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Author: Jia Lu
Publisher:
ISBN:
Category : Nucleotide sequence
Languages : en
Pages : 208
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Book Description
It has been hypothesized that the ground state conformational dynamics of RNA can significantly enhance its functional capacity beyond its static structure modeled by traditional biophysical techniques. Therefore, understanding the dynamic aspects of RNA structures is fundamentally important for fully elucidating the sequence-structure-dynamics-function relationship. Time-resolved fluorescence up-conversion spectroscopy allowed us to resolve the heterogeneous nature of RNA molecules and capture the conformational changes upon ligand binding to advance our understanding of detailed mechanism of conformational dynamics for different RNA molecules. The non-specific base stacking interaction makes a major contribution to the RNA ground state rugged energy landscape and is also the main stabilizing force in RNA. The fluorescent base 2-aminopurine, which is an analog to adenine, was used to characterize the heterogeneity of base stacking patterns in RNA, and get a quantitative description of inter-converting states in the ensemble.
Author: Jia Lu
Publisher:
ISBN:
Category : Nucleotide sequence
Languages : en
Pages : 208
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Book Description
It has been hypothesized that the ground state conformational dynamics of RNA can significantly enhance its functional capacity beyond its static structure modeled by traditional biophysical techniques. Therefore, understanding the dynamic aspects of RNA structures is fundamentally important for fully elucidating the sequence-structure-dynamics-function relationship. Time-resolved fluorescence up-conversion spectroscopy allowed us to resolve the heterogeneous nature of RNA molecules and capture the conformational changes upon ligand binding to advance our understanding of detailed mechanism of conformational dynamics for different RNA molecules. The non-specific base stacking interaction makes a major contribution to the RNA ground state rugged energy landscape and is also the main stabilizing force in RNA. The fluorescent base 2-aminopurine, which is an analog to adenine, was used to characterize the heterogeneity of base stacking patterns in RNA, and get a quantitative description of inter-converting states in the ensemble.
Author: Niyati Jain
Publisher:
ISBN:
Category : RNA.
Languages : en
Pages : 248
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Book Description
RNA is a structurally flexible and dynamic molecule, and rapidly interconverts between multiple conformations. Despite the significant advances in traditional biophysical techniques like NMR spectroscopy and X-ray crystallography it is difficult to resolve the structures of dynamically inter-converting states as these methods measure the average property of an ensemble of molecules. It is necessary to resolve and get detailed descriptions of the multiple conformational structures, their quantitative distribution and their related dynamics in order to understand the ruggedness of the energy landscape. The present study attempts to link the conformational dynamics of RNA to its structure and biological function. Ultrafast time-resolved fluorescence spectroscopy is used to probe the distribution of multiple conformations and their dynamics that occur on a very fast timescales. This tool uses the resolution of time domain behavior of 2-aminopurine fluorescence decay on the ultrafast timescale to capture the characteristics of different structures. The RNAs are labeled with the fluorescent base analog 2-aminopurine to probe the base stacking patterns in RNA. Base stacking interactions is a unique feature that defines nucleic acid structures compared to proteins and are the major stabilizing force in RNA. Chapter 1 discusses the RNA folding mechanism and the relationships between sequence, structure, dynamics and function and explains the advantage of using ultrafast time resolved spectroscopy in defining structure-function relationships in RNA. Chapter 2 discusses the conformational heterogeneity and dynamics in purine-sensing riboswitches. We observed multiple conformations where the ligand is significantly stacked with the bases of the binding pocket and shows a dynamic balance between base stacking interactions and hydrogen bonding to achieve specificity and high affinity by the aptamer domain. Chapter 3 explores the conformational heterogeneity of GAAA tetraloop receptor and the impacts of the tertiary interactions between the receptor and the GAAA tetraloop, where we probe the isolated and GAAA-tetraloop bound receptor. The presence of any bound conformation in the free receptor state leads us to propose the conformational capture mechanism in tetraloop-receptor recognition. Chapter 4 summarizes findings of employing the ultrafast spectroscopy approach in studying riboswitches and the GAAA tetraloop-receptor. Overall our research is an effort to understand the role of conformational dynamics in RNA folding, tertiary interactions, recognition and functions.
Author: Dennis Sean Winston
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Allosteric regulation, when a perturbation at one site in a macromolecule affects the function of a distant site, is widespread in biology. While the study of allostery historically has primarily focused on ligand binding, the concept applies more broadly to any site-specific perturbation including amino acid substitutions, protease cleavage, changes in oligomerization state, and post-translational modification. While there is sometimes a clear and elegant structural explanation for the mechanism of allostery, it is often mediated by conformational dynamics in a way that is not always intuitive. In this work, we focus on two enzyme systems where allosteric regulation is not well-understood: poliovirus 3CD and yeast chorismate mutase. We rely primarily on nuclear magnetic resonance (NMR) relaxation experiments to gain insight into the conformational dynamics of these proteins in order to better understand their allosteric regulation. In the case of poliovirus 3CD, the 3CD precursor is proteolytically processed to produce the 3C and 3D proteins. This production of multiple proteins from the same amino acid sequence is a strategy of expanding the number of protein functions available to viruses, which have very small genomes. 3C is the main protease responsible for cleaving the poliovirus polyprotein and 3D is the RNA-dependent RNA polymerase responsible for replicating the viral RNA. 3CD has different protease specificity from 3C, no polymerase activity, and participates in different protein-protein interactions from 3C and 3D. Structurally, 3CD appears to consist of 3C and 3D domains separated by a flexible linker with no clear structural changes to explain the differences in function. In Chapter 2, we show that there are differences in conformational dynamics between 3CD and its processed products in functionally important regions, suggesting that the function of the 3C and 3D domains of 3CD are allosterically affected by the presence of the 3D & 3C domains. In Chapter 3, we provide the first experimentally determined atomic-level details of poliovirus 3C-phosphoinositide interactions in a membrane context. Membrane binding may alter the conformational ensemble of 3C and 3CD, allowing for further functional regulation of poliovirus proteins over the course of infection. Yeast chorismate mutase (ScCM) catalyzes the conversion of chorismate to prephenate, a key step in the biosynthesis of the aromatic amino acids tyrosine and phenylalanine. ScCM is allosterically inhibited by tyrosine and activated by tryptophan, the end product of the competing pathway. The allosteric regulation has been previously proposed to occur via the Monod-Wyman-Changeux (MWC) model of allostery, where the enzyme fluctuates between states of different activity with an equilibrium constant that is altered by effector binding. In Chapter 4, we use NMR to study conformational fluctuations of ScCM in the absence of effector and show that the MWC model does not fully describe the allosteric regulation by tyrosine and tryptophan binding. Overall, this dissertation contributes to our understanding of the role of conformational dynamics in allosteric regulation across two different proteins.
Author: A. Abragam
Publisher: Oxford University Press
ISBN: 9780198520146
Category : Science
Languages : en
Pages : 666
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Book Description
The Principles of Nuclear Magnetism
Author: Jonathan James Westwood
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
This work focuses on the replicase translational operator (TR) stem loop of the RNA MS2 bacteriophage. Single stranded RNA (ss RNA) viruses are important organisms as they represent pathogenic species in all walks of life including a number of clinically important species such as HIV, Marburg Virus and Ebola. MS2 provides a great model system in which to study regulatory pathways affected by RNA folds due to the extensive biochemical and structural data available. In MS2 the TR stem loop acts as an allosteric switch, via a sequence specific recognition event involving the phage coat protein. Binding of the coat protein dimer to TR signals a switch in the life cycle of the phage from replication to assembly and release. Binding of the coat protein dimer leads to translational repression the viral replicase cistron and also leads to an allosteric conformational change in the protein. TR also contains the AUG start codon for replicase gene and thus is involved in the regulatory pathway of the cistron. Thus any insight to how the folds in the RNA effect binding or translational repression are important for understanding the MS2 virus and other ssRNA viruses like it. The folding ensembles present in solution for a series of RNA oligonucleotides that encompass TR have been examined. Single molecule fluorescence assays suggest that these RNAs exist in solution as differentially base paired/stacked states at equilibrium. What emerges from the experimental is data consistent with an unfolding mechanism in which interruptions to the A- form duplex such as the single stranded loop, the free ends and bulged base of TR, act as nucleation points of unfolding. Additionally substitution of a uracil to a cytosine in the loop causes heterogeneity in the folded and unfolded ensembles relative to the wild-type molecule. This data is used to study folding of the RNAs by 'steered' molecular dynamics (MD) simulations. These show remarkable agreement with experimental data and provide atomistic detail on the molecular interactions which take place during the unfolding pathways studied. The adopted conformers for each simulation provide details about hydrogen bonding between the base pairs of the stem and confirm predicted conformers from apparent dye separation in FRET experiments.
Author: Stefano Crespi
Publisher: Royal Society of Chemistry
ISBN: 183916526X
Category : Science
Languages : en
Pages : 507
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Book Description
Providing critical analysis of emerging and well-established topics, this book is essential reading for anyone wanting to keep up to date with the literature on photochemistry and its applications. Volume 49 combines reviews on the latest advances in photochemical research with specific highlights in the field. The first section includes periodical reports of the recent literature on physical and inorganic aspects, including reviews of the molecules employed as dyes in art, light induced reactions in cryogenic matrices, photobiological systems studied by time-resolved infrared spectroscopy and photophysics, and photochemistry of transition metal complexes. This selection is completed by reviews of the literature on solar photocatalysis for water decontamination and disinfection and for water splitting/hydrogen production. Coverage continues in the second part with highlighted topics, from the use of aromatic carbonyls as photocatalysts and photoinitiators in synthesis, photoinduced and photocatalysed decarboxylation reactions, development of dye-sensitized solar cells, design of luminescent water-soluble systems, and applications of plasmonic nanoparticles. This volume also includes a third section entitled ‘SPR Lectures on Photochemistry’, where leading scientists in photochemistry provide examples to introduce a photochemical topic to academic readers, offering precious assistance to students in this field.
Author: Kazuyuki Akasaka
Publisher: Springer
ISBN: 9401799180
Category : Medical
Languages : en
Pages : 722
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Book Description
This volume covers both the basic concepts and theory of bio-macromolecules under pressure and the various frontiers in high-pressure bioscience and biotechnology. A century has passed since Bridgman discovered the irreversible coagulation of egg white by applying pressure at 700 atmospheres in 1914. Today we are able to monitor pressure-dependent changes in protein structure as a reversible process even at atomic scale with modern spectroscopic techniques. We can study the fluctuating reality of protein structures as designed by nature, which is the basis for all dynamism of life on earth. We are currently facing a new era of high-pressure bioscience, in which pressure is no longer an “odd” or “foreign” variable to life, but rather an integrated part of it. Pressure is used as a crucial variable for disclosing the secrets of nature and as a powerful new tool for enhancing certain reactions in bio-macromolecules and even in living cells for our practical and industrial needs. A dramatic advancement of high-pressure bioscience both in the basic and the applied sciences is thus anticipated in near future, for which sharing the current advanced knowledge on structure and dynamics of bio-macromolecules under pressure among researchers in both fields is crucial. This book serves as a valuable resource not only for those working directly in a pressure-related field, but also for those working in many other fields of the biosciences. Particularly, the basic part of it is intended to serve as a classical text book on high-pressure bioscience to a wide audience including students and researchers in both basic and applied fields in years to come. Readers can focus on topics of immediate interest first, but may wish to go over other chapters if interest arises in a later occasion.
Author: Neocles Leontis
Publisher: Springer Science & Business Media
ISBN: 3642257402
Category : Science
Languages : en
Pages : 402
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Book Description
With the dramatic increase in RNA 3D structure determination in recent years, we now know that RNA molecules are highly structured. Moreover, knowledge of RNA 3D structures has proven crucial for understanding in atomic detail how they carry out their biological functions. Because of the huge number of potentially important RNA molecules in biology, many more than can be studied experimentally, we need theoretical approaches for predicting 3D structures on the basis of sequences alone. This volume provides a comprehensive overview of current progress in the field by leading practitioners employing a variety of methods to model RNA 3D structures by homology, by fragment assembly, and by de novo energy and knowledge-based approaches.
Author: Qiang Cui
Publisher: CRC Press
ISBN: 142003507X
Category : Mathematics
Languages : en
Pages : 448
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Book Description
Rapid developments in experimental techniques continue to push back the limits in the resolution, size, and complexity of the chemical and biological systems that can be investigated. This challenges the theoretical community to develop innovative methods for better interpreting experimental results. Normal Mode Analysis (NMA) is one such technique
Author: Dominik Marx
Publisher: Cambridge University Press
ISBN: 1139477196
Category : Science
Languages : en
Pages : 503
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Book Description
Ab initio molecular dynamics revolutionized the field of realistic computer simulation of complex molecular systems and processes, including chemical reactions, by unifying molecular dynamics and electronic structure theory. This book provides the first coherent presentation of this rapidly growing field, covering a vast range of methods and their applications, from basic theory to advanced methods. This fascinating text for graduate students and researchers contains systematic derivations of various ab initio molecular dynamics techniques to enable readers to understand and assess the merits and drawbacks of commonly used methods. It also discusses the special features of the widely used Car–Parrinello approach, correcting various misconceptions currently found in research literature. The book contains pseudo-code and program layout for typical plane wave electronic structure codes, allowing newcomers to the field to understand commonly used program packages and enabling developers to improve and add new features in their code.
