Mechanism of Conformational Change in Proteins PDF Download

Author: ACS. Division of Biological Chemistry
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Author: Bruce Alberts
Publisher:
ISBN: 9780815332183
Category : Cytology
Languages : en
Pages : 0

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Author: Gregory R. Bowman
Publisher: Springer Science & Business Media
ISBN: 9400776063
Category : Science
Languages : en
Pages : 148

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The aim of this book volume is to explain the importance of Markov state models to molecular simulation, how they work, and how they can be applied to a range of problems. The Markov state model (MSM) approach aims to address two key challenges of molecular simulation: 1) How to reach long timescales using short simulations of detailed molecular models. 2) How to systematically gain insight from the resulting sea of data. MSMs do this by providing a compact representation of the vast conformational space available to biomolecules by decomposing it into states sets of rapidly interconverting conformations and the rates of transitioning between states. This kinetic definition allows one to easily vary the temporal and spatial resolution of an MSM from high-resolution models capable of quantitative agreement with (or prediction of) experiment to low-resolution models that facilitate understanding. Additionally, MSMs facilitate the calculation of quantities that are difficult to obtain from more direct MD analyses, such as the ensemble of transition pathways. This book introduces the mathematical foundations of Markov models, how they can be used to analyze simulations and drive efficient simulations, and some of the insights these models have yielded in a variety of applications of molecular simulation.

Author: John Cavanagh
Publisher: Elsevier
ISBN: 008047103X
Category : Science
Languages : en
Pages : 915

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Book Description
Protein NMR Spectroscopy, Second Edition combines a comprehensive theoretical treatment of NMR spectroscopy with an extensive exposition of the experimental techniques applicable to proteins and other biological macromolecules in solution. Beginning with simple theoretical models and experimental techniques, the book develops the complete repertoire of theoretical principles and experimental techniques necessary for understanding and implementing the most sophisticated NMR experiments. Important new techniques and applications of NMR spectroscopy have emerged since the first edition of this extremely successful book was published in 1996. This updated version includes new sections describing measurement and use of residual dipolar coupling constants for structure determination, TROSY and deuterium labeling for application to large macromolecules, and experimental techniques for characterizing conformational dynamics. In addition, the treatments of instrumentation and signal acquisition, field gradients, multidimensional spectroscopy, and structure calculation are updated and enhanced. The book is written as a graduate-level textbook and will be of interest to biochemists, chemists, biophysicists, and structural biologists who utilize NMR spectroscopy or wish to understand the latest developments in this field. Provides an understanding of the theoretical principles important for biological NMR spectroscopy Demonstrates how to implement, optimize and troubleshoot modern multi-dimensional NMR experiments Allows for the capability of designing effective experimental protocols for investigations of protein structures and dynamics Includes a comprehensive set of example NMR spectra of ubiquitin provides a reference for validation of experimental methods

Author: Derek J. Chadwick
Publisher: John Wiley & Sons
ISBN: 0470514159
Category : Science
Languages : en
Pages : 282

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How the amino acid sequence of a protein determines its three-dimensional structure is a major problem in biology and chemistry. Leading experts in the fields of NMR spectroscopy, X-ray crystallography, protein engineering and molecular modeling offer provocative insights into current views on the protein folding problem and various aspects for future progress.

Author: Swarnendu Tripathi
Publisher:
ISBN:
Category : Calmodulin
Languages : en
Pages : 163

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Book Description
Proteins are flexible and dynamic molecules, which serve crucial functions in essentially all biological events in living cells. An important example is allostery, the coupling between ligand binding and protein conformational change. The primary focus of the research in this dissertation is to elucidate the detailed mechanism of large scale (main-chain) structural changes of specific proteins where conformational flexibility is essential for function. The functional states of proteins can be viewed as a minimum in the free energy landscape. Conformational exchanges between structures within this native (folded) minimum occur with rates controlled by the height of the energy barrier between them. The distribution of the conformational substates is highly complex and the dynamics of transitions between these substates are generally controlled by relatively low probability conformational ensembles. The main challenge is to describe the transition state ensembles at the residue level, giving site specific description of the transition mechanism. To address this important issue I developed an analytical model that accommodates the free energy minima relevant to transition between two particular well-folded conformations. The free energy surface of the protein is approximated using a reference Hamiltonian that corresponds to a polymer in a non-uniform external field that harmonically constrains the fluctuations of the monomers to average positions, uniformly interpolating between two meta-stable native structures. The free energy surfaces are parameterized by conformational flexibility of each residue. Transition routes and the site-resolved structure of the transition state ensembles are determined by constrained minima of the variational free energy surface. I mainly focus on two separate proteins with flexibility determined allosteric transitions to illustrate the model: Calmodulin (CaM) and the N-terminal receiver domain of nitrogen regulatory protein C (NtrC). CaM is a flexible protein and plays an essential role in calcium-mediated eukaryotic cellular signaling. This signal transduction is accomplished primarily through a calcium-induced open/closed conformational change of the CaM domains. I investigate this conformational change of the two domains of CaM independently. Our study illustrates that inherent flexibility is the key determinant of the transition mechanism of the two domains. In particular, our results reveal that C-terminal domain of CaM which is inherently less flexible than its homologous and structurally similar N-terminal domain unfolds partially and refolds during the transition. These findings are also in harmony with molecular dynamics simulations, as well as nuclear magnetic resonance (NMR) measurements characterizing the slow conformational dynamics of the CaM domains. Furthermore, these observations might have some significance on the diverse functions of CaM. NtrC of enteric bacteria is a response regulator and plays a central role in the control of genes involved in nitrogen metabolism. Phosphorylation (activation) of the inactive NtrC, results in large structural changes. NMR studies suggested that allostery in this protein occurs by shifting the preexisting population from the inactive to active state upon phosphorylation. From the folding study of NtrC, I explore that different folding mechanisms of the two states are mainly due to the stabilization of the active conformation upon phosphorylation. I also investigate the mechanism of phosphorylation induced inactive/active conformational change of NtrC. Our results show significant decrease in the flexibility of this protein upon activation due to a large entropic contribution in consistent with the NMR experiments.

Author: Fabian Paul
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Proteins are molecules that are essential for life and carry out an enormous number of functions in organisms. To this end, they change their conformation and bind to other molecules. However, the interplay between conformational change and binding is not fully understood. In this work, this interplay is investigated with molecular dynamics (MD) simulations of the protein-peptide system Mdm2-PMI and by analysis of data from relaxation experiments. The central task it to uncover the binding mechanism, which is described by the sequence of (partial) binding events and conformational change events including their probabilities. In the simplest case, the binding mechanism is described by a two-step model: binding followed by conformational change or conformational change followed by binding. In the general case, longer sequences with multiple conformational changes and partial binding events are possible as well as parallel pathways that differ in their sequences of events. The theory of Markov state models (MSMs) provides the...

Author: Ke-li Han
Publisher: Springer Science & Business Media
ISBN: 3319029703
Category : Medical
Languages : en
Pages : 488

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Book Description
This book discusses how biological molecules exert their function and regulate biological processes, with a clear focus on how conformational dynamics of proteins are critical in this respect. In the last decade, the advancements in computational biology, nuclear magnetic resonance including paramagnetic relaxation enhancement, and fluorescence-based ensemble/single-molecule techniques have shown that biological molecules (proteins, DNAs and RNAs) fluctuate under equilibrium conditions. The conformational and energetic spaces that these fluctuations explore likely contain active conformations that are critical for their function. More interestingly, these fluctuations can respond actively to external cues, which introduces layers of tight regulation on the biological processes that they dictate. A growing number of studies have suggested that conformational dynamics of proteins govern their role in regulating biological functions, examples of this regulation can be found in signal transduction, molecular recognition, apoptosis, protein / ion / other molecules translocation and gene expression. On the experimental side, the technical advances have offered deep insights into the conformational motions of a number of proteins. These studies greatly enrich our knowledge of the interplay between structure and function. On the theoretical side, novel approaches and detailed computational simulations have provided powerful tools in the study of enzyme catalysis, protein / drug design, protein / ion / other molecule translocation and protein folding/aggregation, to name but a few. This work contains detailed information, not only on the conformational motions of biological systems, but also on the potential governing forces of conformational dynamics (transient interactions, chemical and physical origins, thermodynamic properties). New developments in computational simulations will greatly enhance our understanding of how these molecules function in various biological events.

Author:
Publisher: Academic Press
ISBN: 0080865968
Category : Technology & Engineering
Languages : en
Pages : 471

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The remarkable expansion of information leading to a deeper understanding of enzymes on the molecular level necessitated the development of this volume which not only introduces new topics to The Enzymes series but presents new information on some covered in Volume I and II of this edition.

Author: Christophe Chipot
Publisher: Springer Science & Business Media
ISBN: 3540384472
Category : Language Arts & Disciplines
Languages : en
Pages : 528

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Book Description
Free energy constitutes the most important thermodynamic quantity to understand how chemical species recognize each other, associate or react. Examples of problems in which knowledge of the underlying free energy behaviour is required, include conformational equilibria and molecular association, partitioning between immiscible liquids, receptor-drug interaction, protein-protein and protein-DNA association, and protein stability. This volume sets out to present a coherent and comprehensive account of the concepts that underlie different approaches devised for the determination of free energies. The reader will gain the necessary insight into the theoretical and computational foundations of the subject and will be presented with relevant applications from molecular-level modelling and simulations of chemical and biological systems. Both formally accurate and approximate methods are covered using both classical and quantum mechanical descriptions. A central theme of the book is that the wide variety of free energy calculation techniques available today can be understood as different implementations of a few basic principles. The book is aimed at a broad readership of graduate students and researchers having a background in chemistry, physics, engineering and physical biology.