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Valerie Gabelica - One of the best experts on this subject based on the ideXlab platform.
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role of alkali metal ions in g quadruplex Nucleic Acid Structure and stability
Metal ions in life sciences, 2016Co-Authors: Eric Largy, Jean-louis Mergny, Valerie GabelicaAbstract:G-quadruplexes are guanine-rich Nucleic Acids that fold by forming successive quartets of guanines (the G-tetrads), stabilized by intra-quartet hydrogen bonds, inter-quartet stacking, and cation coordination. This specific although highly polymorphic type of secondary Structure deviates significantly from the classical B-DNA duplex. G-quadruplexes are detectable in human cells and are strongly suspected to be involved in a number of biological processes at the DNA and RNA levels. The vast structural polymorphism exhibited by G-quadruplexes, together with their putative biological relevance, makes them attractive therapeutic targets compared to canonical duplex DNA. This chapter focuses on the essential and specific coordination of alkali metal cations by G-quadruplex Nucleic Acids, and most notably on studies highlighting cation-dependent dissimilarities in their stability, Structure, formation, and interconversion. Section 1 surveys G-quadruplex Structures and their interactions with alkali metal ions while Section 2 presents analytical methods used to study G-quadruplexes. The influence of alkali cations on the stability, Structure, and kinetics of formation of G-quadruplex Structures of quadruplexes will be discussed in Sections 3 and 4. Section 5 focuses on the cation-induced interconversion of G-quadruplex Structures. In Sections 3 to 5, we will particularly emphasize the comparisons between cations, most often K(+) and Na(+) because of their prevalence in the literature and in cells.
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Linking molecular models with ion mobility experiments. Illustration with a rigid Nucleic Acid Structure
Journal of Mass Spectrometry, 2015Co-Authors: Valentina D 'atri, Massimiliano Porrini, Frédéric Rosu, Valerie GabelicaAbstract:Ion mobility spectrometry experiments allow the mass spectrometrist to determine an ion's rotationally averaged collision cross section Ω EXP. Molecular modelling is used to visualize what ion three-dimensional Structure(s) is(are) compatible with the experiment. The collision cross sections of candidate molecular models have to be calculated, and the resulting Ω CALC are compared with the experimental data. Researchers who want to apply this strategy to a new type of molecule face many questions: (1) What experimental error is associated with Ω EXP determination, and how to estimate it (in particular when using a calibration for traveling wave ion guides)? (2) How to generate plausible 3D models in the gas phase? (3) Different collision cross section calculation models exist, which have been developed for other analytes than mine. Which one(s) can I apply to my systems? To apply ion mobility spectrometry to Nucleic Acid structural characterization, we explored each of these questions using a rigid Structure which we know is preserved in the gas phase: the tetramolecular G-quadruplex [dTGGGGT] 4 , and we will present these detailed investigation in this tutorial.
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linking molecular models with ion mobility experiments illustration with a rigid Nucleic Acid Structure
Journal of Mass Spectrometry, 2015Co-Authors: Valentina Datri, Frédéric Rosu, Massimiliano Porrini, Valerie GabelicaAbstract:Ion mobility spectrometry experiments allow the mass spectrometrist to determine an ion's rotationally averaged collision cross section ΩEXP. Molecular modelling is used to visualize what ion three-dimensional Structure(s) is(are) compatible with the experiment. The collision cross sections of candidate molecular models have to be calculated, and the resulting ΩCALC are compared with the experimental data. Researchers who want to apply this strategy to a new type of molecule face many questions: (1) What experimental error is associated with ΩEXP determination, and how to estimate it (in particular when using a calibration for traveling wave ion guides)? (2) How to generate plausible 3D models in the gas phase? (3) Different collision cross section calculation models exist, which have been developed for other analytes than mine. Which one(s) can I apply to my systems? To apply ion mobility spectrometry to Nucleic Acid structural characterization, we explored each of these questions using a rigid Structure which we know is preserved in the gas phase: the tetramolecular G-quadruplex [dTGGGGT]4, and we will present these detailed investigation in this tutorial. © 2015 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons Ltd.
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Determination of Equilibrium Association Constants of Ligand–DNA Complexes by Electrospray Mass Spectrometry
Methods in Molecular Biology, 2009Co-Authors: Valerie GabelicaAbstract:Electrospray mass spectrometry can be used to detect ligand-DNA noncovalent complexes formed in solution. This chapter describes how to determine equilibrium association constants of the complexes. Particular attention is devoted to describing how to tune an electrospray mass spectrometer using a 12-mer oligodeoxynucleotides duplex in order to perform these experiments. This protocol can then be applied to any Nucleic Acid Structure that can be ionized with electrospray mass spectrometry.
Wilma K. Olson - One of the best experts on this subject based on the ideXlab platform.
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Nucleic Acid Structure analysis. Mathematics for local Cartesian and helical Structure parameters that are truly comparable between Structures.
Journal of molecular biology, 1994Co-Authors: Marla S. Babcock, Edwin P. D. Pednault, Wilma K. OlsonAbstract:Analyzing Nucleic Acid Structures in a comparable manner has become increasingly important as the number of solved Structures has increased. This paper presents the concepts, mathematics, theorems, and proofs that form the basis of a new program to analyze three-dimensional DNA and RNA Structures. The approach taken here provides numerical data in accordance with guidelines set at a 1988 EMBO workshop. Mathematical definitions are provided for all local structural parameters described in the guidelines. The definitions satisfy the guideline requirements while preserving the original physical intuition of the parameters. In particular, the rotational parameters are true rotations based on a simple physical model (net rotation at constant angular velocity), not Euler angles or angles between vectors and planes as is the case with other approaches. As a result, the mathematical definitions are symmetrical with the property that a 5 degrees tilt is the same as a 5 degrees roll and a 5 degrees twist, except that the rotations take place about different axes. In other approaches, a 5 degrees tilt can mean a different amount of net rotation than a 5 degrees roll or a 5 degrees twist. A second unique feature of the mathematics is that it explicitly incorporates the concept of a pivot point, which is the point about which a base in a base-pair rotates as it buckles, propeller twists, and opens. Pivot points enable one to model the physical motion of bases more accurately. As a result, they greatly reduce and/or eliminate the statistical correlations between rotational and translational parameters that arise as mathematically induced artifacts in other approaches. This paper, together with the statistical analysis in the companion paper for determining the locations of the pivot points, provides everything needed to understand the output of the program as it relates to individual Structures.
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A New Program for the Analysis of Nucleic Acid Structure: Implications for Nucleic Acid Structure Interpretation
Computation of Biomolecular Structures, 1993Co-Authors: Marla S. Babcock, Wilma K. OlsonAbstract:Common ‘nomenclatures’ and ‘definitions’ to be used for the analysis of Nucleic Acid coordinate data were established at an EMBO workshop in September 1988 [Diekmann 1988, 1989; Sarma 1988; Dickerson 1989a; Dickerson et al. 1989]. The ‘definitions’ are simple concepts relating bases within a base pair and neighboring base pair to base pair geometries and are easily implemented for ‘ideal’ uniform coordinate sets. The ramifications of applying the concepts to non-uniform experimental data, however, were neither clearly nor adequately examined at the workshop. Consequently, no definitive mathematics and no specific guidelines were set for translating the ‘definitions’ to a form useful for the interpretation of experimental data. These questions were left to the discretion of the authors of the analysis programs.
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Computational Approaches to Nucleic Acid Structure
Computation of Biomolecular Structures, 1993Co-Authors: Wilma K. OlsonAbstract:A summary of recent efforts to understand the influence of chemical architecture on the conformation, properties, and interactions of Nucleic Acid double helices is presented. The work is a combination of conformational energy calculations, molecular modeling and computer graphics, developments and applications of polymer chain statistics, and Monte Carlo simulation studies. Allatom potential energy studies are used to estimate the base sequence dependent conformations of the right-handed double helix. Simpler energy functions are developed from the atomic level calculations to facilitate the treatment of long chain molecules. The combination of modeling and statistical mechanics is used to demonstrate how variations in local conformation translate into overall changes in macromolecular (secondary and tertiary) Structure. The statistical mechanical studies provide a check of the local conformational predictions by relating the three-dimensional arrangements of the polynucleotide to configuration-dependent properties of the chain. New B-spline and Fourier series modeling techniques offer a way to study the conformation and flexibility of constrained DNA. Monte Carlo studies of linear and closed chains are used to study the distribution of molecular conformations and the flexibility of the Nucleic Acid as a whole.
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Nucleic Acid Structure analysis: a users guide to a collection of new analysis programs.
Journal of biomolecular structure & dynamics, 1993Co-Authors: Maria S. Babcock, Edwin P. D. Pednault, Wilma K. OlsonAbstract:Common nomenclature describing the geometry of Nucleic Acid Structures was established at a 1988 EMBO Workshop on DNA Curvature and Bending (Diekmann, S. (1988) J. Mol. Biol. 208, 787-791; Diekmann, S. (1989) The EMBO Journal 8, 1-4; Sarma, R.H. (1988) J. Biomol. Structure & Dynamics 6, 391-395; Dickerson, R.E. (1989) J. Biomol. Structure & Dynamics 6, 627-634; Dickerson, R.E. et al. (1989) Nuc. Acids Res. 17, 1979-1803). We have subsequently developed and incorporated sophisticated mathematics in a computer program to calculate the parameters described by the guidelines. The program calculates all the local parameters relating complementary bases and neighboring base and base pairs in both Cartesian and helical coordinate frames. In addition, the main mathematical property requested by the EMBO guidelines--that the magnitude of the parameters be independent of strand or direction of measurement--is accomplished without the use of a midway coordinate frame for the rotational parameters. The mathematics preserve the physical intuition used in defining the parameters; in particular, the rotational parameters are true rotations based on a simple physical model (rotation at constant angular velocity for a unit amount of time), not Euler angles or angles between vectors and planes as is the case with other approaches. As a result, the mathematical equations are symmetric with the property that a 5 degrees tilt is the same as a 5 degrees roll or a 5 degrees twist, except that the rotations take place about different axes. In other approaches, a 5 degrees tilt can mean a different amount of net rotation from a 5 degrees roll or a 5 degrees twist. In addition, a great deal of flexibility is built into the program so that the user has control over the analysis, including the input format, the coordinate frame used for the base pairing relationship, the point about which the rotations are performed, and which geometric relationships are analyzed. While there is a great deal of flexibility, the program is easy to use. Interactive queries and user accessible files make the options in the program very convenient to tailor to individual needs. In addition, there is also a program that calculates bond lengths, valence angles, and torsion angles along the Nucleic Acid backbone, and within the sugar and base rings. Another program 'learns' the identities of the bond lengths, valence angles, and torsion angles that the user would like to determine.(ABSTRACT TRUNCATED AT 400 WORDS)
Samuel E Butcher - One of the best experts on this subject based on the ideXlab platform.
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Current Protocols in Nucleic Acid Chemistry - Nucleic Acid Structure Characterization by Small Angle X‐Ray Scattering (SAXS)
Current Protocols in Nucleic Acid Chemistry, 2012Co-Authors: Jordan E Burke, Samuel E ButcherAbstract:Small angle X-ray scattering (SAXS) is a powerful method for investigating macromolecular Structure in solution. SAXS data provide information about the size and shape of a molecule with a resolution of ∼2 to 3 nm. SAXS is particularly useful for the investigation of Nucleic Acids, which scatter X-rays strongly due to the electron-rich phosphate backbone. Therefore, SAXS has become an increasingly popular method for modeling Nucleic Acid Structures, an endeavor made tractable by the highly regular helical nature of Nucleic Acid secondary Structures. Recently, SAXS was used in combination with NMR to filter and refine all-atom models of a U2/U6 small nuclear RNA complex. In this unit, general protocols for sample preparation, data acquisition, and data analysis and processing are given. Additionally, examples of correctly and incorrectly processed SAXS data and expected results are provided.
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Nucleic Acid Structure characterization by small angle X-ray scattering (SAXS).
Current protocols in nucleic acid chemistry, 2012Co-Authors: Jordan E Burke, Samuel E ButcherAbstract:Small angle X-ray scattering (SAXS) is a powerful method for investigating macromolecular Structure in solution. SAXS data provide information about the size and shape of a molecule with a resolution of ∼2 to 3 nm. SAXS is particularly useful for the investigation of Nucleic Acids, which scatter X-rays strongly due to the electron-rich phosphate backbone. Therefore, SAXS has become an increasingly popular method for modeling Nucleic Acid Structures, an endeavor made tractable by the highly regular helical nature of Nucleic Acid secondary Structures. Recently, SAXS was used in combination with NMR to filter and refine all-atom models of a U2/U6 small nuclear RNA complex. In this unit, general protocols for sample preparation, data acquisition, and data analysis and processing are given. Additionally, examples of correctly and incorrectly processed SAXS data and expected results are provided.
Thomas E Cheatham - One of the best experts on this subject based on the ideXlab platform.
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Current Protocols in Nucleic Acid Chemistry - Molecular Modeling of Nucleic Acid Structure: Setup and Analysis
Current protocols in human genetics, 2014Co-Authors: Rodrigo Galindo-murillo, Christina Bergonzo, Thomas E CheathamAbstract:The last in a set of units by the same authors, this unit addresses some important remaining questions about molecular modeling of Nucleic Acids. The unit describes how to choose an appropriate molecular mechanics force field; how to set up and equilibrate the system for accurate simulation of a Nucleic Acid in an explicit solvent by molecular dynamics or Monte Carlo simulation; and how to analyze molecular dynamics trajectories. Curr. Protoc. Nucleic Acid Chem. 56:7.10.1-7.10.21. © 2014 by John Wiley & Sons, Inc. Keywords: Nucleic Acid chemistry; Nucleic Acid Structure and folding; force field review; simulation setup and analysis; simulation protocols; sampling methods
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Current Protocols in Nucleic Acid Chemistry - Molecular modeling of Nucleic Acid Structure.
Current protocols in nucleic acid chemistry, 2013Co-Authors: Rodrigo Galindo-murillo, Christina Bergonzo, Thomas E CheathamAbstract:This unit is the first in a series of four units covering the analysis of Nucleic Acid Structure by molecular modeling. The unit provides an overview of the computer simulation of Nucleic Acids. Topics include the static Structure model, computational graphics and energy models, the generation of an initial model, and characterization of the overall three-dimensional Structure.
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Simulation and modeling of Nucleic Acid Structure, dynamics and interactions.
Current opinion in structural biology, 2004Co-Authors: Thomas E CheathamAbstract:Abstract In moving towards the simulation of larger Nucleic Acid assemblies over longer timescales that include more accurate representations of the environment, we are nearing the end of an era characterized by single nanosecond molecular dynamics simulation of Nucleic Acids. We are excited by the promise and predictability of the modeling methods, yet remain prudently cautious of sampling and force field limitations. Highlights include the accurate representation of subtle drug–DNA interactions, the detailed study of modified and unusual Nucleic Acid Structures, insight into the influence of dynamics on the Structure of DNA, and exploration of the interaction of solvent and ions with Nucleic Acids.
Stephen W White - One of the best experts on this subject based on the ideXlab platform.
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structural evidence for specific s8 rna and s8 protein interactions within the 30s ribosomal subunit ribosomal protein s8 from bacillus stearothermophilus at 1 9 a resolution
Structure, 1996Co-Authors: Christopher Davies, V Ramakrishnan, Stephen W WhiteAbstract:Abstract Background Prokaryotic ribosomal protein S8 is an important RNA-binding protein that occupies a central position within the small ribosomal subunit. It interacts extensively with 16S rRNA and is crucial for the correct folding of the central domain of the rRNA. S8 also controls the synthesis of several ribosomal proteins by binding to mRNA. It binds specifically to very similar sites in the two RNA molecules. Results S8 is divided into two tightly associated domains and contains three regions that are proposed to interact with other ribosomal components: two potential RNA-binding sites, and a hydrophobic patch that may interact with a complementary hydrophobic region of S5. The N-terminal domain fold is found in several proteins including two that bind double-stranded DNA. Conclusions These multiple RNA-binding sites are consistent with the role of S8 in organizing the central domain and agree with the latest models of the 16S RNA which show that the S8 location coincides with a region of complicated Nucleic-Acid Structure. The presence in a wide variety of proteins of a region homologous to the N-terminal domain supports the idea that ribosomal proteins must represent some of the earliest protein molecules.
