A new protein-ligand binding sites prediction method based on the integration of protein sequence conservation information

<p>Abstract</p> <p>Background</p> <p>Prediction of protein-ligand binding sites is an important issue for protein function annotation and structure-based drug design. Nowadays, although many computational methods for ligand-binding prediction have been developed, there is still a demanding to improve the prediction accuracy and efficiency. In addition, most of these methods are purely geometry-based, if the prediction methods improvement could be succeeded by integrating physicochemical or sequence properties of protein-ligand binding, it may also be more helpful to address the biological question in such studies.</p> <p>Results</p> <p>In our study, in order to investigate the contribution of sequence conservation in binding sites prediction and to make up the insufficiencies in purely geometry based methods, a simple yet efficient protein-binding sites prediction algorithm is presented, based on the geometry-based cavity identification integrated with sequence conservation information. Our method was compared with the other three classical tools: PocketPicker, SURFNET, and PASS, and evaluated on an existing comprehensive dataset of 210 non-redundant protein-ligand complexes. The results demonstrate that our approach correctly predicted the binding sites in 59% and 75% of cases among the TOP1 candidates and TOP3 candidates in the ranking list, respectively, which performs better than those of SURFNET and PASS, and achieves generally a slight better performance with PocketPicker.</p> <p>Conclusions</p> <p>Our work has successfully indicated the importance of the sequence conservation information in binding sites prediction as well as provided a more accurate way for binding sites identification.</p

Hollow metal organic frameworks composite prepared via an "escape from the cage" strategy

A step-by-step self-assembly and concurrent self-etching strategy that differs from previous methods used to prepare SiO2@UiO-66-NH2 hollow composite has been reported. The magnetic core was selectively etched to generate a hollow metal-organic framework superstructure. The physical and chemical properties were characterized by TEM and SEM techniques, composition by SEM-EDX. Benefit from the efficient mass transfer and enhanced active sites accessibility, the hollow SiO2@UiO-66-NH2 composite showed higher or comparable catalytic activity than the nano-sized UiO-66-NH2 in the Knoevenagel condensation as a solid basic catalyst. Furthermore, it could be recovered and stable in terms of activity and structure when recycled for at least four times. (C) 2019 Elsevier B.V. All rights reserved

Progress in function and regulation of nitrate transporters in plants

Nitrate transporters can not only uptake and transport nitrate in plants,but also play key roles in many other physiological processes. This article reviewed the multiple functions of nitrate transporter in nitrate accumulation,lateral root development,hormone transport,and stress tolerance,etc. The expression regulation of nitrate transporters was also discussed

Research on Transient DC Bias Analysis and Suppression in EPS DAB DC-DC Converter

During excitation and demagnetization phase for the superconducting magnet, in dual-active-bridge (DAB) converter based power supply, a dc bias may occur in high-frequency transformer and thus lead to the faults. In this paper, an improved transient extend-phase-shift (TEPS) control strategy is proposed to suppress the dc bias without any additional hardware. Unlike the traditional extend-phase-shift (EPS) strategy, the voltages of the transformer are asymmetrical for half a period after changing phase-shift and then remain symmetrical. This makes it take half a switching period for the current of transformer to reach the steady state, and then eliminates the dc bias. The experiment verifies the performance on dc bias suppression. This method provides a good theoretical and experimental basis for the EPS DAB DC-DC converter to realize the optimal control for excitation and demagnetization system in high-field superconducting magnet power supply (SMPS)

TPGS-b-PBAE Copolymer-Based Polyplex Nanoparticles for Gene Delivery and Transfection In Vivo and In Vitro

Poly (β-amino ester) (PBAE) is an exceptional non-viral vector that is widely used in gene delivery, owing to its exceptional biocompatibility, easy synthesis, and cost-effectiveness. However, it carries a high surface positive charge that may cause cytotoxicity. Therefore, hydrophilic d-α-tocopherol polyethylene glycol succinate (TPGS) was copolymerised with PBAE to increase the biocompatibility and to decrease the potential cytotoxicity of the cationic polymer-DNA plasmid polyplex nanoparticles (NPs) formed through electrostatic forces between the polymer and DNA. TPGS-b-PBAE (TBP) copolymers with varying feeding molar ratios were synthesised to obtain products of different molecular weights. Their gene transfection efficiency was subsequently evaluated in HEK 293T cells using green fluorescent protein plasmid (GFP) as the model because free GFP is unable to easily pass through the cell membrane and then express as a protein. The particle size, ζ-potential, and morphology of the TBP2-GFP polyplex NPs were characterised, and plasmid incorporation was confirmed through gel retardation assays. The TBP2-GFP polyplex NPs effectively transfected multiple cells with low cytotoxicity, including HEK 293T, HeLa, Me180, SiHa, SCC-7 and C666-1 cells. We constructed a MUC2 (Mucin2)-targeting CRISPR/cas9 gene editing system in HEK 293T cells, with gene disruption supported by oligodeoxynucleotide (ODN) insertion in vitro. Additionally, we developed an LMP1 (latent membrane protein 1)-targeting CRISPR/cas9 gene editing system in LMP1-overexpressing SCC7 cells, which was designed to cleave fragments expressing the LMP1 protein (related to Epstein–Barr virus infection) and thus to inhibit the growth of the cells in vivo. As evidenced by in vitro and in vivo experiments, this system has great potential for gene therapy applications