DNA and RNA quadruplex ligands (original) (raw)
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Inhibition of G-Quadruplex Helicase Activity As Determined by Surface Plasmon Resonance
ACS Symposium Series, 2011
The ability of G-quadruplex interactive small molecules to inhibit SV40 Large T-Antigen G-quadruplex helicase activity was determined using a surface plasmon resonance based assay. Unwinding of a physiologically relevant intramolecular G-quadruplex DNA substrate was completely inhibited by one novel porphyrin derivative under these conditions. This SPR-based method represents an important strategy for comparing helicase inhibition effectiveness.
2010
Macrocyclic scaffolds are particularly attractive for designing selective G-quadruplex ligands essentially because, on one hand, they show a poor affinity for the "standard" B-DNA conformation and, on the other hand, they fit nicely with the external G-quartets of quadruplexes. Stimulated by the pioneering studies on the cationic porphyrin TMPyP4 and the natural product telomestatin, follow-up studies have developed, rapidly leading to a large diversity of macrocyclic structures with remarkablequadruplex binding properties and biological activities. In this review we summarize the current state of the art in detailing the three main categories of quadruplex-binding macrocycles described so far (telomestatin-like polyheteroarenes, porphyrins and derivatives, polyammonium cyclophanes), and in addressing both synthetic issues and biological aspects.
A Survey of Multiple Sequence Alignment Parallel Tools
Motivation: Multiple sequence alignment is a key problem to most bioinformatics applications, from evolutionary studies to prediction of protein structure, molecular function, intermolecular interactions, gene finding and phylogenitic analysis. The last ten years have witnessed a big improvement to existing multiple alignment tools and the development of new ones. Varieties of parallel architectures have been experimented such as supercomputer, cluster, grid, cloud, and multi-core machine for the purpose of reaching the highest level of accuracy and speed. Results: This paper surveys most popular tools to clarify how parallelism accelerates the processing of large biological data set and improve alignment accuracy. It also introduces a comparative study that aims at guiding biologists to choose the appropriate software depending on their requirements and their hardware potentials.
Water Treatment Chlorination: An Updated Mechanistic Insight Review
Chemistry Research Journal, 2017
Since the 1970s' disinfection by-products (DBPs) detection, the water treatment specialists' main focuses were accorded to the DBPs formation, characterization, regulations and control. Involved stages in disinfection process were at a certain level kept at the side as a black box. This paper is a broad review on chlorination applied in water treatment technology especially in terms of involved mechanisms. Chlorine occasions significant injury to bacterial cells, cell permeability dislocation and nucleic acids and enzymes injury. Hypochlorous acid oxidizes sulfhydryl groups, harms iron-sulfur centers, deactivates nutrient transport, hinders cell respiration, and deteriorates the capacity of cells to keep a sufficient adenylate energy charge to stay viable. All disinfectants are highly efficient killing agents. However, these chemical products are very toxic by their selves. Moreover, they interact with NOM, microorganisms, and algae to produce DBPs which are as well poisonous. Consequently, the use of disinfectants must be avoided upon using physical processes or at least reduced as possible at the lowest level.
DNA A-tracts bending: Polarization effects on electrostatic interactions across their minor groove
Journal of Theoretical Biology, 2008
Bending by the DNA A-tracts constitutes a contentious issue, suggesting deficiencies in the physics employed so far. Here, we inquire as to the importance in this bending of many-body polarization effects on the electrostatic interactions across their narrow minor groove. We have done this on the basis of the findings of Jarque and Buckingham who developed a procedure based on a Monte Carlo simulation for two charges of the same sign embedded in a polarizable medium. Remarkably, the present analysis reveals that for compact DNA conformations, which result from dynamic effects, an overall attractive interaction operates between the phosphate charges; this interaction is especially strong for the narrow minor groove of the A-tracts, suggesting a tendency for DNA to bend toward this groove. This tendency is in agreement with the conclusions of electrophoretic and NMR solution studies. The present analysis is also consistent with the experimental observations that the minor groove is much more easily compressible than the major groove and the bending propensity of the A-tracts is greatly reduced at ''premelting'' temperatures. By contrast, the dielectric screening model predicts a repulsion between the phosphate charges and is not consistent with the aforementioned bending tendency or experimental observations.
iHAT: Interactive hierarchical aggregation table
2011
In the search for single-nucleotide polymorphisms (SNPs), genome wide association studies have become an important technique for the identification of associations between genotype and phenotype of a diverse set of sequence-based data. In this work, we present a methodology for the visual assessment of SNPs using interactive hierarchical aggregation techniques combined with methods known from traditional sequence browsers and cluster heatmaps. Our prototype tool iHAT supports the visualization of multiple sequence alignments, associated metadata, and hierarchical clusterings. Moreover, data-type dependent colormaps and aggregation strategies as well as different filtering options support the user in finding correlations between sequences and metadata. Similar to other visualizations such as parallel coordinates or heatmaps, iHAT is aimed at exploiting the human pattern-recognition ability for spotting patterns that might indicate correlation or anticorrelation. Together with its interactive features and a database backend for fast data retrieval, we consider iHAT as a prototype for a visual analytics system for genome-wide association studies.
Current trends in antimicrobial agent research: chemo- and bioinformatics approaches
Drug Discovery Today, 2010
Databases and chemo-and bioinformatics tools that contain genomic, proteomic and functional information have become indispensable for antimicrobial drug research. The combination of chemoinformatics tools, bioinformatics tools and relational databases provides means of analyzing, linking and comparing online search results. The development of computational tools feeds on a diversity of disciplines, including mathematics, statistics, computer science, information technology and molecular biology. The computational approach to antimicrobial agent discovery and design encompasses genomics, molecular simulation and dynamics, molecular docking, structural and/or functional class prediction, and quantitative structure-activity relationships. This article reviews progress in the development of computational methods, tools and databases used for organizing and extracting biological meaning from antimicrobial research.
Nucleosomal DNA: Kinked, Not Kinked, or Self-Healing Material?
ACS Symposium Series, 2011
We use all atom molecular dynamics simulations to investigate the structure and dynamics of nucleosomal DNA. Our primary focus is characterization of DNA kinking as a function of position and base pair type within the nucleosome. For this purpose we have constructed 16 fully solvated all atom models of the nucleosome and subjected each to molecular dynamics simulations. Each system consists of over 200,000 atoms and is simulated for 16 ns. Combined the systems represent over 3.2 million atoms and 256 ns of nucleosome dynamics. Each system has a different sequence of DNA. The sequences chosen allow us to investigate each base pair type at each of the 147 positions in the nucleosome, as well as, each of the 16 dinucleotide steps at each of the 146 positions in the nucleosome. Within the limits of this approach we demonstrate that threading different DNA sequences onto a given histone core allows for successful initiation of molecular modeling. We also show that location within the nucleosome affects the structure and dynamics of a given base pair step type, i.e. the histones alter the DNA. However this effect is not so strong as to impose the same structure and dynamics on DNA regardless of sequence. Analysis of interaction energies demonstrates that the histone-DNA interactions vary more as a function of position than as a function of sequence. Moreover, the relative contribution from van der Waals interactions and from Coulomb interactions to the total histone-DNA interaction energy also varies with position. Thus the magnitude and the nature of the histone-DNA interactions vary with location. To