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Author: Kalli Kappel
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
RNA molecules perform numerous important biological functions including sensing small molecules, regulating gene expression, and catalyzing reactions in all living systems. For many of these processes, RNAs bind to proteins to form RNA-protein assemblies (RNPs) that carry out processes such as translation of RNA to proteins and splicing of pre-mRNA. The structures and energetics of these RNAs and RNA-protein complexes dictate their sophisticated behavior, but often elude rich experimental characterization. Predictive models of these features would enable powerful interpretation of sparse experimental data and efficient design of new RNAs and RNPs. My work aims to create the first computational tools to calculate RNA-protein binding landscapes, build three-dimensional structures of RNA-protein complexes, automatically model RNA coordinates into cryo-electron microscopy (cryo-EM) density maps, and to accelerate reliable RNA structure determination. My colleagues and I have rigorously assessed the predictive power of these methods through blind tests on functionally and structurally diverse RNAs and RNA-protein complexes. This work has culminated in the determination of several novel three-dimensional structures of RNA molecules including ribozymes, riboswitches, and computationally designed molecules. These results suggest that predictive models of RNA and RNP structure and energetics can now enable accelerated, unbiased structure determination when combined with rapidly acquired experimental data, and will be useful for understanding the complex biological functions of RNAs and RNA-protein complexes.
Author: Kalli Kappel
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
RNA molecules perform numerous important biological functions including sensing small molecules, regulating gene expression, and catalyzing reactions in all living systems. For many of these processes, RNAs bind to proteins to form RNA-protein assemblies (RNPs) that carry out processes such as translation of RNA to proteins and splicing of pre-mRNA. The structures and energetics of these RNAs and RNA-protein complexes dictate their sophisticated behavior, but often elude rich experimental characterization. Predictive models of these features would enable powerful interpretation of sparse experimental data and efficient design of new RNAs and RNPs. My work aims to create the first computational tools to calculate RNA-protein binding landscapes, build three-dimensional structures of RNA-protein complexes, automatically model RNA coordinates into cryo-electron microscopy (cryo-EM) density maps, and to accelerate reliable RNA structure determination. My colleagues and I have rigorously assessed the predictive power of these methods through blind tests on functionally and structurally diverse RNAs and RNA-protein complexes. This work has culminated in the determination of several novel three-dimensional structures of RNA molecules including ribozymes, riboswitches, and computationally designed molecules. These results suggest that predictive models of RNA and RNP structure and energetics can now enable accelerated, unbiased structure determination when combined with rapidly acquired experimental data, and will be useful for understanding the complex biological functions of RNAs and RNA-protein complexes.
Author: Chirlmin Joo
Publisher: Springer Nature
ISBN: 1493997262
Category : Science
Languages : en
Pages : 249
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Book Description
RNA molecules play key roles in all aspects of cellular life, but to do so efficiently, they must work in synergism with proteins. This book addresses how proteins and RNA interact to carry out biological functions such as protein synthesis, regulation of gene expression, genome defense, liquid phase separation and more. The topics addressed in this volume will appeal to researchers in biophysics, biochemistry and structural biology. The book is a useful resource for anybody interested in elucidating the molecular mechanisms and discrete properties of RNA-protein complexes. Included are reviews of key systems such as microRNA and CRISPR/Cas that exemplify how RNA and proteins work together to perform their biological function. Also covered are techniques ranging from single molecule fluorescence and force spectroscopy to crystallography, cryo-EM microscopy, and kinetic modeling.
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:
Publisher: Academic Press
ISBN: 0128019360
Category : Science
Languages : en
Pages : 675
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Book Description
This new volume of Methods in Enzymology continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers research methods in RNA folding and dynamics, RNA-protein interactions and large RNPs. - Continues the legacy of this premier serial with quality chapters on structures of large RNA molecules and their complexes
Author: Takayuki Kimura
Publisher:
ISBN:
Category : Hydrogen bonding
Languages : en
Pages : 146
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Book Description
Computational modeling of RNA-protein interactions remains an important endeavor. However, exclusively all-atom approaches that model RNA-protein interactions via molecular dynamics are often problematic in their application. One possible alternative is the implementation of hierarchical approaches, first efficiently exploring configurational space with a coarse-grained representation of the RNA and protein. Subsequently, the lowest energy set of such coarse-grained models can be used as scaffolds for all-atom placements, a standard method in modeling protein 3D-structure. However, the coarse-grained modeling likely will require improved ribonucleotide-amino acid potentials as applied to coarse-grained structures. As a first step we downloaded 1,345 PDB files and clustered them with PISCES to obtain a non-redundant complex data set. The contacts were divided into nine types with DSSR according to the 3D structure of RNA and then 9 sets of potentials were calculated. The potentials were applied to score fifty thousand poses generated by FTDock for twenty-one standard RNA-protein complexes. The results compare favorably to existing RNA-protein potentials. Future research will optimize and test such combined potentials.
Author: David Russell Bell
Publisher:
ISBN:
Category :
Languages : en
Pages : 230
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Book Description
The aim of computational chemistry is to depict and understand the dynamics and interactions of molecular systems. In addition to increased comprehension in the physical and life sciences, this insight yields important applications to therapeutic design and materials science. In computational chemistry, molecules can be modeled in a number of representations depending on the molecular system and phenomena of interest. In this work, both simplified, coarse-grained representations and all-atom representations are used to model the interactions of RNA, cucurbituril host-guest chemistry, and cadmium selenide quantum dot binding to the Src homology 3 domain. For RNA, a coarse-grained model was developed termed RACER (RnA CoarsE-gRained) to accurately predict RNA structure and folding free energy. After optimization to statistical potentials, RACER accurately predicted the structures of 14 RNAs with an average 4.15Å root mean square deviation (RMSD) to the experimental structure. Further, RACER captured the sequence-specific variation in folding free energy for a set of 6 RNA hairpins and 5 RNA duplexes, with a R2 correlation of 0.96 to experiment. The binding free energies of a cucurbituril host with 14 guests were computed using a polarizable force field and the free energy techniques of Bennett acceptance ratio and the orthogonal space random walk. The polarizable force field captured binding accurately, yet unexpectedly, the orthogonal space random walk method converged slowly, albeit at still reduced computational expense to the Bennett acceptance ratio. Lastly, the nanotoxicity effects of trioctylphosphine oxide coated cadmium selenide quantum dots are investigated with the model Src homology 3 protein domain in complex with its native proline rich motif ligand. With increasing quantum dot concentration, there is an increasing preference for the quantum dots to bind to the proline rich motif active site, inhibiting Src homology 3 function.
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: Carolina Moises Reyes
Publisher:
ISBN:
Category : RNA
Languages : en
Pages : 446
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Book Description
Author: John Eargle
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Translation, the process of reading genetic information and synthesizing the corresponding proteins, is universal and found throughout the three domains of life. The flow of information in translation involves a series of distinct but highly conserved RNA·protein complexes with the ribosome being the largest ribonucleoprotein complex in the cell. As the molecular instantiation of the genetic code, tRNA plays a central role in the translational machinery where it interacts with several proteins and other RNAs during the course of protein synthesis. We use molecular dynamics (MD) simulations informed by evolutionary analysis to investigate the dynamics of several RNA·protein complexes involved in translation. Many analysis methods and tools were developed during the course of this study. We present the evolutionary analysis environment MultiSeq, dynamical network analysis and visualization, and a protocol for the preparation of RNA·protein MD simulations. For several Class I aminoacyl-tRNA synthetases (aaRSs), the rate determining step in aminoacylation is the dissociation of the charged tRNA from the enzyme. Through molecular modeling, internal pKa calculations, and MD simulations, distinct, mechanistically relevant post-transfer states with the charged tRNA (Glu-tRNA(Glu)) bound to glutamyl-tRNA synthetase are considered. The behavior of these nonequilibrium states is characterized as a function of time using dynamical network analysis, local energetics, and changes in free energies to estimate transitions that occur during the release of the tRNA. Dynamical network analysis reveals that there are a large number of suboptimal paths through the protein·RNA complex that can be used for communication between the identity elements on the tRNAs and the catalytic site in the aaRS·tRNA complexes. Residues and nucleotides in the majority of pathways bridging communities, local substructures that are highly intraconnected but loosely interconnected, are evolutionarily conserved and are predicted to be important for allosteric signaling. The same monomers are also found in a majority of the suboptimal paths. Modifying these residues or nucleotides has a large effect on the communication pathways in the protein·RNA complex consistent with kinetic data. The highly conserved general base Glu41 is proposed to be a part of a proton relay system for destabilizing the bound charging amino acid following aminoacylation. Addition of elongation factor Tu (EF-Tu) to the aaRS·tRNA complex stimulates the dissociation of the tRNA core and acceptor stem. We use MD simulations to investigate the dynamics of the EF-Tu·GTP·aa-tRNA(Cys) complex and the roles played by Mg2+ ions and modified nucleosides on the free energy of RNA·protein binding. Combined energetic and evolutionary analyses identify the coevolution of residues in EF-Tu and aa-tRNAs at the binding interface. Highly conserved EF-Tu residues are responsible for both attracting aa-tRNAs as well as providing nearby nonbonded repulsive energies which help fine-tune molecular attraction at the binding interface. The trend in EF-Tu·Cys-tRNA(Cys) binding energies observed as the result of mutating the tRNA agrees with experimental observation. We also predict variations in binding free energies upon misacylation of tRNA(Cys) with D-cysteine or O-phosphoserine and upon changing the protonation state of L-cysteine. Finally, ongoing work is presented on the role of ribosomal signatures in the first steps of ribosomal assembly. Ribosomal signatures are features that are completely conserved within one domain of life but absent from the other domains. Correlations between rRNA signatures and signatures in the ribosomal proteins (r-proteins) show that the rRNA signatures coevolved with both domain specific r-proteins and inserts in universal r-proteins. The largest bacterial structural rRNA signature with such a coevolutionary protein partner is found in the five-way junction of the 16S rRNA 5' domain, which is held together by the universal r-protein S4. We characterize the dynamics and flexibility of the free S4 structural signature and rRNA signature helix 16 (h16) as well as the S4·h16 complex. Investigation into the folding and binding of these components will be carried out using Go-like potentials to bias the complex structure towards its native state.
Author: J. Kjems
Publisher: Elsevier
ISBN: 0080886965
Category : Science
Languages : en
Pages : 249
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Book Description
The central role of RNA in many cellular processes, in biotechnology, and as pharmaceutical agents, has created an interest in experimental methods applied to RNA molecules. This book provides scientists with a comprehensive collection of thoroughly tested up-to-date manuals for investigating RNA-protein complexes in vitro. The protocols can be performed by researchers trained in standard molecular biological techniques and require a minimum of specialized equipment. The procedures include recommendation of suppliers of reagents.
