This work describes the synthesis, characterization and application of a pH- and magnetic-responsive PEG hydrogel (HG) nanocomposite as a platform for drug delivery.

Short non-coding RNAs (sncRNAs) are involved in multiple cellular processes and can be divided into dozens of classes. Among such classes, Y RNAs have been gaining attention, being essential factors for the initiation of DNA replication on vertebrates, as well as potential tumor biomarkers. Homologs have also been described in nematodes and insects, as well as related sequences in bacteria. Methods capable of accurately predicting Y RNA transcripts are lacking. In this work, we developed an attention-based LSTM network and built a classification model able to classify sncRNAs (including Y RNA) di-rectly from nucleotide sequences. A dataset consisting of 45,447 sncRNA sequences, from a wide range of organisms, ob-tained from Rfam 14.3 was built. Performance evaluation demonstrated that our proposed method, NCYPred (Non-Coding/Y RNA Prediction), can accurately predict Y RNA sequences and their homologs, as well as 11 additional classes, achieving results comparable with state-of-the-art methods. We also demonstrate that applying t-SNE on learned sequence represen-tations could be useful for sequence analysis. Our model is freely available as a web-server (https://www.gpea.uem.br/ncypred/).

The development of new drugs against Mycobacterium tuberculosis is an essential strategy for fighting drug resistance. Although 3-dehydroquinate dehydratase (MtDHQ) is known to be a highly relevant target for M. tuberculosis, current research shows new putative inhibitors of MtDHQ selected by a large-scale ensemble-docking strategy combining ligand- and target-based chemoinformatic methods to deep learning. Initial chemical library was reduced from 216 million to approximately 460 thousand after pharmacophore, toxicity and molecular weight filters. Final library was subjected to an ensemble-docking protocol in GOLD which selected the top 300 molecules (GHITS). GHITS displayed different structures and characteristics when compared to known inhibitors (KINH). GHITS were further screened by post-docking analysis in AMMOS2 and deep learning virtual screening in DeepPurpose. DeepPurpose predicted that a number of GHITS had comparable or better affinity for the target than KINH. The best molecule was selected by consensus ranking using GOLD, AMMOS2 and DeepPurpose scores. Molecular dynamics revealed that the top hit displayed consistent and stable binding to MtDHQ, making strong interactions with active-site loop residues. Results forward new putative inhibitors of MtDHQ and reinforce the potential application of artificial intelligence methods for drug design. This work represents the first step in the validation of these molecules as inhibitors of MtDHQ. Graphical Abstract Communicated by Ramaswamy H. Sarma