Ion Channel Structure and Drug Discovery Accelerated by Cryo-EM PDF Download

Author: Shujia Zhu
Publisher: Frontiers Media SA
ISBN: 283250776X
Category : Science
Languages : en
Pages : 166

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Publisher: Academic Press
ISBN: 0128054352
Category : Science
Languages : en
Pages : 488

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Book Description
cryoEM, a new volume in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers research methods and new developments in recording images, the creation, evaluation and validation of 3D maps from the images, model building into maps and refinement of the resulting atomic structures, and applications of essentially single particle methods to helical structures and to sub-tomogram averaging. - Continues the legacy of this premier serial with quality chapters authored by leaders in the field - Covers research methods that determine the structures of biological molecules, a vital step for understanding their function - Contains the technical developments underpinning the advances of cryoEM and captures the exciting insights that have resulted

Author: Jean-Paul Renaud
Publisher: John Wiley & Sons
ISBN: 1118900502
Category : Medical
Languages : en
Pages : 1437

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Book Description
With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins

Author: Ciria Hernandez
Publisher: Frontiers Media SA
ISBN: 2832550169
Category : Science
Languages : en
Pages : 153

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Book Description
Ligand and voltage-gated ion channels are highly regulated protein molecules that cross the cell membrane allowing ion flow from one side of the membrane to the other. They are ubiquitously expressed in human tissues and consist of one of the largest and best understood functional groups of proteins, with more than 400 members spanning nearly 1% of the human genome. They are involved in a variety of fundamental physiological processes, and their malfunction causes numerous diseases. In terms of the challenges faced in the effort to discover specific drugs in ancient and emerging diseases, ion channels are the third-largest class of target proteins after G-protein-coupled receptors (GPCRs) and kinases. 15% of small molecule drug targets have been reported to be voltage- or ligand-gated ion channels, resulting in approximately 150 new drug candidates in preclinical and clinical studies. Of the ion channel targeting drugs found on the market, these were identified more than a decade ago, and many of the current studies are at various stages of scientific approval. Overcoming these challenges has led the field of ion channel drug discovery to transform over the past 15 years through major advancements in genetic target detection, validation, structure-based drug design, and drug modeling of cell-based diseases.

Author: Gary Stephens
Publisher: Springer Nature
ISBN: 3031521978
Category :
Languages : en
Pages : 540

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Author: Jean-Paul Renaud
Publisher: John Wiley & Sons
ISBN: 1118900405
Category : Medical
Languages : en
Pages : 692

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Book Description
With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins

Author: Kurt Wthrich
Publisher: World Scientific
ISBN: 9789810223847
Category : Science
Languages : en
Pages : 770

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Book Description
The volume presents a survey of the research by Kurt Wthrich and his associates during the period 1965 to 1994. A selection of reprints of original papers on the use of NMR spectroscopy in structural biology is supplemented with an introduction, which outlines the foundations and the historical development of the use of NMR spectroscopy for the determination of three-dimensional structures of biological macromolecules in solution. The original papers are presented in groups highlighting protein structure determination by NMR, studies of dynamic properties and hydration of biological macromolecules, and practical applications of the NMR methodology in fields such as enzymology, transcriptional regulation, immunosuppression and protein folding.

Author: Krishnarao Appasani
Publisher: CRC Press
ISBN: 1040118844
Category : Science
Languages : en
Pages : 488

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Book Description
Cryo-electron microscopy, in combination with tomography, has emerged as a new technology for visualizing molecular structures at a resolution beyond even 1 Å. Using this technology has revealed the native molecular details of viruses, membranes, enzymes, ribosomes, and cells. This comprehensive volume brings together authoritative overviews of these methods from structural and biological perspectives. It is a must-have for researchers and graduate students, as well as those working in industry, primarily in the areas of biophysics, structural biology, crystallography, and genomics. Key Features • Focuses on the applications of cryo-EM to structural biology • Documents the importance of cryo-EM/ET approaches in studying the structural determinants of cellular organelle and membrane protein biochemistry • Reviews the applications of high-resolution structures of viruses • Emphasizes structural insights of nuclear and gene machineries • Includes a section focused entirely on the applications of cryo-EM/ET in drug discovery and therapeutic development

Author:
Publisher: Academic Press
ISBN: 0323853773
Category : Science
Languages : en
Pages : 422

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Book Description
Ion Channels Part B, Volume 652 in the Methods in Enzymology series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of topics, including NMDAR, Pannexin, and CALHM, Making NaV1.4 and NaV1.7, TRPVs, Purification native nAChRs, GABAR Radu Aricescu, TRPV5/2, NaV1.5, KATP, TRPA1, TREK-1, SARS-CoV-2 3a ion channel, Ion channel conformational dynamics by encoded unnatural amino acid, Fluorescence lifetime measurement of absolute membrane potential, Fluorescent Toxins as Activity Sensors, FRET Analyses of Ion Channel Protein-Protein Interactions, Control of Ion Channel Gating with Photo-Switchable Tweezers, and Counting Subunits in Kv Channel Complexes. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Enzymology series

Author: Joachim Frank
Publisher: World Scientific Publishing Company
ISBN: 9789813234857
Category : Electron microscopy
Languages : en
Pages : 0

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Book Description
The book reproduces 55 of more than 300 articles written by the author, representing milestones in methods development of single-particle cryo-EM as well as important results obtained by this technique in the study of biological macromolecules and their interactions. Importantly, neither symmetries nor ordered arrangements (as in two-dimensional crystals, helical assemblies, icosahedral viruses) are required. Although the biological applications are mainly in the area of ribosome structure and function, the elucidation of membrane channel structures and their activation and gating mechanisms are represented, as well. The book is introduced by a commentary that explains the original development of concepts, describes the contributions of the author's colleagues and students, and shows how challenges were overcome as the technique matured. Along the way, the ribosome served as an example for a macromolecule with intricate structure and conformational dynamics that pose challenges for three-dimensional visualization. Toward the end of the book -- bringing us to the present time -- molecular structures with near-atomic resolution are presented, and a novel type of computational analysis, manifold embedding, is introduced. Single-particle cryo-EM is currently revolutionizing structural biology, presenting a powerful alternative to X-ray crystallography as a means to solve the structure of biological macromolecules. The book presents in one place a number of articles containing key advances in mathematical and computational methods leading up to the present time. Secondly, the development of the technique over the years is reflected by ever-expanding discoveries in the field of ribosome structure and function. Thirdly, as all histories of ideas, the history of concepts pertaining to this new method of visualization is fascinating all in itself.