This book focuses on the study of how the properties of nanodiscs, such as lipid composition and size, influence the function of the embedding integral membrane protein, bacteriorhodopsin. The author performed systematic studies to show that the lipid composition and the charge of the hydrophobic head and the structure of hydrophilic tails affect the photocycle pathway of bacteriorhodopsin, which is closely associated with its proton-pumping activity. Furthermore, the author demonstrated a highly efficient method for extracting membrane proteins directly from the biological membrane, preserving protein conformation, function and essential native lipids. This book demonstrates optimization and sample preparation, and presents practical methods of preparing membrane protein-embedded nanodisc samples for biophysical studies, which benefit structural and functional studies in the field of membrane protein characterization, both.

This book focuses on the study of how the properties of nanodiscs, such as lipid composition and size, influence the function of the embedding integral membrane protein, bacteriorhodopsin. The author performed systematic studies to show that the lipid composition and the charge of the hydrophobic head and the structure of hydrophilic tails affect the photocycle pathway of bacteriorhodopsin, which is closely associated with its proton-pumping activity. Furthermore, the author demonstrated a highly efficient method for extracting membrane proteins directly from the biological membrane, preserving protein conformation, function and essential native lipids. This book demonstrates optimization and sample preparation, and presents practical methods of preparing membrane protein-embedded nanodisc samples for biophysical studies, which benefit structural and functional studies in the field of membrane protein characterization, both.

This volume of Current Topics in Membranes focuses on Membrane Protein Crystallization, beginning with a review of past successes and general trends, then further discussing challenges of mebranes protein crystallization, cell free production of membrane proteins and novel lipids for membrane protein crystallization. This publication also includes tools to enchance membrane protein crystallization, technique advancements, and crystallization strategies used for photosystem I and its complexes, establishing Membrane Protein Crystallization as a needed, practical reference for researchers.

Exploring current themes in modern computational and membrane protein biophysics, this book presents a comprehensive account of the fundamental principles underlying different methods and techniques used to describe the intriguing mechanisms by which membrane proteins function. The book discusses the experimental approaches employed to study these proteins, with chapters reviewing recent crucial structural advances that have allowed computational biophysicists to discern how these molecular machines work. The book then explores what computational methods are available to researchers and what these have taught us about three key families of membrane proteins: ion channels, transporters and receptors. The book is ideal for researchers in computational chemistry and computational biophysics.

Amphiphilic layers play essential roles in the behaviour of a great variety of disperse systems such as micelles, microemulsions and vesicles. They can also exist as isolated mono- or bilayers, or constitute extended liquid crystalline structures. Although the properties of these different systems may at first sight seem unrelated, theoretical interpretations of them depend on several common concepts. This was the reason for bringing together scientists working in this area for the International Winter School on the Physics of Amphiphilic Layers, which was held at Les Houches, 10-18 February, 1987. The topics treated in the proceedings volume are mono- and bilayers, interactive forces between layers (with special emphasis on steric forces), ordered structures (in particular swollen lamellar phases and defects), vesicles, micelles (including polymer-like systems), microemulsions (especially random bicontinuous structures) and porous media. The importance of thermal fluctuations in the amphiphilic layers is stressed. Recent results are presented and literature references allow readers not familiar with the subject to find any background information they require.

Now in its second edition, the Handbook of Lipid Bilayers is a groundbreaking work that remains the field’s definitive text and only comprehensive source for primary physicochemical data relating to phospholipid bilayers. Along with basic thermodynamic data, coverage includes both dynamic and structural properties of phospholipid bilayers. It is an indispensable reference for users of bilayer model membranes and liposome delivery systems and for those interested in the biophysics of membrane structure. Each chapter in the second edition contains considerable amounts of explanation and elaboration, including, in many cases, extensive analysis of structural connections between the data. New in the Second Edition: Chapters on crystal structures of phospholipids include new structures and more comprehensive data on bond lengths, bond angles, and torsion angles—and all coordinates are Cartesian Wide-angle data is indexed whenever possible to characterize chain-packing modes in gel and crystalline lamellar phases Low-angle data are analyzed in terms of the lipid and water thicknesses Headgroup separations in electron density profiles for phospholipids are included, and a separate section is devoted to the in-depth analysis of electron density profiles that provides the most detailed structural information on fluid lamellar phases Phase diagrams of phospholipid mixtures are vastly expanded and have been redrawn in standardized format to aid intercomparison. Cholesterol, including ternary systems, is now featured. New sections on titration calorimetry, and much extended data on the temperature dependence of transfer rates The greatly expanded chapter on bilayer–bilayer interactions features new and detailed information on the components of interbilayer pressures

This book is the first to be entirely devoted to the challenging art of handling membrane proteins out of their natural environment, a key process in biological and pharmaceutical research, but one plagued with difficulties and pitfalls. Written by one of the foremost experts in the field, Membrane Proteins in Aqueous Solutions is accessible to any member of a membrane biology laboratory. After presenting the structure, functions, dynamics, synthesis, natural environment and lipid interactions of membrane proteins, the author discusses the principles of extracting them with detergents, the mechanisms of detergent-induced destabilization, countermeasures, and recent progress in developing detergents with weaker denaturing properties. Non-conventional alternatives to detergents, including bicelles, nanodiscs, amphipathic peptides, fluorinated surfactants and amphipols, are described, and their relative advantages and drawbacks are compared. The synthesis and solution properties of the various types of amphipols are presented, as well as the formation and properties of membrane protein/amphipol complexes and the transfer of amphipol-trapped proteins to detergents, nanodiscs, lipidic mesophases, or living cells. The final chapters of the book deal with applications: membrane protein in vitro folding and cell-free expression, solution studies, NMR, crystallography, electron microscopy, mass spectrometry, amphipol-mediated immobilization of membrane proteins, and biomedical applications. Important features of the book include introductory sections describing foundations as well as the state-of-the-art for each of the biophysical techniques discussed, and topical tables which organize a widely dispersed literature. Boxes and annexes throughout the book explain technical aspects, and twelve detailed experimental protocols, ranging from in vitro folding of membrane proteins to single-particle electron cryomicroscopy, have been contributed by and commented on by experienced users. Membrane Proteins in Aqueous Solutions offers a concise, accessible introduction to membrane protein biochemistry and biophysics, as well as comprehensive coverage of the properties and uses of conventional and non-conventional surfactants. It will be useful both in basic and applied research laboratories and as a teaching aid for students, instructors, researchers, and professionals within the field.

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

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.