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排序方式: 共有954条查询结果,搜索用时 15 毫秒
41.
Sandra Schlee Kristina Straub Thomas Schwab Thomas Kinateder Rainer Merkl Reinhard Sterner 《Proteins》2019,87(10):815-825
It is an important goal of computational biology to correctly predict the association state of a protein based on its amino acid sequence and the structures of known homologues. We have pursued this goal on the example of anthranilate phosphoribosyltransferase (AnPRT), an enzyme that is involved in the biosynthesis of the amino acid tryptophan. Firstly, known crystal structures of naturally occurring homodimeric AnPRTs were analyzed using the Protein Interfaces, Surfaces, and Assemblies (PISA) service of the European Bioinformatics Institute (EBI). This led to the identification of two hydrophobic “hot spot” amino acids in the protein-protein interface that were predicted to be essential for self-association. Next, in a comprehensive multiple sequence alignment (MSA), naturally occurring AnPRT variants with hydrophilic or charged amino acids in place of hydrophobic residues in the two hot spot positions were identified. Representative variants were characterized in terms of thermal stability, enzymatic activity, and quaternary structure. We found that AnPRT variants with charged residues in both hot spot positions exist exclusively as monomers in solution. Variants with hydrophilic amino acids in one hot spot position occur in both forms, monomer and dimer. The results of the present study provide a detailed characterization of the determinants of the AnPRT monomer-dimer equilibrium and show that analysis of hot spots in combination with MSAs can be a valuable tool in prediction of protein quaternary structures. 相似文献
42.
Sebastian Swanson Venkatesh Sivaraman Gevorg Grigoryan Amy E. Keating 《Protein science : a publication of the Protein Society》2022,31(6)
Despite advances in protein engineering, the de novo design of small proteins or peptides that bind to a desired target remains a difficult task. Most computational methods search for binder structures in a library of candidate scaffolds, which can lead to designs with poor target complementarity and low success rates. Instead of choosing from pre‐defined scaffolds, we propose that custom peptide structures can be constructed to complement a target surface. Our method mines tertiary motifs (TERMs) from known structures to identify surface‐complementing fragments or “seeds.” We combine seeds that satisfy geometric overlap criteria to generate peptide backbones and score the backbones to identify the most likely binding structures. We found that TERM‐based seeds can describe known binding structures with high resolution: the vast majority of peptide binders from 486 peptide‐protein complexes can be covered by seeds generated from single‐chain structures. Furthermore, we demonstrate that known peptide structures can be reconstructed with high accuracy from peptide‐covering seeds. As a proof of concept, we used our method to design 100 peptide binders of TRAF6, seven of which were predicted by Rosetta to form higher‐quality interfaces than a native binder. The designed peptides interact with distinct sites on TRAF6, including the native peptide‐binding site. These results demonstrate that known peptide‐binding structures can be constructed from TERMs in single‐chain structures and suggest that TERM information can be applied to efficiently design novel target‐complementing binders. 相似文献
43.
Imaging mass spectrometry (IMS) has developed into a powerful tool allowing label-free detection of numerous biomolecules in situ. In contrast to shotgun proteomics, proteins/peptides can be detected directly from biological tissues and correlated to its morphology leading to a gain of crucial clinical information. However, direct identification of the detected molecules is currently challenging for MALDI–IMS, thereby compelling researchers to use complementary techniques and resource intensive experimental setups. Despite these strategies, sufficient information could not be extracted because of lack of an optimum data combination strategy/software. Here, we introduce a new open-source software ImShot that aims at identifying peptides obtained in MALDI–IMS. This is achieved by combining information from IMS and shotgun proteomics (LC–MS) measurements of serial sections of the same tissue. The software takes advantage of a two-group comparison to determine the search space of IMS masses after deisotoping the corresponding spectra. Ambiguity in annotations of IMS peptides is eliminated by introduction of a novel scoring system that identifies the most likely parent protein of a detected peptide in the corresponding IMS dataset. Thanks to its modular structure, the software can also handle LC–MS data separately and display interactive enrichment plots and enriched Gene Ontology terms or cellular pathways. The software has been built as a desktop application with a conveniently designed graphic user interface to provide users with a seamless experience in data analysis. ImShot can run on all the three major desktop operating systems and is freely available under Massachusetts Institute of Technology license. 相似文献
44.
45.
Shama Ahmad Aftab Ahmad Keith B. Neeves Tara Hendry-Hofer Joan E. Loader Carl W. White Livia Veress 《Journal of visualized experiments : JoVE》2014,(87)
Cell cultures are indispensable to develop and study efficacy of therapeutic agents, prior to their use in animal models. We have the unique ability to model well differentiated human airway epithelium and heart muscle cells. This could be an invaluable tool to study the deleterious effects of toxic inhaled chemicals, such as chlorine, that can normally interact with the cell surfaces, and form various byproducts upon reacting with water, and limiting their effects in submerged cultures. Our model using well differentiated human airway epithelial cell cultures at air-liqiuid interface circumvents this limitation as well as provides an opportunity to evaluate critical mechanisms of toxicity of potential poisonous inhaled chemicals. We describe enhanced loss of membrane integrity, caspase release and death upon toxic inhaled chemical such as chlorine exposure. In this article, we propose methods to model chlorine exposure in mammalian heart and airway epithelial cells in culture and simple tests to evaluate its effect on these cell types. 相似文献
46.
Daniel J.V.A. dos Santos 《Molecular simulation》2015,41(5-6):455-462
The effect of replacing bis(trifluoromethylsulphonyl)imide ([NTf2]) by hexafluorophosphate ([PF6]) in room temperature ionic liquid (IL) 1-butyl-3-methylimidazolium bis(trifluoromethylsulphonyl)imide ([BMIm][NTf2]) confined between two gold interfaces is herein reported through molecular dynamics simulations using all-atom non-polarisable force-fields. Five systems were studied ranging from pure [BMIm][NTf2] to pure [BMIm][PF6], with [PF6] molar fractions of 0, 0.125, 0.25, 0.375 and 0.5. Special attention was drawn to investigate the impact of the [PF6] anion on the IL, in particular on the first layers of the liquid in close contact with the solid gold surface. 相似文献
47.
Background
The Brain Computer Interfaces (BCI) are devices allowing direct communication between the brain of a user and a machine. This technology can be used by disabled people in order to improve their independence and maximize their capabilities such as finding an object in the environment. Such devices can be realized by the non-invasive measurement of information from the cortex by electroencephalography (EEG).Methods
Our work proposes a novel BCI system that consists of controlling a robot arm based on the user's thought. Four subjects (1 female and 3 males) aged between 20 and 29 years have participated to our experiment. They have been instructed to imagine the execution of movements of the right hand, the left hand, both right and left hands or the movement of the feet depending on the protocol established.EMOTIV EPOC headset was used to record neuronal electrical activities from the subject's scalp, these activities were then sent to the computer for analysis. Feature extraction was performed using the Principal Component Analysis (PCA) method combined with the Fast Fourier transform (FFT) spectrum within the frequency band responsible for sensorimotor rhythms (8 Hz–22 Hz).These features were then fed into a Support Vector Machine (SVM) classifier based on a Radial Base Function (RBF) whose outputs were translated into commands to control the robot arm.Results
The proposed BCI enabled the control of the robot arm in the four directions: right, left, up and down, achieving an averaged accuracy of 85.45% across all the subjects.Conclusion
The results obtained would encourage, with further developments, the use of the proposed BCI to perform more complex tasks such as execution of successive movements or stopping the execution once a searched object is detected. This would provide a useful assistance means for people with motor impairment. 相似文献48.
Germanium Thin Film Protected Lithium Aluminum Germanium Phosphate for Solid‐State Li Batteries 下载免费PDF全文
Yijie Liu Chao Li Bojie Li Hucheng Song Zhu Cheng Minrui Chen Ping He Haoshen Zhou 《Liver Transplantation》2018,8(16)
Solid‐state Li batteries using Na+ superionic conductor type solid electrolyte attracts wide interest because of its safety and high theoretical energy density. The NASCION type solid electrolyte LAGP (Li1.5Al0.5Ge0.5P3O12) shows favorable conductivity as well as good mechanical strength to prevent Li dendrite penetration. However, the instability of LAGP with Li metal remains a great challenge. In this work, an amorphous Ge thin film is sputtered on an LAGP surface, which can not only suppress the reduction reaction of Ge4+ and Li, but also produces intimate contact between the Li metal and the LAGP solid electrolyte. The symmetric cell with the Ge‐coated LAGP solid electrolyte shows superior stability and cycle performance for 100 cycles at 0.1 mA cm?2. A quasi‐solid‐state Li–air battery has also been assembled to further demonstrate this advantage. A stable cycling performance of 30 cycles in ambient air can be obtained. This work helps to achieve a stable and ionic conducting interface in solid‐state Li batteries. 相似文献
49.
Toward Long‐Term Stable and Highly Efficient Perovskite Solar Cells via Effective Charge Transporting Materials 下载免费PDF全文
Perovskite solar cells (PSCs) have advanced quickly with their power conversion efficiency approaching the record of silicon solar cells. However, there is still a big challenge to obtain both high efficiency and long‐term stability for future commercialization of PSCs. The major instability issue is associated with the decomposition or phase transition of perovskite materials that are believed to be intrinsically unstable under outdoor working conditions. Herein, the authors review the approaches that marked important progress in developing new functional electron/hole transporting materials that enabled highly efficient and stable PSCs. The findings that accelerate charge diffusion and that suppress the irrevocable loss of ions diffusing out of perovskite materials and other diffusion processes are highlighted. In addition, derivative interface engineering methods to control the diffusion process of charges/ions/molecules are also reviewed. Finally, the authors propose key research issues in charge transporting materials and interface engineering with regard to the important diffusion processes that will be one of the keys to realize highly efficient and long‐term stable PSCs. 相似文献
50.
Hong Yuan Hong‐Jie Peng Bo‐Quan Li Jin Xie Long Kong Meng Zhao Xiao Chen Jia‐Qi Huang Qiang Zhang 《Liver Transplantation》2019,9(1)
Rechargeable lithium–sulfur batteries have attracted tremendous scientific attention owing to their superior energy density. However, the sulfur electrochemistry involves multielectron redox reactions and complicated phase transformations, while the final morphology of solid‐phase Li2S precipitates largely dominate the battery's performance. Herein, a triple‐phase interface among electrolyte/CoSe2/G is proposed to afford strong chemisorption, high electrical conductivity, and superb electrocatalysis of polysulfide redox reactions in a working lithium–sulfur battery. The triple‐phase interface effectively enhances the kinetic behaviors of soluble lithium polysulfides and regulates the uniform nucleation and controllable growth of solid Li2S precipitates at large current density. Therefore, the cell with the CoSe2/G functional separator delivers an ultrahigh rate cycle at 6.0 C with an initial capacity of 916 mAh g?1 and a capacity retention of 459 mAh g?1 after 500 cycles, and a stable operation of high sulfur loading electrode (2.69–4.35 mg cm?2). This work opens up a new insight into the energy chemistry at interfaces to rationally regulate the electrochemical redox reactions, and also inspires the exploration of related energy storage and conversion systems based on multielectron redox reactions. 相似文献