scholarly journals High-order structures from nucleic acids for biomedical applications

2020 ◽  
Vol 4 (4) ◽  
pp. 1074-1088 ◽  
Author(s):  
Alyssa C. Hill ◽  
Jonathan Hall
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Biomedical Applications ◽  
Dna Nanotechnology ◽  
High Order ◽  
Rna Nanotechnology ◽  
Nucleic Acid Structures ◽  
Order Structures

This article reviews important developments in DNA nanotechnology and RNA nanotechnology and highlights supramolecular nucleic acid structures with biomedical applications.

scholarly journals Structure and Function of Multimeric G-Quadruplexes

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3074 ◽  
Author(s):  
Sofia Kolesnikova ◽  
Edward A. Curtis
Keyword(s):  
Nucleic Acid ◽  
Building Blocks ◽  
Structure And Function ◽  
Limited Information ◽  
Functional Elements ◽  
Future Studies ◽  
And Function ◽  
Nucleic Acid Structures ◽  
Sequence Requirements ◽  
Order Structures

G-quadruplexes are noncanonical nucleic acid structures formed from stacked guanine tetrads. They are frequently used as building blocks and functional elements in fields such as synthetic biology and also thought to play widespread biological roles. G-quadruplexes are often studied as monomers, but can also form a variety of higher-order structures. This increases the structural and functional diversity of G-quadruplexes, and recent evidence suggests that it could also be biologically important. In this review, we describe the types of multimeric topologies adopted by G-quadruplexes and highlight what is known about their sequence requirements. We also summarize the limited information available about potential biological roles of multimeric G-quadruplexes and suggest new approaches that could facilitate future studies of these structures.

scholarly journals Nucleic acid-based nanoengineering: novel structures for biomedical applications

2011 ◽  
Vol 1 (5) ◽  
pp. 702-724 ◽  
Author(s):  
Hanying Li ◽  
Thomas H. LaBean ◽  
Kam W. Leong
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Single Molecule ◽  
Biomedical Applications ◽  
Three Dimensional ◽  
Base Pairs ◽  
Single Molecule Level ◽  
Stimulus Responsive ◽  
Bioactive Agents ◽  
Novel Structures

Nanoengineering exploits the interactions of materials at the nanometre scale to create functional nanostructures. It relies on the precise organization of nanomaterials to achieve unique functionality. There are no interactions more elegant than those governing nucleic acids via Watson–Crick base-pairing rules. The infinite combinations of DNA/RNA base pairs and their remarkable molecular recognition capability can give rise to interesting nanostructures that are only limited by our imagination. Over the past years, creative assembly of nucleic acids has fashioned a plethora of two-dimensional and three-dimensional nanostructures with precisely controlled size, shape and spatial functionalization. These nanostructures have been precisely patterned with molecules, proteins and gold nanoparticles for the observation of chemical reactions at the single molecule level, activation of enzymatic cascade and novel modality of photonic detection, respectively. Recently, they have also been engineered to encapsulate and release bioactive agents in a stimulus-responsive manner for therapeutic applications. The future of nucleic acid-based nanoengineering is bright and exciting. In this review, we will discuss the strategies to control the assembly of nucleic acids and highlight the recent efforts to build functional nucleic acid nanodevices for nanomedicine.

scholarly journals High-yield fabrication of DNA and RNA constructs for single molecule force and torque spectroscopy experiments

2019 ◽  
Vol 47 (22) ◽  
pp. e144-e144 ◽  
Author(s):  
Flávia S Papini ◽  
Mona Seifert ◽  
David Dulin
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Single Molecule ◽  
Magnetic Tweezers ◽  
High Yield ◽  
High Quality ◽  
Single Molecule Biophysics ◽  
Dna And Rna ◽  
Rna Hairpins ◽  
Nucleic Acid Structures

Abstract Single molecule biophysics experiments have enabled the observation of biomolecules with a great deal of precision in space and time, e.g. nucleic acids mechanical properties and protein–nucleic acids interactions using force and torque spectroscopy techniques. The success of these experiments strongly depends on the capacity of the researcher to design and fabricate complex nucleic acid structures, as the outcome and the yield of the experiment also strongly depend on the high quality and purity of the final construct. Though the molecular biology techniques involved are well known, the fabrication of nucleic acid constructs for single molecule experiments still remains a difficult task. Here, we present new protocols to generate high quality coilable double-stranded DNA and RNA, as well as DNA and RNA hairpins with ∼500–1000 bp long stems. Importantly, we present a new approach based on single-stranded DNA (ssDNA) annealing and we use magnetic tweezers to show that this approach simplifies the fabrication of complex DNA constructs, such as hairpins, and converts more efficiently the input DNA into construct than the standard PCR-digestion-ligation approach. The protocols we describe here enable the design of a large range of nucleic acid construct for single molecule biophysics experiments.

HELIX: a new modular nucleic acid crystallization screen

2014 ◽  
Vol 47 (3) ◽  
pp. 948-955 ◽  
Author(s):  
Julia Viladoms ◽  
Gary N. Parkinson
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Data Bank ◽  
Diverse Range ◽  
X Ray Crystallography ◽  
Molecular Weights ◽  
Anomalous Data ◽  
Crystallization Conditions ◽  
Nucleic Acid Structures ◽  
Screen Layout

Crystallization of nucleic acids remains a bottleneck to their structural characterization by X-ray crystallography. A new 96-well-format initial screen for nucleic acids, called HELIX, has been developed at UCL School of Pharmacy, London, on the basis of a detailed analysis of the crystallization conditions from 1450 nucleic acid structures deposited in the Protein Data Bank (PDB), combined with observations and experience acquired in the authors' nucleic acids crystallography laboratory during the crystallization of DNA/RNA quadruplexes and ligand complexes. Despite using traditional buffers, precipitants and salts, the resulting modular screen is designed to offer a variety of approaches to enhance successful crystallization of oligonucleotides with a diverse range of topologies, sequences and molecular weights. HELIX includes a set of 24 conditions divided into four sets that can be mixed (inter- and intra-set) to provide a customizable orthogonal screening tool for experienced users, termed VariX. Additionally, mindful of synchrotron anomalous data collection, cacodylate buffers are avoided in the formulations and an optimized cryocrystallization module is included. This article reviews the crystallization trends and data derived from the PDB and discusses the HELIX screen layout, formulation and results from in-house crystallization trials.

scholarly journals Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

Nanomaterials ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 681 ◽  
Author(s):  
Ryan C. Oliver ◽  
Lewis A. Rolband ◽  
Alanna M. Hutchinson-Lundy ◽  
Kirill A. Afonin ◽  
Joanna K. Krueger
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Neutron Scattering ◽  
Conformational Changes ◽  
Structural Characterization ◽  
Small Angle ◽  
Building Materials ◽  
Functional Characterization ◽  
Dna Nanotechnology ◽  
Biological Studies

Nucleic acid-based technologies are an emerging research focus area for pharmacological and biological studies because they are biocompatible and can be designed to produce a variety of scaffolds at the nanometer scale. The use of nucleic acids (ribonucleic acid (RNA) and/or deoxyribonucleic acid (DNA)) as building materials in programming the assemblies and their further functionalization has recently established a new exciting field of RNA and DNA nanotechnology, which have both already produced a variety of different functional nanostructures and nanodevices. It is evident that the resultant architectures require detailed structural and functional characterization and that a variety of technical approaches must be employed to promote the development of the emerging fields. Small-angle X-ray and neutron scattering (SAS) are structural characterization techniques that are well placed to determine the conformation of nucleic acid nanoparticles (NANPs) under varying solution conditions, thus allowing for the optimization of their design. SAS experiments provide information on the overall shapes and particle dimensions of macromolecules and are ideal for following conformational changes of the molecular ensemble as it behaves in solution. In addition, the inherent differences in the neutron scattering of nucleic acids, lipids, and proteins, as well as the different neutron scattering properties of the isotopes of hydrogen, combined with the ability to uniformly label biological macromolecules with deuterium, allow one to characterize the conformations and relative dispositions of the individual components within an assembly of biomolecules. This article will review the application of SAS methods and provide a summary of their successful utilization in the emerging field of NANP technology to date, as well as share our vision on its use in complementing a broad suite of structural characterization tools with some simulated results that have never been shared before.

scholarly journals Cyclic Automated Model Building (CAB) Applied to Nucleic Acids

Crystals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 280
Author(s):  
Maria Cristina Burla ◽  
Benedetta Carrozzini ◽  
Giovanni Luca Cascarano ◽  
Carmelo Giacovazzo ◽  
Giampiero Polidori
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Model Building ◽  
State Of The Art ◽  
Molecular Replacement ◽  
Dna And Rna ◽  
Protein Model ◽  
Rna Fragments ◽  
Nucleic Acid Structures ◽  
Automated Model Building

Obtaining high-quality models for nucleic acid structures by automated model building programs (AMB) is still a challenge. The main reasons are the rather low resolution of the diffraction data and the large number of rotatable bonds in the main chains. The application of the most popular and documented AMB programs (e.g., PHENIX.AUTOBUILD, NAUTILUS and ARP/wARP) may provide a good assessment of the state of the art. Quite recently, a cyclic automated model building (CAB) package was described; it is a new AMB approach that makes the use of BUCCANEER for protein model building cyclic without modifying its basic algorithms. The applications showed that CAB improves the efficiency of BUCCANEER. The success suggested an extension of CAB to nucleic acids—in particular, to check if cyclically including NAUTILUS in CAB may improve its effectiveness. To accomplish this task, CAB algorithms designed for protein model building were modified to adapt them to the nucleic acid crystallochemistry. CAB was tested using 29 nucleic acids (DNA and RNA fragments). The phase estimates obtained via molecular replacement (MR) techniques were automatically submitted to phase refinement and then used as input for CAB. The experimental results from CAB were compared with those obtained by NAUTILUS, ARP/wARP and PHENIX.AUTOBUILD.

scholarly journals Solving nucleic acid structures by molecular replacement: examples from group II intron studies

2013 ◽  
Vol 69 (11) ◽  
pp. 2174-2185 ◽  
Author(s):  
Marco Marcia ◽  
Elisabeth Humphris-Narayanan ◽  
Kevin S. Keating ◽  
Srinivas Somarowthu ◽  
Kanagalaghatta Rajashankar ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Molecular Replacement ◽  
Cellular Viability ◽  
Rna Molecules ◽  
Search Models ◽  
Key Players ◽  
Group Ii ◽  
Nucleic Acid Structures ◽  
Near Future

Structured RNA molecules are key players in ensuring cellular viability. It is now emerging that, like proteins, the functions of many nucleic acids are dictated by their tertiary folds. At the same time, the number of known crystal structures of nucleic acids is also increasing rapidly. In this context, molecular replacement will become an increasingly useful technique for phasing nucleic acid crystallographic data in the near future. Here, strategies to select, create and refine molecular-replacement search models for nucleic acids are discussed. Using examples taken primarily from research on group II introns, it is shown that nucleic acids are amenable to different and potentially more flexible and sophisticated molecular-replacement searches than proteins. These observations specifically aim to encourage future crystallographic studies on the newly discovered repertoire of noncoding transcripts.

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