Modern research in biology increasingly relies on multiple techniques for describing structures and mechanisms. This book provides an overview of the contemporary integrated biology approaches for solving structures and understanding mechanisms of complex biological systems. It includes several methodology chapters discussing the current developments in the areas of cryo-electron microscopy (EM) and cryo-electron tomography (ET), computational biophysics, solution NMR spectroscopy, solid-state NMR spectroscopy and dynamic nuclear polarization (DNP), electron paramagnetic resonance (EPR), (photo-)chemically induced dynamic nuclear polarization (CIDNP), X-ray crystallography and small-angle X-ray and neutron scattering (SAXS/SANS). Several subsequent chapters demonstrate how these methods are used in synergy to address problems at the forefront of structural biology, with particular emphasis on examples where individual techniques are insufficient. Examples of biological systems include membrane proteins, viral protein assemblies, cytoskeleton protein assemblies, photosynthetic reaction centers, large enzyme complexes and whole cells. The book is targeted to both the current practitioners of structural biology and scientists who are interested in entering the fields of structural biology or biophysical chemistry.

This book presents a new emerging concept of "Integrative Structural Biology". It covers current trends of the molecular and cellular structural biology, providing new methods to observe, validate, and keep the structural models of the large cellular machines with recent scientific results. Structures of very large macromolecular machines in cells are being determined by combining observations from complementary experimental methods. Thus, this volume presents the each methods such as X-ray crystallography, NMR spectroscopy, 3DEM, small-angle scattering (SAS), FRET, crosslinking, and enables the readers to understand the hybrid methods. This book discusses how those integrative models should be represented, validated and archived. A unique highlight of this book is discussion of the data validation and archive, which are big problems in this filed along with the progress of this field. The researchers in biology will be interested in this book as a guide book for learning the current structure biology, but also those in structure biology may use this book as a comprehensive reference to cover broad topics.

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

Computer simulation is an essential tool in studying the chemistry and physics of liquids. Simulations allow us to develop models and to test them against experimental data. This book is an introduction and practical guide to the molecular dynamics and Monte Carlo methods.

The present volume continues the trend established in previous volumes in this series on Advances in Structural Biology. As in the past, diverse topics of current importance relevant to the theme of the series are included in the fourth volume.

Biophysics represents perhaps one of the best examples of interdisciplinary research areas, where concepts and methods from disciplines such as physics, biology, b- chemistry, colloid chemistry, and physiology are integrated. It is by no means a new ?eld of study and has actually been around, initially as quantitative physiology and partly as colloid science, for over a hundred years. For a long time, biophysics has been taught and practiced as a research discipline mostly in medical schools and life sciences departments, and excellent biophysics textbooks have been published that are targeted at a biologically literate audience. With a few exceptions, it is only relatively recently that biophysics has started to be recognized as a physical science and integrated into physics departments’ curr- ula, sometimes under the new name of biological physics. In this period of cryst- lization and possible rede?nition of biophysics, there still exists some uncertainty as to what biophysics might actually represent. A particular tendency among phy- cists is to associate biophysics research with the development of powerful new te- niques that should eventually be used not by physicists to study physical processes in living matter, but by biologists in their biological investigations. There is value in that judgment, and excellent books have been published that introduce the int- ested reader to the use of physical principles for the development of new methods of investigation in life sciences.

In-cell NMR spectroscopy is a relatively new field. Despite its short history, recent in-cell NMR-related publications in major journals indicate that this method is receiving significant general attention. This book provides the first informative work specifically focused on in-cell NMR. It details the historical background of in-cell NMR, host cells for in-cell NMR studies, methods for in-cell biological techniques and NMR spectroscopy, applications, and future perspectives. Researchers in biochemistry, biophysics, molecular biology, cell biology, structural biology as well as NMR analysts interested in biological applications will all find this book valuable reading.

This volume explores strategies and detailed protocols for the preparation of macromolecular complexes and their characterization in view of structural analysis. The chapters in this book are separated into three parts: Part One focuses on sample preparation, and covers strategies for recombinant expression of multiprotein complexes in prokaryotic and eukaryotic hosts, for genome engineering using the CRISPR/Cas9 system and for production of specific binders such as reformatted antibodies and artificial binding proteins. Part Two looks at the biophysical methods that can provide useful indicators for sample optimization, and often complement structural information obtained with core technologies for structure determination—x-ray crystallography and cryo-electron microscopy—by quantitative solution data. Part Three discusses the characterization of multiprotein complexes in a cellular environment using the latest technologies and in vivo approaches. 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. Cutting-edge and authoritative, Multiprotein Complexes: Methods and Protocols is a valuable resource for structural and molecular biologists who need to prepare multi-components for their applications, and for other scientists working on macromolecular assemblies from other angles that need to know the latest approaches that the field has to offer.

Scattering Methods in Structural Biology, Part B, Volume 676 in the Methods in Enzymology serial, highlights advances in the field, presenting chapters on Quality controls, Refining biomolecular structures and ensembles by SAXS-driven molecular dynamics simulations, Data analysis and modelling of small-angle scattering data with contrast variation, Observing protein degradation in solution by the PAN-20S proteasome complex: state-of-the-art and future perspectives of TR-SANS as a complementary tool to NMR, crystallography and Cryo-EM, Extracting structural insights from chemically-specific soft X-ray scattering, Reconstruction of 3D density of biological macromolecules from solution scattering, ATSAS- present state and new developments in computational methods, and much more. Additional chapters cover Modeling Structure and Dynamics of Protein Complexes with SAXS Profiles (FoXSDock and MultiFoXS), Validation of macromolecular flexibility in solution by SAXS, Combining NMR, SAXS and SANS to characterize the structure and dynamics of protein complexes, Application of Molecular Simulation Methods to Analyze SAS Data, and more. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in the Methods in Enzymology serial - Updated release includes the latest information on Small Angle Scattering Methods for Structural Interpretation