Download or read book Validation of Computational Approaches for Studying Disordered and Unfolded Protein Dynamics Using Polymer Models written by and published by . This book was released on 2007 with total page 528 pages. Available in PDF, EPUB and Kindle. Book excerpt: The "protein structure-function" paradigm, which states that proteins adopt nearly rigid 3-dimensional structures that are responsible for their function, is one of the central tenets of molecular biology, yet some proteins and protein domains exist as intrinsically disordered forms. In this dissertation, new approaches to define a metric for the dynamics of disordered proteins are developed which are also readily applicable to the study of non-equilibrium globular protein dynamics. First, standard metrics for comparing protein dynamics are applied to molecular dynamics (MD) simulations of a class of entirely disordered proteins (outside of a small anchoring domain) involved in nucleocytoplasmic transport, the FG-nucleoporins (FG-Nups). After this, clustering and dimensionality reduction techniques are utilized to reveal previously unknown characteristics regarding the convergence properties of disordered protein simulations. Next, the novel application of polymer models is used to assess the efficacy of clustering and dimensionality estimation algorithms applied to MD trajectories. Finally, the results are used to analyze the differences between FG-Nup dynamics and the dynamics of two fast-folding globular proteins, GB1 and Trp-cage. The results indicate that polymer models are an effective tool for validating computational techniques for studying protein simulations, and that the various proteins can be classified by differences in their underlying dynamics
Download or read book Computational Approaches to Protein Dynamics written by Monika Fuxreiter and published by CRC Press. This book was released on 2014-12-24 with total page 458 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Latest Developments on the Role of Dynamics in Protein FunctionsComputational Approaches to Protein Dynamics: From Quantum to Coarse-Grained Methods presents modern biomolecular computational techniques that address protein flexibility/dynamics at all levels of theory. An international contingent of leading researchers in chemistry, physics, an
Download or read book On the Application of Molecular Dynamics Simulations to the Study of Intrinsically Disordered Proteins written by Alan Hicks and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins, polymer chains comprised of amino acids, are one of the fundamental machines that drive life. They perform a wide variety of functions within the cell such as nutrient transport, cell signaling, energy production, DNA repair, enzymatic reactions etc.. It was generally accepted that in order to perform these functions the sequence of amino acids would fold into a low energy structure, i.e. the "structure-function" paradigm. At the turn of the century, a new category of proteins was discovered which did not follow this paradigm, intrinsically disordered proteins (IDPs). In fact, we know now that IDPs perform a variety of functions through folding-upon-binding to partners, forming dynamic fuzzy-complexes, or liquid-liquid phase separation, while maintaining a unfolded/unstructured state in solution. These dynamic, unstructured ensembles are incredibly difficult to characterize using previous methods such as X-ray crystallography. Molecular dynamics (MD) simulations, with previous success modeling structured proteins, became one of the key computational methods for determining the conformational ensembles of IDPs. There are two main problems associated with MD simulations of IDPs: sampling and force-field selection. In this dissertation, we discuss these issues using two intrinsically disordered proteins/regions: Q15, a simple disordered peptide, and ChiZ-NT, disordered region from the TM protein ChiZ in Mycobacterium tuberculosis. In the first chapter, we compare the conformational ensembles of Q15 over a series of temperatures with multiple replicate conventional MD (cMD) simulations as well as two enhanced sampling methods, temperature replica exchange (TREMD) and replica exchange with solute tempering (REST), showing that the conformational ensembles of all three simulations are similar, but only the two enhanced sampling methods could reproduce physically correct temperature dependent helical melting. The second chapter focuses on solving the conformational ensemble and backbone dynamics of ChiZ-NT in solution using long-multiple replicate MD simulations. After extensive force-field validation against various experimental parameters, a viable force-field was found which could model the structural properties, and without initial validation, the backbone dynamics of ChiZ-NT. ChiZ-NT exhibits disparate dynamics in the two halves, and long-MD determined that the dynamics is due to sequence specific interactions. Finally, this force-field is used to sequentially model ChiZ in a Mtb mimetic membrane environment, a previously difficult simulation for IDPs due to both sampling and force field-selection. Again long-multiple replicate MD simulations accurately modeled the structure and dynamics of the disordered region of ChiZ as verified by solution and solid-state NMR. Several IDPs form amphipathic helices upon association with membranes, but ChiZ-NT remains disordered upon association with anionic membranes. The strict characterization by solid-state NMR in combination with MD simulations results in the first identification of a disordered, fuzzy complex between disordered regions and the membrane as has been observed between IDP-protein interactions.
Download or read book The Theory of Polymer Dynamics written by Masao Doi and published by Oxford University Press. This book was released on 1988 with total page 420 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive account of the modern theory for the dynamical properties of polymer solutions. The theory has undergone dramatic evolution over the last two decades due to the introduction of new methods and concepts that have extended the frontier of theory from dilute solutions in which polymers move independently to concentrated solutions where many polymers converge. Among the properties examined are viscoelasticity, diffusion, dynamic light scattering, and electric birefringence. Nonlinear viscoelasticity is discussed in detail on the basis of molecular dynamical models. The book bridges the gap between classical theory and new developments, creating a consistent picture of polymer solution dynamics over the entire concentration range.
Download or read book Nucleocytoplasmic Transport written by Reiner Peters and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Graphical Methods for Data Analysis written by J. M. Chambers and published by CRC Press. This book was released on 2018-01-18 with total page 551 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book present graphical methods for analysing data. Some methods are new and some are old, some require a computer and others only paper and pencil; but they are all powerful data analysis tools. In many situations, a set of data even a large set- can be adequately analysed through graphical methods alone. In most other situations, a few well-chosen graphical displays can significantly enhance numerical statistical analyses.
Download or read book Structure and Dynamics of Confined Polymers written by John J. Kasianowicz and published by Springer Science & Business Media. This book was released on 2002-07-31 with total page 46 pages. Available in PDF, EPUB and Kindle. Book excerpt: Polymers are essential to biology because they can have enough stable degrees of freedom to store the molecular code of heredity and to express the sequences needed to manufacture new molecules. Through these they perform or control virtually every function in life. Although some biopolymers are created and spend their entire career in the relatively large free space inside cells or organelles, many biopolymers must migrate through a narrow passageway to get to their targeted destination. This suggests the questions: How does confining a polymer affect its behavior and function? What does that tell us about the interactions between the monomers that comprise the polymer and the molecules that confine it? Can we design and build devices that mimic the functions of these nanoscale systems? The NATO Advanced Research Workshop brought together for four days in Bikal, Hungary over forty experts in experimental and theoretical biophysics, molecular biology, biophysical chemistry, and biochemistry interested in these questions. Their papers collected in this book provide insight on biological processes involving confinement and form a basis for new biotechnological applications using polymers. In his paper Edmund DiMarzio asks: What is so special about polymers? Why are polymers so prevalent in living things? The chemist says the reason is that a protein made of N amino acids can have any of 20 different kinds at each position along the chain, resulting in 20 N different polymers, and that the complexity of life lies in this variety.
Download or read book Intrinsically Disordered Proteins Studied by NMR Spectroscopy written by Isabella C. Felli and published by Springer. This book was released on 2015-09-19 with total page 428 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). The properties of IDPs and IDPRs are highly complementary to those deriving from the presence of a unique and well-defined three-dimensional fold. Ignored for a long time in high-resolution studies of proteins, intrinsic protein disorder is now recognized as one of the key features for a large variety of cellular functions, where structural flexibility presents a functional advantage in terms of binding plasticity and promiscuity and this volume explores this exciting new research. Recent progress in the field has radically changed our perspective to study IDPs through NMR: increasingly complex IDPs can now be characterized, a wide range of observables can be determined reporting on the structural and dynamic properties, computational methods to describe the structure and dynamics are in continuous development and IDPs can be studied in environments as complex as whole cells. This volume communicates the new exciting possibilities offered by NMR and presents open questions to foster further developments. Intrinsically Disordered Proteins Studied by NMR Spectroscopy provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.
Download or read book Fuzziness written by Monika Fuxreiter and published by Springer Science & Business Media. This book was released on 2012-03-07 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt: Detailed characterization of fuzzy interactions will be of central importance for understanding the diverse biological functions of intrinsically disordered proteins in complex eukaryotic signaling networks. In this volume, Peter Tompa and Monika Fuxreiter have assembled a series of papers that address the issue of fuzziness in molecular interactions. These papers provide a broad overview of the phenomenon of fuzziness and provide compelling examples of the central role played by fuzzy interactions in regulation of cellular signaling processes and in viral infectivity. These contributions summarize the current state of knowledge in this new field and will undoubtedly stimulate future research that will further advance our understanding of fuzziness and its role in biomolecular interactions.
Download or read book From Protein Structure to Function with Bioinformatics written by Daniel John Rigden and published by Springer Science & Business Media. This book was released on 2008-12-11 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins lie at the heart of almost all biological processes and have an incredibly wide range of activities. Central to the function of all proteins is their ability to adopt, stably or sometimes transiently, structures that allow for interaction with other molecules. An understanding of the structure of a protein can therefore lead us to a much improved picture of its molecular function. This realisation has been a prime motivation of recent Structural Genomics projects, involving large-scale experimental determination of protein structures, often those of proteins about which little is known of function. These initiatives have, in turn, stimulated the massive development of novel methods for prediction of protein function from structure. Since model structures may also take advantage of new function prediction algorithms, the first part of the book deals with the various ways in which protein structures may be predicted or inferred, including specific treatment of membrane and intrinsically disordered proteins. A detailed consideration of current structure-based function prediction methodologies forms the second part of this book, which concludes with two chapters, focusing specifically on case studies, designed to illustrate the real-world application of these methods. With bang up-to-date texts from world experts, and abundant links to publicly available resources, this book will be invaluable to anyone who studies proteins and the endlessly fascinating relationship between their structure and function.
Download or read book Normal Mode Analysis written by Qiang Cui and published by CRC Press. This book was released on 2005-12-12 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book Modulation of Protein Function written by Daniel E. Atkinson and published by . This book was released on 1979 with total page 516 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book An Introduction to Markov State Models and Their Application to Long Timescale Molecular Simulation written by Gregory R. Bowman and published by Springer Science & Business Media. This book was released on 2013-12-02 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Homology Molecular Modeling written by Rafael Trindade Maia and published by BoD – Books on Demand. This book was released on 2021-03-10 with total page 147 pages. Available in PDF, EPUB and Kindle. Book excerpt: Homology modeling is an extremely useful and versatile technique that is gaining more and more space and demand in research in computational and theoretical biology. This book, “Homology Molecular Modeling - Perspectives and Applications”, brings together unpublished chapters on this technique. In this book, 7 chapters are intimately related to the theme of molecular modeling, carefully selected and edited for academic and scientific readers. It is an indispensable read for anyone interested in the areas of bioinformatics and computational biology. Divided into 4 sections, the reader will have a didactic and comprehensive view of the theme, with updated and relevant concepts on the subject. This book was organized from researchers to researchers with the aim of spreading the fascinating area of molecular modeling by homology.
Download or read book Protein Allostery in Drug Discovery written by Jian Zhang and published by Springer Nature. This book was released on 2019-11-09 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book focuses on protein allostery in drug discovery. Allosteric regulation, ʹthe second secret of lifeʹ, fine-tunes virtually most biological processes and controls physiological activities. Allostery can both cause human diseases and contribute to development of new therapeutics. Allosteric drugs exhibit unparalleled advantages compared to conventional orthosteric drugs, rendering the development of allosteric modulators as an appealing strategy to improve selectivity and pharmacodynamic properties in drug leads. The Series delineates the immense significance of protein allostery—as demonstrated by recent advances in the repertoires of the concept, its mechanistic mechanisms, and networks, characteristics of allosteric proteins, modulators, and sites, development of computational and experimental methods to predict allosteric sites, small-molecule allosteric modulators of protein kinases and G-protein coupled receptors, engineering allostery, and the underlying role of allostery in precise medicine. Comprehensive understanding of protein allostery is expected to guide the rational design of allosteric drugs for the treatment of human diseases. The book would be useful for scientists and students in the field of protein science and Pharmacology etc.
Download or read book Intrinsically Disordered Proteins written by Birthe B. Kragelund and published by Humana. This book was released on 2021-07-23 with total page 951 pages. Available in PDF, EPUB and Kindle. Book excerpt: The edition details methods to study intrinsically disordered proteins (IDPs) including recent topics such as extremely high-affinity disordered complexes, kinetics that evade established concepts, liquid-liquid phase separation, and novel disorder-driven allosteric mechanisms. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Intrinsically Disordered Proteins: Methods and Protocols aims to help scientists with different backgrounds to further their investigations into these fascinating and dynamic molecules. Chapter 24 is available open access under a CC BY 4.0 license via link.springer.com. Chapters “40 and 42 ” are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Download or read book Coarse Grained Modeling of Biomolecules written by Garegin A. Papoian and published by CRC Press. This book was released on 2017-10-30 with total page 430 pages. Available in PDF, EPUB and Kindle. Book excerpt: "The chapters in this book survey the progress in simulating biomolecular dynamics.... The images conjured up by this work are not yet universally loved, but are beginning to bring new insights into the study of biological structure and function. The future will decide whether this scientific movement can bring forth its Picasso or Modigliani." –from the Foreword by Peter G. Wolynes, Bullard-Welch Foundation Professor of Science, Rice University This book highlights the state-of-art in coarse-grained modeling of biomolecules, covering both fundamentals as well as various cutting edge applications. Coarse-graining of biomolecules is an area of rapid advances, with numerous new force fields having appeared recently and significant progress made in developing a systematic theory of coarse-graining. The contents start with first fundamental principles based on physics, then survey specific state-of-art coarse-grained force fields of proteins and nucleic acids, and provide examples of exciting biological problems that are at large scale, and hence, only amenable to coarse-grained modeling. Introduces coarse-grained models of proteins and nucleic acids. Showcases applications such as genome packaging in nuclei and understanding ribosome dynamics Gives the physical foundations of coarse-graining Demonstrates use of models for large-scale assemblies in modern studies Garegin A. Papoian is the first Monroe Martin Associate Professor with appointments in the Department of Chemistry and Biochemistry and the Institute for Physical Science and Technology at the University of Maryland.
