SMART v1.0: A Database for Small Molecules with Functional Implications in Plants.

We developed SMART v1.0 ( http://smart.omicstudio.cloud ), the first database for small molecules with functional implications in plants. The SMART database is devoted to providing and managing small molecules and their associated structural data, chemoinformatic data, protein targets, pathways and induced phenotype/function information. Currently, SMART v1.0 encompasses 1218 unique small molecules which are involved in multiple biological pathways. SMART v1.0 is featured with user-friendly interfaces, through which pathway-centered visualization of small molecules can be efficiently performed, and multiple types of searches (i.e., text search, structure similarity search and sequence similarity search) can be conveniently conducted. SMART v1.0 is also specifically designed to be a small molecule-sharing database, allowing users to release their newly discovered small molecules to public via the Contribute webpage. The SMART database will facilitate the comprehensive understanding of small molecules in complex biological processes in plants.

Phylogenetic identification of symbiotic protists of five Chinese Reticulitermes species indicates a cospeciation of gut microfauna with host termites.

Symbiotic protists play important roles in the wood digestion of lower termites. Previous studies showed that termites generally possess host-specific flagellate communities. The genus Reticulitermes is particularly interesting because its unique assemblage of gut flagellates bears evidence for transfaunation. The gut fauna of Reticulitermes species in Japan, Europe, and North America had been investigated, but data on species in China are scarce. For the first time, we analyzed the phylogeny of protists in the hindgut of five Reticulitermes species in China. A total of 22 protist phylotypes were affiliated with the family Trichonymphidae, Teranymphidae, Trichomonadidae, and Holomastigotoididae (Phylum Parabasalia), and 45 protist phylotypes were affiliated with the family Pyrsonymphidae (Phylum Preaxostyla). The protist fauna of these five Reticulitermes species is similar to those of Reticulitermes species in other geographical regions. The topology of Trichonymphidae subtree was similar to that of Reticulitermes tree. All Preaxostyla clones were affiliated with the genera Pyrsonympha and Dinenympha (Order Oxymonadida) as in the other Reticulitermes species. The results of this study not only add to the existing information on the flagellates present in other Reticulitermes species but also offer the opportunity to test the hypotheses for the coevolution of symbiotic protists with their host termites.

Steroids-specific target library for steroids target prediction.

Steroids exist universally and play critical roles in various biological processes. Identifying potential targets of steroids is of great significance in studying their physiological and biochemical activities, the side effects and for drug repurposing. Herein, aiming at more precise steroids targets prediction, a steroids-specific target library integrating 3325 PDB or homology modeling structures categorized into 196 proteins was built by considering chemical similarity from DrugBank and biological processes from KEGG. The main properties of this library include: (1) It was manually prepared and checked to eliminate mistakes. (2) The library enriched the possible steroids targets and could decrease the false positives of structure-based target screening for steroids. (3) The ranking by protein name instead of PDB ID could make the screening more efficiency and precise. (4) Protein flexibility was taken into account partially by the different active conformations through the structural redundancy of each category of protein, which leads to more accurate prediction. The case studies of glycocholic acid and 24-epibrassinolide proved its powerful predictive accuracy. In summary, our strategy to build the steroids-specific protein library for steroids target prediction is a promising approach and it provides a novel idea for the target prediction of small molecules.

Structure based in silico identification of potentially non-steroidal brassinosteroids mimics.

Brassinosteroids (BRs) are a class of plant steroid hormones that play indispensable roles in cell elongation, division and plant development. To date, the numerous synthesis of BRs analogs and structure-activity relationship investigations have clearly revealed the key substituent groups relevant to the steroidal activity of BRs. However, due to the limited chemical space studied, the efforts for alternative non-steroidal compounds have produced no remarkable results. To identify potentially non-steroidal BR mimics in this study, vital interacting pharmacophore features were extracted starting from several complex structures of BRs that bound with the receptor Brassinosteroid-Insentive 1 (BRI1) and co-receptor BRI1-associated kinase 1 (BAK1), which were characterized and merged into one comprehensive pharmacophore model. In silico screening of a commercial compound database was carried out by combing pharmacophore modeling, molecular docking and visual analysis. Finally, six non-steroidal molecules were identified and subjected to the in vivo radish hypocotyl elongation assay. As a positive control, the hypocotyls elongation for the naturally most active BR brassinolide (BL) is 152 ± 3% at 100 nM. Moreover, two candidates (4 and 6) show good BRs-like activity with the hypocotyls elongation of 143 ± 1% and 128 ± 3% at the same dose, respectively. Most remarkably, compounds 4 and 6, which have different structures, are predicted to share similar binding modes and proven to exhibit potential BRs-like activity. The two compounds obtained could be valuable leads for the development of BRs-like plant growth regulators.