F. Alonso

2008-01-01

California’s oak-woodlands are a complex, often multi-layered mosaic of grassland, shrubland, and woodland patches. While soil type and depth, topography, aspect, and geological substrate influence the distribution of these patches, disturbance and biological interactions are also important determinants of the patchy distribution of these plant communities. Fire...

Ab initio study of the mechanism of bottom-up synthesis of graphene nanoribbons

NASA Astrophysics Data System (ADS)

Xiao, Zhongcan; Ma, Chuanxu; Zhang, Honghai; Liang, Liangbo; Huang, Jingsong; Lu, Wenchang; Hong, Kunlun; Li, An-Ping; Bernholc, Jerry

Graphene nanoribbons (GNRs) can be fabricated with atomic precision by using molecular precursors deposited on a metal substrate, and potentially form the basis for future molecular-scale electronics. The precursor molecules are first annealed to form a polymer, and further annealing at a higher temperature leads to the formation of a GNR. We systematically study the reaction pathways of this cyclodehydrogenation process, using density functional theory and the nudged elastic band method. We find that the Au substrate reduces the reaction barriers for key steps in the cyclodehydrogenation process: cyclization, hydrogen migration and desorption. Furthermore, our calculations explain recent experiments showing that an STM-tip can induce local polymer-to-GNR transition, which can be used to fabricate atomically precise heterojunctions: at a negative bias, the STM tip injects excess holes into the polymer HOMO state, lowering the energy barrier in agreement with Woodward-Hoffmann rules. At a positive bias, when excess electrons are injected into the LUMO state, the energy barrier is not significantly lowered and the transition is not observed.

The O2-Evolving Complex of Photosystem II: Recent Insights from Quantum Mechanics/Molecular Mechanics (QM/MM), Extended X-ray Absorption Fine Structure (EXAFS), and Femtosecond X-ray Crystallography Data.

PubMed

Askerka, Mikhail; Brudvig, Gary W; Batista, Victor S

2017-01-17

Efficient photoelectrochemical water oxidation may open a way to produce energy from renewable solar power. In biology, generation of fuel due to water oxidation happens efficiently on an immense scale during the light reactions of photosynthesis. To oxidize water, photosynthetic organisms have evolved a highly conserved protein complex, Photosystem II. Within that complex, water oxidation happens at the CaMn 4 O 5 inorganic catalytic cluster, the so-called oxygen-evolving complex (OEC), which cycles through storage "S" states as it accumulates oxidizing equivalents and produces molecular oxygen. In recent years, there has been significant progress in understanding the OEC as it evolves through the catalytic cycle. Studies have combined conventional and femtosecond X-ray crystallography with extended X-ray absorption fine structure (EXAFS) and quantum mechanics/molecular mechanics (QM/MM) methods and have addressed changes in protonation states of μ-oxo bridges and the coordination of substrate water through the analysis of ammonia binding as a chemical analog of water. These advances are thought to be critical to understanding the catalytic cycle since protonation states regulate the relative stability of different redox states and the geometry of the OEC. Therefore, establishing the mechanism for substrate water binding and the nature of protonation/redox state transitions in the OEC is essential for understanding the catalytic cycle of O 2 evolution. The structure of the dark-stable S 1 state has been a target for X-ray crystallography for the past 15 years. However, traditional X-ray crystallography has been hampered by radiation-induced reduction of the OEC. Very recently, a revolutionary X-ray free electron laser (XFEL) technique was applied to PSII to reveal atomic positions at 1.95 Å without radiation damage, which brought us closer than ever to establishing the ultimate structure of the OEC in the S 1 state. However, the atom positions in this crystal structure are still not consistent with high-resolution EXAFS spectroscopy, partially due to the poorly resolved oxygen positions next to Mn centers and partial reduction due to extended dark adaptation of the sample. These inconsistencies led to the new models of the OEC with an alternative low oxidation state and raised questions on the protonation state of the cluster, especially the O5 μ-oxo bridge. This Account summarizes the most recent models of the OEC that emerged from QM/MM, EXAFS and femtosecond X-ray crystallography methods. When PSII in the S 1 state is exposed to light, the S 1 state is advanced to the higher oxidation states and eventually binds substrate water molecules. Identifying the substrate waters is of paramount importance for establishing the water-oxidation mechanism but is complicated by a large number of spectroscopically similar waters. Water analogues can, therefore, be helpful because they serve as spectroscopic markers that help to track the motion of the substrate waters. Due to a close structural and electronic similarity to water, ammonia has been of particular interest. We review three competing hypotheses on substrate water/ammonia binding and compile theoretical and experimental evidence to support them. Binding of ammonia as a sixth ligand to Mn4 during the S 1 → S 2 transition seems to satisfy most of the criteria, especially the most compelling recent EPR data on D1-D61A mutated PSII. Such a binding mode suggests delivery of water from the "narrow" channel through a "carousel" rearrangement of waters around Mn4 upon the S 2 → S 3 transition. An alternative hypothesis suggests water delivery through the "large" channel on the Ca side. However, both water delivery paths lead to a similar S 3 structure, seemingly reaching consensus on the nature of the last detectable S-state intermediate in the Kok cycle before O 2 evolution.

The O 2 -Evolving Complex of Photosystem II: Recent Insights from Quantum Mechanics/Molecular Mechanics (QM/MM), Extended X-ray Absorption Fine Structure (EXAFS), and Femtosecond X-ray Crystallography Data

DOE PAGES

Askerka, Mikhail; Brudvig, Gary W.; Batista, Victor S.

2016-12-21

Efficient photoelectrochemical water oxidation may open a way to produce energy from renewable solar power. In biology, generation of fuel due to water oxidation happens efficiently on an immense scale during the light reactions of photosynthesis. To oxidize water, photosynthetic organisms have evolved a highly conserved protein complex, Photosystem II. Within that complex, water oxidation happens at the CaMn 4O 5 inorganic catalytic cluster, the so-called oxygen-evolving complex (OEC), which cycles through storage “S” states as it accumulates oxidizing equivalents and produces molecular oxygen. In recent years, there has been significant progress in understanding the OEC as it evolves throughmore » the catalytic cycle. Studies have combined conventional and femtosecond X-ray crystallography with extended X-ray absorption fine structure (EXAFS) and quantum mechanics/molecular mechanics (QM/ MM) methods and have addressed changes in protonation states of μ-oxo bridges and the coordination of substrate water through the analysis of ammonia binding as a chemical analog of water. These advances are thought to be critical to understanding the catalytic cycle since protonation states regulate the relative stability of different redox states and the geometry of the OEC. Therefore, establishing the mechanism for substrate water binding and the nature of protonation/redox state transitions in the OEC is essential for understanding the catalytic cycle of O 2 evolution. The structure of the dark-stable S1 state has been a target for X-ray crystallography for the past 15 years. However, traditional Xray crystallography has been hampered by radiation-induced reduction of the OEC. Very recently, a revolutionary X-ray free electron laser (XFEL) technique was applied to PSII to reveal atomic positions at 1.95 Å without radiation damage, which brought us closer than ever to establishing the ultimate structure of the OEC in the S 1 state. However, the atom positions in this crystal structure are still not consistent with high-resolution EXAFS spectroscopy, partially due to the poorly resolved oxygen positions next to Mn centers and partial reduction due to extended dark adaptation of the sample. These inconsistencies led to the new models of the OEC with an alternative low oxidation state and raised questions on the protonation state of the cluster, especially the O5 μ-oxo bridge. This Account summarizes the most recent models of the OEC that emerged from QM/MM, EXAFS and femtosecond X-ray crystallography methods. When PSII in the S 1 state is exposed to light, the S 1 state is advanced to the higher oxidation states and eventually binds substrate water molecules. Identifying the substrate waters is of paramount importance for establishing the water-oxidation mechanism but is complicated by a large number of spectroscopically similar waters. Water analogues can, therefore, be helpful because they serve as spectroscopic markers that help to track the motion of the substrate waters. Due to a close structural and electronic similarity to water, ammonia has been of particular interest. We review three competing hypotheses on substrate water/ammonia binding and compile theoretical and experimental evidence to support them. Binding of ammonia as a sixth ligand to Mn4 during the S 1 → S 2 transition seems to satisfy most of the criteria, especially the most compelling recent EPR data on D1-D61A mutated PSII. Such a binding mode suggests delivery of water from the “narrow” channel through a “carousel” rearrangement of waters around Mn4 upon the S 2 → S 3 transition. An alternative hypothesis suggests water delivery through the “large” channel on the Ca side. However, both water delivery paths lead to a similar S 3 structure, seemingly reaching consensus on the nature of the last detectable S-state intermediate in the Kok cycle before O 2 evolution.« less

The O 2 -Evolving Complex of Photosystem II: Recent Insights from Quantum Mechanics/Molecular Mechanics (QM/MM), Extended X-ray Absorption Fine Structure (EXAFS), and Femtosecond X-ray Crystallography Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Askerka, Mikhail; Brudvig, Gary W.; Batista, Victor S.

Efficient photoelectrochemical water oxidation may open a way to produce energy from renewable solar power. In biology, generation of fuel due to water oxidation happens efficiently on an immense scale during the light reactions of photosynthesis. To oxidize water, photosynthetic organisms have evolved a highly conserved protein complex, Photosystem II. Within that complex, water oxidation happens at the CaMn 4O 5 inorganic catalytic cluster, the so-called oxygen-evolving complex (OEC), which cycles through storage “S” states as it accumulates oxidizing equivalents and produces molecular oxygen. In recent years, there has been significant progress in understanding the OEC as it evolves throughmore » the catalytic cycle. Studies have combined conventional and femtosecond X-ray crystallography with extended X-ray absorption fine structure (EXAFS) and quantum mechanics/molecular mechanics (QM/ MM) methods and have addressed changes in protonation states of μ-oxo bridges and the coordination of substrate water through the analysis of ammonia binding as a chemical analog of water. These advances are thought to be critical to understanding the catalytic cycle since protonation states regulate the relative stability of different redox states and the geometry of the OEC. Therefore, establishing the mechanism for substrate water binding and the nature of protonation/redox state transitions in the OEC is essential for understanding the catalytic cycle of O 2 evolution. The structure of the dark-stable S1 state has been a target for X-ray crystallography for the past 15 years. However, traditional Xray crystallography has been hampered by radiation-induced reduction of the OEC. Very recently, a revolutionary X-ray free electron laser (XFEL) technique was applied to PSII to reveal atomic positions at 1.95 Å without radiation damage, which brought us closer than ever to establishing the ultimate structure of the OEC in the S 1 state. However, the atom positions in this crystal structure are still not consistent with high-resolution EXAFS spectroscopy, partially due to the poorly resolved oxygen positions next to Mn centers and partial reduction due to extended dark adaptation of the sample. These inconsistencies led to the new models of the OEC with an alternative low oxidation state and raised questions on the protonation state of the cluster, especially the O5 μ-oxo bridge. This Account summarizes the most recent models of the OEC that emerged from QM/MM, EXAFS and femtosecond X-ray crystallography methods. When PSII in the S 1 state is exposed to light, the S 1 state is advanced to the higher oxidation states and eventually binds substrate water molecules. Identifying the substrate waters is of paramount importance for establishing the water-oxidation mechanism but is complicated by a large number of spectroscopically similar waters. Water analogues can, therefore, be helpful because they serve as spectroscopic markers that help to track the motion of the substrate waters. Due to a close structural and electronic similarity to water, ammonia has been of particular interest. We review three competing hypotheses on substrate water/ammonia binding and compile theoretical and experimental evidence to support them. Binding of ammonia as a sixth ligand to Mn4 during the S 1 → S 2 transition seems to satisfy most of the criteria, especially the most compelling recent EPR data on D1-D61A mutated PSII. Such a binding mode suggests delivery of water from the “narrow” channel through a “carousel” rearrangement of waters around Mn4 upon the S 2 → S 3 transition. An alternative hypothesis suggests water delivery through the “large” channel on the Ca side. However, both water delivery paths lead to a similar S 3 structure, seemingly reaching consensus on the nature of the last detectable S-state intermediate in the Kok cycle before O 2 evolution.« less

Resonant electronic Raman scattering of below-gap states in molecular-beam epitaxy grown and liquid-encapsulated Czochralski grown GaAs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fluegel, B.; Rice, A. D.; Mascarenhas, A.

Resonant electronic Raman (ER) scattering is used to compare the below-gap excitations in molecular-beam epitaxially grown GaAs and in undoped semi-insulating GaAs substrates. The measurement geometry was designed to eliminate common measurement artifacts caused by the high optical transmission below the fundamental absorption edge. In epitaxial GaAs, ER is a clear Raman signal from the two-electron transitions of donors, eliminating an ambiguity encountered in previous results. In semi-insulating GaAs, ER occurs in a much broader dispersive band well below the bound exciton energies. Furthermore, the difference in the two materials may be due to the occupation of the substrate acceptormore » states in the presence of the midgap state EL2.« less

Biochemistry students' ideas about how an enzyme interacts with a substrate.

PubMed

Linenberger, Kimberly J; Bretz, Stacey Lowery

2015-01-01

Enzyme-substrate interactions are a fundamental concept of biochemistry that is built upon throughout multiple biochemistry courses. Central to understanding enzyme-substrate interactions is specific knowledge of exactly how an enzyme and substrate interact. Within this narrower topic, students must understand the various binding sites on an enzyme and be able to reason from simplistic lock and key or induced fit models to the more complex energetics model of transition state theory. Learning to understand these many facets of enzyme-substrate interactions and reasoning from multiple models present challenges where students incorrectly make connections between concepts or make no connection at all. This study investigated biochemistry students' understanding of enzyme-substrate interactions through the use of clinical interviews and a national administration (N = 707) of the Enzyme-Substrate Interactions Concept Inventory. Findings include misconceptions regarding the nature of enzyme-substrate interactions, naïve ideas about the active site, a lack of energetically driven interactions, and an incomplete understanding of the specificity pocket. © 2015 by the International Union of Biochemistry and Molecular Biology.

Protein Allostery and Conformational Dynamics.

PubMed

Guo, Jingjing; Zhou, Huan-Xiang

2016-06-08

The functions of many proteins are regulated through allostery, whereby effector binding at a distal site changes the functional activity (e.g., substrate binding affinity or catalytic efficiency) at the active site. Most allosteric studies have focused on thermodynamic properties, in particular, substrate binding affinity. Changes in substrate binding affinity by allosteric effectors have generally been thought to be mediated by conformational transitions of the proteins or, alternatively, by changes in the broadness of the free energy basin of the protein conformational state without shifting the basin minimum position. When effector binding changes the free energy landscape of a protein in conformational space, the change affects not only thermodynamic properties but also dynamic properties, including the amplitudes of motions on different time scales and rates of conformational transitions. Here we assess the roles of conformational dynamics in allosteric regulation. Two cases are highlighted where NMR spectroscopy and molecular dynamics simulation have been used as complementary approaches to identify residues possibly involved in allosteric communication. Perspectives on contentious issues, for example, the relationship between picosecond-nanosecond local and microsecond-millisecond conformational exchange dynamics, are presented.

Analysis of oxygen binding-energy variations for BaO on W

NASA Astrophysics Data System (ADS)

Haas, G. A.; Shih, A.; Mueller, D.; Thomas, R. E.

Interatomic Auger analyses have been made of different forms of BaO layers on W substrates. Variations in Auger spectroscopy energies of the Ba4dBa5pO2p interatomic Auger transition were found to be largely governed by the O2p binding energy of the BaO adsorbate. This was illustrated by comparing results of the Auger data values with values derived from O2p binding energies using ultraviolet photoelectron spectroscopy. Very good agreement was observed not only for the W<100> substrate but also for the W<110> substrate which showed two oxygen-induced electronics state. Variations in binding energy were noted for different states of BaO lattice formation and for different amounts of oxidation, ranging from the transition of Ba to BaO and continuing to the BaO 2 stoichiometry and beyond. Effects were also reported for adsorbate alignment and thermal activation (i.e., reduction) of the oxidized state. An empirical relationship was found suggesting that the more tightly bound the O2p states of the BaO adsorbate were, the lower its work function would be. This link between binding energy and work function was observed to be valid not only for cases of poisoning by oxidation, but held as well during reactivation by the subsequent reduction of the oxide. In addition, this relationship also appeared to predict the low work function obtained through the introduction of substances such as Sc to the BaO-W system. Possible qualitative reasons which might contribute to this are discussed in terms of enhanced dipole effects and shifts in band structure.

Epitaxial Ni-Mn-Ga-Co thin films on PMN-PT substrates for multicaloric applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schleicher, B., E-mail: b.schleicher@ifw-dresden.de; Niemann, R.; Schultz, L.

2015-08-07

Multicaloric stacks consisting of a magnetocaloric film on a piezoelectric substrate promise improved caloric properties as the transition temperature can be controlled by both magnetic and electric fields. We present epitaxially grown magnetocaloric Ni-Mn-Ga-Co thin films on ferroelectric Pb(Mg{sub 1/3}Nb{sub 2/3}){sub 0.72}Ti{sub 0.28}O{sub 3} substrates. Structure and microstructure of two samples, being in the austenitic and martensitic state at room temperature, are investigated by X-ray diffraction in two- and four-circle geometry and by atomic force microscopy. In addition, high temperature magnetometry was performed on the latter sample. The combination of these methods allows separating the influence of epitaxial growth andmore » martensitic transformation. A preferential alignment of twin boundaries is observed already in the as-deposited state, which indicates the presence of prestress, without applying an electric field to the substrate. A temperature-magnetic field phase diagram is presented, which demonstrates the inverse magnetocaloric effect of the epitaxial Ni-Mn-Ga-Co film.« less

Active-site copper reduction promotes substrate binding of fungal lytic polysaccharide monooxygenase and reduces stability.

PubMed

Kracher, Daniel; Andlar, Martina; Furtmüller, Paul G; Ludwig, Roland

2018-02-02

Lytic polysaccharide monooxygenases (LPMOs) are a class of copper-containing enzymes that oxidatively degrade insoluble plant polysaccharides and soluble oligosaccharides. Upon reductive activation, they cleave the substrate and promote biomass degradation by hydrolytic enzymes. In this study, we employed LPMO9C from Neurospora crassa , which is active toward cellulose and soluble β-glucans, to study the enzyme-substrate interaction and thermal stability. Binding studies showed that the reduction of the mononuclear active-site copper by ascorbic acid increased the affinity and the maximum binding capacity of LPMO for cellulose. The reduced redox state of the active-site copper and not the subsequent formation of the activated oxygen species increased the affinity toward cellulose. The lower affinity of oxidized LPMO could support its desorption after catalysis and allow hydrolases to access the cleavage site. It also suggests that the copper reduction is not necessarily performed in the substrate-bound state of LPMO. Differential scanning fluorimetry showed a stabilizing effect of the substrates cellulose and xyloglucan on the apparent transition midpoint temperature of the reduced, catalytically active enzyme. Oxidative auto-inactivation and destabilization were observed in the absence of a suitable substrate. Our data reveal the determinants of LPMO stability under turnover and non-turnover conditions and indicate that the reduction of the active-site copper initiates substrate binding. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Quantum transition and decoherence of levitating polaron on helium film thickness under an electromagnetic field

NASA Astrophysics Data System (ADS)

Kenfack, S. C.; Fotue, A. J.; Fobasso, M. F. C.; Djomou, J.-R. D.; Tiotsop, M.; Ngouana, K. S. L.; Fai, L. C.

2017-12-01

We have studied the transition probability and decoherence time of levitating polaron in helium film thickness. By using a variational method of Pekar type, the ground and the first excited states of polaron are calculated above the liquid-helium film placed on the polar substrate. It is shown that the polaron transits from the ground to the excited state in the presence of an external electromagnetic field in the plane. We have seen that, in the helium film, the effects of the magnetic and electric fields on the polaron are opposite. It is also shown that the energy, transition probability and decoherence time of the polaron depend sensitively on the helium film thickness. We found that decoherence time decreases as a function of increasing electron-phonon coupling strength and the helium film thickness. It is seen that the film thickness can be considered as a new confinement in our system and can be adjusted in order to reduce decoherence.

Comparison of molecular orientation and phase transition behaviors in the two kinds of ordered ultrathin films of reversed duckweed polymer ES-3 studied by infrared grazing reflection-absorption spectroscopy

NASA Astrophysics Data System (ADS)

Wang, Qiang; Xu, Weiqing; Zhao, Bing

2003-03-01

A multilayer LB film and a casting film of reversed duckweed polymer ES-3 on Au-evaporated glass slides were investigated by Fourier Transform infrared grazing reflection-absorption spectroscopy. It is found that the two kinds of ordered ultrathin films have different orientation of alkyl chains, nearly perpendicular to the substrate surface for the LB film while rather tilted for the casting film. The studies on their thermal transition behaviors indicate that both of the films have three phase transition processes, respectively, occurring near 65, 105 and 140 °C for the former while near 80, 105 and 140 °C for the latter, but show different transition behavior in the each corresponding transition process. It is referred that at room temperature there are island-like domain structures formed in the LB film, but no ones in the casting film; however, the latter can form the domain structures between the first two transition points due to the desorption of solvents. The formation of domain structure seems to play two important roles, one of which is to make alkyl chains more perpendicular to the substrate surface, and the other to make alkyl chains more packed closely. Thermal cyclic experiments reveal that neither of the films could return to its original state after thermal cyclic treatment up to the temperature, which is above the third transition point, although its alkyl chain becomes highly ordered again.

Mammals of Australia's Tropical Savannas: A Conceptual Model of Assemblage Structure and Regulatory Factors in the Kimberley Region

PubMed Central

Radford, Ian J.; Dickman, Christopher R.; Start, Antony N.; Palmer, Carol; Carnes, Karin; Everitt, Corrin; Fairman, Richard; Graham, Gordon; Partridge, Thalie; Thomson, Allan

2014-01-01

We construct a state-and-transition model for mammals in tropical savannas in northern Australia to synthesize ecological knowledge and understand mammalian declines. We aimed to validate the existence of alternative mammal assemblage states similar to those in arid Australian grasslands, and to speculate on transition triggers. Based on the arid grassland model, we hypothesized that assemblages are partitioned across rainfall gradients and between substrates. We also predicted that assemblages typical of arid regions in boom periods would be prevalent in savannas with higher and more regular rainfall. Data from eight mammal surveys from the Kimberley region, Western Australia (1994 to 2011) were collated. Survey sites were partitioned across rainfall zones and habitats. Data allowed us to identify three assemblage states: State 0:- low numbers of mammals, State II:- dominated by omnivorous rodents and State III:- dominated by rodents and larger marsupials. Unlike arid grasslands, assemblage dominance by insectivorous dasyurids (State I) did not occur in savannas. Mammal assemblages were partitioned across rainfall zones and between substrates as predicted, but—unlike arid regions—were not related strongly to yearly rainfall. Mammal assemblage composition showed high regional stability, probably related to high annual rainfall and predictable wet season resource pulses. As a consequence, we speculate that perpetually booming assemblages in savannas allow top-down control of the ecosystem, with suppression of introduced cats by the dingo, the region's top predator. Under conditions of low or erratic productivity, imposed increasingly by intense fire regimes and introduced herbivore grazing, dingoes may not limit impacts of cats on native mammals. These interacting factors may explain contemporary declines of savanna mammals as well as historical declines in arid Australia. The cat-ecosystem productivity hypothesis raised here differs from the already-articulated cat-habitat structure hypothesis for mammal declines, and we suggest approaches for explicit testing of transition triggers for competing hypotheses. PMID:24670997

Mammals of Australia's tropical savannas: a conceptual model of assemblage structure and regulatory factors in the Kimberley region.

PubMed

Radford, Ian J; Dickman, Christopher R; Start, Antony N; Palmer, Carol; Carnes, Karin; Everitt, Corrin; Fairman, Richard; Graham, Gordon; Partridge, Thalie; Thomson, Allan

2014-01-01

We construct a state-and-transition model for mammals in tropical savannas in northern Australia to synthesize ecological knowledge and understand mammalian declines. We aimed to validate the existence of alternative mammal assemblage states similar to those in arid Australian grasslands, and to speculate on transition triggers. Based on the arid grassland model, we hypothesized that assemblages are partitioned across rainfall gradients and between substrates. We also predicted that assemblages typical of arid regions in boom periods would be prevalent in savannas with higher and more regular rainfall. Data from eight mammal surveys from the Kimberley region, Western Australia (1994 to 2011) were collated. Survey sites were partitioned across rainfall zones and habitats. Data allowed us to identify three assemblage states: State 0:--low numbers of mammals, State II:--dominated by omnivorous rodents and State III:--dominated by rodents and larger marsupials. Unlike arid grasslands, assemblage dominance by insectivorous dasyurids (State I) did not occur in savannas. Mammal assemblages were partitioned across rainfall zones and between substrates as predicted, but-unlike arid regions-were not related strongly to yearly rainfall. Mammal assemblage composition showed high regional stability, probably related to high annual rainfall and predictable wet season resource pulses. As a consequence, we speculate that perpetually booming assemblages in savannas allow top-down control of the ecosystem, with suppression of introduced cats by the dingo, the region's top predator. Under conditions of low or erratic productivity, imposed increasingly by intense fire regimes and introduced herbivore grazing, dingoes may not limit impacts of cats on native mammals. These interacting factors may explain contemporary declines of savanna mammals as well as historical declines in arid Australia. The cat-ecosystem productivity hypothesis raised here differs from the already-articulated cat-habitat structure hypothesis for mammal declines, and we suggest approaches for explicit testing of transition triggers for competing hypotheses.

Action of the Hsp70 chaperone system observed with single proteins

NASA Astrophysics Data System (ADS)

Nunes, João M.; Mayer-Hartl, Manajit; Hartl, F. Ulrich; Müller, Daniel J.

2015-02-01

In Escherichia coli, the binding of non-native protein substrates to the Hsp70 chaperone DnaK is mediated by the co-chaperone DnaJ. DnaJ accelerates ATP hydrolysis on DnaK, by closing the peptide-binding cleft of DnaK. GrpE catalysed nucleotide exchange and ATP re-binding then lead to substrate release from DnaK, allowing folding. Here we refold immunoglobulin 27 (I27) to better understand how DnaJ-DnaK-GrpE chaperones cooperate. When DnaJ is present, I27 is less likely to misfold and more likely to fold, whereas the unfolded state remains unaffected. Thus, the ‘holdase’ DnaJ shows foldase behaviour. Misfolding of I27 is fully abrogated when DnaJ cooperates with DnaK, which stabilizes the unfolded state and increases the probability of folding. Addition of GrpE shifts the unfolded fraction of I27 to pre-chaperone levels. These insights reveal synergistic mechanisms within the evolutionary highly conserved Hsp70 system that prevent substrates from misfolding and promote their productive transition to the native state.

Substrate Temperature effect on the transition characteristics of Vanadium (IV) oxide

NASA Astrophysics Data System (ADS)

Yang, Tsung-Han; Wei, Wei; Jin, Chunming; Narayan, Jay

2008-10-01

One of the semiconductor to metal transition material (SMT) is Vanadium Oxide (VO2) which has a very sharp transition temperature close to 340 K as the crystal structure changes from monoclinic phase (semiconductor) into tetragonal phase (metal phase). We have grown high-quality epitaxial vanadium oxide (VO2) films on sapphire (0001) substrates by pulsed laser deposition for oxygen pressure 10-2torr and obtained interesting results without further annealing treatments. The epitaxial growth via domain matching epitaxy, where integral multiples of planes matched across the film-substrate interface. We were able to control the transition characteristics such as the sharpness (T), amplitude (A) of SMT transition and the width of thermal hysteresis (H) by altering the substrate temperature from 300 ^oC, 400 ^oC, 500 ^oC, and 600 ^oC. We use the XRD to identify the microstructure of film and measure the optical properties of film. Finally the transition characteristics is observed by the resistance with the increase of temperature by Van Der Pauw method from 25 to 100 ^oC to measure the electrical resistivity hystersis loop during the transition temperature.

Structure of the Deactive State of Mammalian Respiratory Complex I.

PubMed

Blaza, James N; Vinothkumar, Kutti R; Hirst, Judy

2018-02-06

Complex I (NADH:ubiquinone oxidoreductase) is central to energy metabolism in mammalian mitochondria. It couples NADH oxidation by ubiquinone to proton transport across the energy-conserving inner membrane, catalyzing respiration and driving ATP synthesis. In the absence of substrates, active complex I gradually enters a pronounced resting or deactive state. The active-deactive transition occurs during ischemia and is crucial for controlling how respiration recovers upon reperfusion. Here, we set a highly active preparation of Bos taurus complex I into the biochemically defined deactive state, and used single-particle electron cryomicroscopy to determine its structure to 4.1 Å resolution. We show that the deactive state arises when critical structural elements that form the ubiquinone-binding site become disordered, and we propose reactivation is induced when substrate binding to the NADH-reduced enzyme templates their reordering. Our structure both rationalizes biochemical data on the deactive state and offers new insights into its physiological and cellular roles. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Testing Geometrical Discrimination within an Enzyme Active Site: Constrained Hydrogen Bonding in the Ketosteroid Isomerase Oxyanion Hole

PubMed Central

Sigala, Paul A.; Kraut, Daniel A.; Caaveiro, Jose M. M.; Pybus, Brandon; Ruben, Eliza A.; Ringe, Dagmar; Petsko, Gregory A.; Herschlag, Daniel

2009-01-01

Enzymes are classically proposed to accelerate reactions by binding substrates within active site environments that are structurally preorganized to optimize binding interactions with reaction transition states rather than ground states. This is a remarkably formidable task considering the limited 0.1 – 1 Å scale of most substrate rearrangements. The flexibility of active site functional groups along the coordinate of substrate rearrangement, the distance scale on which enzymes can distinguish structural rearrangement, and the energetic significance of discrimination on that scale remain open questions that are fundamental to a basic physical understanding of enzyme active sites and catalysis. We bring together high resolution X-ray crystallography, 1H and 19F NMR spectroscopy, quantum mechanical calculations, and transition state analog binding measurements to test the distance scale on which non-covalent forces can constrain side chain and ligand relaxation or translation along a specific coordinate and the energetic consequences of such geometric constraints within the active site of bacterial ketosteroid isomerase (KSI). Our results strongly suggest that packing and binding interactions within the KSI active site can constrain local side chain reorientation and prevent hydrogen bond shortening by 0.1 Å or less. Further, this constraint has substantial energetic effects on ligand binding and stabilization of negative charge within the oxyanion hole. These results provide evidence that subtle geometric effects, indistinguishable in most X-ray crystallographic structures, can have significant energetic consequences and highlight the importance of using synergistic experimental approaches to dissect enzyme function. PMID:18808119

Study of orotidine 5'-monophosphate decarboxylase in complex with the top three OMP, BMP, and PMP ligands by molecular dynamics simulation.

PubMed

Jamshidi, Shirin; Jalili, Seifollah; Rafii-Tabar, Hashem

2015-01-01

Catalytic mechanism of orotidine 5'-monophosphate decarboxylase (OMPDC), one of the nature most proficient enzymes which provides large rate enhancement, has not been fully understood yet. A series of 30 ns molecular dynamics (MD) simulations were run on X-ray structure of the OMPDC from Saccharomyces cerevisiae in its free form as well as in complex with different ligands, namely 1-(5'-phospho-D-ribofuranosyl) barbituric acid (BMP), orotidine 5'-monophosphate (OMP), and 6-phosphonouridine 5'-monophosphate (PMP). The importance of this biological system is justified both by its high rate enhancement and its potential use as a target in chemotherapy. This work focuses on comparing two physicochemical states of the enzyme (protonated and deprotonated Asp91) and three ligands (substrate OMP, inhibitor, and transition state analog BMP and substrate analog PMP). Detailed analysis of the active site geometry and its interactions is properly put in context by extensive comparison with relevant experimental works. Our overall results show that in terms of hydrogen bond occupancy, electrostatic interactions, dihedral angles, active site configuration, and movement of loops, notable differences among different complexes are observed. Comparison of the results obtained from these simulations provides some detailed structural data for the complexes, the enzyme, and the ligands, as well as useful insights into the inhibition mechanism of the OMPDC enzyme. Furthermore, these simulations are applied to clarify the ambiguous mechanism of the OMPDC enzyme, and imply that the substrate destabilization and transition state stabilization contribute to the mechanism of action of the most proficient enzyme, OMPDC.

Anopheles gambiae Purine Nucleoside Phosphorylase: Catalysis, Structure, and Inhibition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor,E.; Rinaldo-Matthis, A.; Li, L.

The purine salvage pathway of Anopheles gambiae, a mosquito that transmits malaria, has been identified in genome searches on the basis of sequence homology with characterized enzymes. Purine nucleoside phosphorylase (PNP) is a target for the development of therapeutic agents in humans and purine auxotrophs, including malarial parasites. The PNP from Anopheles gambiae (AgPNP) was expressed in Escherichia coli and compared to the PNPs from Homo sapiens (HsPNP) and Plasmodium falciparum (PfPNP). AgPNP has kcat values of 54 and 41 s-1 for 2'-deoxyinosine and inosine, its preferred substrates, and 1.0 s-1 for guanosine. However, the chemical step is fast formore » AgPNP at 226 s-1 for guanosine in pre-steady-state studies. 5'-Deaza-1'-aza-2'-deoxy-1'-(9-methylene)-Immucillin-H (DADMe-ImmH) is a transition-state mimic for a 2'-deoxyinosine ribocation with a fully dissociated N-ribosidic bond and is a slow-onset, tight-binding inhibitor with a dissociation constant of 3.5 pM. This is the tightest-binding inhibitor known for any PNP, with a remarkable Km/Ki* of 5.4 x 107, and is consistent with enzymatic transition state predictions of enhanced transition-state analogue binding in enzymes with enhanced catalytic efficiency. Deoxyguanosine is a weaker substrate than deoxyinosine, and DADMe-Immucillin-G is less tightly bound than DADMe-ImmH, with a dissociation constant of 23 pM for AgPNP as compared to 7 pM for HsPNP. The crystal structure of AgPNP was determined in complex with DADMe-ImmH and phosphate to a resolution of 2.2 Angstroms to reveal the differences in substrate and inhibitor specificity. The distance from the N1' cation to the phosphate O4 anion is shorter in the AgPNP{center_dot}DADMe-ImmH{center_dot}PO4 complex than in HsPNP{center_dot}DADMe-ImmH{center_dot}SO4, offering one explanation for the stronger inhibitory effect of DADMe-ImmH for AgPNP.« less

Friction phenomena and phase transition in the underdamped two-dimensional Frenkel-Kontorova model

NASA Astrophysics Data System (ADS)

Yang, Yang; Duan, Wen-Shan; Chen, Jian-Min; Yang, Lei; Tekić, Jasmina; Shao, Zhi-Gang; Wang, Cang-Long

2010-11-01

Locked-to-sliding phase transition has been studied in the driven two-dimensional Frenkel-Kontorova model with the square symmetric substrate potential. It is found that as the driving force increases, the system transfers from the locked state to the sliding state where the motion of particles is in the direction different from that of driving force. With the further increase in driving force, at some critical value, the particles start to move in the direction of driving force. These two critical forces, the static friction or depinning force, and the kinetic friction force for which particles move in the direction of driving force have been analyzed for different system parameters. Different scenarios of phase transitions have been examined and dynamical phases are classified. In the case of zero misfit angle, the analytical expressions for static and kinetic friction force have been obtained.

Adipocyte Glucocorticoid Receptor Deficiency Attenuates Aging- and HFD-Induced Obesity and Impairs the Feeding-Fasting Transition.

PubMed

Mueller, Kristina M; Hartmann, Kerstin; Kaltenecker, Doris; Vettorazzi, Sabine; Bauer, Mandy; Mauser, Lea; Amann, Sabine; Jall, Sigrid; Fischer, Katrin; Esterbauer, Harald; Müller, Timo D; Tschöp, Matthias H; Magnes, Christoph; Haybaeck, Johannes; Scherer, Thomas; Bordag, Natalie; Tuckermann, Jan P; Moriggl, Richard

2017-02-01

Glucocorticoids (GCs) are important regulators of systemic energy metabolism, and aberrant GC action is linked to metabolic dysfunctions. Yet, the extent to which normal and pathophysiological energy metabolism depend on the GC receptor (GR) in adipocytes remains unclear. Here, we demonstrate that adipocyte GR deficiency in mice significantly impacts systemic metabolism in different energetic states. Plasma metabolomics and biochemical analyses revealed a marked global effect of GR deficiency on systemic metabolite abundance and, thus, substrate partitioning in fed and fasted states. This correlated with a decreased lipolytic capacity of GR-deficient adipocytes under postabsorptive and fasting conditions, resulting from impaired signal transduction from β-adrenergic receptors to adenylate cyclase. Upon prolonged fasting, the impaired lipolytic response resulted in abnormal substrate utilization and lean mass wasting. Conversely, GR deficiency attenuated aging-/diet-associated obesity, adipocyte hypertrophy, and liver steatosis. Systemic glucose tolerance was improved in obese GR-deficient mice, which was associated with increased insulin signaling in muscle and adipose tissue. We conclude that the GR in adipocytes exerts central but diverging roles in the regulation of metabolic homeostasis depending on the energetic state. The adipocyte GR is indispensable for the feeding-fasting transition but also promotes adiposity and associated metabolic disorders in fat-fed and aged mice. © 2017 by the American Diabetes Association.

Methods of making composite optical devices employing polymer liquid crystal

DOEpatents

Jacobs, S.D.; Marshall, K.L.; Cerqua, K.A.

1991-10-08

Composite optical devices are disclosed using polymer liquid crystal materials both as optical and adhesive elements. The devices are made by assembling a heated polymer liquid crystal compound, while in a low viscosity form between optically transparent substrates. The molecules of the polymer are oriented, while in the liquid crystalline state and while above the glass transition temperature (T[sub g]) of the polymer, to provide the desired optical effects, such as polarization, and selective reflection. The liquid crystal polymer cements the substrates together to form an assembly providing the composite optical device. 7 figures.

Unusual enzymatic glycoside cleavage mechanisms.

PubMed

Jongkees, Seino A K; Withers, Stephen G

2014-01-21

Over the sixty years since Koshland initially formulated the classical mechanisms for retaining and inverting glycosidases, researchers have assembled a large body of supporting evidence and have documented variations of these mechanisms. Recently, however, researchers have uncovered a number of completely distinct mechanisms for enzymatic cleavage of glycosides involving elimination and/or hydration steps. In family GH4 and GH109 glycosidases, the reaction proceeds via transient NAD(+)-mediated oxidation at C3, thereby acidifying the proton at C2 and allowing for elimination across the C1-C2 bond. Subsequent Michael-type addition of water followed by reduction at C3 generates the hydrolyzed product. Enzymes employing this mechanism can hydrolyze thioglycosides as well as both anomers of activated substrates. Sialidases employ a conventional retaining mechanism in which a tyrosine functions as the nucleophile, but in some cases researchers have observed off-path elimination end products. These reactions occur via the normal covalent intermediate, but instead of an attack by water on the anomeric center, the catalytic acid/base residue abstracts an adjacent proton. These enzymes can also catalyze hydration of the enol ether via the reverse pathway. Reactions of α-(1,4)-glucan lyases also proceed through a covalent intermediate with subsequent abstraction of an adjacent proton to give elimination. However, in this case, the departing carboxylate "nucleophile" serves as the base in a concerted but asynchronous syn-elimination process. These enzymes perform only elimination reactions. Polysaccharide lyases, which act on uronic acid-containing substrates, also catalyze only elimination reactions. Substrate binding neutralizes the charge on the carboxylate, which allows for abstraction of the proton on C5 and leads to an elimination reaction via an E1cb mechanism. These enzymes can also cleave thioglycosides, albeit slowly. The unsaturated product of polysaccharide lyases can then serve as a substrate for a hydration reaction carried out by unsaturated glucuronyl hydrolases. This hydration is initiated by protonation at C4 and proceeds in a Markovnikov fashion rather than undergoing a Michael-type addition, giving a hemiketal at C5. This hemiketal then undergoes a rearrangement that results in cleavage of the anomeric bond. These enzymes can also hydrolyze thioglycosides efficiently and slowly turn over substrates with inverted anomeric configuration. The mechanisms discussed in this Account proceed through transition states that involve either positive or negative charges, unlike the exclusively cationic transition states of the classical Koshland retaining and inverting glycosidases. In addition, the distribution of this charge throughout the substrate can vary substantially. The nature of these mechanisms and their transition states means that any inhibitors or inactivators of these unusual enzymes probably differ from those presently used for Koshland retaining or inverting glycosidases.

Emission and reflection spectra from AlxGa1-xN/GaN single heterostructures

NASA Astrophysics Data System (ADS)

Reynolds, D. C.; Hoelscher, J.; Litton, C. W.; Collins, T. C.; Fitch, R.; Via, G. D.; Gillespie, J.; Crespo, A.; Jenkins, T. J.; Saxler, A.

2003-10-01

Emission and reflection spectra from AlGaN/GaN single heterostructures grown on SiC substrates were investigated. Two-dimensional electron gas (2DEG) transitions were observed in both emission and reflection. The transitions are sharp, associated with the excited state of the 2DEG, reflect the conservation of the K-selection rule, and are excitonlike. The transitions are also associated with both the A- and B-valence bands. To verify the origin of the reflection and emission spectra, the top AlGaN layer was removed by reactive ion etching. After etching, only the excitonic reflection and emission spectra associated with GaN were observed.

Microfabricated ion frequency standard

DOEpatents

Schwindt, Peter; Biedermann, Grant; Blain, Matthew G.; Stick, Daniel L.; Serkland, Darwin K.; Olsson, III, Roy H.

2010-12-28

A microfabricated ion frequency standard (i.e. an ion clock) is disclosed with a permanently-sealed vacuum package containing a source of ytterbium (Yb) ions and an octupole ion trap. The source of Yb ions is a micro-hotplate which generates Yb atoms which are then ionized by a ultraviolet light-emitting diode or a field-emission electron source. The octupole ion trap, which confines the Yb ions, is formed from suspended electrodes on a number of stacked-up substrates. A microwave source excites a ground-state transition frequency of the Yb ions, with a frequency-doubled vertical-external-cavity laser (VECSEL) then exciting the Yb ions up to an excited state to produce fluorescent light which is used to tune the microwave source to the ground-state transition frequency, with the microwave source providing a precise frequency output for the ion clock.

Molecular dynamics simulation of bovine pancreatic ribonuclease A-CpA and transition state-like complexes.

PubMed

Formoso, Elena; Matxain, Jon M; Lopez, Xabier; York, Darrin M

2010-06-03

The mechanisms of enzymes are intimately connected with their overall structure and dynamics in solution. Experimentally, it is considerably challenging to provide detailed atomic level information about the conformational events that occur at different stages along the chemical reaction path. Here, theoretical tools may offer new potential insights that complement those obtained from experiments that may not yield an unambiguous mechanistic interpretation. In this study, we apply molecular dynamics simulations of bovine pancreatic ribonuclease A, an archetype ribonuclease, to study the conformational dynamics, structural relaxation, and differential solvation that occur at discrete stages of the transesterification and cleavage reaction. Simulations were performed with explicit solvation with rigorous electrostatics and utilize recently developed molecular mechanical force field parameters for transphosphorylation and hydrolysis transition state analogues. Herein, we present results for the enzyme complexed with the dinucleotide substrate cytidilyl-3',5'-adenosine (CpA) in the reactant, and transphosphorylation and hydrolysis transition states. A detailed analysis of active site structures and hydrogen-bond patterns is presented and compared. The integrity of the overall backbone structure is preserved in the simulations and supports a mechanism whereby His12 stabilizes accumulating negative charge at the transition states through hydrogen-bond donation to the nonbridge oxygens. Lys41 is shown to be highly versatile along the reaction coordinate and can aid in the stabilization of the dianionic transition state, while being poised to act as a general acid catalyst in the hydrolysis step.

Molecular Dynamics Simulation of Bovine Pancreatic Ribonuclease A - CpA and Transition State-like Complexes

PubMed Central

Formoso, Elena; Matxain, Jon M.; Lopez, Xabier; York, Darrin M.

2010-01-01

The mechanisms of enzymes are intimately connected with their overall structure and dynamics in solution. Experimentally it is considerably challenging to provide detailed atomic level information about the conformational events that occur at different stages along the chemical reaction path. Here, theoretical tools may offer new potential insights that complement those obtained from experiments that may not yield an unambiguous mechanistic interpretation. In this study we apply molecular dynamics simulations of bovine pancreatic ribonuclease A, an archetype ribonuclease, in order to study the conformational dynamics, structural relaxation, and differential solvation that occurs at discreet stages of the transesterification and cleavage reaction. Simulations were performed with explicit solvation with rigorous electrostatics, and utilize recently developed molecular mechanical force field parameters for transphosphorylation and hydrolysis transition state analogs. Herein, we present results for the enzyme complexed with the dinucleotide substrate cytidilyl-3′,5′-adenosine (CpA) in the reactant, and transphosphorylation and hydrolysis transition states. A detailed analysis of active site structures and hydrogen bond patterns are presented and compared. The integrity of the overall backbone structure is preserved in the simulations, and support a mechanism whereby His12 stabilizes accumulating negative charge at the transition states through hydrogen bond donation to the non-bridge oxygens. Lys41 is shown to be highly versatile along the reaction coordinate, and can aid in the stabilization of the dianionic transition state, while being poised to act as a general acid catalyst in the hydrolysis step. PMID:20455590

Effect of the substrate on the insulator-metal transition of vanadium dioxide films

NASA Astrophysics Data System (ADS)

Kovács, György J.; Bürger, Danilo; Skorupa, Ilona; Reuther, Helfried; Heller, René; Schmidt, Heidemarie

2011-03-01

Single-phase vanadium dioxide films grown on (0001) sapphire and (001) silicon substrates show a very different insulator-metal electronic transition. A detailed description of the growth mechanisms and the substrate-film interaction is given, and the characteristics of the electronic transition are described by the morphology and grain boundary structure. (Tri-)epitaxy-stabilized columnar growth of VO2 takes place on the sapphire substrate, whereas on silicon the expected Zone II growth is identified. We have found that in the case of the Si substrate the reasons for the broader hysteresis and the lower switching amplitude are the formation of an amorphous insulating VOx (x > 2.6) phase coexisting with VO2 and the high vanadium vacancy concentration of the VO2. These phenomena are the result of the excess oxygen during the growth and the interaction between the silicon substrate and the growing film.

Substrate influence on the interlayer electron-phonon couplings in fullerene films probed with doubly-resonant SFG spectroscopy.

PubMed

Elsenbeck, Dennis; Das, Sushanta K; Velarde, Luis

2017-07-19

We present doubly-resonant sum frequency generation (DR-SFG) spectra of fullerene thin films on metallic and dielectric substrates as a way to investigate the interplay between nuclear and electronic coupling at buried interfaces. Modal and substrate selectivity in the electronic enhancement of the C 60 vibrational signatures is demonstrated for excitation wavelengths spanning the visible range. While the SFG response of the totally symmetric A g (2) mode of fullerene is distinctly coupled to the optically allowed electronic transition corresponding to the HOMO-LUMO+1 of C 60 (ca. 2.6 eV), the T 1u (4) vibrational mode appears to be coupled to a symmetry-forbidden HOMO-LUMO transition at lower energies (ca. 2.0 eV). For dielectric substrates, the DR-SFG intensity of the T 1u (4) mode shows lack of enhancement for upconversion wavelengths off-resonance with the optically-dark LUMO. However, the T 1u (4) mode shows a unique coupling to an intermediate state (∼2.4 eV) only for the fullerene films on the gold substrate. We attribute this coupling to unique interactions at the buried C 60 /gold interface. These results demonstrate the occurrence of clear electron-phonon couplings at the C 60 /substrate interfaces and shed light on the impact of these couplings on the optical response of electronically excited fullerene. This coupling may influence charge and energy transport in organic electronic devices mediated by vibrational motions. We also demonstrate a potential use of this added selectivity in chemical imaging.

Tuning the magnetic properties of LaCoO3 thin films by epitaxial strain

NASA Astrophysics Data System (ADS)

Fuchs, D.; Arac, E.; Pinta, C.; Schuppler, S.; Schneider, R.; v. Löhneysen, H.

2008-01-01

Ferromagnetic order can be induced in LaCoO3 (LCO) thin films by epitaxial strain. Here, we show that the magnetic properties can be “tuned” by epitaxial strain imposed on LCO thin films by the epitaxial growth on various substrate materials, i.e., (001) oriented SrLaAlO4 , LaAlO3 , SrLaGaO4 , (LaAlO3)0.3(Sr2AlTaO6)0.7 , and SrTiO3 . The lattice mismatch at room temperature of the in-plane lattice parameters between the substrate, as , and bulk LCO, ab , ranges from -1.31% to +2.63% . Single-phase, ⟨001⟩ oriented LCO thin films were grown by pulsed laser deposition on all these substrates. Due to the difference of the thermal-expansion coefficients between LCO and the substrates, the films experience an additional tensile strain of about +0.3% during the cooling process after the deposition at Ts=650°C . The film lattice parameters display an elastic behavior, i.e., an increase of the in-plane film lattice parameter with increasing as . From the ratio between the out-of-plane and in-plane strain, we obtain a Poisson ratio of ν≈1/3 . All films show a ferromagnetic transition as determined from magnetization measurements. The magnetization increases strongly with increasing tensile strain, whereas the transition temperature TC after a rapid initial rise appears to saturate at TC≈85K above a=3.86Å . The effective magnetic moment μeff in the paramagnetic state increases almost linearly as a function of the mean lattice parameter ⟨a⟩ , indicating an enhanced population of higher spin states, i.e., intermediate- or high-spin states. The experimental results are discussed in terms of a decrease of the octahedral-site rotation with increasing tensile strain.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sokolov, Andrei; Kirianov, Eugene; Zlenko, Albina

The effect of substrates on the magnetic and transport properties of Ni{sub 2}Mn{sub 1.5}In{sub 0.5} ultra-thin films were studied theoretically and experimentally. High quality 8-nm films were grown by laser-assisted molecular beam epitaxy deposition. Magneto-transport measurements revealed that the films undergo electronic structure transformation similar to those of bulk materials at the martensitic transformation. The temperature of the transformation depends strongly on lattice parameters of the substrate. To explain this behavior, we performed DFT calculations on the system and found that different substrates change the relative stability of the ferromagnetic (FM) austenite and ferrimagnetic (FiM) martensite states. We conclude thatmore » the energy difference between the FM austenite and FiM martensite states in Ni{sub 2}Mn{sub 1.5}In{sub 0.5} films grown on MgO (001) substrates is ΔE = 0.20 eV per NiMnIn f.u, somewhat lower compared to ΔE = 0.24 eV in the bulk material with the same lattice parameters. When the lattice parameters of Ni{sub 2}Mn{sub 1.5}In{sub 0.5} film have values close to those of the MgO substrate, the energy difference becomes ΔE = 0.08 eV per NiMnIn f.u. These results suggest the possibility to control the martensitic transition in thin films through substrate engineering.« less

Local phase transitions in driven colloidal suspensions

NASA Astrophysics Data System (ADS)

Scacchi, A.; Brader, J. M.

2018-02-01

Using dynamical density functional theory and Brownian dynamics simulations, we investigate the influence of a driven tracer particle on the density distribution of a colloidal suspension at a thermodynamic state point close to the liquid side of the binodal. In bulk systems, we find that a localised region of the colloid-poor phase, a 'cavitation bubble', forms behind the moving tracer. The extent of the cavitation bubble is investigated as a function of both the size and velocity of the tracer. The addition of a confining boundary enables us to investigate the interaction between the local phase instability at the substrate and that at the particle surface. When both the substrate and tracer interact repulsively with the colloids we observe the formation of a colloid-poor bridge between the substrate and the tracer. When a shear flow is applied parallel to the substrate the bridge becomes distorted and, at sufficiently high shear-rates, disconnects from the substrate to form a cavitation bubble.

Identification of key residues for protein conformational transition using elastic network model.

PubMed

Su, Ji Guo; Xu, Xian Jin; Li, Chun Hua; Chen, Wei Zu; Wang, Cun Xin

2011-11-07

Proteins usually undergo conformational transitions between structurally disparate states to fulfill their functions. The large-scale allosteric conformational transitions are believed to involve some key residues that mediate the conformational movements between different regions of the protein. In the present work, a thermodynamic method based on the elastic network model is proposed to predict the key residues involved in protein conformational transitions. In our method, the key functional sites are identified as the residues whose perturbations largely influence the free energy difference between the protein states before and after transition. Two proteins, nucleotide binding domain of the heat shock protein 70 and human/rat DNA polymerase β, are used as case studies to identify the critical residues responsible for their open-closed conformational transitions. The results show that the functionally important residues mainly locate at the following regions for these two proteins: (1) the bridging point at the interface between the subdomains that control the opening and closure of the binding cleft; (2) the hinge region between different subdomains, which mediates the cooperative motions between the corresponding subdomains; and (3) the substrate binding sites. The similarity in the positions of the key residues for these two proteins may indicate a common mechanism in their conformational transitions.

Substrate transport pathway inside outward open conformation of EmrD: a molecular dynamics simulation study.

PubMed

Xianwei, Tan; Diannan, Lu; Boxiong, Wang

2016-07-19

The EmrD transporter, which is a classical major facilitator superfamily (MFS) protein, can extrude a range of drug molecules out of E. coil. The drug molecules transport through the channel of MFS in an outward open state, an important issue in research about bacterial drug resistance, which however, is still unknown. In this paper, we construct a starting outward-open model of the EmrD transporter using a state transition method. The starting model is refined by a conventional molecular dynamics simulation. Locally enhanced sampling simulation (LES) is used to validate the outward-open model of EmrD. In the locally enhanced sampling simulation, ten substrates are placed along the channel of the outward-open EmrD, and these substrates are sampled in the outward-open center cavity. It is found that the translocation pathway of these substrates from the inside to the outside of the cell through the EmrD transporter is composed of two sub-pathways, one sub-pathway, including H2, H4, and H5, and another sub-pathway, including H8, H10, and H11. The results give us have a further insight to the ways of substrate translocation of an MFS protein. The model method is based on common features of an MFS protein, so this modeling method can be used to construct various MFS protein models which have a desired state with other conformations not known in the alternating-access mechanism.

How Mg2+ ions lower the SN2@P barrier in enzymatic triphosphate hydrolysis.

PubMed

van Bochove, Marc A; Roos, Goedele; Fonseca Guerra, Célia; Hamlin, Trevor A; Bickelhaupt, F Matthias

2018-04-03

Our quantum chemical activation strain analyses demonstrate how Mg2+ lowers the barrier of the enzymatic triphosphate hydrolysis through two distinct mechanisms: (a) weakening of the leaving-group bond, thereby decreasing activation strain; and (b) transition state (TS) stabilization through enhanced electrophilicity of the triphosphate PPP substrate, thereby strengthening the interaction with the nucleophile.

Superconducting articles of manufacture and method of producing same

DOEpatents

Newkirk, Lawrence R.; Valencia, Flavio A.

1980-01-01

Bulk coatings of Nb.sub.3 Ge with high superconducting transition temperatures bonded to metallic substrates and a chemical vapor deposition method for producing such coatings on metallic substrates are disclosed. In accordance with the method, a Nb.sub.3 Ge coating having a transition temperature in excess of 21.5 K may be tightly bonded to a copper substrate.

Inverting Steric Effects: Using "Attractive" Noncovalent Interactions To Direct Silver-Catalyzed Nitrene Transfer.

PubMed

Huang, Minxue; Yang, Tzuhsiung; Paretsky, Jonathan D; Berry, John F; Schomaker, Jennifer M

2017-12-06

Nitrene transfer (NT) reactions represent powerful and direct methods to convert C-H bonds into amine groups that are prevalent in many commodity chemicals and pharmaceuticals. The importance of the C-N bond has stimulated the development of numerous transition-metal complexes to effect chemo-, regio-, and diastereoselective NT. An ongoing challenge is to understand how subtle interactions between catalyst and substrate influence the site-selectivity of the C-H amination event. In this work, we explore the underlying reasons why Ag(tpa)OTf (tpa = tris(pyridylmethyl)amine) prefers to activate α-conjugated C-H bonds over 3° alkyl C(sp 3 )-H bonds and apply these insights to reaction optimization and catalyst design. Experimental results suggest possible roles of noncovalent interactions (NCIs) in directing the NT; computational studies support the involvement of π···π and Ag···π interactions between catalyst and substrate, primarily by lowering the energy of the directed transition state and reaction conformers. A simple Hess's law relationship can be employed to predict selectivities for new substrates containing competing NCIs. The insights presented herein are poised to inspire the design of other catalyst-controlled C-H functionalization reactions.

Expression and purification of isotopically labeled peptide inhibitors and substrates of cAMP-dependant protein kinase A for NMR analysis.

PubMed

Masterson, Larry R; Bortone, Nadia; Yu, Tao; Ha, Kim N; Gaffarogullari, Ece C; Nguyen, Oanh; Veglia, Gianluigi

2009-04-01

Extensive X-ray crystallographic studies carried out on the catalytic-subunit of protein kinase A (PKA-C) enabled the atomic characterization of inhibitor and/or substrate peptide analogues trapped at its active site. Yet, the structural and dynamic transitions of these peptides from the free to the bound state are missing. These conformational transitions are central to understanding molecular recognition and the enzymatic cycle. NMR spectroscopy allows one to study these phenomena under functionally relevant conditions. However, the amounts of isotopically labeled peptides required for this technique present prohibitive costs for solid-phase peptide synthesis. To enable NMR studies, we have optimized both expression and purification of isotopically enriched substrate/inhibitor peptides using a recombinant fusion protein system. Three of these peptides correspond to the cytoplasmic regions of the wild-type and lethal mutants of the membrane protein phospholamban, while the fourth peptide correspond to the binding epitope of the heat-stable protein kinase inhibitor (PKI(5-24)). The target peptides were fused to the maltose binding protein (MBP), which is further purified using a His(6) tag approach. This convenient protocol allows for the purification of milligram amounts of peptides necessary for NMR analysis.

Transition of yeast Can1 transporter to the inward-facing state unveils an α-arrestin target sequence promoting its ubiquitylation and endocytosis.

PubMed

Gournas, Christos; Saliba, Elie; Krammer, Eva-Maria; Barthelemy, Céline; Prévost, Martine; André, Bruno

2017-10-15

Substrate-transport-elicited endocytosis is a common control mechanism of membrane transporters avoiding excess uptake of external compounds, though poorly understood at the molecular level. In yeast, endocytosis of transporters is triggered by their ubiquitylation mediated by the Rsp5 ubiquitin-ligase, recruited by α-arrestin-family adaptors. We here report that transport-elicited ubiquitylation of the arginine transporter Can1 is promoted by transition to an inward-facing state. This conformational change unveils a region of the N-terminal cytosolic tail targeted by the Art1 α-arrestin, which is activated via the TORC1 kinase complex upon arginine uptake. Can1 mutants altered in the arginine-binding site or a cytosolic tripeptide sequence permanently expose the α-arrestin-targeted region so that Art1 activation via TORC1 is sufficient to trigger their endocytosis. We also provide evidence that substrate-transport elicited endocytosis of other amino acid permeases similarly involves unmasking of a cytosolic Art1-target region coupled to activation of Art1 via TORC1. Our results unravel a mechanism likely involved in regulation of many other transporters by their own substrates. They also support the emerging view that transporter ubiquitylation relies on combinatorial interaction rules such that α-arrestins, stimulated via signaling cascades or in their basal state, recognize transporter regions permanently facing the cytosol or unveiled during transport. © 2017 Gournas et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Substrate effects on photoluminescence and low temperature phase transition of methylammonium lead iodide hybrid perovskite thin films

NASA Astrophysics Data System (ADS)

Shojaee, S. A.; Harriman, T. A.; Han, G. S.; Lee, J.-K.; Lucca, D. A.

2017-07-01

We examine the effects of substrates on the low temperature photoluminescence (PL) spectra and phase transition in methylammonium lead iodide hybrid perovskite (CH3NH3PbI3) thin films. Structural characterization at room temperature with X-ray diffraction (XRD), scanning electron microscopy (SEM), and Raman spectroscopy indicated that while the chemical structure of films deposited on glass and quartz was similar, the glass substrate induced strain in the perovskite films and suppressed the grain growth. The luminescence response and phase transition of the perovskite thin films were studied by PL spectroscopy. The induced strain was found to affect both the room temperature and low temperature PL spectra of the hybrid perovskite films. In addition, it was found that the effects of the glass substrate inhibited a tetragonal to orthorhombic phase transition such that it occurred at lower temperatures.

Quantum mechanical approaches to in silico enzyme characterization and drug design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nilmeier, J P; Fattebert, J L; Jacobson, M P

2012-01-17

The astonishing, exponentially increasing rates of genome sequencing has led to one of the most significant challenges for the biological and computational sciences in the 21st century: assigning the likely functions of the encoded proteins. Enzymes represent a particular challenge, and a critical one, because the universe of enzymes is likely to contain many novel functions that may be useful for synthetic biology, or as drug targets. Current approaches to protein annotation are largely based on bioinformatics. At the simplest level, this annotation involves transferring the annotations of characterized enzymes to related sequences. In practice, however, there is no simple,more » sequence based criterion for transferring annotations, and bioinformatics alone cannot propose new enzymatic functions. Structure-based computational methods have the potential to address these limitations, by identifying potential substrates of enzymes, as we and others have shown. One successful approach has used in silico 'docking' methods, more commonly applied in structure-based drug design, to identify possible metabolite substrates. A major limitation of this approach is that it only considers substrate binding, and does not directly assess the potential of the enzyme to catalyze a particular reaction using a particular substrate. That is, substrate binding affinity is necessary but not sufficient to assign function. A reaction profile is ultimately what is needed for a more complete quantitative description of function. To address this rather fundamental limitation, they propose to use quantum mechanical methods to explicitly compute transition state barriers that govern the rates of catalysis. Although quantum mechanical, and mixed quantum/classical (QM/MM), methods have been used extensively to investigate enzymatic reactions, the focus has been primarily on elucidating complex reaction mechanisms. Here, the key catalytic steps are known, and they use these methods quantify substrate specificity. That is, we bring the power of quantum mechanics to bear on the problem of annotating enzyme function, which is a novel approach. Although it has been clear to us at the Jacobson group for some time that enzyme specificity may be encoded in transition states, rather than simply substrate recognition, the main limitation has always been computational expense. Using a hierarchy of different methods, they can reduce the list of plausible substrates of an enzyme to a small number in most cases, but even identifying the transition states for a dozen plausible substrates requires significant computational effort, beyond what is practical using standard QM/MM methods. For this project, they have chosen two enzyme superfamilies which they have used as 'model systems' for functional assignment. The enolase superfamily is a large group of {alpha}-{beta} barrel enzymes with highly diverse substrates and chemical transformations. Despite decades of work, over a third of the superfamily remains unassigned, which means that the remaining cases are by definition difficult to assign. They have focused on acid sugar dehydratases, and have considerable expertise on the matter. They are also interested in the isoprenoid synthase superfamily, which is of central interest to the synthetic biology community, because these enzymes are used by nature to create complex rare natural products of medicinal value. the most notable example of this is the artemisinin, an antimalarial compound that is found in trace amounts in the wormwod root. From the standpoint of enzyme function assignment, these enzymes are intriguing because they use a small number of chemically simple substrates to generate, potentially, tens of thousands of different products. Hence, substrate binding specificity is only a small part of the challenge; the key is determining how the enzyme directs the carbocation chemistry to specific products. These more complex modeling approaches clearly require quantum mechanical methods.« less

Strain tuning of electronic structure in Bi 4Ti 3O 12-LaCoO 3 epitaxial thin films

DOE PAGES

Choi, Woo Seok; Lee, Ho Nyung

2015-05-08

In this study, we investigated the crystal and electronic structures of ferroelectric Bi 4Ti 3O 12 single-crystalline thin films site-specifically substituted with LaCoO 3 (LCO). The epitaxial films were grown by pulsed laser epitaxy on NdGaO 3 and SrTiO 3 substrates to vary the degree of strain. With increasing the LCO substitution, we observed a systematic increase in the c-axis lattice constant of the Aurivillius phase related with the modification of pseudo-orthorhombic unit cells. These compositional and structural changes resulted in a systematic decrease in the band gap, i.e., the optical transition energy between the oxygen 2p and transition-metal 3dmore » states, based on a spectroscopic ellipsometry study. In particular, the Co 3d state seems to largely overlap with the Ti t 2g state, decreasing the band gap. Interestingly, the applied tensile strain facilitates the band-gap narrowing, demonstrating that epitaxial strain is a useful tool to tune the electronic structure of ferroelectric transition-metal oxides.« less

The Cassie-Wenzel transition of fluids on nanostructured substrates: Macroscopic force balance versus microscopic density-functional theory.

PubMed

Tretyakov, Nikita; Papadopoulos, Periklis; Vollmer, Doris; Butt, Hans-Jürgen; Dünweg, Burkhard; Daoulas, Kostas Ch

2016-10-07

Classical density functional theory is applied to investigate the validity of a phenomenological force-balance description of the stability of the Cassie state of liquids on substrates with nanoscale corrugation. A bulk free-energy functional of third order in local density is combined with a square-gradient term, describing the liquid-vapor interface. The bulk free energy is parameterized to reproduce the liquid density and the compressibility of water. The square-gradient term is adjusted to model the width of the water-vapor interface. The substrate is modeled by an external potential, based upon the Lennard-Jones interactions. The three-dimensional calculation focuses on substrates patterned with nanostripes and square-shaped nanopillars. Using both the force-balance relation and density-functional theory, we locate the Cassie-to-Wenzel transition as a function of the corrugation parameters. We demonstrate that the force-balance relation gives a qualitatively reasonable description of the transition even on the nanoscale. The force balance utilizes an effective contact angle between the fluid and the vertical wall of the corrugation to parameterize the impalement pressure. This effective angle is found to have values smaller than the Young contact angle. This observation corresponds to an impalement pressure that is smaller than the value predicted by macroscopic theory. Therefore, this effective angle embodies effects specific to nanoscopically corrugated surfaces, including the finite range of the liquid-solid potential (which has both repulsive and attractive parts), line tension, and the finite interface thickness. Consistently with this picture, both patterns (stripes and pillars) yield the same effective contact angles for large periods of corrugation.

Fractional quantum Hall effect in strained graphene: Stability of Laughlin states in disordered pseudomagnetic fields

NASA Astrophysics Data System (ADS)

Bagrov, Andrey A.; Principi, Alessandro; Katsnelson, Mikhail I.

2017-03-01

We address the question of the stability of the fractional quantum Hall effect in the presence of pseudomagnetic disorder generated by mechanical deformations of a graphene sheet. Neglecting the potential disorder and taking into account only strain-induced random pseudomagnetic fields, it is possible to write down a Laughlin-like trial ground-state wave function explicitly. Exploiting the Laughlin plasma analogy, we demonstrate that in the case of fluctuating pseudomagnetic fluxes of a relatively small amplitude, the fractional quantum Hall effect is always stable upon the deformations. By contrast, in the case of bubble-induced pseudomagnetic fields in graphene on a substrate (a small number of large fluxes) the disorder can be strong enough to cause a glass transition in the corresponding classical Coulomb plasma, resulting in the destruction of the fractional quantum Hall regime and in a quantum phase transition to a nonergodic state of the lowest Landau level.

Wetting Behavior in Colloid-Polymer Mixtures at Different Substrates.

PubMed

Wijting, Willem K; Besseling, Nicolaas A M; Cohen Stuart, Martien A

2003-09-25

We present experimental observations on wetting phenomena in depletion interaction driven, phase separated colloidal dispersions. The contact angle of the colloidal liquid-gas interface at a solid substrate was determined for a series of compositions. Upon approach to the critical point, a transition occurs from partial to complete wetting. The interaction with the substrate was manipulated by modifying the substrate with a polymer. In that case, a transition from partial to complete drying is observed upon approach to the critical point.

Competing feedbacks drive state transitions during initial catchment evolution: Examples from post-mining landscape and ecosystems evolution

NASA Astrophysics Data System (ADS)

Hinz, Christoph; Wolfgang, Schaaf; Werner, Gerwin

2014-05-01

Within the context of severely disturbed landscapes with little or no ecological memory, such as post-mining landscapes, we propose a simple framework that explains the catchment evolution as a result of competing feedbacks influenced by the initial conditions and the atmospheric drivers such as rainfall intermittency and intensity. The first stage of the evolution is dominated by abiotic feedbacks triggered by rainfall and subsequent fluid flow causing particle mobilisation on the surface and in the subsurface leading to flow concentration or in some instances to densification of surface and subsurface substrates. Subsequently, abiotic-biotic feedbacks start to compete in the sense that biological activity generally stabilizes substrate by preventing particle mobilisation and hence contribute to converting the substrate to a habitat. We suggest that these competing feedbacks may generate alternative stable states in particular under semi-arid and arid climatic conditions, while in temperate often energy limited environments biological process "outcompete" abiotic processes leading to a stable state, in particular from the water balance point of view for comparable geomorphic situations. To illustrate this framework, we provide examples from post-mining landscapes, in which soil, water and vegetation was monitored. In case of arid regions in Australia, we provide evidence that the initial conditions of a mine waste disposal "locked" the system into a state that was limited by water and nutrient storage capacity while at the same time it was stable from a geomorphic point of view for the observation period. The cause of the system to be locked in, is the very high hydraulic conductivity of the substrate, that has not undergone any changes during the first years. In contrast to this case study, we illustrate how this framework explains the evolution of an artificial catchment (Hühnerwasser Catchment) in Lusatia (150 km southeast of Berlin, Germany). During the initial phase of development the catchment changed very rapidly due to sediment transport, drainage network formation, and soil crusting very similar to geomorphic processes observed in arid and semi-arid landscapes void of dense vegetation. Hydraulic properties changed rapidly after few wet and dry cycles, indicative of particle mobilisation and trapping in the subsurface. Accordingly, the hydrological regime was controlled by rapid surface runoff enhanced through crust formation and at the same time a shallow ground water system developed. This surface runoff regime peeked about two years initialisation as shown by a maximum area of drainage channels. A major, fairly rapid transition occurred between three and five years after placement, in which the sediment transport ceased and vegetation coverage of the drainage channel exceeded 90%. The transition represents the onset of a transpiration dominated regime that is further enhanced by change of the plant composition of the vegetation with tree recruitment from the surrounding forming significant clusters in the catchment. This transition in the third year was also seen in a significant increase in soil fauna and plant diversity.

High-intensity pulse light sintering of silver nanowire transparent films on polymer substrates: the effect of the thermal properties of substrates on the performance of silver films.

PubMed

Jiu, Jinting; Sugahara, Tohru; Nogi, Masaya; Araki, Teppei; Suganuma, Katsuaki; Uchida, Hiroshi; Shinozaki, Kenji

2013-12-07

Silver nanowire (AgNW) films with a random mesh structure have attracted considerable attention as high-performance flexible transparent electrodes that can replace the expensive and brittle ITO-sputtered films widely used in displays, touch screens, and solar cells. Methods such as heating, pressure treatment, and light treatment are usually used to obtain an optically transparent and electrically conductive film comparable to those of commercial ITO. However, the adhesion between the AgNW film and the substrate is so weak that other overcoatings or extra treatments are necessary. Here, a high-intensity pulsed light (HIPL) sintering technique was developed to rapidly and simply sinter the AgNW film and thus achieve strong adhesion and even high conductivity on these flexible polymer substrates which will be widely applied to the printing of electronic devices. The conductivity of the AgNW film closely depended on the thermal performance of substrates, and the adhesion was determined by the soft state of the substrate surface originating from the glass transition or melting of substrates with light intensity. The rapid sintering technique can be popularized to fabricate new devices on these polymer substrates by considering the thermal properties of the substrate to improve the performance of devices.

Structural transition of secondary phase oxide nanorods in epitaxial YBa2Cu3O7-δ films on vicinal substrates

NASA Astrophysics Data System (ADS)

Shi, Jack J.; Wu, Judy Z.

2012-12-01

A theoretical study of a structural transition of secondary phase oxide nanorods in epitaxial YBa2Cu3O7-δ films on vicinal SrTiO3 substrates is presented. Two possible types of film/substrate interface are considered, with one assuming complete coherence, while the other is defective as manifested by the presence of antiphase grain boundaries. Only in the former case does the increase of the vicinal angle of the substrate lead to a substantial change of the strain field in the film, resulting in a transition of the nanorod orientation from the normal to the in-plane direction of the film. The calculated threshold vicinal angle for the onset of the transition and lattice deformation of the YBa2Cu3O7-δ film due to the inclusion of the nanorods is in very good agreement with experimental observations. This result sheds lights on the understanding of the role of the film/substrate lattice mismatch in controlling self-assembly of dopant nanostructures in matrix films.

Regulation of ATP production: dependence on calcium concentration and respiratory state.

PubMed

Fink, Brian D; Bai, Fan; Yu, Liping; Sivitz, William I

2017-08-01

Nanomolar free calcium enhances oxidative phosphorylation. However, the effects over a broad concentration range, at different respiratory states, or on specific energy substrates are less clear. We examined the action of varying [Ca 2+ ] over respiratory states ranging 4 to 3 on skeletal muscle mitochondrial respiration, potential, ATP production, and H 2 O 2 production using ADP recycling to clamp external [ADP]. Calcium at 450 nM enhanced respiration in mitochondria energized by the complex I substrates, glutamate/malate (but not succinate), at [ADP] of 4-256 µM, but more substantially at intermediate respiratory states and not at all at state 4. Using varied [Ca 2+ ], we found that the stimulatory effects on respiration and ATP production were most prominent at nanomolar concentrations, but inhibitory at 10 µM or higher. ATP production decreased more than respiration at 10 µM calcium. However, potential continued to increase up to 10 µM; suggesting a calcium-induced inability to utilize potential for phosphorylation independent of opening of the mitochondrial permeability transition pore (MTP). This effect of 10 µM calcium was confirmed by direct determination of ATP production over a range of potential created by differing substrate concentrations. Consistent with past reports, nanomolar [Ca 2+ ] had a stimulatory effect on utilization of potential for phosphorylation. Increasing [Ca 2+ ] was positively and continuously associated with H 2 O 2 production. In summary, the stimulatory effect of calcium on mitochondrial function is substrate dependent and most prominent over intermediate respiratory states. Calcium stimulates or inhibits utilization of potential for phosphorylation dependent on concentration with inhibition at higher concentration independent of MTP opening.

Molecular modeling studies of substrate binding by penicillin acylase.

PubMed

Chilov, G G; Stroganov, O V; Svedas, V K

2008-01-01

Molecular modeling has revealed intimate details of the mechanism of binding of natural substrate, penicillin G (PG), in the penicillin acylase active center and solved questions raised by analysis of available X-ray structures, mimicking Michaelis complex, which substantially differ in the binding pattern of the PG leaving group. Three MD trajectories were launched, starting from PDB complexes of the inactive mutant enzyme with PG (1FXV) and native penicillin acylase with sluggishly hydrolyzed substrate analog penicillin G sulfoxide (1GM9), or from the complex obtained by PG docking. All trajectories converged to a similar PG binding mode, which represented the near-to-attack conformation, consistent with chemical criteria of how reactive Michaelis complex should look. Simulated dynamic structure of the enzyme-substrate complex differed significantly from 1FXV, resembling rather 1GM9; however, additional contacts with residues bG385, bS386, and bN388 have been found, which were missing in X-ray structures. Combination of molecular docking and molecular dynamics also clarified the nature of extremely effective phenol binding in the hydrophobic pocket of penicillin acylase, which lacked proper explanation from crystallographic experiments. Alternative binding modes of phenol were probed, and corresponding trajectories converged to a single binding pattern characterized by a hydrogen bond between the phenol hydroxyl and the main chain oxygen of bS67, which was not evident from the crystal structure. Observation of the trajectory, in which phenol moved from its steady bound to pre-dissociation state, mapped the consequence of molecular events governing the conformational transitions in a coil region a143-a146 coupled to substrate binding and release of the reaction products. The current investigation provided information on dynamics of the conformational transitions accompanying substrate binding and significance of poorly structured and flexible regions in maintaining catalytic framework.

Asparagine 285 plays a key role in transition state stabilization in rabbit muscle creatine kinase

PubMed Central

Borders, Charles L.; MacGregor, Katherine M.; Edmiston, Paul L.; Gbeddy, Elikem R.K.; Thomenius, Michael J.; Mulligan, Guy B.; Snider, Mark J.

2003-01-01

To explore the possibility that asparagine 285 plays a key role in transition state stabilization in phosphagen kinase catalysis, the N285Q, N285D, and N285A site-directed mutants of recombinant rabbit muscle creatine kinase (rmCK) were prepared and characterized. Kinetic analysis of phosphocreatine formation showed that the catalytic efficiency of each N285 mutant was reduced by approximately four orders of magnitude, with the major cause of activity loss being a reduction in kcat in comparison to the recombinant native CK. The data for N285Q still fit a random-order, rapid-equilibrium mechanism, with either MgATP or creatine binding first with affinities very nearly equal to those for native CK. However, the affinity for the binding of the second substrate is reduced approximately 10-fold, suggesting that addition of a single methylene group at position 285 disrupts the symphony of substrate binding. The data for the N285A mutant only fit an ordered binding mechanism, with MgATP binding first. Isosteric replacement to form the N285D mutant has almost no effect on the KM values for either creatine or MgATP, thus the decrease in activity is due almost entirely to a 5000-fold reduction in kcat. Using the quenching of the intrinsic CK tryptophan fluorescence by added MgADP (Borders et al. 2002), it was found that, unlike native CK, none of the mutants have the ability to form a quaternary TSAC. We use these data to propose that asparagine 285 indeed plays a key role in transition state stabilization in the reaction catalyzed by creatine kinase and other phosphagen kinases. PMID:12592023

Asparagine 285 plays a key role in transition state stabilization in rabbit muscle creatine kinase.

PubMed

Borders, Charles L; MacGregor, Katherine M; Edmiston, Paul L; Gbeddy, Elikem R K; Thomenius, Michael J; Mulligan, Guy B; Snider, Mark J

2003-03-01

To explore the possibility that asparagine 285 plays a key role in transition state stabilization in phosphagen kinase catalysis, the N285Q, N285D, and N285A site-directed mutants of recombinant rabbit muscle creatine kinase (rmCK) were prepared and characterized. Kinetic analysis of phosphocreatine formation showed that the catalytic efficiency of each N285 mutant was reduced by approximately four orders of magnitude, with the major cause of activity loss being a reduction in k(cat) in comparison to the recombinant native CK. The data for N285Q still fit a random-order, rapid-equilibrium mechanism, with either MgATP or creatine binding first with affinities very nearly equal to those for native CK. However, the affinity for the binding of the second substrate is reduced approximately 10-fold, suggesting that addition of a single methylene group at position 285 disrupts the symphony of substrate binding. The data for the N285A mutant only fit an ordered binding mechanism, with MgATP binding first. Isosteric replacement to form the N285D mutant has almost no effect on the K(M) values for either creatine or MgATP, thus the decrease in activity is due almost entirely to a 5000-fold reduction in k(cat). Using the quenching of the intrinsic CK tryptophan fluorescence by added MgADP (Borders et al. 2002), it was found that, unlike native CK, none of the mutants have the ability to form a quaternary TSAC. We use these data to propose that asparagine 285 indeed plays a key role in transition state stabilization in the reaction catalyzed by creatine kinase and other phosphagen kinases.

The "Transport Specificity Ratio": a structure-function tool to search the protein fold for loci that control transition state stability in membrane transport catalysis

PubMed Central

King, Steven C

2004-01-01

Background In establishing structure-function relationships for membrane transport proteins, the interpretation of phenotypic changes can be problematic, owing to uncertainties in protein expression levels, sub-cellular localization, and protein-folding fidelity. A dual-label competitive transport assay called "Transport Specificity Ratio" (TSR) analysis has been developed that is simple to perform, and circumvents the "expression problem," providing a reliable TSR phenotype (a constant) for comparison to other transporters. Results Using the Escherichia coli GABA (4-aminobutyrate) permease (GabP) as a model carrier, it is demonstrated that the TSR phenotype is largely independent of assay conditions, exhibiting: (i) indifference to the particular substrate concentrations used, (ii) indifference to extreme changes (40-fold) in transporter expression level, and within broad limits (iii) indifference to assay duration. The theoretical underpinnings of TSR analysis predict all of the above observations, supporting that TSR has (i) applicability in the analysis of membrane transport, and (ii) particular utility in the face of incomplete information on protein expression levels and initial reaction rate intervals (e.g., in high-throughput screening situations). The TSR was used to identify gab permease (GabP) variants that exhibit relative changes in catalytic specificity (kcat/Km) for [14C]GABA (4-aminobutyrate) versus [3H]NA (nipecotic acid). Conclusions The TSR phenotype is an easily measured constant that reflects innate molecular properties of the transition state, and provides a reliable index of the difference in catalytic specificity that a carrier exhibits toward a particular pair of substrates. A change in the TSR phenotype, called a Δ(TSR), represents a specificity shift attributable to underlying changes in the intrinsic substrate binding energy (ΔGb) that translocation catalysts rely upon to decrease activation energy (). TSR analysis is therefore a structure-function tool that enables parsimonious scanning for positions in the protein fold that couple to the transition state, creating stability and thereby serving as functional determinants of catalytic power (efficiency, or specificity). PMID:15548327

Enzyme Architecture: Self-Assembly of Enzyme and Substrate Pieces of Glycerol-3-Phosphate Dehydrogenase into a Robust Catalyst of Hydride Transfer.

PubMed

Reyes, Archie C; Amyes, Tina L; Richard, John P

2016-11-23

The stabilization of the transition state for hlGPDH-catalyzed reduction of DHAP due to the action of the phosphodianion of DHAP and the cationic side chain of R269 is between 12.4 and 17 kcal/mol. The R269A mutation of glycerol-3-phosphate dehydrogenase (hlGPDH) results in a 9.1 kcal/mol destabilization of the transition state for enzyme-catalyzed reduction of dihydroxyacetone phosphate (DHAP) by NADH, and there is a 6.7 kcal/mol stabilization of this transition state by 1.0 M guanidine cation (Gua + ) [J. Am. Chem. Soc. 2015, 137, 5312-5315]. The R269A mutant shows no detectable activity toward reduction of glycolaldehyde (GA), or activation of this reaction by 30 mM HPO 3 2- . We report the unprecedented self-assembly of R269A hlGPDH, dianions (X 2- = FPO 3 2- , HPO 3 2- , or SO 4 2- ), Gua + and GA into a functioning catalyst of the reduction of GA, and fourth-order reaction rate constants k cat /K GA K X K Gua . The linear logarithmic correlation (slope = 1.0) between values of k cat /K GA K X for dianion activation of wildtype hlGPDH-catalyzed reduction of GA and k cat /K GA K X K Gua shows that the electrostatic interaction between exogenous dianions and the side chain of R269 is not significantly perturbed by cutting hlGPDH into R269A and Gua + pieces. The advantage for connection of hlGPDH (R269A mutant + Gua + ) and substrate pieces (GA + HP i ) pieces, (ΔG S ‡ ) HPi+E+Gua = 5.6 kcal/mol, is nearly equal to the sum of the advantage to connection of the substrate pieces, (ΔG S ‡ ) GA+HPi = 3.3 kcal/mol, for wildtype hlGPDH-catalyzed reaction of GA + HP i , and for connection of the enzyme pieces, (ΔG S ‡ ) E+Gua = 2.4 kcal/mol, for Gua + activation of the R269A hlGPDH-catalyzed reaction of DHAP.

Characterization of pulsed laser deposition grown V2O3 converted VO2

NASA Astrophysics Data System (ADS)

Majid, Suhail; Shukla, D. K.; Rahman, F.; Gautam, Kamini; Sathe, V. G.; Choudhary, R. J.; Phase, D. M.

2016-10-01

Controllable tuning of Metal-insulator transition in VxOy thin film has been a field of extensive research. However controlled synthesis of desired Vanadium oxide phase is a challenging task. We have successfully achieved VO2 phase on Silicon substrate after post deposition annealing treatment to the PLD grown as deposited V2O3 thin films. The annealed thin film was characterized by x-ray diffraction (XRD), resistivity, Raman spectroscopy, X-ray absorption spectroscopy (XAS) and X-ray photoelectron spectroscopy (XPS) measurements. XRD confirms the crystalline nature and growth of VO2 phase in thin film. The characteristic MIT was observed from resistivity measurements and transition temperature appeared at lower value around 336 K, compared to bulk VO2. The structural transition accompanied with MIT from lower temperature monoclinic phase to higher temperature Rutile phase became evident from temperature dependent Raman measurements. Chemical state of vanadium was examined using XAS and XPS measurements which confirm the presence of +4 oxidation state of vanadium in thin film.

Epitaxial VO2 thin-film-based radio-frequency switches with electrical activation

NASA Astrophysics Data System (ADS)

Lee, Jaeseong; Lee, Daesu; Cho, Sang June; Seo, Jung-Hun; Liu, Dong; Eom, Chang-Beom; Ma, Zhenqiang

2017-09-01

Vanadium dioxide (VO2) is a correlated material exhibiting a sharp insulator-to-metal phase transition (IMT) caused by temperature change and/or bias voltage. We report on the demonstration of electrically triggered radio-frequency (RF) switches based on epitaxial VO2 thin films. The highly epitaxial VO2 and SnO2 template layer was grown on a (001) TiO2 substrate by pulsed laser deposition (PLD). A resistance change of the VO2 thin films of four orders of magnitude was achieved with a relatively low threshold voltage, as low as 13 V, for an IMT phase transition. VO2 RF switches also showed high-frequency responses of insertion losses of -3 dB at the on-state and return losses of -4.3 dB at the off-state over 27 GHz. Furthermore, an intrinsic cutoff frequency of 17.4 THz was estimated for the RF switches. The study on electrical IMT dynamics revealed a phase transition time of 840 ns.

Strain effect on the magnetic and transport properties of LaCoO3 thin films

NASA Astrophysics Data System (ADS)

Li, Y.; Peng, S. J.; Wang, D. J.; Wu, K. M.; Wang, S. H.

2018-05-01

LaCoO3 (LCO) has attracted much attention due to the unique magnetic transition and spin transition of Co3+ ions. Epitaxial LCO film exhibits an unexpected ferromagnetism, in contrast to the non-magnetism of bulk LCO. An in-depth study on the property of strained LCO film is of great importance. We have fabricated 30 nm LCO films on various substrates and studied the magnetic and transport properties of films in different strain states (compressed strain for LCO/LaAlO3, tensile strain for LCO/(LaAlO3)0.3(Sr2TaAlO6)0.35, SrTiO3). The in-plane tensiled LCO films exhibit ferromagnetic ground state at 5K and magnetic transition with TC around 85K, while compressed LCO/LaAlO3 film has a negligibly small moment signal. Our results reveal that in-plane tensile strain and tetragonal distortion are much more favorable for stabilizing the FM order in LCO films.

Electronic and geometric structure of thin CoO(100) films studied by angle-resolved photoemission spectroscopy and Auger electron diffraction

NASA Astrophysics Data System (ADS)

Heiler, M.; Chassé, A.; Schindler, K.-M.; Hollering, M.; Neddermeyer, H.

2000-05-01

We have prepared ordered thin films of CoO by evaporating cobalt in an O 2 atmosphere on to a heated (500 K) Ag(100) substrate. The geometric and electronic structure of the films was characterized by means of Auger electron diffraction (AED) and angle-resolved photoemission spectroscopy (ARUPS), respectively. The experimental AED results were compared with simulated data, which showed that the film grows in (100) orientation on the Ag(100) substrate. Synchrotron-radiation-induced photoemission investigations were performed in the photon energy range from 25 eV to 67 eV. The dispersion of the transitions was found to be similar to that of previous results on a single-crystal CoO(100) surface. The resonance behaviour of the photoemission lines in the valence-band region was investigated by constant-initial-state (CIS) spectroscopy. The implications of this behaviour for assignment of the photoemission lines to specific electronic transitions is discussed and compared with published theoretical models of the electronic structure.

Capturing Hammerhead Ribozyme Structures in Action by Modulating General Base Catalysis

PubMed Central

Chi, Young-In; Martick, Monika; Lares, Monica; Kim, Rosalind; Scott, William G; Kim, Sung-Hou

2008-01-01

We have obtained precatalytic (enzyme–substrate complex) and postcatalytic (enzyme–product complex) crystal structures of an active full-length hammerhead RNA that cleaves in the crystal. Using the natural satellite tobacco ringspot virus hammerhead RNA sequence, the self-cleavage reaction was modulated by substituting the general base of the ribozyme, G12, with A12, a purine variant with a much lower pKa that does not significantly perturb the ribozyme's atomic structure. The active, but slowly cleaving, ribozyme thus permitted isolation of enzyme–substrate and enzyme–product complexes without modifying the nucleophile or leaving group of the cleavage reaction, nor any other aspect of the substrate. The predissociation enzyme-product complex structure reveals RNA and metal ion interactions potentially relevant to transition-state stabilization that are absent in precatalytic structures. PMID:18834200

On the growth mechanisms of polar (100) surfaces of ceria on copper (100)

NASA Astrophysics Data System (ADS)

Hackl, Johanna; Duchoň, Tomáš; Gottlob, Daniel M.; Cramm, Stefan; Veltruská, Kateřina; Matolín, Vladimír; Nemšák, Slavomír; Schneider, Claus M.

2018-05-01

We present a study of temperature dependent growth of nano-sized ceria islands on a Cu (100) substrate. Low-energy electron microscopy, micro-electron diffraction, X-ray absorption spectroscopy, and photoemission electron microscopy are used to determine the morphology, shape, chemical state, and crystal structure of the grown islands. Utilizing real-time observation capabilities, we reveal a three-way interaction between the ceria, substrate, and local oxygen chemical potential. The interaction manifests in the reorientation of terrace boundaries on the Cu (100) substrate, characteristic of the transition between oxidized and metallic surface. The reorientation is initiated at nucleation sites of ceria islands, whose growth direction is influenced by the proximity of the terrace boundaries. The grown ceria islands were identified as fully stoichiometric CeO2 (100) surfaces with a (2 × 2) reconstruction.

The role of electron-electron repulsion in the problem of epitaxial graphene on a metal: Simple estimates

NASA Astrophysics Data System (ADS)

Davydov, S. Yu.

2017-08-01

For single-layer graphene placed on a metal substrate, the influence of intra- and interatomic Coulomb repulsion of electrons ( U and G, respectively) on its phase diagram is considered in the framework of an extended Hartree-Fock theory. The general solution of the problem is presented, on the basis of which special cases allowing for analytical consideration are analyzed: free and epitaxial graphene with and without regard for the energy of the electron transition between neighboring atoms of graphene. Three regions of the phase diagram are considered: spin and charge density waves (SDW and CDW, respectively) and the semimetal (SM) state uniform in the spin and charge. The main attention is paid to undoped graphene. It is shown that the allowance for the interaction with a metal substrate expands the SM existence domain. However, in all the considered cases, the boundary between the SDW and CDW states is described by the equation U = zG, where z = 3 is the number of nearest neighbors in graphene. The widening of the SM state region also results from the doping of graphene, and the effect is independent of the sign of free carriers introduced into epitaxial graphene by the substrate. According to estimates made, the only state possible in the buffer layer is the metal-type SM state, whereas, in epitaxial graphene, the CDW state is possible. The influence of temperature on the phase diagram of epitaxial graphene is discussed.

Ambiguous Role of Growth-Induced Defects on the Semiconductor-to-Metal Characteristics in Epitaxial VO2/TiO2 Thin Films.

PubMed

Mihailescu, Cristian N; Symeou, Elli; Svoukis, Efthymios; Negrea, Raluca F; Ghica, Corneliu; Teodorescu, Valentin; Tanase, Liviu C; Negrila, Catalin; Giapintzakis, John

2018-04-25

Controlling the semiconductor-to-metal transition temperature in epitaxial VO 2 thin films remains an unresolved question both at the fundamental as well as the application level. Within the scope of this work, the effects of growth temperature on the structure, chemical composition, interface coherency and electrical characteristics of rutile VO 2 epitaxial thin films grown on TiO 2 substrates are investigated. It is hereby deduced that the transition temperature is lower than the bulk value of 340 K. However, it is found to approach this value as a function of increased growth temperature even though it is accompanied by a contraction along the V 4+ -V 4+ bond direction, the crystallographic c-axis lattice parameter. Additionally, it is demonstrated that films grown at low substrate temperatures exhibit a relaxed state and a strongly reduced transition temperature. It is suggested that, besides thermal and epitaxial strain, growth-induced defects may strongly affect the electronic phase transition. The results of this work reveal the difficulty in extracting the intrinsic material response to strain, when the exact contribution of all strain sources cannot be effectively determined. The findings also bear implications on the limitations in obtaining the recently predicted novel semi-Dirac point phase in VO 2 /TiO 2 multilayer structures.

Reversible switching of fluorophore property based on intrinsic conformational transition of adenylate kinase during its catalytic cycle.

PubMed

Fujii, Akira; Hirota, Shun; Matsuo, Takashi

2013-07-17

Adenylate kinase shows a conformational transition (OPEN and CLOSED forms) during substrate binding and product release to mediate the phosphoryl transfer between ADP and ATP/AMP. The protein motional characteristics will be useful to construct switching systems of fluorophore properties caused by the catalytic cycle of the enzyme. This paper demonstrates in situ reversible switching of a fluorophore property driven by the conformational transition of the enzyme. The pyrene-conjugated mutant adenylate kinase is able to switch the monomer/excimer emission property of pyrene on addition of ADP or P(1)P(5)-di(adenosine-5')pentaphosphate (Ap5A, a transition state analog). The observation under the dilute condition (~0.1 μM) indicates that the emission spectral change was caused by the motion of a protein molecule and not led by protein-protein interactions through π-π stacking of pyrene rings. The switching can be reversibly conducted by using hexokinase-coupling reaction. The fashion of the changes in emission intensities at various ligand concentrations is different between ADP, Mg(2+)-bound ADP, and Mg(2+)-bound Ap5A. The emission property switching is repeatable by a sequential addition of a substrate in a one-pot process. It is proposed that the property of a synthetic molecule on the enzyme surface is switchable in response to the catalytic cycle of adenylate kinase.

Structural phase transitions in SrTiO 3 nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Han; Liu, Sizhan; Scofield, Megan E.

2017-07-31

Pressure dependent structural measurements on monodispersed nanoscale SrTiO3 samples with average diameters of 10 to ~80 nm were conducted to enhance the understanding of the structural phase diagram of nanoscale SrTiO3. A robust pressure independent polar structure was found in the 10 nm sample for pressures up to 13 GPa, while a size dependent cubic to tetragonal transition occurs (at P = Pc) for larger particle sizes. The results suggest that the growth of ~10 nm STO particles on substrates with significant lattice mismatch may maintain a polar state for a large range of strain values, possibly enabling device use.

Nonequilibrium phase transitions, fluctuations and correlations in an active contractile polar fluid.

PubMed

Gowrishankar, Kripa; Rao, Madan

2016-02-21

We study the patterning, fluctuations and correlations of an active polar fluid consisting of contractile polar filaments on a two-dimensional substrate, using a hydrodynamic description. The steady states generically consist of arrays of inward pointing asters and show a continuous transition from a moving lamellar phase, a moving aster street, to a stationary aster lattice with no net polar order. We next study the effect of spatio-temporal athermal noise, parametrized by an active temperature TA, on the stability of the ordered phases. In contrast to its equilibrium counterpart, we find that the active crystal shows true long range order at low TA. On increasing TA, the asters dynamically remodel, concomitantly we find novel phase transitions characterized by bond-orientational and polar order upon "heating".

Design of biomimetic catalysts by molecular imprinting in synthetic polymers: the role of transition state stabilization.

PubMed

Wulff, Günter; Liu, Junqiu

2012-02-21

The impressive efficiency and selectivity of biological catalysts has engendered a long-standing effort to understand the details of enzyme action. It is widely accepted that enzymes accelerate reactions through their steric and electronic complementarity to the reactants in the rate-determining transition states. Thus, tight binding to the transition state of a reactant (rather than to the corresponding substrate) lowers the activation energy of the reaction, providing strong catalytic activity. Debates concerning the fundamentals of enzyme catalysis continue, however, and non-natural enzyme mimics offer important additional insight in this area. Molecular structures that mimic enzymes through the design of a predetermined binding site that stabilizes the transition state of a desired reaction are invaluable in this regard. Catalytic antibodies, which can be quite active when raised against stable transition state analogues of the corresponding reaction, represent particularly successful examples. Recently, synthetic chemistry has begun to match nature's ability to produce antibody-like binding sites with high affinities for the transition state. Thus, synthetic, molecularly imprinted polymers have been engineered to provide enzyme-like specificity and activity, and they now represent a powerful tool for creating highly efficient catalysts. In this Account, we review recent efforts to develop enzyme models through the concept of transition state stabilization. In particular, models for carboxypeptidase A were prepared through the molecular imprinting of synthetic polymers. On the basis of successful experiments with phosphonic esters as templates to arrange amidinium groups in the active site, the method was further improved by combining the concept of transition state stabilization with the introduction of special catalytic moieties, such as metal ions in a defined orientation in the active site. In this way, the imprinted polymers were able to provide both an electrostatic stabilization for the transition state through the amidinium group as well as a synergism of transition state recognition and metal ion catalysis. The result was an excellent catalyst for carbonate hydrolysis. These enzyme mimics represent the most active catalysts ever prepared through the molecular imprinting strategy. Their catalytic activity, catalytic efficiency, and catalytic proficiency clearly surpass those of the corresponding catalytic antibodies. The active structures in natural enzymes evolve within soluble proteins, typically by the refining of the folding of one polypeptide chain. To incorporate these characteristics into synthetic polymers, we used the concept of transition state stabilization to develop soluble, nanosized carboxypeptidase A models using a new polymerization method we term the "post-dilution polymerization method". With this methodology, we were able to prepare soluble, highly cross-linked, single-molecule nanoparticles. These particles have controlled molecular weights (39 kDa, for example) and, on average, one catalytically active site per particle. Our strategies have made it possible to obtain efficient new enzyme models and further advance the structural and functional analogy with natural enzymes. Moreover, this bioinspired design based on molecular imprinting in synthetic polymers offers further support for the concept of transition state stabilization in catalysis.

Use of an Improved Matching Algorithm to Select Scaffolds for Enzyme Design Based on a Complex Active Site Model.

PubMed

Huang, Xiaoqiang; Xue, Jing; Lin, Min; Zhu, Yushan

2016-01-01

Active site preorganization helps native enzymes electrostatically stabilize the transition state better than the ground state for their primary substrates and achieve significant rate enhancement. In this report, we hypothesize that a complex active site model for active site preorganization modeling should help to create preorganized active site design and afford higher starting activities towards target reactions. Our matching algorithm ProdaMatch was improved by invoking effective pruning strategies and the native active sites for ten scaffolds in a benchmark test set were reproduced. The root-mean squared deviations between the matched transition states and those in the crystal structures were < 1.0 Å for the ten scaffolds, and the repacking calculation results showed that 91% of the hydrogen bonds within the active sites are recovered, indicating that the active sites can be preorganized based on the predicted positions of transition states. The application of the complex active site model for de novo enzyme design was evaluated by scaffold selection using a classic catalytic triad motif for the hydrolysis of p-nitrophenyl acetate. Eighty scaffolds were identified from a scaffold library with 1,491 proteins and four scaffolds were native esterase. Furthermore, enzyme design for complicated substrates was investigated for the hydrolysis of cephalexin using scaffold selection based on two different catalytic motifs. Only three scaffolds were identified from the scaffold library by virtue of the classic catalytic triad-based motif. In contrast, 40 scaffolds were identified using a more flexible, but still preorganized catalytic motif, where one scaffold corresponded to the α-amino acid ester hydrolase that catalyzes the hydrolysis and synthesis of cephalexin. Thus, the complex active site modeling approach for de novo enzyme design with the aid of the improved ProdaMatch program is a promising approach for the creation of active sites with high catalytic efficiencies towards target reactions.

Use of an Improved Matching Algorithm to Select Scaffolds for Enzyme Design Based on a Complex Active Site Model

PubMed Central

Huang, Xiaoqiang; Xue, Jing; Lin, Min; Zhu, Yushan

2016-01-01

Active site preorganization helps native enzymes electrostatically stabilize the transition state better than the ground state for their primary substrates and achieve significant rate enhancement. In this report, we hypothesize that a complex active site model for active site preorganization modeling should help to create preorganized active site design and afford higher starting activities towards target reactions. Our matching algorithm ProdaMatch was improved by invoking effective pruning strategies and the native active sites for ten scaffolds in a benchmark test set were reproduced. The root-mean squared deviations between the matched transition states and those in the crystal structures were < 1.0 Å for the ten scaffolds, and the repacking calculation results showed that 91% of the hydrogen bonds within the active sites are recovered, indicating that the active sites can be preorganized based on the predicted positions of transition states. The application of the complex active site model for de novo enzyme design was evaluated by scaffold selection using a classic catalytic triad motif for the hydrolysis of p-nitrophenyl acetate. Eighty scaffolds were identified from a scaffold library with 1,491 proteins and four scaffolds were native esterase. Furthermore, enzyme design for complicated substrates was investigated for the hydrolysis of cephalexin using scaffold selection based on two different catalytic motifs. Only three scaffolds were identified from the scaffold library by virtue of the classic catalytic triad-based motif. In contrast, 40 scaffolds were identified using a more flexible, but still preorganized catalytic motif, where one scaffold corresponded to the α-amino acid ester hydrolase that catalyzes the hydrolysis and synthesis of cephalexin. Thus, the complex active site modeling approach for de novo enzyme design with the aid of the improved ProdaMatch program is a promising approach for the creation of active sites with high catalytic efficiencies towards target reactions. PMID:27243223

Pinning transition in shrinking nanobubbles

NASA Astrophysics Data System (ADS)

Tan, Beng Hau; An, Hongjie; Ohl, Claus-Dieter

Surface nanobubbles are unusually long-lived gaseous domains that form on immersed substrates. Although liquid droplets are known to grow or shrink in either an unpinned (constant contact angle) or a pinned (constant footprint radius) mode, surface nanobubbles have only ever been observed in the pinned state. Theory suggests that, provided the nanobubbles are sustained by supersaturated liquid, they are indefinitely stable in the pinned mode, but rapidly dissolve into bulk liquid if not. Yet many basic aspects of the line pinning are not yet clarified, such as its magnitude or the conditions in which it becomes dominant. In this talk we present experiments with total internal fluorescence microscopy in which nanobubbles nucleated with a temperature difference method initially shrink in an unpinned mode, before transitioning to a pinned state. Using a simple energy balance we recover an estimate for the pinning force on each nanobubble.

Analysis of current-driven oscillatory dynamics of single-layer homoepitaxial islands on crystalline conducting substrates

NASA Astrophysics Data System (ADS)

Dasgupta, Dwaipayan; Kumar, Ashish; Maroudas, Dimitrios

2018-03-01

We report results of a systematic study on the complex oscillatory current-driven dynamics of single-layer homoepitaxial islands on crystalline substrate surfaces and the dependence of this driven dynamical behavior on important physical parameters, including island size, substrate surface orientation, and direction of externally applied electric field. The analysis is based on a nonlinear model of driven island edge morphological evolution that accounts for curvature-driven edge diffusion, edge electromigration, and edge diffusional anisotropy. Using a linear theory of island edge morphological stability, we calculate a critical island size at which the island's equilibrium edge shape becomes unstable, which sets a lower bound for the onset of time-periodic oscillatory dynamical response. Using direct dynamical simulations, we study the edge morphological dynamics of current-driven single-layer islands at larger-than-critical size, and determine the actual island size at which the migrating islands undergo a transition from steady to time-periodic asymptotic states through a subcritical Hopf bifurcation. At the highest symmetry of diffusional anisotropy examined, on {111} surfaces of face-centered cubic crystalline substrates, we find that more complex stable oscillatory states can be reached through period-doubling bifurcation at island sizes larger than those at the Hopf points. We characterize in detail the island morphology and dynamical response at the stable time-periodic asymptotic states, determine the range of stability of these oscillatory states terminated by island breakup, and explain the morphological features of the stable oscillating islands on the basis of linear stability theory.

Phosphoryl transfer reaction snapshots in crystals: Insights into the mechanism of protein kinase a catalytic subunit

DOE PAGES

Das, Amit; Gerlits, Oksana O.; Heller, William T.; ...

2015-06-19

To study the catalytic mechanism of phosphorylation catalyzed by cAMP-dependent protein kinase (PKA) a structure of the enzyme-substrate complex representing the Michaelis complex is of specific interest as it can shed light on the structure of the transition state. However, all previous crystal structures of the Michaelis complex mimics of the PKA catalytic subunit (PKAc) were obtained with either peptide inhibitors or ATP analogs. Here we utilized Ca 2+ ions and sulfur in place of the nucleophilic oxygen in a 20-residue pseudo-substrate peptide (CP20) and ATP to produce a close mimic of the Michaelis complex. In the ternary reactant complex,more » the thiol group of Cys-21 of the peptide is facing Asp-166 and the sulfur atom is positioned for an in-line phosphoryl transfer. Replacement of Ca 2+ cations with Mg 2+ ions resulted in a complex with trapped products of ATP hydrolysis: phosphate ion and ADP. As a result, the present structural results in combination with the previously reported structures of the transition state mimic and phosphorylated product complexes complete the snapshots of the phosphoryl transfer reaction by PKAc, providing us with the most thorough picture of the catalytic mechanism to date.« less

Transition-state characterization: a new approach combining inhibitor analogues and variation in enzyme structure.

PubMed

Phillips, M A; Kaplan, A P; Rutter, W J; Bartlett, P A

1992-02-04

A new strategy of potentially broad application for probing transition-state (TS) analogy in enzymatic systems is described in this paper. The degree to which a series of phosphonate inhibitors act as TS analogues of rat carboxypeptidase A1 has been determined for the wild-type enzyme, for the R127K, R127M, and R127A mutants, and for the R127A mutant in the presence of 0.5 M guanidine hydrochloride. The impact that the mutations have on the inverse second-order rate constants (Km/kcat) for substrate hydrolysis is mirrored by the effect on the inhibition constants (Ki) for the corresponding phosphonate inhibitors. These results demonstrate that the phosphonate moiety mimics some of the electronic as well as the geometric characteristics of the TS. A similar but distinctly separate correlation is observed for tripeptide analogues in comparison to analogues of the dipeptide Cbz-Gly-Phe, reflecting an anomalous mode of binding for the latter system. The selective rate increases and corresponding enhancement in inhibitor binding observed on addition of 0.5 M guanidine hydrochloride to the R127A mutant indicate that the exogenous cation can assume the role played by Arg-127 in stabilizing the TS and in providing substrate selectivity at the P2 position.

Anomalous Elasticity of 4He Films at the Quantum Phase Transition

NASA Astrophysics Data System (ADS)

Shirahama, Keiya; Takahashi, Daisuke; Kogure, Takayuki; Yoshimura, Hitomi; Higashino, Rama

4 He films on solid substrates exhibit a quantum phase transition between localized (nonsuperfluid) and superfluid states by changing coverage n. We have made torsional oscillator (TO) studies for 4He films adsorbed on nanoporous glasses. A TO with localized films showed an apparent ''supersolid'' behavior, an increase in TO frequency f with broad peak in Q-1. Combining with FEM analyses for TO's with different designs, we conclude that the behavior results from the softening of adsorbed 4He films at high temperatures. The features in f and Q-1 are fitted well to a Debye-like activation with a distributed energy gap Δ, so the elasticity is accounted by thermal excitation of localized atoms to an ''extended'' state. As the critical coverage nc approaches the gap decreases to zero with a powerlaw Δ ~(n -nc) 1 . 2 . Assuming that the 4He chemical potential μ (n) is located in the middle of the gap, we can estimate the elastic constant κ-1 =n2 ∂μ / ∂n . The elasticity agrees with shear moduli of 4He films obtained from the FEM analysis within factor of three. The energetics proposed from the elastic behavior naturally explains other properties of He films adsorbed on disordered substrates.

Investigating mycobacterial topoisomerase I mechanism from the analysis of metal and DNA substrate interactions at the active site.

PubMed

Cao, Nan; Tan, Kemin; Annamalai, Thirunavukkarasu; Joachimiak, Andrzej; Tse-Dinh, Yuk-Ching

2018-06-14

We have obtained new crystal structures of Mycobacterium tuberculosis topoisomerase I, including structures with ssDNA substrate bound to the active site, with and without Mg2+ ion present. Significant enzyme conformational changes upon DNA binding place the catalytic tyrosine in a pre-transition state position for cleavage of a specific phosphodiester linkage. Meanwhile, the enzyme/DNA complex with bound Mg2+ ion may represent the post-transition state for religation in the enzyme's multiple-step DNA relaxation catalytic cycle. The first observation of Mg2+ ion coordinated with the TOPRIM residues and DNA phosphate in a type IA topoisomerase active site allows assignment of likely catalytic role for the metal and draws a comparison to the proposed mechanism for type IIA topoisomerases. The critical function of a strictly conserved glutamic acid in the DNA cleavage step was assessed through site-directed mutagenesis. The functions assigned to the observed Mg2+ ion can account for the metal requirement for DNA rejoining but not DNA cleavage by type IA topoisomerases. This work provides new structural insights into a more stringent requirement for DNA rejoining versus cleavage in the catalytic cycle of this essential enzyme, and further establishes the potential for selective interference of DNA rejoining by this validated TB drug target.

Solid-state reaction of iron on β-SiC

NASA Astrophysics Data System (ADS)

Kaplan, R.; Klein, P. H.; Addamiano, A.

1985-07-01

The solid-state reaction between Fe and β-SiC has been studied using Auger-electron and electron-energy-loss spectroscopies and ion sputter profiling. Fe films from submonolayer coverage to 1000 Å thickness were grown in ultrahigh vacuum, and annealed at temperatures up to 550 °C. Auger line-shape changes occurred even for initial Fe coverage at 190 °C, indicating substantial bond alteration in the SiC substrate. A 1000-Å film was largely consumed by reaction with Si and C diffused from the substrate during a 500 °C anneal, and exhibited both Fe silicide and carbide throughout most of its original volume and free C present as graphite primarily at the surface. As an aid in identifying the reaction products studied in this work, Auger line shapes were first determined for the SiLVV peak in Fe silicide and for the CKLL transition in Fe carbide.

Thermopower analysis of the electronic structure around the metal-insulator transition in V1-xWxO2

NASA Astrophysics Data System (ADS)

Katase, Takayoshi; Endo, Kenji; Ohta, Hiromichi

2014-10-01

The electronic structure across the metal-insulator (MI) transition of electron-doped V1-xWxO2 epitaxial films (x =0-0.06) grown on α-Al2O3 substrates was studied by means of thermopower (S) measurements. Significant increase of |S | values accompanied by MI transition was observed, and the transition temperatures of S (TS) decreased with x in a good linear relation with MI transition temperatures. |S| values of V1-xWxO2 films at T>TS were constant at low values of 23μVK-1 independently of x, which reflects a metallic electronic structure, whereas those at T

Method for applying a diffusion barrier interlayer for high temperature components

DOEpatents

Wei, Ronghua; Cheruvu, Narayana S.

2016-03-08

A coated substrate and a method of forming a diffusion barrier coating system between a substrate and a MCrAl coating, including a diffusion barrier coating deposited onto at least a portion of a substrate surface, wherein the diffusion barrier coating comprises a nitride, oxide or carbide of one or more transition metals and/or metalloids and a MCrAl coating, wherein M includes a transition metal or a metalloid, deposited on at least a portion of the diffusion barrier coating, wherein the diffusion barrier coating restricts the inward diffusion of aluminum of the MCrAl coating into the substrate.

Structure of the unliganded form of the proprotein convertase furin suggests activation by a substrate-induced mechanism

PubMed Central

Dahms, Sven O.; Arciniega, Marcelino; Steinmetzer, Torsten; Huber, Robert; Than, Manuel E.

2016-01-01

Proprotein convertases (PCs) are highly specific proteases required for the proteolytic modification of many secreted proteins. An unbalanced activity of these enzymes is connected to pathologies like cancer, atherosclerosis, hypercholesterolaemia, and infectious diseases. Novel protein crystallographic structures of the prototypical PC family member furin in different functional states were determined to 1.8–2.0 Å. These, together with biochemical data and modeling by molecular dynamics calculations, suggest essential elements underlying its unusually high substrate specificity. Furin shows a complex activation mechanism and exists in at least four defined states: (i) the “off state,” incompatible with substrate binding as seen in the unliganded enzyme; (ii) the active “on state” seen in inhibitor-bound furin; and the respective (iii) calcium-free and (iv) calcium-bound forms. The transition from the off to the on state is triggered by ligand binding at subsites S1 to S4 and appears to underlie the preferential recognition of the four-residue sequence motif of furin. The molecular dynamics simulations of the four structural states reflect the experimental observations in general and provide approximations of the respective stabilities. Ligation by calcium at the PC-specific binding site II influences the active-site geometry and determines the rotamer state of the oxyanion hole-forming Asn295, and thus adds a second level of the activity modulation of furin. The described crystal forms and the observations of different defined functional states may foster the development of new tools and strategies for pharmacological intervention targeting furin. PMID:27647913

Hysteresis and change of transition temperature in thin films of Fe([Me{sub 2}Pyrz]{sub 3}BH){sub 2}, a new sublimable spin-crossover molecule

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davesne, V.; Gruber, M.; Physikalisches Institut, Karlsruhe Institute of Technology, Wolfgang-Gaede-Str. 1, 76131 Karlsruhe

2015-05-21

Thin films of the spin-crossover (SCO) molecule Fe([Me{sub 2}Pyrz]{sub 3}BH){sub 2} (Fe-pyrz) were sublimed on Si/SiO{sub 2} and quartz substrates, and their properties investigated by X-ray absorption and photoemission spectroscopies, optical absorption, atomic force microscopy, and superconducting quantum interference device. Contrary to the previously studied Fe(phen){sub 2}(NCS){sub 2}, the films are not smooth but granular. The thin films qualitatively retain the typical SCO properties of the powder sample (SCO, thermal hysteresis, soft X-ray induced excited spin-state trapping, and light induced excited spin-state trapping) but present intriguing variations even in micrometer-thick films: the transition temperature decreases when the thickness is decreased,more » and the hysteresis is affected. We explain this behavior in the light of recent studies focusing on the role of surface energy in the thermodynamics of the spin transition in nano-structures. In the high-spin state at room temperature, the films have a large optical gap (∼5 eV), decreasing at thickness below 50 nm, possibly due to film morphology.« less

A reduced-amide inhibitor of Pin1 binds in a conformation resembling a twisted-amide transition state.

PubMed

Xu, Guoyan G; Zhang, Yan; Mercedes-Camacho, Ana Y; Etzkorn, Felicia A

2011-11-08

The mechanism of the cell cycle regulatory peptidyl prolyl isomerase (PPIase), Pin1, was investigated using reduced-amide inhibitors designed to mimic the twisted-amide transition state. Inhibitors, R-pSer-Ψ[CH(2)N]-Pro-2-(indol-3-yl)ethylamine, 1 [R = fluorenylmethoxycarbonyl (Fmoc)] and 2 (R = Ac), of Pin1 were synthesized and bioassayed. Inhibitor 1 had an IC(50) value of 6.3 μM, which is 4.5-fold better for Pin1 than our comparable ground-state analogue, a cis-amide alkene isostere-containing inhibitor. The change of Fmoc to Ac in 2 improved aqueous solubility for structural determination and resulted in an IC(50) value of 12 μM. The X-ray structure of the complex of 2 bound to Pin1 was determined to 1.76 Å resolution. The structure revealed that the reduced amide adopted a conformation similar to the proposed twisted-amide transition state of Pin1, with a trans-pyrrolidine conformation of the prolyl ring. A similar conformation of substrate would be destabilized relative to the planar amide conformation. Three additional reduced amides, with Thr replacing Ser and l- or d-pipecolate (Pip) replacing Pro, were slightly weaker inhibitors of Pin1.

Visualizing Active-Site Dynamics in Single Crystals of HePTP: Opening of the WPD Loop Involves Coordinated Movement of the E Loop

DOE Office of Scientific and Technical Information (OSTI.GOV)

D Critton; L Tautz; R Page

2011-12-31

Phosphotyrosine hydrolysis by protein tyrosine phosphatases (PTPs) involves substrate binding by the PTP loop and closure over the active site by the WPD loop. The E loop, located immediately adjacent to the PTP and WPD loops, is conserved among human PTPs in both sequence and structure, yet the role of this loop in substrate binding and catalysis is comparatively unexplored. Hematopoietic PTP (HePTP) is a member of the kinase interaction motif (KIM) PTP family. Compared to other PTPs, KIM-PTPs have E loops that are unique in both sequence and structure. In order to understand the role of the E loopmore » in the transition between the closed state and the open state of HePTP, we identified a novel crystal form of HePTP that allowed the closed-state-to-open-state transition to be observed within a single crystal form. These structures, which include the first structure of the HePTP open state, show that the WPD loop adopts an 'atypically open' conformation and, importantly, that ligands can be exchanged at the active site, which is critical for HePTP inhibitor development. These structures also show that tetrahedral oxyanions bind at a novel secondary site and function to coordinate the PTP, WPD, and E loops. Finally, using both structural and kinetic data, we reveal a novel role for E-loop residue Lys182 in enhancing HePTP catalytic activity through its interaction with Asp236 of the WPD loop, providing the first evidence for the coordinated dynamics of the WPD and E loops in the catalytic cycle, which, as we show, is relevant to multiple PTP families.« less

Indium selenide monolayer: strain-enhanced optoelectronic response and dielectric environment-tunable 2D exciton features

NASA Astrophysics Data System (ADS)

Ben Amara, Imen; Hichri, Aida; Jaziri, Sihem

2017-12-01

Electronic and optical performances of the β-InSe monolayer (ML) are considerably boosted by tuning the corresponding band energies through lattice in-plane compressive strain engineering. First principles calculations show an indirect-direct gap transition with a large bandgap size. The crossover is due to different responses of the near-gap state energies with respect to strain. This is explained by the variation of In-Se bond length, the bond nature of near-band-edge electronic orbital and of the momentum angular contribution versus in-plane compressive strain. The effective masses of charge carriers are also found to be highly modulated and significantly light at the indirect-direct-gap transition. The tuned optical response of the resulting direct-gap ML β-InSe is evaluated versus applied energy to infer the allowed optical transitions, dielectric constants, semiconductor-metal behavior and refractive index. The environmental dielectric engineering of exciton behavior of the resulting direct-gap ML β-InSe is handled within the effective mass Wannier-Mott model and is expected to be important. Our results highlight the increase of binding energy and red-shifted exciton energy with decreasing screening substrates, resulting in a stable exciton at room temperature. The intensity and energy of the ground-state exciton emission are expected to be strongly influenced under substrate screening effect. According to our findings, the direct-gap ML β-InSe assures tremendous 2D optoelectronic and nanoelectronic merits that could overcome several limitations of unstrained ML β-InSe.

Real-time observation of the conformational dynamics of mitochondrial Hsp70 by spFRET.

PubMed

Sikor, Martin; Mapa, Koyeli; von Voithenberg, Lena Voith; Mokranjac, Dejana; Lamb, Don C

2013-05-29

The numerous functions of the important class of molecular chaperones, heat shock proteins 70 (Hsp70), rely on cycles of intricate conformational changes driven by ATP-hydrolysis and regulated by cochaperones and substrates. Here, we used Förster resonance energy transfer to study the conformational dynamics of individual molecules of Ssc1, a mitochondrial Hsp70, in real time. The intrinsic dynamics of the substrate-binding domain of Ssc1 was observed to be uncoupled from the dynamic interactions between substrate- and nucleotide-binding domains. Analysis of the fluctuations in the interdomain separation revealed frequent transitions to a nucleotide-free state. The nucleotide-exchange factor Mge1 did not induce ADP release, as expected, but rather facilitated binding of ATP. These results indicate that the conformational cycle of Ssc1 is more elaborate than previously thought and provide insight into how the Hsp70s can perform a wide variety of functions.

Heat-sink free CW operation of injection microdisk lasers grown on Si substrate with emission wavelength beyond 1.3  μm.

PubMed

Kryzhanovskaya, Natalia; Moiseev, Eduard; Polubavkina, Yulia; Maximov, Mikhail; Kulagina, Marina; Troshkov, Sergey; Zadiranov, Yury; Guseva, Yulia; Lipovskii, Andrey; Tang, Mingchu; Liao, Mengya; Wu, Jiang; Chen, Siming; Liu, Huiyun; Zhukov, Alexey

2017-09-01

High-performance injection microdisk (MD) lasers grown on Si substrate are demonstrated for the first time, to the best of our knowledge. Continuous-wave (CW) lasing in microlasers with diameters from 14 to 30 μm is achieved at room temperature. The minimal threshold current density of 600  A/cm 2 (room temperature, CW regime, heatsink-free uncooled operation) is comparable to that of high-quality MD lasers on GaAs substrates. Microlasers on silicon emit in the wavelength range of 1320-1350 nm via the ground state transition of InAs/InGaAs/GaAs quantum dots. The high stability of the lasing wavelength (dλ/dI=0.1  nm/mA) and the low specific thermal resistance of 4×10 -3 °C×cm 2 /W are demonstrated.

Effect of tacticity on the structure and glass transition temperature of polystyrene adsorbed onto solid surfaces

NASA Astrophysics Data System (ADS)

Negash, Solomon; Tatek, Yergou B.; Tsige, Mesfin

2018-04-01

We have carried out atomistic (all-atom) molecular dynamics simulations to investigate the effect of tacticity on the structure and glass transition temperature (Tg) of polystyrene (PS) thin films adsorbed on two distinct types of solid substrates. The systems consist of thin films made of atactic, isotactic, and syndiotactic PS chains supported by graphite or hydroxylated α-quartz substrates, which are known to be atomically flat but chemically and structurally different. We have observed a marked dependence of the film structure on substrate type as well as on tacticity. For instance, rings' orientation near substrate surfaces depends on substrate type for atactic PS and isotactic PS films, while no such dependence is observed for syndiotactic PS films whose interfacial structure seems to result from their propensity to adopt the trans conformation rather than their specific interaction with the substrates. Moreover, our results indicate that glass transition temperatures of substrate supported polystyrene films are higher compared to those of the corresponding free-standing films. More specifically, PS films on graphite exhibit larger Tg values than those on α-quartz, and we have noticed that syndiotactic PS has the largest Tg irrespective of the substrate type. Furthermore, the local Tg in the region of the film in contact with the substrates shows a strong tacticity and substrate dependence, whereas no dependencies were found for the local Tg in the middle of the film. Substrate-film interaction energy and chains' dynamics near substrate-film interfaces were subsequently investigated in order to substantiate the obtained Tgs, and it was found that films with higher Tgs are strongly adsorbed on the substrates and/or exhibit smaller interfacial chains' dynamics essentially due to steric hindrance.

Zipping and Unzipping of Adenylate Kinase: Atomistic Insights into the Ensemble of Open ↔ Closed Transitions

PubMed Central

Beckstein, Oliver; Denning, Elizabeth J.; Perilla, Juan R.; Woolf, Thomas B.

2009-01-01

Adenylate kinase (AdK), a phosphotransferase enzyme, plays an important role in cellular energy homeostasis. It undergoes a large conformational change between an open and a closed state, even in the absence of substrate. We investigate the apo-AdK transition at the atomic level both with free energy calculations and our new dynamic importance sampling (DIMS) molecular dynamics (MD) method. DIMS is shown to sample biologically relevant conformations as verified by comparing an ensemble of hundreds of DIMS transitions to AdK crystal structure intermediates. The simulations reveal in atomic detail how hinge regions partially and intermittently unfold during the transition. Conserved salt bridges are seen to have important structural and dynamic roles; in particular four ionic bonds are identified that open in a sequential, zipper-like fashion and thus dominate the free energy landscape of the transition. Transitions between the closed and open conformations only have to overcome moderate free energy barriers. Unexpectedly, the closed and open state encompass broad free energy basins that contain conformations differing in domain hinge motions by up to 40°. The significance of these extended states is discussed in relation to recent experimental FRET measurements. Taken together, these results demonstrate how a small number of cooperative key interactions can shape the overall dynamics of an enzyme and suggest an “all-or-nothing” mechanism for the opening and closing of AdK. Our efficient DIMS-MD computer simulation approach can provide a detailed picture of a functionally important macromolecular transition and thus help to interpret and suggest experiments to probe the conformational landscape of dynamic proteins such as AdK. PMID:19751742

Role of interfacial transition layers in VO2/Al2O3 heterostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Honghui; Chisholm, Matthew F; Yang, Tsung-Han

2011-01-01

Epitaxial VO2 films grown by pulsed laser deposition (PLD) on c-cut sapphire substrates ((0001) Al2O3) were studied by aberration-corrected scanning transmission electron microscopy (STEM). A number of film/substrate orientation relationships were found and are discussed in the context of the semiconductor-metal transition (SMT) characteristics. A structurally and electronically modified buffer layer was revealed on the interface and was attributed to the interface free-energy minimization process of accommodating the symmetry mismatch between the substrate and the film. This interfacial transition layer is expected to affect the SMT behavior when the interfacial region is a significant fraction of the VO2 film thickness.

Dynamic-compliance and viscosity of PET and PEN

NASA Astrophysics Data System (ADS)

Weick, Brian L.

2016-05-01

Complex dynamic-compliance and in-phase dynamic-viscosity data are presented and analyzed for PET and PEN advanced polyester substrates used for magnetic tapes. Frequency-temperature superposition is used to predict long-term behavior. Temperature and frequency ranges for the primary glass transition and secondary transitions are discussed and compared for PET and PEN. Shift factors from frequency-temperature superposition are used to determine activation energies for the transitions, and WLF parameters are determined for the polyester substrates.

Dynamic-compliance and viscosity of PET and PEN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weick, Brian L.

Complex dynamic-compliance and in-phase dynamic-viscosity data are presented and analyzed for PET and PEN advanced polyester substrates used for magnetic tapes. Frequency-temperature superposition is used to predict long-term behavior. Temperature and frequency ranges for the primary glass transition and secondary transitions are discussed and compared for PET and PEN. Shift factors from frequency-temperature superposition are used to determine activation energies for the transitions, and WLF parameters are determined for the polyester substrates.

Effects of different binders on microstructure and phase composition of hydroxyapatite Nd-YAG laser clad coatings

NASA Astrophysics Data System (ADS)

Chien, C. S.; Hong, T. F.; Han, T. J.; Kuo, T. Y.; Liao, T. Y.

2011-01-01

The laser clad coating technique can help to produce metallurgical bonding with high bonding strength between the coating layer and the substrate, which has been gradually applied for hydroxyapatite (HA) coating on metallic substrates. In this study, HA powder is mixed with two different binders, namely water glass (WG) and polyvinyl alcohol (PVA), respectively, and is then clad on Ti-6Al-4V substrates using an Nd:YAG laser system under various processing conditions. The microstructure, chemical composition and hardness of the coating layer and transition layer of the various samples are then systematically explored. The experimental results show that the coating layers of the various samples all contain both cellular dendrites and rod-like piled structures, while the transition layers contain only cellular dendrites. For all samples, the coating layer consists mostly of CaTiO 3, Ca 2P 2O 7, CaO and HA phases, whereas the transition layer contains primarily CaTiO 3, Ca 2P 2O 7, Ti 3P, Ti and HA phases. In addition, the transition layer of the WG samples also contains SiO 2 and Si 2Ti phases. In all of the specimens, the transition layer has a higher average hardness than the substrate or coating layer. Moreover, the transition layer in the WG sample is harder than that in the PVA sample.

Structure-based Insights into the Catalytic Power and Conformational Dexterity of Peroxiredoxins

PubMed Central

Hall, Andrea; Nelson, Kimberly; Poole, Leslie B.

2011-01-01

Abstract Peroxiredoxins (Prxs), some of nature's dominant peroxidases, use a conserved Cys residue to reduce peroxides. They are highly expressed in organisms from all kingdoms, and in eukaryotes they participate in hydrogen peroxide signaling. Seventy-two Prx structures have been determined that cover much of the diversity of the family. We review here the current knowledge and show that Prxs can be effectively classified by a structural/evolutionary organization into six subfamilies followed by specification of a 1-Cys or 2-Cys mechanism, and for 2-Cys Prxs, the structural location of the resolving Cys. We visualize the varied catalytic structural transitions and highlight how they differ depending on the location of the resolving Cys. We also review new insights into the question of how Prxs are such effective catalysts: the enzyme activates not only the conserved Cys thiolate but also the peroxide substrate. Moreover, the hydrogen-bonding network created by the four residues conserved in all Prx active sites stabilizes the transition state of the peroxidatic SN2 displacement reaction. Strict conservation of the peroxidatic active site along with the variation in structural transitions provides a fascinating picture of how the diverse Prxs function to break down peroxide substrates rapidly. Antioxid. Redox Signal. 15, 795–815. PMID:20969484

Quantification of substrate and cellular strains in stretchable 3D cell cultures: an experimental and computational framework.

PubMed

González-Avalos, P; Mürnseer, M; Deeg, J; Bachmann, A; Spatz, J; Dooley, S; Eils, R; Gladilin, E

2017-05-01

The mechanical cell environment is a key regulator of biological processes . In living tissues, cells are embedded into the 3D extracellular matrix and permanently exposed to mechanical forces. Quantification of the cellular strain state in a 3D matrix is therefore the first step towards understanding how physical cues determine single cell and multicellular behaviour. The majority of cell assays are, however, based on 2D cell cultures that lack many essential features of the in vivo cellular environment. Furthermore, nondestructive measurement of substrate and cellular mechanics requires appropriate computational tools for microscopic image analysis and interpretation. Here, we present an experimental and computational framework for generation and quantification of the cellular strain state in 3D cell cultures using a combination of 3D substrate stretcher, multichannel microscopic imaging and computational image analysis. The 3D substrate stretcher enables deformation of living cells embedded in bead-labelled 3D collagen hydrogels. Local substrate and cell deformations are determined by tracking displacement of fluorescent beads with subsequent finite element interpolation of cell strains over a tetrahedral tessellation. In this feasibility study, we debate diverse aspects of deformable 3D culture construction, quantification and evaluation, and present an example of its application for quantitative analysis of a cellular model system based on primary mouse hepatocytes undergoing transforming growth factor (TGF-β) induced epithelial-to-mesenchymal transition. © 2017 The Authors. Journal of Microscopy published by JohnWiley & Sons Ltd on behalf of Royal Microscopical Society.

A simulation study on the constancy of cardiac energy metabolites during workload transition.

PubMed

Saito, Ryuta; Takeuchi, Ayako; Himeno, Yukiko; Inagaki, Nobuya; Matsuoka, Satoshi

2016-12-01

The cardiac energy metabolites such as ATP, phosphocreatine, ADP and NADH are kept relatively constant during physiological cardiac workload transition. How this is accomplished is not yet clarified, though Ca 2+ has been suggested to be one of the possible mechanisms. We constructed a detailed mathematical model of cardiac mitochondria based on experimental data and studied whether known Ca 2+ -dependent regulation mechanisms play roles in the metabolite constancy. Model simulations revealed that the Ca 2+ -dependent regulation mechanisms have important roles under the in vitro condition of isolated mitochondria where malate and glutamate were mitochondrial substrates, while they have only a minor role and the composition of substrates has marked influence on the metabolite constancy during workload transition under the simulated in vivo condition where many substrates exist. These results help us understand the regulation mechanisms of cardiac energy metabolism during physiological cardiac workload transition. The cardiac energy metabolites such as ATP, phosphocreatine, ADP and NADH are kept relatively constant over a wide range of cardiac workload, though the mechanisms are not yet clarified. One possible regulator of mitochondrial metabolism is Ca 2+ , because it activates several mitochondrial enzymes and transporters. Here we constructed a mathematical model of cardiac mitochondria, including oxidative phosphorylation, substrate metabolism and ion/substrate transporters, based on experimental data, and studied whether the Ca 2+ -dependent activation mechanisms play roles in metabolite constancy. Under the in vitro condition of isolated mitochondria, where malate and glutamate were used as mitochondrial substrates, the model well reproduced the Ca 2+ and inorganic phosphate (P i ) dependences of oxygen consumption, NADH level and mitochondrial membrane potential. The Ca 2+ -dependent activations of the aspartate/glutamate carrier and the F 1 F o -ATPase, and the P i -dependent activation of Complex III were key factors in reproducing the experimental data. When the mitochondrial model was implemented in a simple cardiac cell model, simulation of workload transition revealed that cytoplasmic Ca 2+ concentration ([Ca 2+ ] cyt ) within the physiological range markedly increased NADH level. However, the addition of pyruvate or citrate attenuated the Ca 2+ dependence of NADH during the workload transition. Under the simulated in vivo condition where malate, glutamate, pyruvate, citrate and 2-oxoglutarate were used as mitochondrial substrates, the energy metabolites were more stable during the workload transition and NADH level was almost insensitive to [Ca 2+ ] cyt . It was revealed that mitochondrial substrates have a significant influence on metabolite constancy during cardiac workload transition, and Ca 2+ has only a minor role under physiological conditions. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Intersubband absorption of p-type wurtzite GaN/AlN quantum well for fiber-optics telecommunication

NASA Astrophysics Data System (ADS)

Park, Seoung-Hwan; Ahn, Doyeol; Park, Chan-Yong

2017-11-01

The intersubband transition of wurtzite (WZ) p-type GaN/AlN quantum well (QW) structures grown on GaN substrate was investigated theoretically using the multiband effective-mass theory. The peak value of the TE-polarization absorption spectrum is found to be similar to that of the TM-polarization absorption spectrum. The absorption coefficients for TE- and TM-polarizations are mainly attributed to the absorption from the ground state (m1 = 1) because holes are mainly confined in ground states near the band-edge in an investigated range of the carrier density. We observe that a transition wavelength of 1.55 μm can be obtained for the QW structure with a relatively thin (˜16 Å) well width. Thus, we expect that a p-type WZ AlN/GaN heterostructure is applicable for a photodetector application for fiber-optic communications with normal incidence of wave.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Menges, F.; Spieser, M.; Riel, H.

The thermal radiative near field transport between vanadium dioxide and silicon oxide at submicron distances is expected to exhibit a strong dependence on the state of vanadium dioxide which undergoes a metal-insulator transition near room temperature. We report the measurement of near field thermal transport between a heated silicon oxide micro-sphere and a vanadium dioxide thin film on a titanium oxide (rutile) substrate. The temperatures of the 15 nm vanadium dioxide thin film varied to be below and above the metal-insulator-transition, and the sphere temperatures were varied in a range between 100 and 200 °C. The measurements were performed using a vacuum-basedmore » scanning thermal microscope with a cantilevered resistive thermal sensor. We observe a thermal conductivity per unit area between the sphere and the film with a distance dependence following a power law trend and a conductance contrast larger than 2 for the two different phase states of the film.« less

Structural phase transitions in SrTiO 3 nanoparticles

DOE PAGES

Zhang, Han; Liu, Sizhan; Scofield, Megan E.; ...

2017-08-04

We present that pressure dependent structural measurements on monodispersed nanoscale SrTiO 3 samples with average diameters of 10 to ~80 nm were conducted to enhance the understanding of the structural phase diagram of nanoscale SrTiO 3. A robust pressure independent polar structure was found in the 10 nm sample for pressures up to 13 GPa, while a size dependent cubic to tetragonal transition occurs (at P = P c) for larger particle sizes. In conclusion, the results suggest that the growth of ~10 nm STO particles on substrates with significant lattice mismatch may maintain a polar state for a largemore » range of strain values, possibly enabling device use.« less

Engineering Electronic Properties of Strongly Correlated Metal Thin Films

NASA Astrophysics Data System (ADS)

Eaton, Craig

This dissertation reports on advances in synthesis and characterization of high quality perovskite metals with strong electron correlation. These materials have attracted considerable attention for their potential application as an active electronic material in logic applications utilizing the Mott type metal-to-insulator transition. CaVO3 and SrVO3 correlated metal oxide films have been grown by hybrid-molecular beam epitaxy (MBE), where alkaline earth cations are supplied using a conventional effusion cell and the transition metal vanadium is supplied using the metal-organic precursor vanadium (V) oxytriisopropoxide. Oxygen is available in both molecular and remote plasma activated forms. Titanate-based band insulators, namely SrTiO3 and CaTiO3, have also been grown using titanium tetra-isopropoxide as metal-organic precursor. The grown films have been characterized using reflection high energy electron diffraction (RHEED), X-ray diffraction (XRD), atomic force microscopy (AFM), transition electron microscopy (TEM), and electrical properties have been determined using temperature dependent resistivity and Hall measurements. Optimized films exhibit high quality Kiessig fringes, with substrate limited rocking curve widths of 8 arc seconds in the case of CaVO3 and 17 arc seconds in the case of SrVO3. Both vanadate films grew in a step-flow mode with atomic steps visible after growth by AFM. In SrVO3, the perovskite phase remained present with a gradual lattice expansion away from the optimal cation flux ratio. For CaVO3, the films remained phase pure and with little change in lattice parameter throughout a growth window that spanned a 30% range in cation flux ratios. While an abrupt increase of lattice parameter was found for CaVO3 films grown under Carich conditions, films grown under V-rich conditions revealed a gradual reduction in lattice parameter, in contrast to SrVO3 where all defects have been shown to increase unit cell volume. Low resistivity and high residual resistivity ration complex vanadate thin films have been demonstrated. Methods for growing minimally strained SrVO3 films on (LaAlO 3)0.3(Sr2AlTaO6)0.7 substrates (0.7% tensile) were expanded to other substrates with different lattice mismatches, namely SrTiO3 (1.8% tensile) and LaAlO3 (1.3% compressive). Varying strain modifies bond angles or overlap, and can give rise to an insulating ground state. Changes in the film surface morphology derived from atomic force microscopy (AFM) was used to discriminate optimal growth conditions on each substrate. Films grown at each strain state remain strongly metallic at 10 nm thickness. Low temperature resistivity measurements, which demonstrates a marked increase in low temperature resistivity with respect to those films grown at optimized growth parameters, were found to be substrate dependent. The thickness of films grown on SrTiO3 are optimized for maximum thickness without cracking. Use of epitaxial strain as a mechanism for enabling a Mott transition was not demonstrated at strains and conditions attempted within this study. The experimental support of this hypothesis could not be experimentally confirmed within the range of strains studied here. Finally, high quality epitaxial SrTiO3-SrVO3-SrTiO 3 heterostructures are grown on (LaAlO3)0.3(Sr 2AlTaO6)0.7 substrates by hybrid MBE. RHEED, XRD, and TEM showed that these structures are of high structural quality, with atomically and chemically abrupt interfaces. By fixing the thickness of the SrTiO3 confinement layers to be 15 nm and decreasing the thickness of the SrVO3 from 50 nm down to 1.2 nm, it has been demonstrated that the system transitions from a strongly-correlated metal to an insulating state, as shown by temperature dependent resistivity and carrier concentration measurements. For films with thickness larger than 1.2 nm, the resistivity versus temperature is described by Fermi liquid behavior. Below this critical thickness the material undergoes an electronic phase transition into a variable-range hopping insulating phase. The results of this dissertation show that high quality vanadate thin films can be grown by hybrid MBE. Their electronic ground state, metallic in the bulk phase, can be effectively changed using geometrical confinement, while epitaxial strain was found to have a negligible effect. The ability to grow CaVO3 in a self-regulated fashion holds promise that the favorable growth kinetics in hybrid MBE might be a general characteristic of the metalorganic precursor employed.

The behavior of commensurate-incommensurate transitions using the phase field crystal model

NASA Astrophysics Data System (ADS)

Zhang, Tinghui; Lu, Yanli; Chen, Zheng

2018-02-01

We study the behavior of the commensurate-incommensurate (CI) transitions by using a phase field crystal model. The model is capable of modeling both elastic and plastic deformation and can simulate the evolution of the microstructure of the material at the atomic scale and the diffusive time scale, such as for adsorbed monolayer. Specifically, we study the behavior of the CI transitions as a function of lattice mismatch and the amplitude of substrate pinning potential. The behavior of CI phase transitions is revealed with the increase of the amplitude of pinning potential in some certain lattice mismatches. We find that for the negative lattice mismatch absorbed monolayer undergoes division, reorganization and displacement as increasing the amplitude of substrate pinning potential. In addition, for the positive mismatch absorbed monolayer undergoes a progress of phase transformation after a complete grain is split. Our results accord with simulations for atomic models of absorbed monolayer on a substrate surface.

Photoluminescence properties of Eu3+ doped HfO2 coatings formed by plasma electrolytic oxidation of hafnium

NASA Astrophysics Data System (ADS)

Stojadinović, Stevan; Tadić, Nenad; Ćirić, Aleksandar; Vasilić, Rastko

2018-03-01

Plasma electrolytic oxidation was used for synthesis of Eu3+ doped monoclinic HfO2 coatings on hafnium substrate. Results of photoluminescence (PL) measurements show the existence of two distinct regions: one that is related to the blue emission originating from oxygen vacancy defects in HfO2 and the other one characterized with a series of sharp orange-red emission peaks related to f-f transitions of Eu3+ from excited level 5D0 to lower levels 7FJ (J = 0, 1, 2, 3, and 4). PL peaks appearing in excitation spectra of obtained coatings are attributed either to charge transfer state of Eu3+ or to direct excitation of the Eu3+ ground state 7F0 into higher levels of the 4f-manifold. PL of formed coatings increases with PEO time due to an increase of oxygen vacancy defects and the content of Eu3+. Acquired experimental data suggest that hypersensitive electrical dipole transition is much more intense than the magnetic dipole transition, indicating that Eu3+ ions occupy a non-inversion symmetry sites.

Dynamically achieved active site precision in enzyme catalysis.

PubMed

Klinman, Judith P

2015-02-17

CONSPECTUS: The grand challenge in enzymology is to define and understand all of the parameters that contribute to enzymes' enormous rate accelerations. The property of hydrogen tunneling in enzyme reactions has moved the focus of research away from an exclusive focus on transition state stabilization toward the importance of the motions of the heavy atoms of the protein, a role for reduced barrier width in catalysis, and the sampling of a protein conformational landscape to achieve a family of protein substates that optimize enzyme-substrate interactions and beyond. This Account focuses on a thermophilic alcohol dehydrogenase for which the chemical step of hydride transfer is rate determining across a wide range of experimental conditions. The properties of the chemical coordinate have been probed using kinetic isotope effects, indicating a transition in behavior below 30 °C that distinguishes nonoptimal from optimal C-H activation. Further, the introduction of single site mutants has the impact of either enhancing or eliminating the temperature dependent transition in catalysis. Biophysical probes, which include time dependent hydrogen/deuterium exchange and fluorescent lifetimes and Stokes shifts, have also been pursued. These studies allow the correlation of spatially resolved transitions in protein motions with catalysis. It is now possible to define a long-range network of protein motions in ht-ADH that extends from a dimer interface to the substrate binding domain across to the cofactor binding domain, over a distance of ca. 30 Å. The ongoing challenge to obtaining spatial and temporal resolution of catalysis-linked protein motions is discussed.

Impact-Induced Glass Transition in Elastomeric Coatings

NASA Astrophysics Data System (ADS)

Roland, C. M.

2013-03-01

When an elastomer layer is applied to the front surface of steel, the resistance to penetration by hard projectiles increases significantly. It is not obvious why a soft polymer should affect this property of metals, and most rubbers do not. However, we have found that a few are very effective; the requirement is that the polymer undergo a viscoelastic phase transition upon impact. This means that the frequency of its segmental dynamics correspond to the impact frequency. The latter is estimated as the ratio of the projectile velocity to the coating thickness, and is on the order of 105 s-1 for the experiments herein. Our data and a non-linear dynamics finite-element analysis offer support for this resonance condition as a primary mechanism underlying the penetration-resistance of elastomer-coated metal substrates. The impact-induced phase transition causes large energy absorption, decreasing the kinetic energy of the impacting projectile. However, this energy absorption only accounts for about half the enhanced stopping power of the elastomer/steel bilayer. An additional mechanism is lateral spreading of the impact force, resulting from the transient hardening of the elastomeric during its transition to the glassy state - the modulus of the rubber increases 1000-fold over a time period of microseconds. The penetration-resistance is a very nonlinear function of the coating thickness. Moreover, tests on various metals show that hardness is the principal substrate parameter controlling the contribution of the coating. This work was supported by the Office of Naval Research.

Preparation and modification of VO2 thin film on R-sapphire substrate by rapid thermal process

NASA Astrophysics Data System (ADS)

Zhu, Nai-Wei; Hu, Ming; Xia, Xiao-Xu; Wei, Xiao-Ying; Liang, Ji-Ran

2014-04-01

The VO2 thin film with high performance of metal-insulator transition (MIT) is prepared on R-sapphire substrate for the first time by magnetron sputtering with rapid thermal process (RTP). The electrical characteristic and THz transmittance of MIT in VO2 film are studied by four-point probe method and THz time domain spectrum (THz-TDS). X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and search engine marketing (SEM) are employed to analyze the crystalline structure, valence state, surface morphology of the film. Results indicate that the properties of VO2 film which is oxidized from the metal vanadium film in oxygen atmosphere are improved with a follow-up RTP modification in nitrogen atmosphere. The crystallization and components of VO2 film are improved and the film becomes compact and uniform. A better phase transition performance is shown that the resistance changes nearly 3 orders of magnitude with a 2-°C hysteresis width and the THz transmittances are reduced by 64% and 60% in thermal and optical excitation respectively.

Dielectric response and structure of in-plane tensile strained BaTiO3 thin films grown on the LaNiO3 buffered Si substrate

NASA Astrophysics Data System (ADS)

Qiao, Liang; Bi, Xiaofang

2008-02-01

Highly (001)-textured BaTiO3 films were grown epitaxially on the LaNiO3 buffered Si substrate. A strong in-plane tensile strain has been revealed by using x-ray diffraction and high resolution transmission electron microscopy. The BaTiO3 film has exhibited a small remnant polarization, indicating the presence of ca1/ca2/ca1/ca2 polydomain state in the film. Temperature dependent dielectric permittivity has demonstrated that two phase transitions occurred at respective temperatures of 170 and 30°C. The result was discussed in detail based on the misfit strain-temperature phase diagrams theory.

Dissecting the Catalytic Mechanism of Betaine-Homocysteine S-Methyltransferase Using Intrinsic Tryptophan Fluorescence and Site-Directed Mutagenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castro, C.; Gratson, A.A.; Evans, J.C.

2010-03-05

Betaine-homocysteine S-methyltransferase (BHMT) is a zinc-dependent enzyme that catalyzes the transfer of a methyl group from glycine betaine (Bet) to homocysteine (Hcy) to form dimethylglycine (DMG) and methionine (Met). Previous studies in other laboratories have indicated that catalysis proceeds through the formation of a ternary complex, with a transition state mimicked by the inhibitor S-({delta}-carboxybutyl)-l-homocysteine (CBHcy). Using changes in intrinsic tryptophan fluorescence to determine the affinity of human BHMT for substrates, products, or CBHcy, we now demonstrate that the enzyme-substrate complex reaches its transition state through an ordered bi-bi mechanism in which Hcy is the first substrate to bind andmore » Met is the last product released. Hcy, Met, and CBHcy bind to the enzyme to form binary complexes with K{sub d} values of 7.9, 6.9, and 0.28 {micro}M, respectively. Binary complexes with Bet and DMG cannot be detected with fluorescence as a probe, but Bet and DMG bind tightly to BHMT-Hcy to form ternary complexes with K{sub d} values of 1.1 and 0.73 {micro}M, respectively. Mutation of each of the seven tryptophan residues in human BHMT provides evidence that the enzyme undergoes two distinct conformational changes that are reflected in the fluorescence of the enzyme. The first is induced when Hcy binds, and the second, when Bet binds. As predicted by the crystal structure of BHMT, the amino acids Trp44 and Tyr160 are involved in binding Bet, and Glu159 in binding Hcy. Replacing these residues by site-directed mutagenesis significantly reduces the catalytic efficiency (V{sub max}/K{sub m}) of the enzyme. Replacing Tyr77 with Phe abolishes enzyme activity.« less

Enzyme activation through the utilization of intrinsic dianion binding energy.

PubMed

Amyes, T L; Malabanan, M M; Zhai, X; Reyes, A C; Richard, J P

2017-03-01

We consider 'the proposition that the intrinsic binding energy that results from the noncovalent interaction of a specific substrate with the active site of the enzyme is considerably larger than is generally believed. An important part of this binding energy may be utilized to provide the driving force for catalysis, so that the observed binding energy represents only what is left over after this utilization' [Jencks,W.P. (1975) Adv. Enzymol. Relat. Areas. Mol. Biol. , , 219-410]. The large ~12 kcal/mol intrinsic substrate phosphodianion binding energy for reactions catalyzed by triosephosphate isomerase (TIM), orotidine 5'-monophosphate decarboxylase and glycerol-3-phosphate dehydrogenase is divided into 4-6 kcal/mol binding energy that is expressed on the formation of the Michaelis complex in anchoring substrates to the respective enzyme, and 6-8 kcal/mol binding energy that is specifically expressed at the transition state in activating the respective enzymes for catalysis. A structure-based mechanism is described where the dianion binding energy drives a conformational change that activates these enzymes for catalysis. Phosphite dianion plays the active role of holding TIM in a high-energy closed active form, but acts as passive spectator in showing no effect on transition-state structure. The result of studies on mutant enzymes is presented, which support the proposal that the dianion-driven enzyme conformational change plays a role in enhancing the basicity of side chain of E167, the catalytic base, by clamping the base between a pair of hydrophobic side chains. The insight these results provide into the architecture of enzyme active sites and the development of strategies for the de novo design of protein catalysts is discussed. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Substrate induced changes in atomically thin 2-dimensional semiconductors: Fundamentals, engineering, and applications

NASA Astrophysics Data System (ADS)

Sun, Yinghui; Wang, Rongming; Liu, Kai

2017-03-01

Substrate has great influences on materials syntheses, properties, and applications. The influences are particularly crucial for atomically thin 2-dimensional (2D) semiconductors. Their thicknesses are less than 1 nm; however, the lateral sizes can reach up to several inches or more. Therefore, these materials must be placed onto a variety of substrates before subsequent post-processing techniques for final electronic or optoelectronic devices. Recent studies reveal that substrates have been employed as ways to modulate the optical, electrical, mechanical, and chemical properties of 2D semiconductors. In this review, we summarize recent progress upon the effects of substrates on properties of 2D semiconductors, mostly focused on 2D transition metal dichalcogenides, through viewpoints of both fundamental physics and device applications. First, we discuss various effects of substrates, including interface strain, charge transfer, dielectric screening, and optical interference. Second, we show the modulation of 2D semiconductors by substrate engineering, including novel substrates (patterned substrates, 2D-material substrates, etc.) and active substrates (phase transition materials, ferroelectric materials, flexible substrates, etc.). Last, we present prospectives and challenges in this research field. This review provides a comprehensive understanding of the substrate effects, and may inspire new ideas of novel 2D devices based on substrate engineering.

Pattern zoology in biaxially pre-stretched elastic bilayers: from wrinkles and creases to fracture-like ridges

NASA Astrophysics Data System (ADS)

Al-Rashed, Rashed; Lopez JiméNez, Francisco; Reis, Pedro

The wrinkling of elastic bilayers under compression has been explored as a method to produce reversible surface topography, with applications ranging from microfluidics to tunable optics. We introduce a new experimental system to study the effects of pre-stretching on the instability patterns that result from the biaxial compression of thin shells bound to an elastic substrate. A pre-stretched substrate is first prepared by pressurizing an initially flat elastomeric disk and bulging it into a nearly hemispherical thick shell. The substrate is then coated with a thin layer of a polymer suspension, which, upon curing, results in a thin shell of nearly constant thickness. Releasing the pre-stretch in the substrate by deflating the system places the outer film in a state of biaxial compression, resulting in a variety of buckling patterns. We explore the parameter space by systematically varying the pre-stretch, the substrate/film stiffness mismatch, and the thickness of the film. This results in a continuous transition between different buckling patterns, from the dimples and wrinkles that are traditionally associated with the buckling of elastic bilayers, to creases and high aspect ratio `fracture-like' ridges, where the pre-stretch plays an essential role.

Statistical properties of fluctuating enzymes with dynamic cooperativity using a first passage time distribution formalism.

PubMed

Singh, Divya; Chaudhury, Srabanti

2017-04-14

We study the temporal fluctuations in catalytic rates for single enzyme reactions undergoing slow transitions between two active states. We use a first passage time distribution formalism to obtain the closed-form analytical expressions of the mean reaction time and the randomness parameter for reaction schemes where conformational fluctuations are present between two free enzyme conformers. Our studies confirm that the sole presence of free enzyme fluctuations yields a non Michaelis-Menten equation and can lead to dynamic cooperativity. The randomness parameter, which is a measure of the dynamic disorder in the system, converges to unity at a high substrate concentration. If slow fluctuations are present between the enzyme-substrate conformers (off-pathway mechanism), dynamic disorder is present at a high substrate concentration. Our results confirm that the dynamic disorder at a high substrate concentration is determined only by the slow fluctuations between the enzyme-substrate conformers and the randomness parameter is greater than unity. Slow conformational fluctuations between free enzymes are responsible for the emergence of dynamic cooperativity in single enzymes. Our theoretical findings are well supported by comparison with experimental data on the single enzyme beta-galactosidase.

Structural changes in the S 3 state of the oxygen evolving complex in photosystem II

DOE PAGES

Hatakeyama, Makoto; Ogata, Koji; Fujii, Katsushi; ...

2016-03-19

The S 3 state of the Mn 4CaO 5-cluster in photosystem II was investigated by DFT calculations and compared with EXAFS data. Considering previously proposed mechanism; a water molecule is inserted into an open coordination site of Mn upon S 2 to S 3 transition that becomes a substrate water, we examined if the water insertion is essential for the S 3 formation, or if one cannot eliminate other possible routes that do not require a water insertion at the S 3 stage. The novel S 3 state structure consisting of only short 2.7–2.8 Å MnMn distances was discussed.

Structural changes in the S 3 state of the oxygen evolving complex in photosystem II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatakeyama, Makoto; Ogata, Koji; Fujii, Katsushi

The S 3 state of the Mn 4CaO 5-cluster in photosystem II was investigated by DFT calculations and compared with EXAFS data. Considering previously proposed mechanism; a water molecule is inserted into an open coordination site of Mn upon S 2 to S 3 transition that becomes a substrate water, we examined if the water insertion is essential for the S 3 formation, or if one cannot eliminate other possible routes that do not require a water insertion at the S 3 stage. The novel S 3 state structure consisting of only short 2.7–2.8 Å MnMn distances was discussed.

Key Mutations Alter the Cytochrome P450 BM3 Conformational Landscape and Remove Inherent Substrate Bias*

PubMed Central

Butler, Christopher F.; Peet, Caroline; Mason, Amy E.; Voice, Michael W.; Leys, David; Munro, Andrew W.

2013-01-01

Cytochrome P450 monooxygenases (P450s) have enormous potential in the production of oxychemicals, due to their unparalleled regio- and stereoselectivity. The Bacillus megaterium P450 BM3 enzyme is a key model system, with several mutants (many distant from the active site) reported to alter substrate selectivity. It has the highest reported monooxygenase activity of the P450 enzymes, and this catalytic efficiency has inspired protein engineering to enable its exploitation for biotechnologically relevant oxidations with structurally diverse substrates. However, a structural rationale is lacking to explain how these mutations have such effects in the absence of direct change to the active site architecture. Here, we provide the first crystal structures of BM3 mutants in complex with a human drug substrate, the proton pump inhibitor omeprazole. Supported by solution data, these structures reveal how mutation alters the conformational landscape and decreases the free energy barrier for transition to the substrate-bound state. Our data point to the importance of such “gatekeeper” mutations in enabling major changes in substrate recognition. We further demonstrate that these mutants catalyze the same 5-hydroxylation reaction as performed by human CYP2C19, the major human omeprazole-metabolizing P450 enzyme. PMID:23828198

X-Ray Reflectometry of DMPS Monolayers on a Water Substrate

NASA Astrophysics Data System (ADS)

Tikhonov, A. M.; Asadchikov, V. E.; Volkov, Yu. O.; Roshchin, B. S.; Ermakov, Yu. A.

2017-12-01

The molecular structure of dimyristoyl phosphatidylserine (DMPS) monolayers on a water substrate in different phase states has been investigated by X-ray reflectometry with a photon energy of 8 keV. According to the experimental data, the transition from a two-dimensional expanded liquid state to a solid gel state (liquid crystal) accompanied by the ordering of the hydrocarbon tails C14H27 of the DMPS molecule occurs in the monolayer as the surface pressure rises. The monolayer thickness is 20 ± 3 and 28 ± 2 Å in the liquid and solid phases, respectively, with the deflection angle of the molecular tail axis from the normal to the surface in the gel phase being 26° ± 8°. At least a twofold decrease in the degree of hydration of the polar lipid groups also occurs under two-dimensional monolayer compression. The reflectometry data have been analyzed using two approaches: under the assumption about the presence of two layers with different electron densities in the monolayer and without any assumptions about the transverse surface structure. Both approaches demonstrate satisfactory agreement between themselves in describing the experimental results.

Enzyme Active Site Interactions by Raman/FTIR, NMR, and Ab Initio Calculations

PubMed Central

Deng, Hua

2017-01-01

Characterization of enzyme active site structure and interactions at high resolution is important for the understanding of the enzyme catalysis. Vibrational frequency and NMR chemical shift measurements of enzyme-bound ligands are often used for such purpose when X-ray structures are not available or when higher resolution active site structures are desired. This review is focused on how ab initio calculations may be integrated with vibrational and NMR chemical shift measurements to quantitatively determine high-resolution ligand structures (up to 0.001 Å for bond length and 0.01 Å for hydrogen bonding distance) and how interaction energies between bound ligand and its surroundings at the active site may be determined. Quantitative characterization of substrate ionic states, bond polarizations, tautomeric forms, conformational changes and its interactions with surroundings in enzyme complexes that mimic ground state or transition state can provide snapshots for visualizing the substrate structural evolution along enzyme-catalyzed reaction pathway. Our results have shown that the integration of spectroscopic studies with theoretical computation greatly enhances our ability to interpret experimental data and significantly increases the reliability of the theoretical analysis. PMID:24018325

IR visible sum-frequency vibrational spectroscopy of Biphenyl-3 methylene thiol monolayer on gold and silver: effect of the visible wavelength on the SFG spectrum

NASA Astrophysics Data System (ADS)

Humbert, C.; Dreesen, L.; Mani, A. A.; Caudano, Y.; Lemaire, J.-J.; Thiry, P. A.; Peremans, A.

2002-04-01

We measured IR-visible sum-frequency generation spectra of CH 3-(C 6H 4) 2-(CH 2) 3-S-H (Biphenyl-3) self-assembled monolayers on a silver and a gold substrate. For the latter substrate, we observed different interference patterns between the resonant signal of the CH vibration and the non-resonant contribution of the substrate as a function of the visible beam wavelength. The non-linear response of the gold substrate is enhanced around 480 nm corresponding to the s-d interband transition. Such effect is not observed for the silver substrate the interband transition of which is located out of the investigated visible spectral range of 450-700 nm.

Strain-engineered growth of two-dimensional materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahn, Geun Ho; Amani, Matin; Rasool, Haider

The application of strain to semiconductors allows for controlled modification of their band structure. This principle is employed for the manufacturing of devices ranging from high-performance transistors to solid-state lasers. Traditionally, strain is typically achieved via growth on lattice-mismatched substrates. For two-dimensional (2D) semiconductors, this is not feasible as they typically do not interact epitaxially with the substrate. Here in this paper, we demonstrate controlled strain engineering of 2D semiconductors during synthesis by utilizing the thermal coefficient of expansion mismatch between the substrate and semiconductor. Using WSe 2 as a model system, we demonstrate stable built-in strains ranging from 1%more » tensile to 0.2% compressive on substrates with different thermal coefficient of expansion. Consequently, we observe a dramatic modulation of the band structure, manifested by a strain-driven indirect-to-direct bandgap transition and brightening of the dark exciton in bilayer and monolayer WSe 2, respectively. The growth method developed here should enable flexibility in design of more sophisticated devices based on 2D materials.« less

Strain-engineered growth of two-dimensional materials

DOE PAGES

Ahn, Geun Ho; Amani, Matin; Rasool, Haider; ...

2017-09-20

The application of strain to semiconductors allows for controlled modification of their band structure. This principle is employed for the manufacturing of devices ranging from high-performance transistors to solid-state lasers. Traditionally, strain is typically achieved via growth on lattice-mismatched substrates. For two-dimensional (2D) semiconductors, this is not feasible as they typically do not interact epitaxially with the substrate. Here in this paper, we demonstrate controlled strain engineering of 2D semiconductors during synthesis by utilizing the thermal coefficient of expansion mismatch between the substrate and semiconductor. Using WSe 2 as a model system, we demonstrate stable built-in strains ranging from 1%more » tensile to 0.2% compressive on substrates with different thermal coefficient of expansion. Consequently, we observe a dramatic modulation of the band structure, manifested by a strain-driven indirect-to-direct bandgap transition and brightening of the dark exciton in bilayer and monolayer WSe 2, respectively. The growth method developed here should enable flexibility in design of more sophisticated devices based on 2D materials.« less

Kinetic Evidence of an Apparent Negative Activation Enthalpy in an Organocatalytic Process

PubMed Central

Han, Xiao; Lee, Richmond; Chen, Tao; Luo, Jie; Lu, Yixin; Huang, Kuo-Wei

2013-01-01

A combined kinetic and computational study on our tryptophan-based bifunctional thiourea catalyzed asymmetric Mannich reactions reveals an apparent negative activation enthalpy. The formation of the pre-transition state complex has been unambiguously confirmed and these observations provide an experimental support for the formation of multiple hydrogen bonding network between the substrates and the catalyst. Such interactions allow the creation of a binding cavity, a key factor to install high enantioselectivity. PMID:23990028

Structural basis for the mechanism and substrate specificity of glycocyamine kinase, a phosphagen kinase family member

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Kap; Pullalarevu, Sadhana; Surabian, Karen Talin

2010-03-12

Glycocyamine kinase (GK), a member of the phosphagen kinase family, catalyzes the Mg{sup 2+}-dependent reversible phosphoryl group transfer of the N-phosphoryl group of phosphoglycocyamine to ADP to yield glycocyamine and ATP. This reaction helps to maintain the energy homeostasis of the cell in some multicelullar organisms that encounter high and variable energy turnover. GK from the marine worm Namalycastis sp. is heterodimeric, with two homologous polypeptide chains, {alpha} and {beta}, derived from a common pre-mRNA by mutually exclusive N-terminal alternative exons. The N-terminal exon of GK{beta} encodes a peptide that is different in sequence and is 16 amino acids longermore » than that encoded by the N-terminal exon of GK{alpha}. The crystal structures of recombinant GK{alpha}{beta} and GK{beta}{beta} from Namalycastis sp. were determined at 2.6 and 2.4 {angstrom} resolution, respectively. In addition, the structure of the GK{beta}{beta} was determined at 2.3 {angstrom} resolution in complex with a transition state analogue, Mg{sup 2+}-ADP-NO{sub 3}{sup -}-glycocyamine. Consistent with the sequence homology, the GK subunits adopt the same overall fold as that of other phosphagen kinases of known structure (the homodimeric creatine kinase (CK) and the monomeric arginine kinase (AK)). As with CK, the GK N-termini mediate the dimer interface. In both heterodimeric and homodimeric GK forms, the conformations of the two N-termini are asymmetric, and the asymmetry is different than that reported previously for the homodimeric CKs from several organisms. The entire polypeptide chains of GK{alpha}{beta} are structurally defined, and the longer N-terminus of the {beta} subunit is anchored at the dimer interface. In GK{beta}{beta} the 24 N-terminal residues of one subunit and 11 N-terminal residues of the second subunit are disordered. This observation is consistent with a proposal that the GK{alpha}{beta} amino acids involved in the interface formation were optimized once a heterodimer emerged as the physiological form of the enzyme. As a consequence, the homodimer interface (either solely {alpha} or solely {beta} chains) has been corrupted. In the unbound state, GK exhibits an open conformation analogous to that observed with ligand-free CK or AK. Upon binding the transition state analogue, both subunits of GK undergo the same closure motion that clasps the transition state analogue, in contrast to the transition state analogue complexes of CK, where the corresponding transition state analogue occupies only one subunit, which undergoes domain closure. The active site environments of the GK, CK, and AK at the bound states reveal the structural determinants of substrate specificity. Despite the equivalent binding in both active sites of the GK dimer, the conformational asymmetry of the N-termini is retained. Thus, the coupling between the structural asymmetry and negative cooperativity previously proposed for CK is not supported in the case of GK.« less

Rational Modulation of the Induced-Fit Conformational Change for Slow-Onset Inhibition in Mycobacterium tuberculosis InhA.

PubMed

Lai, Cheng-Tsung; Li, Huei-Jiun; Yu, Weixuan; Shah, Sonam; Bommineni, Gopal R; Perrone, Victoria; Garcia-Diaz, Miguel; Tonge, Peter J; Simmerling, Carlos

2015-08-04

Slow-onset enzyme inhibitors are the subject of considerable interest as an approach to increasing the potency of pharmaceutical compounds by extending the residence time of the inhibitor on the target (the lifetime of the drug-receptor complex). However, rational modulation of residence time presents significant challenges because it requires additional mechanistic insight, such as the nature of the transition state for postbinding isomerization. Our previous work, based on X-ray crystallography, enzyme kinetics, and molecular dynamics simulation, suggested that the slow step in inhibition of the Mycobacterium tuberculosis enoyl-ACP reductase InhA involves a change in the conformation of the substrate binding loop from an open state in the initial enzyme-inhibitor complex to a closed state in the final enzyme-inhibitor complex. Here, we use multidimensional free energy landscapes for loop isomerization to obtain a computational model for the transition state. The results suggest that slow-onset inhibitors crowd key side chains on helices that slide past each other during isomerization, resulting in a steric clash. The landscapes become significantly flatter when residues involved in the steric clash are replaced with alanine. Importantly, this lower barrier can be increased by rational inhibitor redesign to restore the steric clash. Crystallographic studies and enzyme kinetics confirm the predicted effects on loop structure and flexibility, as well as inhibitor residence time. These loss and regain of function studies validate our mechanistic hypothesis for interactions controlling substrate binding loop isomerization, providing a platform for the future design of inhibitors with longer residence times and better in vivo potency. Similar opportunities for slow-onset inhibition via the same mechanism are identified in other pathogens.

Functional role of a mobile loop of Escherichia coli dihydrofolate reductase in transition-state stabilization.

PubMed

Li, L; Falzone, C J; Wright, P E; Benkovic, S J

1992-09-01

The function of a highly mobile loop in Escherichia coli dihydrofolate reductase was studied by constructing a mutant (DL1) using cassette mutagenesis that had four residues deleted in the middle section of the loop (Met16-Ala19) and a glycine inserted to seal the gap. This part of the loop involves residues 16-20 and is disordered in the X-ray crystal structures of the apoprotein and the NADP+ binary complex but forms a hairpin turn that folds over the nicotinamide moiety of NADP+ and the pteridine moiety of folate in the ternary complex [Bystroff, C., & Kraut, J. (1991) Biochemistry 30, 2227-2239]. The steady-state and pre-steady-state kinetics and two-dimensional 1H NMR spectra were analyzed and compared to the wild-type protein. The kinetics on the DL1 mutant enzyme show that the KM value for NADPH (5.3 microM), the KM for dihydrofolate (2 microM), the rate constant for the release of the product tetrahydrofolate (10.3 s-1), and the intrinsic pKa value (6.2) are similar to those exhibited by the wild-type enzyme. However, the hydride-transfer rate declines markedly from the wild-type value of 950 s-1 to 1.7 s-1 for the DL1 mutant and when taken with data for substrate binding indicates that the loop contributes to substrate flux by a factor of 3.5 x 10(4). Thus, the mobility of loop I may provide a mechanism of recruiting hydrophobic residues which can properly align the nicotinamide and pteridine rings for the hydride-transfer process (a form of transition-state stabilization).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of membrane deformability and bond formation/dissociation rates on adhesion dynamics of a spherical capsule in shear flow.

PubMed

Zhang, Ziying; Du, Jun; Wei, Zhengying; Wang, Zhen; Li, Minghui

2018-02-01

Cellular adhesion plays a critical role in biological systems and biomedical applications. Cell deformation and biophysical properties of adhesion molecules are of significance for the adhesion behavior. In the present work, dynamic adhesion of a deformable capsule to a planar substrate, in a linear shear flow, is numerically simulated to investigate the combined influence of membrane deformability (quantified by the capillary number) and bond formation/dissociation rates on the adhesion behavior. The computational model is based on the immersed boundary-lattice Boltzmann method for the capsule-fluid interaction and a probabilistic adhesion model for the capsule-substrate interaction. Three distinct adhesion states, detachment, rolling adhesion and firm adhesion, are identified and presented in a state diagram as a function of capillary number and bond dissociation rate. The impact of bond formation rate on the state diagram is further investigated. Results show that the critical bond dissociation rate for the transition of rolling or firm adhesion to detachment is strongly related to the capsule deformability. At the rolling-adhesion state, smaller off rates are needed for larger capillary number to increase the rolling velocity and detach the capsule. In contrast, the critical off rate for firm-to-detach transition slightly increases with the capillary number. With smaller on rate, the effect of capsule deformability on the critical off rates is more pronounced and capsules with moderate deformability are prone to detach by the shear flow. Further increasing of on rate leads to large expansion of both rolling-adhesion and firm-adhesion regions. Even capsules with relatively large deformability can maintain stable rolling adhesion at certain off rate.

Sapphire substrate-induced effects in VO2 thin films grown by oxygen plasma-assisted pulsed laser deposition

NASA Astrophysics Data System (ADS)

Skuza, J. R.; Scott, D. W.; Pradhan, A. K.

2015-11-01

We investigate the structural and electronic properties of VO2 thin films on c-plane sapphire substrates with three different surface morphologies to control the strain at the substrate-film interface. Only non-annealed substrates with no discernible surface features (terraces) provided a suitable template for VO2 film growth with a semiconductor-metal transition (SMT), which was much lower than the bulk transition temperature. In addition to strain, oxygen vacancy concentration also affects the properties of VO2, which can be controlled through deposition conditions. Oxygen plasma-assisted pulsed laser deposition allows favorable conditions for VO2 film growth with SMTs that can be easily tailored for device applications.

Transition between 'base' and 'tip' carbon nanofiber growth modes

NASA Astrophysics Data System (ADS)

Melechko, Anatoli V.; Merkulov, Vladimir I.; Lowndes, Douglas H.; Guillorn, Michael A.; Simpson, Michael L.

2002-04-01

Carbon nanofibers (CNFs) have been synthesized by catalytically controlled dc glow discharge plasma-enhanced chemical vapor deposition (PECVD). Both base-type and tip-type nanofibers have been produced on identical substrates. We have observed a sharp transition between these two growth modes by controlling the kinetics of the growth process without changing the substrate and catalyst materials. This transition is brought about by changing the parameters used in the deposition process such as the flow ratio of the carbonaceous and etchant gasses and others. This study of the initial growth stages as a function of time for both regimes provides a basis for a model of the growth mode transition.

Role of protein conformational mobility in enzyme catalysis: acylation of alpha-chymotrypsin by specific peptide substrates.

PubMed

Hengge, Alvan C; Stein, Ross L

2004-01-27

To probe the mechanistic origins of convex Eyring plots that have been observed for alpha-chymotrypsin (alpha-CT)-catalyzed hydrolysis of specific p-nitroanilide substrates [Case, A., and Stein, R. L. (2003) Biochemistry 42, 3335-3348], we determined the temperature-dependence of (15)N-kinetic isotope effects for the alpha-CT-catalyzed hydrolysis of N-succinyl-Phe p-nitroanilide (Suc-Phe-pNA). To provide an interpretational context for these enzymatic isotope effects, we also determined 15N-KIE for alkaline hydrolysis of p-nitroacetanilide. In 0.002 and 2 N hydroxide (30 degrees C), 15N-KIE values are 1.035 and 0.995 (+/-0.001), respectively, and are consistent with the reported [HO-]-dependent change in rate-limiting step from leaving group departure from an anionic tetrahedral intermediate in dilute base, to hydroxide attack in concentrated base. For the alpha-CT-catalyzed hydrolysis of Suc-Phe-pNA, 15N-KIE is on kc/Km and thus reflects structural features of transition states for all reaction steps up to and including acylation of the active site serine. The isotope effect at 35 degrees C is 1.014 (+/-0.001) and suggests that in the transition state for this reaction, departure of leaving group from the tetrahedral intermediate is well advanced. Significantly, 15N-KIE does not vary over the temperature range 5-45 degrees C. This result eliminates one of the competing hypotheses for the convex Eyring plot observed for this reaction, that is, a temperature-dependent change in rate-limiting step within the chemical manifold of acylation, but supports a mechanism in which an isomerization of enzyme conformation is coupled to active site chemistry. We finally suggest that the near absolute temperature-independence of 15N-KIE may point to a unique transition state for this process.

Speeding Up Sigmatropic Shifts-To Halve or to Hold.

PubMed

Tantillo, Dean J

2016-04-19

Catalysis is common. Rational catalyst design, however, is at the frontier of chemical science. Although the histories of physical organic and synthetic organic chemistry boast key chapters involving [3s,3s] sigmatropic shifts, catalysis of these reactions is much less common than catalysis of ostensibly more complex processes. The comparative dearth of catalysts for sigmatropic shifts is perhaps a result of the perception that transition state structures for these reactions, like their reactants, are nonpolar and therefore not amenable to selective stabilization and its associated barrier lowering. However, as demonstrated in this Account, transition state structures for [3s,3s] sigmatropic shifts can in fact have charge distributions that differ significantly from those of reactants, even for hydrocarbon substrates, allowing for barriers to be decreased and rates increased. In some cases, differences in charge distribution result from the inclusion of heteroatoms at specific positions in reactants, but in other cases differences are actually induced by catalysts. Perhaps surprisingly, strategies for complexation of transition state structures that remain nonpolar are also possible. In general, the strategies for catalysis employed can be characterized as involving either mechanistic intervention, where a catalyst induces a change from the concerted mechanism expected for a [3s,3s] sigmatropic shift to a multistep process (cutting the transformation into halves or smaller pieces) whose overall barrier is decreased relative to the concerted process, or transition state complexation, where a catalyst simply binds (holds) more tightly to the transition state structure for a [3s,3s] sigmatropic shift than to the reactant, leading to a lower barrier in the presence of the catalyst. Both of these strategies can be considered to be biomimetic in that enzymes frequently induce multistep processes and utilize selective transition state stabilization for the steps involved. In addition, transition state complexation was the principle around which catalytic antibodies were originally designed. The field of catalysis of sigmatropic shifts is now ready for rational design. The studies described here all provide evidence for the origins of rate acceleration, derived in large part from the results of quantum chemical calculations, that can now be applied to the design of new catalysts for [3s,3s] and other sigmatropic shifts.

Determining the transition-state structure for different SN2 reactions using experimental nucleophile carbon and secondary alpha-deuterium kinetic isotope effects and theory.

PubMed

Westaway, Kenneth C; Fang, Yao-ren; MacMillar, Susanna; Matsson, Olle; Poirier, Raymond A; Islam, Shahidul M

2008-10-16

Nucleophile (11)C/ (14)C [ k (11)/ k (14)] and secondary alpha-deuterium [( k H/ k D) alpha] kinetic isotope effects (KIEs) were measured for the S N2 reactions between tetrabutylammonium cyanide and ethyl iodide, bromide, chloride, and tosylate in anhydrous DMSO at 20 degrees C to determine whether these isotope effects can be used to determine the structure of S N2 transition states. Interpreting the experimental KIEs in the usual fashion (i.e., that a smaller nucleophile KIE indicates the Nu-C alpha transition state bond is shorter and a smaller ( k H/ k D) alpha is found when the Nu-LG distance in the transition state is shorter) suggests that the transition state is tighter with a slightly shorter NC-C alpha bond and a much shorter C alpha-LG bond when the substrate has a poorer halogen leaving group. Theoretical calculations at the B3LYP/aug-cc-pVDZ level of theory support this conclusion. The results show that the experimental nucleophile (11)C/ (14)C KIEs can be used to determine transition-state structure in different reactions and that the usual method of interpreting these KIEs is correct. The magnitude of the experimental secondary alpha-deuterium KIE is related to the nucleophile-leaving group distance in the S N2 transition state ( R TS) for reactions with a halogen leaving group. Unfortunately, the calculated and experimental ( k H/ k D) alpha's change oppositely with leaving group ability. However, the calculated ( k H/ k D) alpha's duplicate both the trend in the KIE with leaving group ability and the magnitude of the ( k H/ k D) alpha's for the ethyl halide reactions when different scale factors are used for the high and the low energy vibrations. This suggests it is critical that different scaling factors for the low and high energy vibrations be used if one wishes to duplicate experimental ( k H/ k D) alpha's. Finally, neither the experimental nor the theoretical secondary alpha-deuterium KIEs for the ethyl tosylate reaction fit the trend found for the reactions with a halogen leaving group. This presumably is found because of the bulky (sterically hindered) leaving group in the tosylate reaction. From every prospective, the tosylate reaction is too different from the halogen reactions to be compared.

Mode pumping experiments on biomolecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Austin, R.H.; Erramilli, S.; Xie, A.

1995-12-31

We will explore several aspects of protein dynamics and energy transfer that can be explored by using the intense, picosecond, tunable mid-IR output of the FEL. In order of appearance they are: (1) Saturation recovery and inter-level coupling of the low temperature amide-I band in acetanilide. This is a continuation of earlier experiments to test soliton models in crystalline hydrogen bonded solids. In this experiment we utilize the sub-picosecond time resolution and low repetition rate of the Stanford SCLA FEL to do both T{sub 1} and T{sub 2} relaxation measurements at 1650 cm{sup -1}. (2) Probing the influence of collectivemore » dynamics in sensory rhodopsin. In this experiment we use the FIR output of the Stanford FIREFLY FEL to determine the lifetime of collective modes in the photo-active protein sensory rhodopsin, and begin experiments on the influence of collective modes on retinal reaction dynamics. (3) Probing the transition states of enzymes. This experiment, in the initial stages, attempts to use the intense IR output of the FEL to probe and influence the reaction path of a transition state analog for the protein nucleoside hydrolase. The transition state of the inosine substrate is believed to have critical modes softened by the protein so that bond-breaking paths show absorption at approximately 800 cm{sup -1}. A form of action spectrum using FEL excitation will be used to probe this state.« less

A new structural framework for integrating replication protein A into DNA processing machinery

PubMed Central

Brosey, Chris A.; Yan, Chunli; Tsutakawa, Susan E.; Heller, William T.; Rambo, Robert P.; Tainer, John A.; Ivanov, Ivaylo; Chazin, Walter J.

2013-01-01

By coupling the protection and organization of single-stranded DNA (ssDNA) with recruitment and alignment of DNA processing factors, replication protein A (RPA) lies at the heart of dynamic multi-protein DNA processing machinery. Nevertheless, how RPA coordinates biochemical functions of its eight domains remains unknown. We examined the structural biochemistry of RPA’s DNA-binding activity, combining small-angle X-ray and neutron scattering with all-atom molecular dynamics simulations to investigate the architecture of RPA’s DNA-binding core. The scattering data reveal compaction promoted by DNA binding; DNA-free RPA exists in an ensemble of states with inter-domain mobility and becomes progressively more condensed and less dynamic on binding ssDNA. Our results contrast with previous models proposing RPA initially binds ssDNA in a condensed state and becomes more extended as it fully engages the substrate. Moreover, the consensus view that RPA engages ssDNA in initial, intermediate and final stages conflicts with our data revealing that RPA undergoes two (not three) transitions as it binds ssDNA with no evidence for a discrete intermediate state. These results form a framework for understanding how RPA integrates the ssDNA substrate into DNA processing machinery, provides substrate access to its binding partners and promotes the progression and selection of DNA processing pathways. PMID:23303776

A new structural framework for integrating replication protein A into DNA processing machinery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brosey, Chris; Yan, Chunli; Tsutakawa, Susan

2013-01-17

By coupling the protection and organization of single-stranded DNA (ssDNA) with recruitment and alignment of DNA processing factors, replication protein A (RPA) lies at the heart of dynamic multi-protein DNA processing machinery. Nevertheless, how RPA coordinates biochemical functions of its eight domains remains unknown. We examined the structural biochemistry of RPA's DNA-binding activity, combining small-angle X-ray and neutron scattering with all-atom molecular dynamics simulations to investigate the architecture of RPA's DNA-binding core. The scattering data reveal compaction promoted by DNA binding; DNA-free RPA exists in an ensemble of states with inter-domain mobility and becomes progressively more condensed and less dynamicmore » on binding ssDNA. Our results contrast with previous models proposing RPA initially binds ssDNA in a condensed state and becomes more extended as it fully engages the substrate. Moreover, the consensus view that RPA engages ssDNA in initial, intermediate and final stages conflicts with our data revealing that RPA undergoes two (not three) transitions as it binds ssDNA with no evidence for a discrete intermediate state. These results form a framework for understanding how RPA integrates the ssDNA substrate into DNA processing machinery, provides substrate access to its binding partners and promotes the progression and selection of DNA processing pathways.« less

Reduced-Amide Inhibitor of Pin1 Binds in a Conformation Resembling a Twisted-Amide Transition State†

PubMed Central

Xu, Guoyan G.; Zhang, Yan; Mercedes-Camacho, Ana Y.; Etzkorn, Felicia A.

2011-01-01

The mechanism of the cell cycle regulatory peptidyl prolyl isomerase (PPIase), Pin1, was investigated using reduced-amide inhibitors designed to mimic the twisted-amide transition state. Inhibitors, R–pSer–Ψ[CH2N]–Pro–2-(indol-3-yl)-ethylamine, 1 (R = fluorenylmethoxycarbonyl, Fmoc), and 2 (R = Ac), of Pin1 were synthesized and bioassayed. Inhibitor 1 had an IC50 value of 6.3 μM, which is 4.5-fold better inhibition for Pin1 than our comparable ground state analogue, a cis-amide alkene isostere containing inhibitor. The change of Fmoc to Ac in 2 improved aqueous solubility for structural determination, and resulted in an IC50 value of 12 μM. The X-ray structure of the complex of 2 bound to Pin1 was determined to 1.76 Å resolution. The structure revealed that the reduced amide adopted a conformation similar to the proposed twisted-amide transition state of Pin1, with a trans-pyrrolidine conformation of the prolyl ring. A similar conformation of substrate would be destabilized relative to the planar amide conformation. Three additional reduced amides, with Thr replacing Ser, and l- or d-pipecolate (Pip) replacing Pro, were slightly weaker inhibitors of Pin1. PMID:21980916

Simulation studies of glassy nanoclusters

NASA Astrophysics Data System (ADS)

Bowles, Richard

2015-03-01

Glassy materials are amorphous solids usually formed by rapidly cooling a liquid below its equilibrium freezing temperature, trapping the particles in a liquid-like structure at the glass transition temperature. While appearing throughout nature and industry, these systems continue to challenge the way we think about the dynamics and thermodynamics of condensed matter and a fundamental understanding of the glass state remains elusive. This talk describes molecular simulation studies of glassy behaviour in binary Lennard-Jones nanoclusters. We show that the relaxation dynamics of the clusters is nonuniform and the core of the cluster goes through a glass transition at higher temperatures than at the surface. As the nanoclusters are cooled, they also exhibit a fragile-strong crossover in their dynamics and we explore how this phenomena is linked to the potential energy landscape of the clusters. Finally, we compare the properties of nanoclusters formed through vapour condensation, directly to the glassy state, with those of glassy clusters formed through traditional supercooling. The condensation clusters are shown to form ultra-stable glassy states analogous to the ultra-stable glasses formed by thin film vapour deposition onto a cold substrate. In all, our work suggests that nanoscale clusters exhibit some unique glassy features, while also offering potential insights into the fundamental nature of the glass transition.

Altered Enthalpy-Entropy Compensation in Picomolar Transition State Analogues of Human Purine Nucleoside Phosphorylase†

PubMed Central

Edwards, Achelle A.; Mason, Jennifer M.; Clinch, Keith; Tyler, Peter C.; Evans, Gary B.; Schramm, Vern L.

2009-01-01

Human purine nucleoside phosphorylase (PNP) belongs to the trimeric class of PNPs and is essential for catabolism of deoxyguanosine. Genetic deficiency of PNP in humans causes a specific T-cell immune deficiency and transition state analogue inhibitors of PNP are in development for treatment of T-cell cancers and autoimmune disorders. Four generations of Immucillins have been developed, each of which contains inhibitors binding with picomolar affinity to human PNP. Full inhibition of PNP occurs upon binding to the first of three subunits and binding to subsequent sites occurs with negative cooperativity. In contrast, substrate analogue and product bind without cooperativity. Titrations of human PNP using isothermal calorimetery indicate that binding of a structurally rigid first-generation Immucillin (K d = 56 pM) is driven by large negative enthalpy values (ΔH = −21.2 kcal/mol) with a substantial entropic (-TΔS) penalty. The tightest-binding inhibitors (K d = 5 to 9 pM) have increased conformational flexibility. Despite their conformational freedom in solution, flexible inhibitors bind with high affinity because of reduced entropic penalties. Entropic penalties are proposed to arise from conformational freezing of the PNP·inhibitor complex with the entropy term dominated by protein dynamics. The conformationally flexible Immucillins reduce the system entropic penalty. Disrupting the ribosyl 5’-hydroxyl interaction of transition state analogues with PNP causes favorable entropy of binding. Tight binding of the seventeen Immucillins is characterized by large enthalpic contributions, emphasizing their similarity to the transition state. By introducing flexibility into the inhibitor structure, the enthalpy-entropy compensation pattern is altered to permit tighter binding. PMID:19425594

Reversible monolayer-to-crystalline phase transition in amphiphilic silsesquioxane at the air-water interface

DOE PAGES

Banerjee, R.; Sanyal, M. K.; Bera, M. K.; ...

2015-02-17

We report on the counter intuitive reversible crystallisation of two-dimensional monolayer of Trisilanolisobutyl Polyhedral Oligomeric SilSesquioxane (TBPOSS) on water surface using synchrotron x-ray scattering measurements. Amphiphilic TBPOSS form rugged monolayers and Grazing Incidence X-ray Scattering (GIXS) measurements reveal that the in-plane inter-particle correlation peaks, characteristic of two-dimensional system, observed before transition is replaced by intense localized spots after transition. The measured x-ray scattering data of the non-equilibrium crystalline phase on the air-water interface could be explained with a model that assumes periodic stacking of the TBPOSS dimers. These crystalline stacking relaxes upon decompression and the TBPOSS layer retains its initialmore » monolayer state. The existence of these crystals in compressed phase is confirmed by atomic force microscopy measurements by lifting the materials on a solid substrate.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Shifeng; Wang, Shuyu; Lu, Ming

In this paper, vanadium thin films were deposited on sapphire substrates by DC magnetron sputtering and then oxidized in a tube furnace filled with oxygen under different temperatures and oxygen flow rates. The significant influence of the oxygen flow rate and oxidation temperature on the electrical and structural properties of the vanadium oxide thin films were investigated systematically. It shows the pure vanadium dioxide (VO 2) state can only be obtained in a very narrow temperature and oxygen flow rate range. The resistivity change during the metal-insulator transition varies from 0.2 to 4 orders of magnitude depending on the oxidationmore » condition. Large thermal hysteresis during the metal-insulator phase transition was observed during the transition compared to the results in literature. Proper oxidation conditions can significantly reduce the thermal hysteresis. Finally, the fabricated VO 2 thin films showed the potential to be applied in the development of electrical sensors and other smart devices.« less

Ideal glass transitions in thin films: An energy landscape perspective

NASA Astrophysics Data System (ADS)

Truskett, Thomas M.; Ganesan, Venkat

2003-07-01

We introduce a mean-field model for the potential energy landscape of a thin fluid film confined between parallel substrates. The model predicts how the number of accessible basins on the energy landscape and, consequently, the film's ideal glass transition temperature depend on bulk pressure, film thickness, and the strength of the fluid-fluid and fluid-substrate interactions. The predictions are in qualitative agreement with the experimental trends for the kinetic glass transition temperature of thin films, suggesting the utility of landscape-based approaches for studying the behavior of confined fluids.

Large interdomain rearrangement triggered by suppression of micro- to millisecond dynamics in bacterial Enzyme I

NASA Astrophysics Data System (ADS)

Venditti, Vincenzo; Tugarinov, Vitali; Schwieters, Charles D.; Grishaev, Alexander; Clore, G. Marius

2015-01-01

Enzyme I (EI), the first component of the bacterial phosphotransfer signal transduction system, undergoes one of the largest substrate-induced interdomain rearrangements documented to date. Here we characterize the perturbations generated by two small molecules, the natural substrate phosphoenolpyruvate and the inhibitor α-ketoglutarate, on the structure and dynamics of EI using NMR, small-angle X-ray scattering and biochemical techniques. The results indicate unambiguously that the open-to-closed conformational switch of EI is triggered by complete suppression of micro- to millisecond dynamics within the C-terminal domain of EI. Indeed, we show that a ligand-induced transition from a dynamic to a more rigid conformational state of the C-terminal domain stabilizes the interface between the N- and C-terminal domains observed in the structure of the closed state, thereby promoting the resulting conformational switch and autophosphorylation of EI. The mechanisms described here may be common to several other multidomain proteins and allosteric systems.

Growth optimization and electronic structure of ultrathin CoO films on Ag(001): A LEED and photoemission study

NASA Astrophysics Data System (ADS)

Barman, Sukanta; Menon, Krishnakumar S. R.

2018-04-01

We present here a detailed growth optimization of CoO thin film on Ag(001) involving the effects of different growth parameters on the electronic structure. A well-ordered stoichiometric growth of 5 ML CoO film has been observed at 473 K substrate temperature and 1 × 10-6 mbar oxygen partial pressure. The growth at lower substrate temperature and oxygen partial pressure show non-stoichiometric impurity phases which have been investigated further to correlate the growth parameters with surface electronic structure. The coverage dependent valence band electronic structure of the films grown at optimized condition reveals the presence of interfacial states near the Fermi edge (EF) for lower film coverages. Presence of interfacial states in the stoichiometric films rules out their defect-induced origin. We argue that this is an intrinsic feature of transition metal monoxides like NiO, CoO, MnO in the low coverage regime.

Electrical transport properties of small diameter single-walled carbon nanotubes aligned on ST-cut quartz substrates

PubMed Central

2014-01-01

A method is introduced to isolate and measure the electrical transport properties of individual single-walled carbon nanotubes (SWNTs) aligned on an ST-cut quartz, from room temperature down to 2 K. The diameter and chirality of the measured SWNTs are accurately defined from Raman spectroscopy and atomic force microscopy (AFM). A significant up-shift in the G-band of the resonance Raman spectra of the SWNTs is observed, which increases with increasing SWNTs diameter, and indicates a strong interaction with the quartz substrate. A semiconducting SWNT, with diameter 0.84 nm, shows Tomonaga-Luttinger liquid and Coulomb blockade behaviors at low temperatures. Another semiconducting SWNT, with a thinner diameter of 0.68 nm, exhibits a transition from the semiconducting state to an insulating state at low temperatures. These results elucidate some of the electrical properties of SWNTs in this unique configuration and help pave the way towards prospective device applications. PMID:25170326

PGC-1α and fasting-induced PDH regulation in mouse skeletal muscle.

PubMed

Gudiksen, Anders; Pilegaard, Henriette

2017-04-01

The purpose of the present study was to examine whether lack of skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α ) affects the switch in substrate utilization from a fed to fasted state and the fasting-induced pyruvate dehydrogenase (PDH) regulation in skeletal muscle. Skeletal muscle-specific PGC-1 α knockout (MKO) mice and floxed littermate controls were fed or fasted for 24 h. Fasting reduced PDHa activity, increased phosphorylation of all four known sites on PDH-E1 α and increased pyruvate dehydrogenase kinase (PDK4) and sirtuin 3 (SIRT3) protein levels, but did not alter total acetylation of PDH-E1 α Lack of muscle PGC-1 α did not affect the switch from glucose to fat oxidation in the transition from the fed to fasted state, but was associated with lower and higher respiratory exchange ratio (RER) in the fed and fasted state, respectively. PGC-1 α MKO mice had lower skeletal muscle PDH-E1 α , PDK1, 2, 4, and pyruvate dehydrogenase phosphatase (PDP1) protein content than controls, but this did not prevent the fasting-induced increase in PDH-E1 α phosphorylation in PGC-1 α MKO mice. However, lack of skeletal muscle PGC-1 α reduced SIRT3 protein content, increased total lysine PDH-E1 α acetylation in the fed state, and prevented a fasting-induced increase in SIRT3 protein. In conclusion, skeletal muscle PGC-1 α is required for fasting-induced upregulation of skeletal muscle SIRT3 and maintaining high fat oxidation in the fasted state, but is dispensable for preserving the capability to switch substrate during the transition from the fed to the fasted state and for fasting-induced PDH regulation in skeletal muscle. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Structural and In Vivo Studies on Trehalose-6-Phosphate Synthase from Pathogenic Fungi Provide Insights into Its Catalytic Mechanism, Biological Necessity, and Potential for Novel Antifungal Drug Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miao, Yi; Tenor, Jennifer L.; Toffaletti, Dena L.

ABSTRACT The disaccharide trehalose is critical to the survival of pathogenic fungi in their human host. Trehalose-6-phosphate synthase (Tps1) catalyzes the first step of trehalose biosynthesis in fungi. Here, we report the first structures of eukaryotic Tps1s in complex with substrates or substrate analogues. The overall structures of Tps1 fromCandida albicansandAspergillus fumigatusare essentially identical and reveal N- and C-terminal Rossmann fold domains that form the glucose-6-phosphate and UDP-glucose substrate binding sites, respectively. These Tps1 structures with substrates or substrate analogues reveal key residues involved in recognition and catalysis. Disruption of these key residues severely impaired Tps1 enzymatic activity. Subsequent cellularmore » analyses also highlight the enzymatic function of Tps1 in thermotolerance, yeast-hypha transition, and biofilm development. These results suggest that Tps1 enzymatic functionality is essential for the fungal stress response and virulence. Furthermore, structures of Tps1 in complex with the nonhydrolyzable inhibitor, validoxylamine A, visualize the transition state and support an internal return-like catalytic mechanism that is generalizable to other GT-B-fold retaining glycosyltransferases. Collectively, our results depict key Tps1-substrate interactions, unveil the enzymatic mechanism of these fungal proteins, and pave the way for high-throughput inhibitor screening buttressed and guided by the current structures and those of high-affinity ligand-Tps1 complexes. IMPORTANCEInvasive fungal diseases have emerged as major threats, resulting in more than 1.5 million deaths annually worldwide. This epidemic has been further complicated by increasing resistance to all major classes of antifungal drugs in the clinic. Trehalose biosynthesis is essential for the fungal stress response and virulence. Critically, this biosynthetic pathway is absent in mammals, and thus, the two enzymes that carry out trehalose biosynthesis, namely, trehalose-6-phosphate synthase (Tps1) and trehalose-6-phosphate phosphatase (Tps2), are prominent targets for antifungal intervention. Here, we report the first eukaryotic Tps1 structures from the pathogenic fungiCandida albicansandAspergillus fumigatusin complex with substrates, substrate analogues, and inhibitors. These structures reveal key protein-substrate interactions, providing atomic-level scaffolds for structure-guided drug design of novel antifungals that target Tps1.« less

Structural and In Vivo Studies on Trehalose-6-Phosphate Synthase from Pathogenic Fungi Provide Insights into Its Catalytic Mechanism, Biological Necessity, and Potential for Novel Antifungal Drug Design.

PubMed

Miao, Yi; Tenor, Jennifer L; Toffaletti, Dena L; Maskarinec, Stacey A; Liu, Jiuyu; Lee, Richard E; Perfect, John R; Brennan, Richard G

2017-07-25

The disaccharide trehalose is critical to the survival of pathogenic fungi in their human host. Trehalose-6-phosphate synthase (Tps1) catalyzes the first step of trehalose biosynthesis in fungi. Here, we report the first structures of eukaryotic Tps1s in complex with substrates or substrate analogues. The overall structures of Tps1 from Candida albicans and Aspergillus fumigatus are essentially identical and reveal N- and C-terminal Rossmann fold domains that form the glucose-6-phosphate and UDP-glucose substrate binding sites, respectively. These Tps1 structures with substrates or substrate analogues reveal key residues involved in recognition and catalysis. Disruption of these key residues severely impaired Tps1 enzymatic activity. Subsequent cellular analyses also highlight the enzymatic function of Tps1 in thermotolerance, yeast-hypha transition, and biofilm development. These results suggest that Tps1 enzymatic functionality is essential for the fungal stress response and virulence. Furthermore, structures of Tps1 in complex with the nonhydrolyzable inhibitor, validoxylamine A, visualize the transition state and support an internal return-like catalytic mechanism that is generalizable to other GT-B-fold retaining glycosyltransferases. Collectively, our results depict key Tps1-substrate interactions, unveil the enzymatic mechanism of these fungal proteins, and pave the way for high-throughput inhibitor screening buttressed and guided by the current structures and those of high-affinity ligand-Tps1 complexes. IMPORTANCE Invasive fungal diseases have emerged as major threats, resulting in more than 1.5 million deaths annually worldwide. This epidemic has been further complicated by increasing resistance to all major classes of antifungal drugs in the clinic. Trehalose biosynthesis is essential for the fungal stress response and virulence. Critically, this biosynthetic pathway is absent in mammals, and thus, the two enzymes that carry out trehalose biosynthesis, namely, trehalose-6-phosphate synthase (Tps1) and trehalose-6-phosphate phosphatase (Tps2), are prominent targets for antifungal intervention. Here, we report the first eukaryotic Tps1 structures from the pathogenic fungi Candida albicans and Aspergillus fumigatus in complex with substrates, substrate analogues, and inhibitors. These structures reveal key protein-substrate interactions, providing atomic-level scaffolds for structure-guided drug design of novel antifungals that target Tps1. Copyright © 2017 Miao et al.

A Forty Year Odyssey in Metallo-Organic Chemistry.

PubMed

Nicholas, Kenneth M

2015-07-17

In this invited Perspective, I provide a personal account highlighting several of my group's research contributions in metallo-organic chemistry over the past 40 years. Our early work focused primarily in stoichiometric structure/reactivity of transition metal-organic compounds and their use in organic synthesis. More recent efforts have centered on the discovery and development of new metal-catalyzed organic reactions via reactive metal-organic intermediates. The major research findings that are described here include (1) propargyl-cobalt complexes as electrophilic agents for C-C and C-Nu coupling; (2) the activation of carbon dioxide by metal complexes; (3) metal-promoted C-H nitrogenation reactions; (4) oxo-metal catalyzed deoxygenation reactions; and (5) catalyst discovery via dynamic templating with substrate- and transition-state analogues.

Tuning Magnetic Order in Transition Metal Oxide Thin Films

NASA Astrophysics Data System (ADS)

Grutter, Alexander John

In recent decades, one of the most active and promising areas of condensed matter research has been that of complex oxides. With the advent of new growth techniques such as pulsed laser deposition and molecular beam epitaxy, a wealth of new magnetic and electronic ground states have emerged in complex oxide heterostructures. The wide variety of ground states in complex oxides is well known and generally attributed to the unprecedented variety of valence, structure, and bonding available in these systems. The tunability of this already diverse playground of states and interactions is greatly multiplied in thin films and heterostructures by the addition of parameters such as substrate induced strain and interfacial electronic reconstruction. Thus, recent studies have shown emergent properties such as the stabilization of ferromagnetism in a paramagnetic system, conductivity at the interface of two insulators, and even exchange bias at the interface between a paramagnet and a ferromagnet. Despite these steps forward, there remains remarkable disagreement on the mechanisms by which these emergent phenomena are stabilized. The contributions of strain, stoichiometry, defects, intermixing, and electronic reconstruction are often very difficult to isolate in thin films and superlattices. This thesis will present model systems for isolating the effects of strain and interfacial electronic interactions on the magnetic state of complex oxides from alternative contributions. We will focus first on SrRuO3, an ideal system in which to isolate substrate induced strain effects. We explore the effects of structural distortions in the simplest case of growth on (100) oriented substrates. We find that parameters including saturated magnetic moment and Curie temperature are all highly tunable through substrate induced lattice distortions. We also report the stabilization of a nonmagnetic spin-zero configuration of Ru4+ in tetragonally distorted films under tensile strain. Through growth on (110) and (111) oriented substrates we explore the effects of different distortion symmetries on SrRuO3 and demonstrate the first reported strain induced transition to a high-spin state of Ru 4+. Finally, we examine the effects of strain on SrRuO3 thin films and demonstrate a completely reversible universal out-of-plane magnetic easy axis on films grown on different substrate orientations. Having demonstrated the ability to tune nearly every magnetic parameter of SrRuO 3 through strain, we turn to magnetic properties at interfaces. We study the emergent interfacial ferromagnetism in superlattices of the paramagnetic metal CaRuO3 and the antiferromagnetic insulator CaMnO3 and demonstrate that the interfacial ferromagnetic layer in this system is confined to a single unit cell of CaMnO3 at the interface. We discuss the remarkable oscillatory dependence of the saturated magnetic moment on the thickness of the CaMnO3 layers and explore mechanisms by which this oscillation may be stabilized. We find long range coherence of the antiferromagnetism of the CaMnO3 layers across intervening layers of paramagnetic CaRuO3. Finally, we utilize the system of LaNiO3/CaMnO3 to separate the effects of intermixing and interfacial electronic reconstruction and conclusively demonstrate intrinsic interfacial ferromagnetism at the interface between a paramagnetic metal and an antiferromagnetic insulator. We find that the emergent ferromagnetism is stabilized through interfacial double exchange and that the leakage of conduction electrons from the paramagnetic metal to the antiferromagnetic insulator is critical to establishing the ferromagnetic ground state.

Molecular beam epitaxy of quasi-freestanding transition metal disulphide monolayers on van der Waals substrates: a growth study

NASA Astrophysics Data System (ADS)

Hall, Joshua; Pielić, Borna; Murray, Clifford; Jolie, Wouter; Wekking, Tobias; Busse, Carsten; Kralj, Marko; Michely, Thomas

2018-04-01

Based on an ultra-high vacuum compatible two-step molecular beam epitaxy synthesis with elemental sulphur, we grow clean, well-oriented, and almost defect-free monolayer islands and layers of the transition metal disulphides MoS2, TaS2 and WS2. Using scanning tunneling microscopy and low energy electron diffraction we investigate systematically how to optimise the growth process, and provide insight into the growth and annealing mechanisms. A large band gap of 2.55 eV and the ability to move flakes with the scanning tunneling microscope tip both document the weak interaction of MoS2 with its substrate consisting of graphene grown on Ir(1 1 1). As the method works for the synthesis of a variety of transition metal disulphides on different substrates, we speculate that it could be of great use for providing hitherto unattainable high quality monolayers of transition metal disulphides for fundamental spectroscopic investigations.

Accurate identification of layer number for few-layer WS2 and WSe2 via spectroscopic study.

PubMed

Li, Yuanzheng; Li, Xinshu; Yu, Tong; Yang, Guochun; Chen, Heyu; Zhang, Cen; Feng, Qiushi; Ma, Jiangang; Liu, Weizhen; Xu, Haiyang; Liu, Yichun; Liu, Xinfeng

2018-03-23

Transition metal dichalcogenides (TMDs) with a typical layered structure are highly sensitive to their layer number in optical and electronic properties. Seeking a simple and effective method for layer number identification is very important to low-dimensional TMD samples. Herein, a rapid and accurate layer number identification of few-layer WS 2 and WSe 2 is proposed via locking their photoluminescence (PL) peak-positions. As the layer number of WS 2 /WSe 2 increases, it is found that indirect transition emission is more thickness-sensitive than direct transition emission, and the PL peak-position differences between the indirect and direct transitions can be regarded as fingerprints to identify their layer number. Theoretical calculation confirms that the notable thickness-sensitivity of indirect transition derives from the variations of electron density of states of W atom d-orbitals and chalcogen atom p-orbitals. Besides, the PL peak-position differences between the indirect and direct transitions are almost independent of different insulating substrates. This work not only proposes a new method for layer number identification via PL studies, but also provides a valuable insight into the thickness-dependent optical and electronic properties of W-based TMDs.

Theoretical reflections on the structural polymorphism of the oxygen-evolving complex in the S2 state and the correlations to substrate water exchange and water oxidation mechanism in photosynthesis.

PubMed

Guo, Yu; Li, Hui; He, Lan-Lan; Zhao, Dong-Xia; Gong, Li-Dong; Yang, Zhong-Zhi

2017-10-01

The structural polymorphism of the oxygen-evolving complex is of great significance to photosynthetic water oxidation. Employing density functional theory calculations, we have made further advisement on the interconversion mechanism of O5 transfer in the S 2 state, mainly focusing on the potentiality of multi-state reactivity and spin transitions. Then, O5 protonation is proven impossible in S 2 for irreversibility of the interconversion, which serves as an auxiliary judgment for the protonation state of O5 in S 1 . Besides, the structural polymorphism could also be archived by alternative mechanisms involving Mn3 ligand exchange, one of which with Mn3(III) makes sense to substrate water exchange in S 2 , although being irresponsible for the derivations of the observed EPR signals. During the water exchange, high-spin states would prevail to facilitate electron transfer between the ferromagnetically coupled Mn centers. In addition, water exchange in S 1 could account for the closed-cubane structure as the initial form entering S 2 at cryogenic temperatures. With regard to water oxidation, the structural flexibility and variability in both S 2 and S 3 guarantee smooth W2-O5 coupling in S 4 , according to the substrate assignments from water exchange kinetics. Within this theoretical framework, the new XFEL findings on S 1 -S 3 can be readily rationalized. Finally, an alternative mechanistic scenario for OO bond formation with ·OH radical near O4 is presented, followed by water binding to the pivot Mn4(III) from O4 side during S 4 -S 0 . This may diversify the substrate sources combined with the Ca channel in water delivery for the forthcoming S-cycle. Copyright © 2017. Published by Elsevier B.V.

Strain stabilization and thickness dependence of magnetism in epitaxial transition metal monosilicide thin films on Si(111)

NASA Astrophysics Data System (ADS)

Geisler, Benjamin; Kratzer, Peter

2013-09-01

We present a comprehensive study of different 3d transition metal monosilicides in their ground state crystal structure (B20), ranging from equilibrium bulk over biaxially strained bulk to epitaxial thin films on Si(111), by means of density functional theory. The magnetic properties of MnSi and FeSi films are found to be considerably modified due to the epitaxial strain induced by the substrate. In MnSi bulk material, which can be seen as a limit of thick films, we find a strain-induced volume expansion, an increase of the magnetic moments, and a significant rise of the energy difference between different spin configurations. The latter can be associated with an increase of the Curie temperature, which is in accordance with recent experimental results. While a ferromagnetic spin alignment is found to be the ground state also for ultrathin films, we show that for films of intermediate thickness a partially compensating magnetic ordering is more favorable; however, the films retain a net magnetic moment. Furthermore, we analyze the orbital structure in FeSi around the band gap, which can be located somewhere in the density of states for all studied B20 transition metal monosilicides, and find that FeSi becomes metallic and ferromagnetic under epitaxial strain. Finally, the influence of on-site electronic correlation and the reliability of ab initio calculations for 3d transition metal monosilicides are discussed.

Fermi surface and quantum well states of V(110) films on W(110)

NASA Astrophysics Data System (ADS)

Krupin, Oleg; Rotenberg, Eli; Kevan, S. D.

2007-09-01

Using angle-resolved photoemission spectroscopy, we have measured the Fermi surface of V(110) films epitaxially grown on a W(110) substrate. We compare our results for thicker films to existing calculations and measurements for bulk vanadium and find generally very good agreement. For thinner films, we observe and analyse a diverse array of quantum well states that split and distort the Fermi surface segments. We have searched unsuccessfully for a thickness-induced topological transition associated with contact between the zone-centre jungle gym and zone-boundary hole ellipsoid Fermi surface segments. We also find no evidence for ferromagnetic splitting of any bands on this surface.

Noncovalent Organocatalysis Based on Hydrogen Bonding: Elucidation of Reaction Paths by Computational Methods

NASA Astrophysics Data System (ADS)

Etzenbach-Effers, Kerstin; Berkessel, Albrecht

In this article, the functions of hydrogen bonds in organocatalytic reactions are discussed on atomic level by presenting DFT studies of selected examples. Theoretical investigation provides a detailed insight in the mechanism of substrate activation and orientation, and the stabilization of transition states and intermediates by hydrogen bonding (e.g. oxyanion hole). The examples selected comprise stereoselective catalysis by bifunctional thioureas, solvent catalysis by fluorinated alcohols in epoxidation by hydrogen peroxide, and intramolecular cooperative hydrogen bonding in TADDOL-type catalysts.

An In Situ Directing Group Strategy for Chiral Anion Phase-Transfer Fluorination of Allylic Alcohols

PubMed Central

2015-01-01

An enantioselective fluorination of allylic alcohols under chiral anion phase-transfer conditions is reported. The in situ generation of a directing group proved crucial for achieving effective enantiocontrol. In the presence of such a directing group, a range of acyclic substrates underwent fluorination to afford highly enantioenriched α-fluoro homoallylic alcohols. Mechanistic studies suggest that this transformation proceeds through a concerted enantiodetermining transition state involving both C–F bond formation and C–H bond cleavage. PMID:25203796

Electrodeposition of biaxially textured layers on a substrate

DOEpatents

Bhattacharya, Raghu N; Phok, Sovannary; Spagnol, Priscila; Chaudhuri, Tapas

2013-11-19

Methods of producing one or more biaxially textured layer on a substrate, and articles produced by the methods, are disclosed. An exemplary method may comprise electrodepositing on the substrate a precursor material selected from the group consisting of rare earths, transition metals, actinide, lanthanides, and oxides thereof. An exemplary article (150) may comprise a biaxially textured base material (130), and at least one biaxially textured layer (110) selected from the group consisting of rare earths, transition metals, actinides, lanthanides, and oxides thereof. The at least one biaxially textured layer (110) is formed by electrodeposition on the biaxially textured base material (130).

Controlling phase separation in vanadium dioxide thin films via substrate engineering

NASA Astrophysics Data System (ADS)

Gilbert Corder, Stephanie N.; Jiang, Jianjuan; Chen, Xinzhong; Kittiwatanakul, Salinporn; Tung, I.-Cheng; Zhu, Yi; Zhang, Jiawei; Bechtel, Hans A.; Martin, Michael C.; Carr, G. Lawrence; Lu, Jiwei; Wolf, Stuart A.; Wen, Haidan; Tao, Tiger H.; Liu, Mengkun

2017-10-01

The strong electron-lattice interactions in correlated electron systems provide unique opportunities for altering the material properties with relative ease and flexibility. In this Rapid Communication, we use localized strain control via a focused-ion-beam patterning of Ti O2 substrates to demonstrate that one can selectively engineer the insulator-to-metal transition temperature, the fractional component of the insulating and metallic phases, and the degree of optical anisotropy down to the length scales of the intrinsic phase separation in V O2 thin films without altering the quality of the films. The effects of localized strain control on the strongly correlated electron system are directly visualized by state-of-the-art IR near-field imaging and spectroscopy techniques and x-ray microdiffraction measurements.

Controlling phase separation in vanadium dioxide thin films via substrate engineering

DOE PAGES

Gilbert Corder, Stephanie N.; Jiang, Jianjuan; Chen, Xinzhong; ...

2017-10-23

The strong electron-lattice interactions in correlated electron systems provide unique opportunities for altering the material properties with relative ease and flexibility. Here in this Rapid Communication, we use localized strain control via a focused-ion-beam patterning of TiO 2 substrates to demonstrate that one can selectively engineer the insulator-to-metal transition temperature, the fractional component of the insulating and metallic phases, and the degree of optical anisotropy down to the length scales of the intrinsic phase separation in VO 2 thin films without altering the quality of the films. The effects of localized strain control on the strongly correlated electron system aremore » directly visualized by state-of-the-art IR near-field imaging and spectroscopy techniques and x-ray microdiffraction measurements.« less

Dielectric properties of betaine phosphite and deuterated betaine phosphite films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balashova, E. V., E-mail: balashova@mail.ioffe.ru; Krichevtsov, B. B.; Zaitseva, N. V.

2011-01-15

Polycrystalline films of betaine phosphite (BPI) and deuterated BPI have been grown by evaporation on LiNbO{sub 3}, {alpha}-SiO{sub 2}, {alpha}-Al{sub 2}O{sub 3}, and NdGaO{sub 3} substrates. These films consist of large single-crystal blocks in which the polar axis (b) lies in the substrate plane. The results of studying the dielectric properties of the films using interdigital electrodes, X-ray diffraction, and block images in a polarized-light microscope in reflection are reported. The film transition into the ferroelectric state at T = T{sub c} is accompanied by strong anomalies of the capacitance of the film/interdigital structure/substrate structure. The deuteration of BPI filmsmore » leads to an increase in their temperature T{sub c}: from T{sub c} = 200 K for BPI-based structures to T{sub c} = 280 K for structures with a high degree of deuteration (d {approx} 90%).« less

Real-time observation of the conformational dynamics of mitochondrial Hsp70 by spFRET

PubMed Central

Sikor, Martin; Mapa, Koyeli; von Voithenberg, Lena Voith; Mokranjac, Dejana; Lamb, Don C

2013-01-01

The numerous functions of the important class of molecular chaperones, heat shock proteins 70 (Hsp70), rely on cycles of intricate conformational changes driven by ATP-hydrolysis and regulated by cochaperones and substrates. Here, we used Förster resonance energy transfer to study the conformational dynamics of individual molecules of Ssc1, a mitochondrial Hsp70, in real time. The intrinsic dynamics of the substrate-binding domain of Ssc1 was observed to be uncoupled from the dynamic interactions between substrate- and nucleotide-binding domains. Analysis of the fluctuations in the interdomain separation revealed frequent transitions to a nucleotide-free state. The nucleotide-exchange factor Mge1 did not induce ADP release, as expected, but rather facilitated binding of ATP. These results indicate that the conformational cycle of Ssc1 is more elaborate than previously thought and provide insight into how the Hsp70s can perform a wide variety of functions. PMID:23624933

Competitive photocyclization/rearrangement of 4-aryl-1,1-dicyanobutenes controlled by intramolecular charge-transfer interaction. Effect of medium polarity, temperature, pressure, excitation wavelength, and confinement.

PubMed

Ito, Tadashi; Nishiuchi, Emi; Fukuhara, Gaku; Inoue, Yoshihisa; Mori, Tadashi

2011-09-01

A series of 4-aryl-1,1-dicyanobutenes (1a-1f) with different substituents were synthesized to control the intramolecular donor-acceptor or charge-transfer (C-T) interactions in the ground state. Photoexcitation of these C-T substrates led to competitive cyclization and rearrangement, the ratio being critically controlled by various environmental factors, such as solvent polarity, temperature and static pressure, and also by excitation wavelength and supramolecular confinement (polyethylene voids). In non-polar solvents, the rearrangement was dominant (>10 : 1) for all examined substrates, while the cyclization was favoured in polar solvents, in particular at low temperatures. Selective excitation at the C-T band further enhanced the cyclization up to >50 : 1 ratios. More importantly, the cyclization/rearrangement ratio was revealed to be a linear function of the C-T transition energy. However, the substrates with a sterically demanding or highly electron-donating substituent failed to give the cyclization product.

Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

PubMed Central

Byers, Jeffery A.; Jamison, Timothy F.

2013-01-01

Despite the myriad of selective enzymatic reactions that occur in water, chemists have rarely capitalized on the unique properties of this medium to govern selectivity in reactions. Here we report detailed mechanistic investigations of a water-promoted reaction that displays high selectivity for what is generally a disfavored product. A combination of structural and kinetic data indicates not only that synergy between substrate and water suppresses undesired pathways but also that water promotes the desired pathway by stabilizing charge in the transition state, facilitating proton transfer, doubly activating the substrate for reaction, and perhaps most remarkably, reorganizing the substrate into a reactive conformation that leads to the observed product. This approach serves as an outline for a general strategy of exploiting solvent-solute interactions to achieve unusual reactivity in chemical reactions. These findings may also have implications in the biosynthesis of the ladder polyether natural products, such as the brevetoxins and ciguatoxins. PMID:24046369

Wetting Transitions in ^4He/^3He Mixtures on Cesium

NASA Astrophysics Data System (ADS)

Ross, David

1997-03-01

Over the last several years, helium on cesium has proven to be an ideal model system for the study of wetting and wetting transitions(E. Cheng, M.W. Cole, W.F. Saam, and J. Treiner, Phys. Rev. Lett. 67), 1007 (1991).^,(J.E. Rutledge and P. Taborek, Phys. Rev. Lett. 69), 937 (1992).^,(D. Ross, J.E. Rutledge, and P. Taborek, Phys. Rev. Lett. 76), 2350 (1996).. This presentation will focus on the adsorption of binary liquid mixtures of the helium isotopes, ^3He and ^4He, on cesium substrates over a range of temperatures extending from 0.2 K to 1.0 K. The results, spanning ^3He concentrations from 0 to 1, constitute the first experimentally constructed complete wetting phase diagram for a two component liquid at a weakly binding substrate. The wetting behavior is particularly interesting in the vicinity of bulk liquid phase separation. A wetting transition of the ^4He rich liquid between the ^3He rich liquid and the cesium substrate has been found with Tw = 0.53 K. The surface phase transition line associated with this wetting transition is found to extend to both sides of the bulk phase separation line. On the ^3He rich side it is a prewetting line, and on the ^4He rich side it becomes a line of triple point induced dewetting transitions. General arguments indicate that this behavior should be typical of a large class of binary liquid mixtures at weakly binding substrates.

Biochemical profiling in silico--predicting substrate specificities of large enzyme families.

PubMed

Tyagi, Sadhna; Pleiss, Juergen

2006-06-25

A general high-throughput method for in silico biochemical profiling of enzyme families has been developed based on covalent docking of potential substrates into the binding sites of target enzymes. The method has been tested by systematically docking transition state--analogous intermediates of 12 substrates into the binding sites of 20 alpha/beta hydrolases from 15 homologous families. To evaluate the effect of side chain orientations to the docking results, 137 crystal structures were included in the analysis. A good substrate must fulfil two criteria: it must bind in a productive geometry with four hydrogen bonds between the substrate and the catalytic histidine and the oxyanion hole, and a high affinity of the enzyme-substrate complex as predicted by a high docking score. The modelling results in general reproduce experimental data on substrate specificity and stereoselectivity: the differences in substrate specificity of cholinesterases toward acetyl- and butyrylcholine, the changes of activity of lipases and esterases upon the size of the acid moieties, activity of lipases and esterases toward tertiary alcohols, and the stereopreference of lipases and esterases toward chiral secondary alcohols. Rigidity of the docking procedure was the major reason for false positive and false negative predictions, as the geometry of the complex and docking score may sensitively depend on the orientation of individual side chains. Therefore, appropriate structures have to be identified. In silico biochemical profiling provides a time efficient and cost saving protocol for virtual screening to identify the potential substrates of the members of large enzyme family from a library of molecules.

Effects of Solid Fraction on Droplet Wetting and Vapor Condensation: A Molecular Dynamic Simulation Study.

PubMed

Gao, Shan; Liao, Quanwen; Liu, Wei; Liu, Zhichun

2017-10-31

Recently, numerous studies focused on the wetting process of droplets on various surfaces at a microscale level. However, there are a limited number of studies about the mechanism of condensation on patterned surfaces. The present study performed the dynamic wetting behavior of water droplets and condensation process of water molecules on substrates with different pillar structure parameters, through molecular dynamic simulation. The dynamic wetting results indicated that droplets exhibit Cassie state, PW state, and Wenzel state successively on textured surfaces with decreasing solid fraction. The droplets possess a higher static contact angle and a smaller spreading exponent on textured surfaces than those on smooth surfaces. The condensation processes, including the formation, growth, and coalescence of a nanodroplet, are simulated and quantitatively recorded, which are difficult to be observed by experiments. In addition, a wetting transition and a dewetting transition were observed and analyzed in condensation on textured surfaces. Combining these simulation results with previous theoretical and experimental studies will guide us to understand the hypostasis and mechanism of the condensation more clearly.

Optical spectroscopy of excited exciton states in MoS2 monolayers in van der Waals heterostructures

NASA Astrophysics Data System (ADS)

Robert, C.; Semina, M. A.; Cadiz, F.; Manca, M.; Courtade, E.; Taniguchi, T.; Watanabe, K.; Cai, H.; Tongay, S.; Lassagne, B.; Renucci, P.; Amand, T.; Marie, X.; Glazov, M. M.; Urbaszek, B.

2018-01-01

The optical properties of MoS2 monolayers are dominated by excitons, but for spectrally broad optical transitions in monolayers exfoliated directly onto SiO2 substrates detailed information on excited exciton states is inaccessible. Encapsulation in hexagonal boron nitride (hBN) allows approaching the homogenous exciton linewidth, but interferences in the van der Waals heterostructures make direct comparison between transitions in optical spectra with different oscillator strength more challenging. Here we reveal in reflectivity and in photoluminescence excitation spectroscopy the presence of excited states of the A exciton in MoS2 monolayers encapsulated in hBN layers of calibrated thickness, allowing us to extrapolate an exciton binding energy of ≈220 meV. We theoretically reproduce the energy separations and oscillator strengths measured in reflectivity by combining the exciton resonances calculated for a screened two-dimensional Coulomb potential with transfer matrix calculations of the reflectivity for the van der Waals structure. Our analysis shows a very different evolution of the exciton oscillator strength with principal quantum number for the screened Coulomb potential as compared to the ideal two-dimensional hydrogen model.

Dynamically Achieved Active Site Precision in Enzyme Catalysis

PubMed Central

2015-01-01

Conspectus The grand challenge in enzymology is to define and understand all of the parameters that contribute to enzymes’ enormous rate accelerations. The property of hydrogen tunneling in enzyme reactions has moved the focus of research away from an exclusive focus on transition state stabilization toward the importance of the motions of the heavy atoms of the protein, a role for reduced barrier width in catalysis, and the sampling of a protein conformational landscape to achieve a family of protein substates that optimize enzyme–substrate interactions and beyond. This Account focuses on a thermophilic alcohol dehydrogenase for which the chemical step of hydride transfer is rate determining across a wide range of experimental conditions. The properties of the chemical coordinate have been probed using kinetic isotope effects, indicating a transition in behavior below 30 °C that distinguishes nonoptimal from optimal C–H activation. Further, the introduction of single site mutants has the impact of either enhancing or eliminating the temperature dependent transition in catalysis. Biophysical probes, which include time dependent hydrogen/deuterium exchange and fluorescent lifetimes and Stokes shifts, have also been pursued. These studies allow the correlation of spatially resolved transitions in protein motions with catalysis. It is now possible to define a long-range network of protein motions in ht-ADH that extends from a dimer interface to the substrate binding domain across to the cofactor binding domain, over a distance of ca. 30 Å. The ongoing challenge to obtaining spatial and temporal resolution of catalysis-linked protein motions is discussed. PMID:25539048

Modulation of magnetic interaction in Bismuth ferrite through strain and spin cycloid engineering

NASA Astrophysics Data System (ADS)

Yadav, Rama Shanker; Reshi, Hilal Ahmad; Pillai, Shreeja; Rana, D. S.; Shelke, Vilas

2016-12-01

Bismuth ferrite, a widely studied room temperature multiferroic, provides new horizons of multifunctional behavior in phase transited bulk and thin film forms. Bismuth ferrite thin films were deposited on lattice mismatched LaAlO3 substrate using pulsed laser deposition technique. X-ray diffraction confirmed nearly tetragonal (T-type) phase of thin film involving role of substrate induced strain. The film thickness of 56 nm was determined by X-ray reflectivity measurement. The perfect coherence and epitaxial nature of T- type film was observed through reciprocal space mapping. The room temperature Raman measurement of T-type bismuth ferrite thin film also verified phase transition with appearance of only few modes. In parallel, concomitant La and Al substituted Bi1-xLaxFe0.95Al0.05O3 (x = 0.1, 0.2, 0.3) bulk samples were synthesized using solid state reaction method. A structural phase transition into orthorhombic (Pnma) phase at x = 0.3 was observed. The structural distortion at x = 0.1, 0.2 and phase transition at x = 0.3 substituted samples were also confirmed by changes in Raman active modes. The remnant magnetization moment of 0.199 emu/gm and 0.28 emu/gm were observed for x = 0.2 and 0.3 bulk sample respectively. The T-type bismuth ferrite thin film also showed high remnant magnetization of around 20emu/cc. The parallelism in magnetic behavior between T-type thin film and concomitant La and Al substituted bulk samples is indication of modulation, frustration and break in continuity of spiral spin cycloid.

Polymer brushes: a controllable system with adjustable glass transition temperature of fragile glass formers.

PubMed

Xie, Shi-Jie; Qian, Hu-Jun; Lu, Zhong-Yuan

2014-01-28

We present results of molecular dynamics simulations for coarse-grained polymer brushes in a wide temperature range to investigate the factors that affect the glass transition in these systems. We focus on the influences of free surface, polymer-substrate interaction strength, grafting density, and chain length not only on the change of glass transition temperature Tg, but also the fragility D of the glass former. It is found that the confinement can enhance the dependence of the Tg on the cooling rate as compared to the bulk melt. Our layer-resolved analysis demonstrates that it is possible to control the glass transition temperature Tg of polymer brushes by tuning the polymer-substrate interaction strength, the grafting density, and the chain length. Moreover, we find quantitative differences in the influence range of the substrate and the free surface on the density and dynamics. This stresses the importance of long range cooperative motion in glass formers near the glass transition temperature. Furthermore, the string-like cooperative motion analysis demonstrates that there exists a close relation among glass transition temperature Tg, fragility D, and string length ⟨S⟩. The polymer brushes that possess larger string length ⟨S⟩ tend to have relatively higher Tg and smaller D. Our results suggest that confining a fragile glass former through forming polymer brushes changes not only the glass transition temperature Tg, but also the very nature of relaxation process.

A Markov State-based Quantitative Kinetic Model of Sodium Release from the Dopamine Transporter

NASA Astrophysics Data System (ADS)

Razavi, Asghar M.; Khelashvili, George; Weinstein, Harel

2017-01-01

The dopamine transporter (DAT) belongs to the neurotransmitter:sodium symporter (NSS) family of membrane proteins that are responsible for reuptake of neurotransmitters from the synaptic cleft to terminate a neuronal signal and enable subsequent neurotransmitter release from the presynaptic neuron. The release of one sodium ion from the crystallographically determined sodium binding site Na2 had been identified as an initial step in the transport cycle which prepares the transporter for substrate translocation by stabilizing an inward-open conformation. We have constructed Markov State Models (MSMs) from extensive molecular dynamics simulations of human DAT (hDAT) to explore the mechanism of this sodium release. Our results quantify the release process triggered by hydration of the Na2 site that occurs concomitantly with a conformational transition from an outward-facing to an inward-facing state of the transporter. The kinetics of the release process are computed from the MSM, and transition path theory is used to identify the most probable sodium release pathways. An intermediate state is discovered on the sodium release pathway, and the results reveal the importance of various modes of interaction of the N-terminus of hDAT in controlling the pathways of release.

New open conformation of SMYD3 implicates conformational selection and allostery

PubMed Central

Spellmon, Nicholas; Sun, Xiaonan; Xue, Wen; Holcomb, Joshua; Chakravarthy, Srinivas; Shang, Weifeng; Edwards, Brian; Sirinupong, Nualpun; Li, Chunying; Yang, Zhe

2016-01-01

SMYD3 plays a key role in cancer cell viability, adhesion, migration and invasion. SMYD3 promotes formation of inducible regulatory T cells and is involved in reducing autoimmunity. However, the nearly “closed” substrate-binding site and poor in vitro H3K4 methyltransferase activity have obscured further understanding of this oncogenically related protein. Here we reveal that SMYD3 can adopt an “open” conformation using molecular dynamics simulation and small-angle X-ray scattering. This ligand-binding-capable open state is related to the crystal structure-like closed state by a striking clamshell-like inter-lobe dynamics. The two states are characterized by many distinct structural and dynamical differences and the conformational transition pathway is mediated by a reversible twisting motion of the C-terminal domain (CTD). The spontaneous transition from the closed to open states suggests two possible, mutually non-exclusive models for SMYD3 functional regulation and the conformational selection mechanism and allostery may regulate the catalytic or ligand binding competence of SMYD3. This study provides an immediate clue to the puzzling role of SMYD3 in epigenetic gene regulation. PMID:28050603

Ultrasonic studies of high-temperature superconductors

NASA Astrophysics Data System (ADS)

Feller, Jeffrey Robert

1997-09-01

This dissertation consists roughly of two parts. The first part deals with YBa2Cu3O7-δ (YBCO) films deposited on piezoelectric (LiNbO3) substrates. Interdigital surface acoustic wave (SAW) devices (delay lines operating at center frequencies of 50 and 100 MHz) fabricated from YBCO films are examined; insertion loss measurements are presented, and electrode resistance effects are analyzed using equivalent circuit models. Sheet resistance and 168 MHz SAW attenuation measurements of a granular YBCO film on LiNbO3 are also presented. The experimental data are discussed in terms of a percolation theory that models the film as an array of identical YBCO grains connected by resistive junctions which, in the superconducting state behave as Josephson junctions. The normal state resistances of the junctions are assumed to be randomly distributed. In the second part of the dissertation, a number of novel techniques (SAW 'bridges,' the high frequency interdigital proximity probe, and weak acoustic coupling sampled continuous wave spectrometry), used in the study of the vortex state and structural transitions in the normal state of YBCO films and single crystals, are described. Evidence of the existence of a first order structural transition in the vicinity of 220 K is provided.

Hybrid Quantum/Classical Molecular Dynamics Simulations of the Proton Transfer Reactions Catalyzed by Ketosteroid Isomerase: Analysis of Hydrogen Bonding, Conformational Motions, and Electrostatics

PubMed Central

Chakravorty, Dhruva K.; Soudackov, Alexander V.; Hammes-Schiffer, Sharon

2009-01-01

Hybrid quantum/classical molecular dynamics simulations of the two proton transfer reactions catalyzed by ketosteroid isomerase are presented. The potential energy surfaces for the proton transfer reactions are described with the empirical valence bond method. Nuclear quantum effects of the transferring hydrogen increase the rates by a factor of ~8, and dynamical barrier recrossings decrease the rates by a factor of 3–4. For both proton transfer reactions, the donor-acceptor distance decreases substantially at the transition state. The carboxylate group of the Asp38 side chain, which serves as the proton acceptor and donor in the first and second steps, respectively, rotates significantly between the two proton transfer reactions. The hydrogen bonding interactions within the active site are consistent with the hydrogen bonding of both Asp99 and Tyr14 to the substrate. The simulations suggest that a hydrogen bond between Asp99 and the substrate is present from the beginning of the first proton transfer step, whereas the hydrogen bond between Tyr14 and the substrate is virtually absent in the first part of this step but forms nearly concurrently with the formation of the transition state. Both hydrogen bonds are present throughout the second proton transfer step until partial dissociation of the product. The hydrogen bond between Tyr14 and Tyr55 is present throughout both proton transfer steps. The active site residues are more mobile during the first step than during the second step. The van der Waals interaction energy between the substrate and the enzyme remains virtually constant along the reaction pathway, but the electrostatic interaction energy is significantly stronger for the dienolate intermediate than for the reactant and product. Mobile loop regions distal to the active site exhibit significant structural rearrangements and, in some cases, qualitative changes in the electrostatic potential during the catalytic reaction. These results suggest that relatively small conformational changes of the enzyme active site and substrate strengthen the hydrogen bonds that stabilize the intermediate, thereby facilitating the proton transfer reactions. Moreover, the conformational and electrostatic changes associated with these reactions are not limited to the active site but rather extend throughout the entire enzyme. PMID:19799395

SUPECA kinetics for scaling redox reactions in networks of mixed substrates and consumers and an example application to aerobic soil respiration

NASA Astrophysics Data System (ADS)

Tang, Jin-Yun; Riley, William J.

2017-09-01

Several land biogeochemical models used for studying carbon-climate feedbacks have begun explicitly representing microbial dynamics. However, to our knowledge, there has been no theoretical work on how to achieve a consistent scaling of the complex biogeochemical reactions from microbial individuals to populations, communities, and interactions with plants and mineral soils. We focus here on developing a mathematical formulation of the substrate-consumer relationships for consumer-mediated redox reactions of the form A + BE→ products, where products could be, e.g., microbial biomass or bioproducts. Under the quasi-steady-state approximation, these substrate-consumer relationships can be formulated as the computationally difficult full equilibrium chemistry problem or approximated analytically with the dual Monod (DM) or synthesizing unit (SU) kinetics. We find that DM kinetics is scaling inconsistently for reaction networks because (1) substrate limitations are not considered, (2) contradictory assumptions are made regarding the substrate processing rate when transitioning from single- to multi-substrate redox reactions, and (3) the product generation rate cannot be scaled from one to multiple substrates. In contrast, SU kinetics consistently scales the product generation rate from one to multiple substrates but predicts unrealistic results as consumer abundances reach large values with respect to their substrates. We attribute this deficit to SU's failure to incorporate substrate limitation in its derivation. To address these issues, we propose SUPECA (SU plus the equilibrium chemistry approximation - ECA) kinetics, which consistently imposes substrate and consumer mass balance constraints. We show that SUPECA kinetics satisfies the partition principle, i.e., scaling invariance across a network of an arbitrary number of reactions (e.g., as in Newton's law of motion and Dalton's law of partial pressures). We tested SUPECA kinetics with the equilibrium chemistry solution for some simple problems and found SUPECA outperformed SU kinetics. As an example application, we show that a steady-state SUPECA-based approach predicted an aerobic soil respiration moisture response function that agreed well with laboratory observations. We conclude that, as an extension to SU and ECA kinetics, SUPECA provides a robust mathematical representation of complex soil substrate-consumer interactions and can be applied to improve Earth system model (ESM) land models.