3D pharmacophore models are three‐dimensional ensembles of chemically defined interactions of a ligand in its bioactive conformation. They represent an elegant way to decipher chemically encoded ligand information and have therefore become a valuable tool in drug design. In this review, we provide an overview on the basic concept of this method and summarize key studies for applying 3D pharmacophore models in virtual screening and mechanistic studies for protein functionality. Moreover, we discuss recent developments in the field. The combination of 3D pharmacophore models with molecular dynamics simulations could be a quantum leap forward since these approaches consider macromolecule–ligand interactions as dynamic and therefore show a physiologically relevant interaction pattern. Other trends include the efficient usage of 3D pharmacophore information in machine learning and artificial intelligence applications or freely accessible web servers for 3D pharmacophore modeling. The recent developments show that 3D pharmacophore modeling is a vibrant field with various applications in drug discovery and beyond. This article is categorized under: Computer and Information Science > Chemoinformatics Computer and Information Science > Computer Algorithms and Programming Molecular and Statistical Mechanics > Molecular Interactions

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The nerve guidance conduit (NGC) is a promising clinical strategy for regenerating the critical-sized peripheral nerve injury. In this study, the polysaccharide chitin is used to fabricate the hydrogel film for inducing the impaired sciatic nerve regeneration through incorporating the conductive poly­(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs) and modifying with cell adhesive tetrapeptide Cys–Arg–Gly–Asp (CRGD) (ChT-PEDOT-p). The partial deacetylation process of chitin for exposing the amino groups is performed to (i) improve the electrostatic interaction between chitin and the negatively charged PEDOT for enhancing the composite hydrogel strength and (ii) offer the active sites for peptide modification. The as-prepared hydrogel remarkably promotes the in vitro RSC-96 cell adhesion and proliferation, as well as the Schwann cell activity-related gene S100, NF-200, and myelin basic protein (MBP) expression. Function of gastrocnemius muscle and thickness of myelinated axon in chitin/PEDOT groups are analogous to the autograft in 10 mm rat sciatic nerve defect. Immunofluorescence, immunohistochemistry, western blotting, and toluidine blue staining analyses on the regenerated sciatic nerve explain that the attachment and proliferation enhancement of Schwann cells and angiogenesis are the vital factors for the chitin/PEDOT composite to facilitate the nerve regeneration. This work provides an applicable chitin-based NGC material for accelerating the peripheral nerve restoration.

MicroRNA (miR)-101 copy loss is an early event in the development of human lung cancer, and it occurs in 29% of all lung cancer incidences. In addition, miR-101 expression in non-small cell lung cancer (NSCLC) is known to be downregulated. The aim of the present study was to explore the roles and mechanisms of the long non-coding (lnc)-RNA pro-transition associated RNA (PTAR) on NSCLC cell proliferation, migration and invasion in association with miR-101. Reverse transcription-quantitative PCR analysis was performed to detect the expression of lncRNA PTAR in 30 paired human NSCLC tissues and the corresponding para-tumor tissues. PTAR was amplified and cloned into the expression vector pCDNA3.1. Then, PTAR-overexpression plasmids or small interfering (si)-RNA-PTAR was transfected into A549 cells for 48 h, after which cell proliferation and the cell cycle distribution were evaluated. In addition, Transwell chamber and cell scratch-wound assays were conducted to analyze A549 cell migration and invasion. A luciferase activity assay was evaluated to determine the interaction between PTAR and miR-101. Furthermore, our results demonstrated that in human NSCLC tissues and cell lines, lncRNA PTAR expression was upregulated compared with normal lung tissues and cell lines, respectively. Additionally, PTAR transfection was observed to promote A549 cell proliferation, migration and invasion; opposing effects were observed with siRNA-PTAR transfection. The luciferase activity assay revealed that PTAR could act as a sponge to bind miR-101. Thus, miR-101 plays a role in NSCLC tumorigenesis and progression. In conclusion, lncRNA PTAR was proposed to promote NSCLC cell growth through sponging and inactivating miR-101, which may be a possible mechanism underlying miR-101 copy loss in human NSCLC.