Nicotinamide dinucleotide binding to transhydrogenase purified from Escherichia coli was investigated by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Detergent-free transhydrogenase was deposited as a thin film on an ATR prism, and spectra were recorded during perfusion with buffers in the presence and absence of dinucleotide (NADP(+), NADPH, NAD(+), or NADH) in both H(2)O and D(2)O media. IR spectral changes were attributable to the bound dinucleotides and to changes in the protein itself. The dissociation constant of NADPH was estimated to be approximately 5 muM from a titration of the magnitude of the IR changes against the nucleotide concentration. IR spectra of related model compounds were used to assign principle bands of the dinucleotides. This information was combined with IR data on amino acids and with protein crystallographic data to identify interactions between specific parts of the dinucleotides and their binding sites in the protein. Several IR bands of bound nucleotide were sharpened and/or shifted relative to those in aqueous solution, reflecting a restriction to motion and a change in environment upon binding. Alterations in the protein secondary structure indicated by amide I/II changes were distinctly different for NADP(H) and for NAD(H) binding. The data suggest that NADP(H) binding leads to perturbation of a deeply buried part of the polypeptide backbone and to protonation of a carboxylic acid residue. 相似文献
Infrared multiple-photon dissociation (IR-MPD) spectroscopy has been applied to singly-charged complexes involving the transition metals Ag(+) and Zn(2+) with the aromatic amino acid phenylalanine. These studies are complemented by DFT calculations. For [Phe+Ag](+) the calculations favor a tridentate charge solvation N/O/ring structure. The experimental spectrum strongly supports this as the predominant binding geometry and, in particular, rules out a significant presence of the salt-bridge conformation. Zn(2+) forms a deprotonated dimer complex with Phe, [Zn+Phe(2)-H](+), in which the +2 oxidation state serves as a useful biomimetic model for zinc protein sites. A number of low-energy conformations were located, of which the lowest-energy conformer predicted by the calculations involves a Phe ligand deprotonated on the carboxylic acid, while the other Phe ligand is in the tridentate charge solvation conformation. The calculated IR spectrum of this conformer gives a close fit to the experimental spectrum, strongly supporting this as the predominant binding geometry. This most stable calculated complex is characterized by N/ O/ring metal chelation with a tetrahedral-type coordination core of Zn(2+) to N and O of both ligands. Another similar tightly chelated structure shows a square-planar-type coordination core, but this structure is computed to be less stable and gives a less satisfactory match to the experimental spectrum. This preference for the tetrahedral geometry of the Lewis-basic atomic ligands parallels the common Zn(II) coordination geometry in proteins. The number of clearly identifiable peaks resolved in the IR-MPD spectra as well as the much-improved matches between the observed spectra and the DFT-calculated spectra of the most stable geometries compared to previous studies are noteworthy for systems of this size and complexity. These results demonstrate that IR spectroscopy of transition metal-amino acid complexes in combination with DFT calculations is a very powerful structural tool, readily applicable to biomimetic systems that model, for example, the reaction centers of proteins in the solvent-free environment. In addition, we present a novel ion-capturing method for Fourier transform ion cyclotron resonance mass spectrometry which removes the necessity of a buffer gas pulse, while allowing ion trapping at moderate voltages with apparently reduced collisional excitation of the ions. 相似文献
For suitable bounded operator semigroups (etA)t≥0 in a Banach space, we characterize the estimate ‖AetA‖≤c/F(t) for large t, where F is a function satisfying a sublinear growth condition. The characterizations are by holomorphy estimates on the semigroup,
and by estimates on powers of the resolvent. We give similar characterizations of the difference estimate ‖Tn−Tn+1‖≤c/F(n) for a power-bounded linear operator T, when F(n) grows faster than n1/2 for large n. 相似文献
The tensor rank decomposition, or canonical polyadic decomposition, is the decomposition of a tensor into a sum of rank-1 tensors. The condition number of the tensor rank decomposition measures the sensitivity of the rank-1 summands with respect to structured perturbations. Those are perturbations preserving the rank of the tensor that is decomposed. On the other hand, the angular condition number measures the perturbations of the rank-1 summands up to scaling. We show for random rank-2 tensors that the expected value of the condition number is infinite for a wide range of choices of the density. Under a mild additional assumption, we show that the same is true for most higher ranks \(r\ge 3\) as well. In fact, as the dimensions of the tensor tend to infinity, asymptotically all ranks are covered by our analysis. On the contrary, we show that rank-2 tensors have finite expected angular condition number. Based on numerical experiments, we conjecture that this could also be true for higher ranks. Our results underline the high computational complexity of computing tensor rank decompositions. We discuss consequences of our results for algorithm design and for testing algorithms computing tensor rank decompositions.
How likely is it that Magnus Carlsen will achieve his goal of a 2900 Elo rating? At what level of play does Magnus have a reasonable chance of reaching the 2900 goal? These two questions are of great current interest to Magnus and the chess community. The probabilistic properties of Elo's rating system are well known, and together with a Brownian motion model of rating evolution, we use simulation-based methods to address these questions. Our model assesses that Magnus has a 4.5% chance of reaching 2900 if he continues his 2020–2022 level of play. However, this increases dramatically to % chance if he can repeat his hot streak performance of 2019 which is not an easy undertaking. The probabilities are intimately related to Elo's choice -factor used for grandmaster chess play. Finally, we conclude with a discussion of the policy issues involved with the choice of -factor. 相似文献
Pyrazolones represent an important structural motif in active pharmaceutical ingredients. Their asymmetric synthesis is thus widely studied. Still, a generally highly enantio- and diastereoselective 1,4-addition to nitroolefins providing products with adjacent stereocenters is elusive. In this article, a new polyfunctional CuII-1,2,3-triazolium-aryloxide catalyst is presented which enables this reaction type with high stereocontrol. DFT studies revealed that the triazolium stabilizes the transition state by hydrogen bonding between C(5)−H and the nitroolefin and verify a cooperative mode of activation. Moreover, they show that the catalyst adopts a rigid chiral cage/pore structure by intramolecular hydrogen bonding, by which stereocontrol is achieved. Control catalyst systems confirm the crucial role of the triazolium, aryloxide and CuII, requiring a sophisticated structural orchestration for high efficiency. The addition products were used to form pyrazolidinones by chemoselective C=N reduction. These heterocycles are shown to be valuable precursors toward β,γ’-diaminoamides by chemoselective nitro and N−N bond reductions. Morphological profiling using the Cell painting assay identified biological activities for the pyrazolidinones and suggest modulation of DNA synthesis as a potential mode of action. One product showed biological similarity to Camptothecin, a lead structure for cancer therapy. 相似文献
A comparative study in the framework of large deformations has been conducted to get insight into micro mechanical response of particulate polymeric composites. The propound model enables finite element predictions of displacement response and resulting debonding of a three-phase material subjected to incremental loading conditions. Predictions employ a unit cell of certain shape under specified loading and constraints. The proposed model involves nonlinear material properties and incorporates a strong or weak non-homogeneous interphase region. The interphase toughness is expressed in terms of the adhesion efficiency between the filler and the matrix, though contact conditions are preserved utilizing special contact elements. Interfacial nonlinear spring joint elements regulate debonding initialization, in relation to the imposed failure criterion. Numerical results are presented and discussed for axial tensile and compressive loadings for a variety of values of the imposed parameters. 相似文献
Bulk polymerizations of methyl methacrylate (MMA) at 60°C initiated with 2,2′-azoisobutyronitrile are influenced by the presence of an organic π-donor such as tetrathiafulvalene (TTF). Upon addition of TTF, the ratio of weight- to number-average molecular weights M̄w/M̄n are significantly reduced and the thermal stability of the poly(methyl methacrylate) samples is increased. Kinetic investigations indicate that TTF acts as a retarder on the polymerization mechanism. 相似文献