Decaprenylphosphoryl-β-d-ribose oxidase (DprE1) is the flavoprotein subunit of decaprenylphosphoryl-d-ribose epimerase involved in cell wall synthesis in Mycobacterium tuberculosis and catalyzes the conversion of decaprenylphosphoryl ribose to decaprenylphosphoryl arabinose. DprE1 is a potential target against tuberculosis, including multidrug-resistant tuberculosis. We identified potential DprE1 inhibitors from the ChemDiv dataset through virtual screening based on pharmacophore and molecular docking. Thirty selected compounds were subjected to absorption, distribution, metabolism, excretion, and toxicity prediction with the Discovery Studio software package. Two compounds were obtained as hits for inhibiting DprE1 activity in M. tuberculosis and are suitable for further in vitro and in vivo evaluation.

Isoimperatorin (QHS) is a phytoconstituent found in the methanolic extracts obtained from the roots of Angelica dahurica, which contains anti-inflammatory, anti-bacterial, analgesic, anti-tumor, and vasodilatory activities. QHS possesses potent antagonistic activity against lipopolysaccharide (LPS)-induced inflammation; however, the mechanism of action remains unclear. In this study, we investigated the anti-inflammatory effect of QHS and explored the underlying mechanisms. The QHS was purchased from Jiangsu Yongjian Pharmaceutical Co., Ltd. (Jiangsu, China). We performed MTT assay, real-time PCR, ELISA, and western blotting experiments to assess the anti-inflammatory activity and the possible mechanism of QHS in vitro. Molecular docking was performed to study the binding of QHS and myeloid differentiation protein-2 (MD-2) and elucidate the possible anti-inflammatory mechanism. QHS had no significant effect on cell viability. Moreover, pre-treatment with QHS significantly decreased the release of inflammatory cytokines and mediators including NO, TNF-α, IL-6, and IL-1β. In addition, real-time PCR showed that QHS decreased the mRNA expressions of iNOS, COX-2 TNF-α, IL-6, and IL-1β. Western blotting indicated that QHS could inhibit the expression of the proteins associated with the LPS-TLR4/MD-2-NF-κB signaling pathway. Lastly, molecular docking revealed a possible binding mechanism between QHS and MD-2. QHS exhibited anti-inflammatory activity when combined with MD-2, regulating the LPS-TLR4/MD-2-NF-κB signaling pathway, and inhibiting the release and expression of inflammatory cytokines and mediators. Furthermore, QHS can be used as a potential TLR4 antagonist, which blocks MD-2 binding, for treating inflammatory responses induced by LPS.

Ubiquitin is an important type of protein after translational modification. Ubiquitin has the ability to take part in several cellular regulations among several biological processions. At the same time, ubiquitin plays key roles in the enzymatic process. So as to construct the new tool to classify the ubiquitin amino acid residues, we employed the random forest model to classify the ubiquitin sites utilizing the experimentally identified ubiquitinated protein sequences of A. thaliana. More detailed, we utilized the k-spaced amino acid pair (CKSAAP) encoding and binary encoding to deal with the potential protein segments. The proposed tools can obtain 72.83 in Sp, 72.42 in Sn, 72.63 in Acc, and 0.4525 in MCC. With these performances, such tools can obtain the available results in the dataset of Arabidopsis.