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Proteins are continuously synthesized during cell growth and proliferation. At the same time, excessive and misfolded proteins have to be degraded, otherwise they are a burden to cells. Protein degradation is essential to maintain proteostasis in cells, and dysfunction of protein degradation systems results in numerous diseases such as cancer and neurodegenerative diseases. Despite the importance of protein degradation, the degradation pathways of many proteins remain to be explored. Here, we comprehensively investigated the degradation of newly synthesized proteins in human cells by integrating metabolic labeling, click chemistry, and multiplexed proteomics, and systematic and quantitative analysis of newly synthesized proteins first revealed the degradation pathways of many proteins. Bioinformatic analysis demonstrates that proteins degraded through two major pathways have distinct properties and functions. Proteins degraded through the ubiquitin-proteasome pathway contain more disordered structures, whereas those through the autophagy-lysosome pathway have significantly higher hydrophobicity. Systematic and quantitative investigation of the dynamics of newly synthesized proteins provides unprecedented and valuable information about protein degradation, which leads to a better understanding of protein properties and cellular activities.Systematic quantification of the dynamics of newly synthesized proteins first reveals the degradation pathways of many proteins in human cells, and proteins degraded through each of the two major pathways have distinct properties and functions. 相似文献
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Haopeng Wang Ninghang Lin Kaveh Kahen Hamid Badiei Kaveh Jorabchi 《Journal of the American Society for Mass Spectrometry》2014,25(4):692-695
We present plasma-assisted reaction chemical ionization (PARCI) for elemental analysis of halogens in organic compounds. Organohalogens are broken down to simple halogen-containing molecules (e.g., HBr) in a helium microwave-induced plasma followed by negative mode chemical ionization (CI) in the afterglow region. The reagent ions for CI originate from penning ionization of gases (e.g., N2) introduced into the afterglow region. The performance of PARCI-mass spectrometry (MS) is evaluated using flow injection analyses of organobromines, demonstrating 5–8 times better sensitivities compared with inductively coupled plasma MS. We show that compound-dependent sensitivities in PARCI-MS mainly arise from sample introduction biases. Figure
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Two different order reduction methods of the deterministic and stochastic systems are discussed in this paper. First, the transient proper orthogonal
decomposition (T-POD) method is introduced based on the high-dimensional nonlinear dynamic system. The optimal order reduction conditions of the T-POD
method are provided by analyzing the rotor-bearing system with pedestal looseness fault at both ends. The efficiency of the T-POD method is verified via comparing with the results of the original system. Second, the polynomial dimensional
decomposition (PDD) method is applied to the 2 DOFs spring system considering
the uncertain stiffness to study the amplitude-frequency response. The numerical
results obtained by the PDD method agree well with the Monte Carlo simulation
(MCS) method. The results of the PDD method can approximate to MCS better
with the increasing of the polynomial order. Meanwhile, the Uniform-Legendre
polynomials can eliminate perturbation of the PDD method to a certain extent
via comparing it with the Gaussian-Hermite polynomials. 相似文献
4.
Neuraminidase is a significant anti‐influenza target that plays crucial role in virus replication cycle. The discovery of 150‐cavity in Group‐1 neuraminidase provides us a novel mentality of designing inhibitor which can bind with both conserved site and 150‐cavity. In order to discover novel dual‐site‐binding inhibitors, a 3D chemical‐feature‐based pharmacophore model was established to cover dual‐site in neuraminidase. The dual‐site‐binding model was consistent in predicting the binding conformation of Group‐1 neuraminidase inhibitor and applied for virtual screening of Specs database. Compound 4 (ZINC05790048) that aligned well to the model was selected after multiple filtrations for molecular dynamics simulations, indicating improved binding energy with neuraminidase. It can sever as the lead compound for a novel series of inhibitors. 相似文献
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Ko YJ Shakya A Wang H Grubisic A Zheng W Götz M Ganteför G Bowen KH Jena P Kiran B 《The Journal of chemical physics》2010,133(12):124308
The equilibrium structure, stability, and electronic properties of the Al(13)X (X=H,Au,Li,Na,K,Rb,Cs) clusters have been studied using a combination of photoelectron spectroscopy experiment and density functional theory. All these clusters constitute 40 electron systems with 39 electrons contributed by the 13 Al atoms and 1 electron contributed by each of the X (X=H,Au,Li,Na,K,Rb,Cs) atom. A systematic study allows us to investigate whether all electrons contributed by the X atoms are alike and whether the structure, stability, and properties of all the magic clusters are similar. Furthermore, quantitative agreement between the calculated and the measured electron affinities and vertical detachment energies enable us to identify the ground state geometries of these clusters both in neutral and anionic configurations. 相似文献
7.
A novel ligand‐based pharmacophore model for KDR kinase was generated on the basis of chemical features of 30 KDR kinase inhibitors. This pharmacophore model consists of one hydrogen‐bond acceptor, one hydrogen‐bond donor and two hydrophobic groups. Several methods have been used to validate the model, suggesting that it can serve as a reliable tool for virtual screening to facilitate the discovery of novel KDR inhibitors. The model was then used as database search query from the National Cancer Institute (NCI) database for the rational design to identify new hit compound. 相似文献
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Ma B Wang L Dong H Gao R Geng Y Zhu Y Qiu Y 《Physical chemistry chemical physics : PCCP》2011,13(7):2656-2658
PbS QDs have been synthesized by an in situ photocatalysis method using the photocatalytic activity of nanocrystalline TiO(2) films. Both the photovoltaic response and size of the synthesized PbS QDs were analyzed. Compared with the conventional synthesis route, this method is simpler and produces less waste. 相似文献
10.
Marcela R. Beltrán Fernando Buendía Zamudio Vikas Chauhan Prasenjit Sen Haopeng Wang Yeon Jae Ko Kit Bowen 《The European Physical Journal D - Atomic, Molecular, Optical and Plasma Physics》2013,67(3):1-8
We present an analysis of Na-He collisional profiles at high density and very low temperature in a unified line shape semi-classical theory which contains the impact as well the quasistatic limits. Clearly understanding the variation of shape of the two fine-structure components of the 3s?3p line with increasing helium density allows us to understand experimental spectra of a Na atom attached to He nanodroplets. We compare our collisional approach to path integral Monte Carlo calculations using the same ab initio Na-He molecular potentials. 相似文献