James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40206, USA; Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY, 40206, USA; Department of Medicine, University of Louisville, Louisville, KY, 40206, USA. Electronic address:
Published: September 2018
AI Article Synopsis
Article Abstract
Over the past two decades biologists and bioinformaticians have unearthed substantial evidence supporting a role for G-quadruplexes as important mediators of biological processes. This includes telomere damage signaling, transcriptional activity, and splicing. Both their structural heterogeneity and their abundance in oncogene promoters makes them ideal targets for drug discovery. Currently, there are hundreds of deposited DNA and RNA quadruplex atomic structures which have allowed researchers to begin using in silico drug screening approaches to develop novel stabilizing ligands. Here we provide a review of the past decade of G-quadruplex virtual drug discovery approaches and campaigns. With this we introduce relevant virtual screening platforms followed by a discussion of best practices to assist future G4 VS campaigns.
Overexpression of c-Myc is a key factor in the development of leukemia and other malignancies, highlighting the urgent need for novel drugs to inhibit c-Myc protein levels. DNA G-quadruplexes (G4) have emerged as potential regulatory targets for c-Myc expression. Previous studies identified trovafloxacin, a topoisomerase II inhibitor, as a novel c-Myc G4 stabilizer.
Cancer's persistent growth often relies on its ability to maintain telomere length and tolerate the accumulation of DNA damage. This study explores a computational approach to identify compounds that can simultaneously target both G-quadruplex (G4) structures and poly(ADP-ribose) polymerase (PARP)1 enzyme, offering a potential multipronged attack on cancer cells. We employed a hybrid virtual screening (VS) protocol, combining the power of machine learning with traditional structure-based methods.
The efficient detection of the foodborne pathogen has historically been hampered by the constraints of traditional methods, characterized by protracted culture periods and intricate DNA extraction processes for PCR. To address this, our research innovatively focuses on the crucial and relatively uncharted virulence factor, the Outer Membrane Protein D (OmpD) in . By harmoniously integrating the power of virtual screening and site-directed mutagenesis, we unveiled aptamers exhibiting marked specificity for OmpD.
National R&D Center for Se-rich Agricultural Products Processing, Hubei Engineering Research Center for Deep Processing of Green Se-rich Agricultural Products, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University Wuhan 430023 China
Human telomere sequences (TTAGGG) fold into G-quadruplexes with different conformations in K and Na solutions, which are highlighted for their potential as antitumor drug targets. Moreover, human multimeric G-quadruplexes have been broadly studied potentially for screening ligands with higher selectivity than monomeric G-quadruplexes. Most insects have telomeres consisting of pentanucleotide (TTAGG) repeats, which fold into an antiparallel structured G-quadruplex with a two-layer G-planar in a K solution.
The study presents 'G4-QuadScreen', a user-friendly computational tool for identifying MTDLs against G4s. Also, it offers a few hit MTDLs based on in silico and in vitro approaches. Multi-tasking QSAR models were developed using linear discriminant analysis and random forest machine learning techniques for predicting the responses of interest (G4 interaction, G4 stabilization, G4 selectivity, and cytotoxicity) considering the variations in the experimental conditions (e.
