Download or read book Markov State Models for Protein and RNA Folding written by Gregory Ross Bowman and published by Stanford University. This book was released on 2010 with total page 279 pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding the molecular bases of human health could greatly augment our ability to prevent and treat diseases. For example, a deeper understanding of protein folding would serve as a reference point for understanding, preventing, and reversing protein misfolding in diseases like Alzheimer's. Unfortunately, the small size and tremendous flexibility of proteins and other biomolecules make it difficult to simultaneously monitor their thermodynamics and kinetics with sufficient chemical detail. Atomistic Molecular Dynamics (MD) simulations can provide a solution to this problem in some cases; however, they are often too short to capture biologically relevant timescales with sufficient statistical accuracy. We have developed a number of methods to address these limitations. In particular, our work on Markov State Models (MSMs) now makes it possible to map out the conformational space of biomolecules by combining many short simulations into a single statistical model. Here we describe our use of MSMs to better understand protein and RNA folding. We chose to focus on these folding problems because of their relevance to misfolding diseases and the fact that any method capable of describing such drastic conformational changes should also be applicable to less dramatic but equally important structural rearrangements like allostery. One of the key insights from our folding simulations is that protein native states are kinetic hubs. That is, the unfolded ensemble is not one rapidly mixing set of conformations. Instead, there are many non-native states that can each interconvert more rapidly with the native state than with one another. In addition to these general observations, we also demonstrate how MSMs can be used to make predictions about the structural and kinetic properties of specific systems. Finally, we explain how MSMs and other enhanced sampling algorithms can be used to drive efficient sampling.
Download or read book Metastability and Markov State Models in Molecular Dynamics written by Christof Schütte and published by American Mathematical Soc.. This book was released on 2013-12-26 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: Applications in modern biotechnology and molecular medicine often require simulation of biomolecular systems in atomic representation with immense length and timescales that are far beyond the capacity of computer power currently available. As a consequence, there is an increasing need for reduced models that describe the relevant dynamical properties while at the same time being less complex. In this book the authors exploit the existence of metastable sets for constructing such a reduced molecular dynamics model, the so-called Markov state model (MSM), with good approximation properties on the long timescales. With its many examples and illustrations, this book is addressed to graduate students, mathematicians, and practical computational scientists wanting an overview of the mathematical background for the ever-increasing research activity on how to construct MSMs for very different molecular systems ranging from peptides to proteins, from RNA to DNA, and via molecular sensors to molecular aggregation. This book bridges the gap between mathematical research on molecular dynamics and its practical use for realistic molecular systems by providing readers with tools for performing in-depth analysis of simulation and data-analysis methods. Titles in this series are co-published with the Courant Institute of Mathematical Sciences at New York University.
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 Modulation of Protein Function written by and published by . This book was released on 1979 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Biological Sequence Analysis written by Richard Durbin and published by Cambridge University Press. This book was released on 1998-04-23 with total page 372 pages. Available in PDF, EPUB and Kindle. Book excerpt: Probabilistic models are becoming increasingly important in analysing the huge amount of data being produced by large-scale DNA-sequencing efforts such as the Human Genome Project. For example, hidden Markov models are used for analysing biological sequences, linguistic-grammar-based probabilistic models for identifying RNA secondary structure, and probabilistic evolutionary models for inferring phylogenies of sequences from different organisms. This book gives a unified, up-to-date and self-contained account, with a Bayesian slant, of such methods, and more generally to probabilistic methods of sequence analysis. Written by an interdisciplinary team of authors, it aims to be accessible to molecular biologists, computer scientists, and mathematicians with no formal knowledge of the other fields, and at the same time present the state-of-the-art in this new and highly important field.
Download or read book Biomolecular Simulations in Structure Based Drug Discovery written by Francesco L. Gervasio and published by John Wiley & Sons. This book was released on 2019-04-29 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: A guide to applying the power of modern simulation tools to better drug design Biomolecular Simulations in Structure-based Drug Discovery offers an up-to-date and comprehensive review of modern simulation tools and their applications in real-life drug discovery, for better and quicker results in structure-based drug design. The authors describe common tools used in the biomolecular simulation of drugs and their targets and offer an analysis of the accuracy of the predictions. They also show how to integrate modeling with other experimental data. Filled with numerous case studies from different therapeutic fields, the book helps professionals to quickly adopt these new methods for their current projects. Experts from the pharmaceutical industry and academic institutions present real-life examples for important target classes such as GPCRs, ion channels and amyloids as well as for common challenges in structure-based drug discovery. Biomolecular Simulations in Structure-based Drug Discovery is an important resource that: -Contains a review of the current generation of biomolecular simulation tools that have the robustness and speed that allows them to be used as routine tools by non-specialists -Includes information on the novel methods and strategies for the modeling of drug-target interactions within the framework of real-life drug discovery and development -Offers numerous illustrative case studies from a wide-range of therapeutic fields -Presents an application-oriented reference that is ideal for those working in the various fields Written for medicinal chemists, professionals in the pharmaceutical industry, and pharmaceutical chemists, Biomolecular Simulations in Structure-based Drug Discovery is a comprehensive resource to modern simulation tools that complement and have the potential to complement or replace laboratory assays for better results in drug design.
Download or read book Protein Conformational Dynamics written by Ke-li Han and published by Springer Science & Business Media. This book was released on 2014-01-20 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Stochastic Processes in Physics and Chemistry written by N.G. Van Kampen and published by Elsevier. This book was released on 1992-11-20 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new edition of Van Kampen's standard work has been completely revised and updated. Three major changes have also been made. The Langevin equation receives more attention in a separate chapter in which non-Gaussian and colored noise are introduced. Another additional chapter contains old and new material on first-passage times and related subjects which lay the foundation for the chapter on unstable systems. Finally a completely new chapter has been written on the quantum mechanical foundations of noise. The references have also been expanded and updated.
Download or read book Computational Approaches for Understanding Dynamical Systems Protein Folding and Assembly written by and published by Academic Press. This book was released on 2020-03-04 with total page 552 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational Approaches for Understanding Dynamical Systems: Protein Folding and Assembly, Volume 170 in the Progress in Molecular Biology and Translational Science series, provides the most topical, informative and exciting monographs available on a wide variety of research topics. The series includes in-depth knowledge on the molecular biological aspects of organismal physiology, with this release including chapters on Pairwise-Additive and Polarizable Atomistic Force Fields for Molecular Dynamics Simulations of Proteins, Scale-consistent approach to the derivation of coarse-grained force fields for simulating structure, dynamics, and thermodynamics of biopolymers, Enhanced sampling and free energy methods, and much more.
Download or read book RNA protein Interactions written by Kiyoshi Nagai and published by Oxford University Press, USA. This book was released on 1994 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: The study of RNA-protein interactions is crucial to understanding the mechanisms and control of gene expression and protein synthesis. The realization that RNAs are often far more biologically active than was previously appreciated has stimulated a great deal of new research in this field. Uniquely, in this book, the world's leading researchers have collaborated to produce a comprehensive and current review of RNA-protein interactions for all scientists working in this area. Timely, comprehensive, and authoritative, this new Frontiers title will be invaluable for all researchers in molecular biology, biochemistry and structural biology.
Download or read book Computational Approaches for Studying Enzyme Mechanism Part B written by and published by Academic Press. This book was released on 2016-08-03 with total page 538 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational Approaches for Studying Enzyme Mechanism, Part B is the first of two volumes in the Methods in Enzymology series that focuses on computational approaches for studying enzyme mechanism. The serial achieves the critically acclaimed gold standard of laboratory practices and remains one of the most highly respected publications in the molecular biosciences. Each volume is eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with over 550 volumes, the series remains a prominent and essential publication for researchers in all fields of the life sciences and biotechnology, including biochemistry, chemical biology, microbiology, synthetic biology, cancer research, genetics, and other fields of study. - Focuses on computational approaches for studying enzyme mechanism - Continues the legacy of this premier serial with quality chapters authored by leaders in the field - Covers research methods in intermediate filament associated proteins, and contains sections on such topics as lamin-associated proteins, intermediate filament-associated proteins and plakin, and other cytoskeletal cross-linkers
Download or read book Pacific Symposium on Biocomputing 2010 Kamuela Hawaii USA 4 8 January 2010 written by Russ B. Altman and published by World Scientific. This book was released on 2009-10-23 with total page 502 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Pacific Symposium on Biocomputing (PSB) 2010 is an international, multidisciplinary conference for the presentation and discussion of current research in the theory and application of computational methods in problems of biological significance. Presentations are rigorously peer reviewed and are published in an archival proceedings volume. PSB 2010 will be held on January 4 - 8, 2010 in Kohala Coast, Hawaii. Tutorials and workshops will be offered prior to the start of the conference. PSB 2010 will bring together top researchers from the US, Asia Pacific, and around the world to exchange research results and address pertinent issues in all aspects of computational biology. It is a forum for the presentation of work in databases, algorithms, interfaces, visualization, modeling, and other computational methods, as applied to biological problems, with emphasis on applications in data-rich areas of molecular biology. The PSB has been designed to be responsive to the need for critical mass in sub-disciplines within biocomputing. For that reason, it is the only meeting whose sessions are defined dynamically each year in response to specific proposals. PSB sessions are organized by leaders of research in biocomputing's "hot topics". In this way, the meeting provides an early forum for serious examination of emerging methods and approaches in this rapidly changing field.
Download or read book Biocomputing 2010 Proceedings Of The Pacific Symposium written by Russ B Altman and published by World Scientific. This book was released on 2009-10-23 with total page 500 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Pacific Symposium on Biocomputing (PSB) 2010 is an international, multidisciplinary conference for the presentation and discussion of current research in the theory and application of computational methods in problems of biological significance. Presentations are rigorously peer reviewed and are published in an archival proceedings volume. PSB 2010 will be held on January 4 - 8, 2010 in Kohala Coast, Hawaii. Tutorials and workshops will be offered prior to the start of the conference.PSB 2010 will bring together top researchers from the US, Asia Pacific, and around the world to exchange research results and address pertinent issues in all aspects of computational biology. It is a forum for the presentation of work in databases, algorithms, interfaces, visualization, modeling, and other computational methods, as applied to biological problems, with emphasis on applications in data-rich areas of molecular biology.The PSB has been designed to be responsive to the need for critical mass in sub-disciplines within biocomputing. For that reason, it is the only meeting whose sessions are defined dynamically each year in response to specific proposals. PSB sessions are organized by leaders of research in biocomputing's “hot topics”. In this way, the meeting provides an early forum for serious examination of emerging methods and approaches in this rapidly changing field.
Download or read book RNA Polymerases as Molecular Motors written by Robert Landick and published by Royal Society of Chemistry. This book was released on 2021-11-23 with total page 295 pages. Available in PDF, EPUB and Kindle. Book excerpt: To thrive, every living cell must continuously gauge and respond to changes in its environment. These changes are ultimately implemented by modulating gene expression, a process that relies on transcription by Nature’s most multivalent molecular machine, the RNA polymerase. This book covers progress made over the past decade understanding how this machine functions to compute the cellular state, from the atomistic structural level responsible for chemistry to the integrative level at which RNA polymerase interacts with the other key molecular machineries of the cell.
Download or read book Advanced Sampling and Modeling in Molecular Simulations for Slow and Large Scale Biomolecular Dynamics written by Xiakun Chu and published by Frontiers Media SA. This book was released on 2022-01-07 with total page 164 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Concepts in Bioscience Engineering written by Richard Dods and published by Springer Nature. This book was released on 2020-02-21 with total page 377 pages. Available in PDF, EPUB and Kindle. Book excerpt: This textbook teaches bioengineers critical concepts about protein three dimensional structures, how proteins fold, and how the folding affects the functioning of the protein. Protein folding has profound effects on the discovery of biopharmaceutical drugs (especially the transport of immunological compounds to their site of action) as well as on tissue engineering. Dr. Dods covers topics in easily understood terms through the use of glossaries heading each chapter and footnotes and summaries at the end of each chapter. The chapters cover disordered proteins and large sequences of disorder that exists within proteins, secondary structure (α-helix and β-pleated structure), tertiary and quaternary structure, post-translational changes, proteopathies, bioengineering approaches used to study protein folding, and computer software for protein folding. For each of these topics the elements of biomolecular imaging, cellular and tissue engineering, and health care systems engineering are built. Molecular engineering concepts such as site-directed mutagenesis are addressed. For reinforcement of the concepts presented in this text, activities and problems (Queries) are included in the chapter.
Download or read book Artificial Chemistries written by Wolfgang Banzhaf and published by MIT Press. This book was released on 2024-03-19 with total page 572 pages. Available in PDF, EPUB and Kindle. Book excerpt: An introduction to the fundamental concepts of the emerging field of Artificial Chemistries, covering both theory and practical applications. The field of Artificial Life (ALife) is now firmly established in the scientific world, but it has yet to achieve one of its original goals: an understanding of the emergence of life on Earth. The new field of Artificial Chemistries draws from chemistry, biology, computer science, mathematics, and other disciplines to work toward that goal. For if, as it has been argued, life emerged from primitive, prebiotic forms of self-organization, then studying models of chemical reaction systems could bring ALife closer to understanding the origins of life. In Artificial Chemistries (ACs), the emphasis is on creating new interactions rather than new materials. The results can be found both in the virtual world, in certain multiagent systems, and in the physical world, in new (artificial) reaction systems. This book offers an introduction to the fundamental concepts of ACs, covering both theory and practical applications. After a general overview of the field and its methodology, the book reviews important aspects of biology, including basic mechanisms of evolution; discusses examples of ACs drawn from the literature; considers fundamental questions of how order can emerge, emphasizing the concept of chemical organization (a closed and self-maintaining set of chemicals); and surveys a range of applications, which include computing, systems modeling in biology, and synthetic life. An appendix provides a Python toolkit for implementing ACs.
