The residue located at 15 positions before the most conserved residue in TM7 (7.35 of Ballesteros–Weinstein number) plays important roles in ligand binding and the receptor activity for class A GPCRs. Nevertheless, its regulation mechanism has not been clearly clarified in experiments, and some controversies also exist for its impact on μ-opioid receptors (μOR) bound by agonists. Thus, we chose the μ-opioid receptor (μOR) of class A GPCRs as a representative and utilized a microsecond accelerated molecular dynamics simulation (aMD) coupled with a protein structure network (PSN) to explore the effect of W3187.35 on its functional activity induced by the agonist endomorphin2 mainly by a comparison of the wild system and its W7.35A mutant. When endomorphin2 binds to the wild-type μOR, TM6 in μOR moves outward to form an open intracellular conformation that is beneficial to accommodating the β-arrestin transducer, rather than the G-protein transducer due to the clash with the α5 helix of G-protein, thus acting as a β-arrestin biased agonist. However, the W318A mutation induces the intracellular part of μOR to form a closed state, which disfavors coupling with either G-protein or β-arrestin. The allosteric pathway analysis further reveals that the binding of endomorphin2 to the wild-type μOR transmits more activation signals to the β-arrestin binding site while the W318A mutation induces more structural signals to transmit to common binding residues of the G protein and β-arrestin. More interestingly, the residue at the 7.35 position regulates the shortest allosteric pathway in indirect ways by influencing the interactions between other ligand-binding residues and endomorphin2. W2936.48 and F2896.44 are important for regulating the different activities of μOR induced either by the agonist or by the mutation. Y3367.53, F3438.50, and D3408.47 play crucial roles in activating the β-arrestin biased signal induced by the agonist endomorphin2, while L1583.43 and V2866.41 devote important contributions to the change in the activity of endomorphin2 from the β-arrestin biased agonist to the antagonist upon the W318A mutation.
When measuring the surface subsidence of unstable areas such as railroad beds and large construction fields, it is not practical to always find stable positions to install measurement instruments. Yet installing those instruments in unstable positions will cause measurement errors or even the complete failure of long-term subsidence surveillance. In this paper, the innovative concept and its method of "displacement-relay videometrics" are proposed. With the method, a double-headed camera is designed, and two constraints, the "fixation constraint" and the "homologous constraint", are established to construct the displacement-relay measurement equations, which can concurrently give the subsidence of the points to be measured and the positions where the cameras are fixed. The method and its measurement system are thus capable of automatically measuring the surface subsidence under the condition that the cameras are mounted on unstable locations over long durations. Therefore, the method has the broad prospect of undertaking automatic, long-term and continuous measurement for surface subsidence in engineering projects such as railroad beds, bridges and the ground beds of tall buildings. The proposed method opens a new area that cameras can be mounted on unstable platform to make high accuracy measurements, which is of great significance for applications. videometrics, displacement relay, subsidence surveillance, series camera network Citation: Yu Q F, Jiang G W, Shang Y, et al. A displacement-relay videometric method for surface subsidence surveillance in unstable areas. Sci China Tech Sci,
A radial unbalanced magnetic pull (UMP) can be produced by an eccentric rotor and leads vibrations in large hydro-turbine generators. The influence of nonlinear UMP on the radial vibration of a large hydro-turbine generator is analyzed in this paper. The UMP is determined as a function of eccentricities and field currents by means of a simple analytical method instead of the finite element (FE) method. The analytical method employs the no-load characteristic curve of an electrical machine and saturation effects of the ferromagnetic materials are taken into consideration. FE rotor model of a large hydro-turbine generator unit, taking account of guide bearings, thrust bearing and periodic forces, is developed to investigate the influence of UMP on radial vibrations. The FE rotor model and the analytical method for UMP constitute the computational model. UMP is calculated under different rotor eccentricities and field currents by the proposed method. Comparing with other analytical methods, the effectiveness of the proposed method is verified. Dynamic responses of the FE model under different analytical methods for UMP are calculated to investigate the difference in vibration between different analytical methods. A simulated excitation test is performed and a comparative analysis between the calculated results and the field data is provided. The computational model is proved to be reasonable according to the analysis.
The relationship of structural characters of the tripeptidic amine-bisamido-thiol (N 3 S type) chelators with the lipophilicity, configuration, and stability of four [99m TcO]N 3 S and one [ReO]N 3 S chelates is studied here. The results show that the hydroxymethyl group on the two N 3 S chelators, RP294 and RP435, has inhibited neither the formation nor interconversion of syn and anti stereoisomers of the chelates, while the tert-butyl group on RP455 and RP535 has prevented the anti isomer from converting to the syn one both in acidic and neutral solutions. The interconversion rates of a stereoisomer can be accelerated at higher pH.
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