Biological and Medical Physics, Biomedical Engineering – serie

Escherichia coli, commonly referred to as E. coli, has been the organism of choice for molecular genetics for decades. Its machinery and mobile behavior is one of the most fascinating topics for cell scientists. Scientists and engineers, not trained in microbiology, and who would like to learn more about living machines, can see it as a unique example. This cross-disciplinary monograph covers more than thirty years of research and is accessible to graduate students and scientists alike.

Emergent Computation emphasizes the interrelationship of the different classes of languages studied in mathematical linguistics (regular, context-free, context-sensitive, and type 0) with aspects to the biochemistry of DNA, RNA, and proteins. In addition, aspects of sequential machines such as parity checking and semi-groups are extended to the study of the Biochemistry of DNA, RNA, and proteins. Mention is also made of the relationship of algebraic topology, knot theory, complex fields, quaternions, and universal turing machines and the biochemistry of DNA, RNA, and proteins.Emergent Computation tries to avoid an emphasis upon mathematical abstraction ("elegance") at the expense of ignoring scientific facts known to Biochemists. Emergent Computation is based entirely upon papers published by scientists in well-known and respected professional journals. These papers are based upon current research.A few examples of what is not ignored to gain "elegance":- DNA exists as triple and quadruple strands - Watson-Crick complementary bases have mismatches - There can be more than four bases in DNA - There are more than sixty-four codons - There may be more that twenty amino acids in proteins While Emergent Computation emphasizes bioinformatics applications, the last chapter studies mathematical linguistics applied to areas such as languages found in birds, insects, medical applications, anthropology, etc.Emergent Computation tries to avoid unnecessary mathematical abstraction while still being rigorous. The demands made upon the knowledge of chemistry or mathematics is minimized as well. The collected technical references are valuable in itself for additional reading.

The text is aimed at a broad audience of students and other individuals interested in furthering their understanding of how cells regulate and coordinate their core activities. Malfunction in the control layer is responsible for a host of human disorders ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. This book will be useful to students and individuals in medicine and pharmacology interested in broadening their understanding of how the control layer works. To further that goal, there are chapters on cancers and apoptosis, and on bacteria and viruses. In those chapters not specifically devoted to pathogens, connections between diseases, drugs and signaling are made. The audience for this book includes students in chemistry, physics and computer science who intend to work in biological and medical physics, and bioinformatics and systems biology. The first five chapters of the book are mainly background and review chapters.Signaling in the immune, endocrine (hormonal) and nervous systems is covered along with cancer, apoptosis and gene regulation.

The fields of biological and medical physics and biomedical engineering are broad, multidisciplinary and dyanmic. They lie at the crossroads of frontier - search in physics, biology, chemistry, and medicine. The Biological & Me- cal Physics/Biomedical Engineering Series is intended to be comprehensive, covering a broad range of topics important to the study of the physical, che- cal and biological sciences. Its goal is to provide scientists and engineers with textbooks, monographs, and reference works to address the growing need for information. Books in the series emphasize established and emergent areas of science - cluding molecular, membrane, and mathematical biophysics; photosynthetic - ergy harvesting and conversion; information processing; physical principles of genetics; sensory communications; automata networks, neural networks, and cellular automata. Equally important will be coverage of applied aspects of b- logical and medical physics and biomedical engineering such as molecular el- tronic components and devices, biosensors, medicine, imaging, physical prin- ples of renewable energy production, advanced prostheses, and environmental control and engineering. Elias Greenbaum Oak Ridge, TN M. Zamir Department of Applied Mathematics University of Western Ontario London, Ontario, N6A 5B7 CANADA zamir@uwo.ca Library of Congress Cataloging-in-Publication Data Zamir, M. (Mair) The physics of coronary blood flow / M. Zamir. p. cm. — (Biological and medical physics, biomedical engineering) Includes bibliographical references and index. 1. Coronary circulation. 2. Hemodynamics. 3. Blood flow. I. Title. II. Series. QP108.Z36 2005 612.1?7—dc22 2005042502 ISBN-10: 0-387-25297-5 e-ISBN: 0-387-26019-6 Printed on acid-free paper.

An ultimate goal of modern biology is to understand how the genetic blueprint of cells(genotype)determinesthestructure,function,andbehaviorofalivingorganism (phenotype). At the center of this scienti?c endeavor is characterizing the bioch- ical and cellular roles of proteins, the working molecules of the machinery of life. A key to understanding of functional proteins is the knowledge of their folded str- tures in a cell, as the structures provide the basis for studying proteins’ functions and functional mechanisms at the molecular level. Researchers working on structure determination have traditionally selected - dividual proteins due to their functional importance in a biological process or pa- way of particular interest. Major research organizations often have their own protein X-ray crystallographic or/and nuclear magnetic resonance facilities for structure - termination, which have been conducted at a rate of a few to dozens of structures a year. Realizing the widening gap between the rates of protein identi?cation (through DNA sequencing and identi?cation of potential genes through bioinformatics an- ysis) and the determination of protein structures, a number of large scienti?c init- tives have been launched in the past few years by government funding agencies in the United States, Europe, and Japan, with the intention to solve protein structures en masse, an effort called structural genomics. A number of structural genomics centers (factory-like facilities) have been established that promise to produce solved protein structures in a similar fashion to DNA sequencing.

Volume Two of this two-volume sequence presents a comprehensive overview of protein structure prediction methods and includes protein threading, De novo methods, applications to membrane proteins and protein complexes, structure-based drug design, as well as structure prediction as a systems problem. A series of appendices review the biological and chemical basics related to protein structure, computer science for structural informatics, and prerequisite mathematics and statistics.

Ion channels are biological nanotubes that are formed by membrane proteins. Because ion channels regulate all electrical activities in living cells, understanding their mechanisms at a molecular level is a fundamental problem in biology. This book deals with recent breakthroughs in ion-channel research that have been brought about by the combined effort of experimental biophysicists and computational physicists, who together are beginning to unravel the story of these exquisitely designed biomolecules. With chapters by leading experts, the book is aimed at researchers in nanodevices and biosensors, as well as advanced undergraduate and graduate students in biology and the physical sciences. Key FeaturesPresents the latest information on the molecular mechanisms of ion permeation through membrane ion channelsUses schematic diagrams to illustrate important concepts in biophysicsWritten by leading researchers in the area of ion channel investigations

Artificial sight is a frontier area of modern ophthalmology combining the multidisciplinary skills of surgical ophthalmology, biomedical engineering, biological physics, and psychophysical testing. Many scientific, engineering, and surgical challenges must be surmounted before widespread practical applications can be realized. The goal of Artificial Sight is to summarize the state-of-the-art research in this exciting area, and to describe some of the current approaches and initiatives that may help patients in a clinical setting. The Editors are active researchers in the fields of artificial sight, biomedical engineering and biological physics. They have received numerous professional awards and recognition for their work. The artificial sight team at the Doheny Eye Institute, led by Dr. Mark Humayun, is a world leader in this area of biomedical engineering and clinical research.Key FeaturesIntroduces and assesses the state of the art for a broad audience of biomedical engineers, biophysicists, and clinical researchersDescribes advances in microelectronics, microfabrication, surgical implantation, and psychophysical testing of visual prosthesesOutlines the promise of artificial sight and the challenges that must be met

Covers the principle physical and biological aspects of radiation therapy. This book addresses practical clinical considerations in the planning and delivering of that therapy. It also emphasizes the importance of the assessment of uncertainties.

Cell motility is a fascinating example of cell behavior which is fundamentally important to a number of biological and pathological processes. It is based on a complex self-organized mechano-chemical machine consisting of cytoskeletal filaments and molecular motors. In general, the cytoskeleton is responsible for the movement of the entire cell and for movements within the cell. The main challenge in the field of cell motility is to develop a complete physical description on how and why cells move. For this purpose new ways of modeling the properties of biological cells have to be found. This long term goal can only be achieved if new experimental techniques are developed to extract physical information from these living systems and if theoretical models are found which bridge the gap between molecular and mesoscopic length scales. Cell Motility gives an authoritative overview of the fundamental biological facts, theoretical models, and current experimental developments in this fascinating area.

Significant progress has been made in the development of neural prostheses to restore human functions and improve the quality of human life. Biomedical engineers and neuroscientists around the world are working to improve design and performance of existing devices and to develop novel devices for artificial vision, artificial limbs, and brain–machine interfaces. This book, Implantable Neural Prostheses 1: Devices and Applications,ispart one of a two-book series and describes state-of-the-art advances in techniques associated with implantable neural prosthetic devices and their applications. Devices covered include sensory prosthetic devices, such as visual implants, cochlear implants, auditory midbrain implants, and spinal cord stimulators. Motor prosthetic devices, such as deep brain stimulators, Bion microstimu- tors, the brain control and sensing interface, and cardiac electro-stimulation devices are also included. Progress in magnetic stimulation that may offer a non-invasive approach to prosthetic devices is introduced. Regulatory approval of implantable medical devices in the United States and Europe is also discussed.

Depite the rapid expansion of the field of biophysics, there are very few books that comprehensively treat specific topics in this area. Recently, the field of single molecule biophysics has developed very quickly, and a few books specifically treating single molecule methods are beginning to appear. However, the promise of single molecule biophysics is to contribute to the understanding of specific fields of biology using new methods. This book would focus on the specific topic of the biophysics of DNA-protein interactions, and would include the use of new approaches, including both bulk methods as well as single molecule methods. This would make the book attractive to anyone working in the general area of DNA-protein interactions, which is of course a much wider market than just single molecule biophysicists or even biophysicists.The subject of the book will be the biophysics of DNA-protein interactions, and will include new methods and results that describe the physical mechanism by which proteins interact with DNA. For example, there has been much recent work on the mechanism by which proteins search for specific binding sites on DNA. A few chapters will be devoted to experiments and theory that shed light on this important problem. We will also cover proteins that alter DNA properties to facilitate interactions important for transcription or replication. Another section of the book will cover the biophysical mechanism by which motor proteins interact with DNA. Finally, we will cover larger protein-DNA complexes, such as replication forks, recombination complexes, DNA repair interactions, and their chromatin context.

Signi?cant progress has been made in the development of neural prostheses for restoration of human functions and improvement of the quality of life. Biomedical engineers and neuroscientists around the world are working to improve the design and performance of existing devices and to develop novel devices for arti?cial vision, arti?cial limbs, and brain-machine interfaces. This book, Implantable Neural Prostheses 2: Techniques and Engineering Approaches, is part two of a two-volume sequence that describes state-of-the-art advances in techniques associated with implantable neural prosthetic devices. The techniques covered include biocompatibility and biostability, hermetic packaging, electrochemical techniques for neural stimulation applications, novel electrode materials and testing, thin-?lm ?exible microelectrode arrays, in situ char- terization of microelectrode arrays, chip-size thin-?lm device encapsulation, microchip-embedded capacitors and microelectronics for recording, stimulation, and wireless telemetry. The design process in the development of medical devices is also discussed. Advances in biomedical engineering, microfabrication technology, and neu- science have led to improved medical-device designs and novel functions. However, many challenges remain. This book focuses on the engineering approaches, R&D advances, and technical challenges of medical implants from an engineering p- spective. We are grateful to leading researchers from academic institutes, national laboratories, as well as design engineers and professionals from the medical device industry who have contributed to the book. Part one of this series covers designs of implantable neural prosthetic devices and their clinical applications.

In today’s world, three great classes of non-infectious diseases – the metabolic syndromes (such as type 2 diabetes and atherosclerosis), the cancers, and the neurodegenerative disorders – have risen to the fore. These diseases, all associated with increasing age of an individual, have proven to be remarkably complex and difficult to treat. This is because, in large measure, when the cellular signaling pathways responsible for maintaining homeostasis and health of the body become dysregulated, they generate equally stable disease states. As a result the body may respond positively to a drug, but only for a while and then revert back to the disease state. Cellular Signaling in Health and Disease summarizes our current understanding of these regulatory networks in the healthy and diseased states, showing which molecular components might be prime targets for drug interventions. This is accomplished by presenting models that explain in mechanistic, molecular detail how a particular part of the cellular signaling web operates properly in health and improperly in disease.The stability of the health- and disease-associated states is dynamic and supported by multiple feedback loops acting positively and negatively along with linkages between pathways. During the past few years an ongoing series of important discoveries have been made that advance our understanding of how the body works and may guide us on how to better deal with these diseases. These include the discovery of chronic inflammation as a causal factor in all of these disease classes, the appearance of reactive oxygen species as a messenger molecule that can act both positively and negatively, the propensity of proteins to misfold into aggregation- and disease-prone forms, and the rise of epigenetics including the emergence of small non-coding RNA with important regulatory functions out of the so-called junk RNA. Chapters are devoted to each of these classes of findings with additional detailsintegrated into the chapters dealing directly with the diseases. The connections responsible for maintaining stability are explored in depth.

A reissue of a classic book, corrected, edited, and typeset, to be published in the Biological Physics Series. Intended for undergraduate courses in biophysics, biological physics, physiology, medical physics, and biomedical engineering, this book is an introduction to statistical physics with examples and problems from the medical and biological sciences. Topics include the elements of the theory of probability, Poisson statistics, thermal equilibrium, entropy and free energy, and the second law of thermodynamics. Chapters include problems and references. The book can be used as a supplement to standard introductory physics courses, and as a text for medical schools, medical physics courses, and biology departments. The three volumes combined present all the major topics in physics. Originally published in 1974 from the authors's typescript, this reissue will be edited, corrected, typeset, the art redrawn, and an index added. These books are being reissued by Springer in the Biological Physics Series in response to frequent requests to provide these texts to satisfy the growing need among students and practitioners in the medical and biological sciences with a working knowledge of the physical sciences. The books are also in demand in physics departments either as supplements to traditional intro texts or as main text for those departments offering courses with biological or medical physics orientation. A solutions manual will be available. The authors are recognized experts in the field, and are under contract for an upperlevel/grad text in biological physics. Benedeck was the recepient of the 1995 Irving Lanmuir Prize from the American Physical Society for Chemical Physics, and the 1994 Biological Physics Prize by the American Physical Society.

A reissue of a classic book, corrected, edited, and typeset, to be published in the Biological Physics Series. Intended for undergraduate courses in biophysics, biological physics, physiology, medical physics, and biomedical engineering, this book is an introduction to mechanics with examples and problems from the medical and biological sciences. The book covers standard topics of kinematics, dynamics,statics, momentum, and feeedback, control and stability but with emphasis on physical and biological systems. Chapters include problems and references. The book can be used as a supplement to standard introductory physics courses, and as a text for medical schools, medical physics courses, and biology departments. The three volumes combined present all the major topics in physics. Originally published in 1974 from the authors's typescript, this reissue will be edited, corrected, typeset, the art redrawn, and an index added. These books are being reissued by Springer in the Biological Physics Series in response to frequent requests to provide these texts to satisfy the growing need among students and practitioners in the medical and biological sciences with a working knowledge of the physical sciences. The books are also in demand in physics departments either as supplements to traditional intro texts or as main text for those departments offering courses with biological or medical physics orientation. A solutions manual will be available. The authors are recognized experts in the field, and are under contract for an upperlevel/grad text in biological physics. Benedeck was the recepient of the 1995 Irving Lanmuir Prize from the American Physical Society for Chemical Physics, and the 1994 Biological Physics Prize by the American Physical Society.

The field of biological physics is a broad, multidisciplinary, and dynamic one, touching on many areas of research in physics, biology, chemistry and medicine. New findings are published in a large number of publications within these disci­ plines, making it difficult for students and scientists working in biological physics to keep up with advances occurring in disciplines other than their own. The Bi­ ological Physics Series is intended therefore to be a comprehensive one covering a broad range of topics important to the study of biological physics. Its goal is to provide scientists and engineers with text books, monographs and reference books to address the growing need for information. Books in the Biological Physics Series will emphasize frontier areas of science including molecular, membrane, and mathematical biophysics; photosynthetic en­ ergy harvesting and conversion; information processing; physical principles of ge­ netics; sensory communications; automata networks, neural networks, and cellu­ lar automata. Equally important will be coverage of current and potential applied aspects of biological physics such as biomolecular electronic components and de­ vices, biosensors, medicine, imaging, physical principles of renewable energy pro­ duction, and environmental control and engineering. We are fortunate to have a distinguished roster of consulting editors on the Editorial Board, reflecting the breadth of biological physics. We believe that the Biological Physics Series can help advance the knowledge in the field by providing a home for publications in the field and that scientists and practitioners from many disciplines will find much to learn from the upcoming volumes.

Classic texts in the field of analysis of flow in blood vessels have been written over the years and what these say is still valid today. However, our knowledge of pathophysiological mechanisms has changed with increasing rapidity over the past 20 years, as has our ability to visualize the three­ dimensional geometry of blood flow and blood flow velocity distribution within the in vivo blood vessels. Consequently, with the increased need to fully exploit the new imaging capabilities and our additional biological knowledge, this book is a welcome addition to our armamentarium used to achieve those new goals. the past pulsatile flow (and consequent wave reflections) was Whereas in often seen as "frosting on the cake" of analysis of blood flow problems or perhaps as an issue that should be understood only in a general sense, our new capabilities and understanding require more accurate analyses of spe­ cific systems, not just of constructs based on statistical data describing a vascular tree. Examples of this new need include the situation where the detailed branching geometry of an arterial tree is known from imaging and it is desired to see to what extent local fluid dynamic characteristics can explain the specific localization of disease such as atherosclerosis, or of the extent to which the heterogeneity of perfusion throughout an organ can be attributed to the vascular tree branching geometry or to the mechani­ cal properties of the vascular walls.

A reissue of a 3-volume set of classic books, newly edited and typeset to be published in the Biological Physics Series. Intended for undergraduate courses in biophysics, biological physics, physiology, medical physics, and biomedical engineering, these books are introductions to mechanics, statistical physics, and electricty and magnetism with examples and problems from the medical and biological sciences. The books can be used as supplements to standard introductory physics courses, and as texts for medical schools, medical physics courses, and biology departments. The three volumes combined present all the major topics in physics.Originally published in 1974 from the authors's typescript, these reissues will be edited, corrected, typeset, the art redrawn, and an index added. These books are being reissued by Springer in the Biological Physics Series in response to frequent requests to provide these texts to satisfy the growing need among students and practitioners in the medical and biological sciences with a working knowledge of the physical sciences.The books are also in demand in physics departments either as supplements to traditional intro texts or as main text for those departments offering courses with biological or medical physics orientation. Solutions manuals will be available. The authors are recognized experts in the field, and are under contract for an upperlevel/grad text in biological physics. Benedeck was the recepient of the 1995 Irving Lanmuir Prize from the American Physical Society for Chemical Physics, and the 1994 Biological Physics Prize by the American Physical Society.

Molecular nanotechnology is an emerging technology that allows us to build materials and systems with atomic and molecular precision by manipulating atoms and molecules at very small scales, ultimately at the single molecule scale. Since the properties of materials depend on how their atoms are arranged, the ability to manipulate atoms and molecules at the nano-scale will allow us to create new materials, to improve current materials, and to build systems heretofore only dreamt of. The implications of this technology are great: continued revolutions in computer chip technology, continued revolutions in manufacturing, new and stronger materials, and highly precise medical instruments and treatments.It is only recently that advances in scanning probe microscopy, biotechnology (mainly protein and genetic engineering), and solution-phase chemistry have been defined as tools to implement the technology. These and other advances in the technologies of physics, chemistry and biology are converging to provide the methodology for a molecular-scale technology.This book provides the professional with an overview of current methodologies in the field, with emphasis on the implementation of current research.

This book provides an introduction to two important aspects of modern bioch- istry, molecular biology, and biophysics: computer simulation and data analysis. My aim is to introduce the tools that will enable students to learn and use some f- damental methods to construct quantitative models of biological mechanisms, both deterministicandwithsomeelementsofrandomness;tolearnhowconceptsofpr- ability can help to understand important features of DNA sequences; and to apply a useful set of statistical methods to analysis of experimental data. The availability of very capable but inexpensive personal computers and software makes it possible to do such work at a much higher level, but in a much easier way, than ever before. TheExecutiveSummaryofthein?uential2003reportfromtheNationalAcademy of Sciences, “BIO 2010: Transforming Undergraduate Education for Future - search Biologists” [12], begins The interplay of the recombinant DNA, instrumentation, and digital revolutions has p- foundly transformed biological research. The con?uence of these three innovations has led to important discoveries, such as the mapping of the human genome. How biologists design, perform, and analyze experiments is changing swiftly. Biological concepts and models are becoming more quantitative, and biological research has become critically dependent on concepts and methods drawn from other scienti?c disciplines. The connections between the biological sciences and the physical sciences, mathematics, and computer science are rapidly becoming deeper and more extensive.

Physics and the life sciences have established new connections within the past few decades, resulting in biological physics as an established subfield with strong groups working in many physics departments. These interactions between physics and biology form a two-way street with physics providing new tools and concepts for understanding life, while biological systems can yield new insights into the physics of complex systems. To address the challenges of this interdisciplinary area, The Physics of Proteins: An Introduction to Biological Physics and Molecular Biophysics is divided into three interconnected sections. In Parts I and II, early chapters introduce the terminology and describe the main biological systems that physicists will encounter. Similarities between biomolecules, glasses, and solids are stressed with an emphasis on the fundamental concepts of living systems. The central section (Parts III and IV) delves into the dynamics of complex systems. A main theme is the realization that biological systems, in particular proteins, do not exist in unique conformations but can assume a very large number of slightly different structures. This complexity is captured in the concept of a free energy landscape and leads to the conclusion that fluctuations are crucial for the functioning of biological systems. The final chapter of this section challenges the reader to apply these concepts to a problem that appears in the current literature. An extensive series of appendices (Part V) provide descriptions of the key physical tools and analytical methods that have proven powerful in the study of the physics of proteins. The appendices are designed to be consulted throughout the section on protein dynamics without breaking the deductive flow of the logic in the central section of the book.

Recent studies have shown that novel processing and modeling techniques may be used to create patient-specific prostheses, artificial tissues, and other implants using data obtained from magnetic resonance imaging, computed tomography, or other imaging techniques. For example, customized prostheses may be fabricated that possess suitable features, including geometry, size, and weight, for a given medical condition. Many advances have been made in the development of patient-specific implants in the past decade, yet this information is not readily available to scientists and students. Printed Biomaterials: Novel Processing and Modeling Techniques for Medicine and Surgery provides the biomaterials scientist and engineer, as well as advanced undergraduate or graduate students, with a comprehensive discussion of contemporary medical implant research and development. The development of printed biomaterials is multidisciplinary, and includes concepts traditionally associated with engineering, materials science, medicine, and surgery. This text highlights important topics in these core fields in order to provide the fundamentals necessary to comprehend current processing and modeling technologies and to develop new ones.

Escherichia coli, commonly referred to as E. coli, has been the organism of choice for molecular genetics for decades. Its machinery and mobile behavior is one of the most fascinating topics for cell scientists. Scientists and engineers, not trained in microbiology, and who would like to learn more about living machines, can see it as a unique example. This cross-disciplinary monograph covers more than thirty years of research and is accessible to graduate students and scientists alike.

Emergent Computation emphasizes the interrelationship of the different classes of languages studied in mathematical linguistics (regular, context-free, context-sensitive, and type 0) with aspects to the biochemistry of DNA, RNA, and proteins. In addition, aspects of sequential machines such as parity checking and semi-groups are extended to the study of the Biochemistry of DNA, RNA, and proteins. Mention is also made of the relationship of algebraic topology, knot theory, complex fields, quaternions, and universal turing machines and the biochemistry of DNA, RNA, and proteins.Emergent Computation tries to avoid an emphasis upon mathematical abstraction ("elegance") at the expense of ignoring scientific facts known to Biochemists. Emergent Computation is based entirely upon papers published by scientists in well-known and respected professional journals. These papers are based upon current research. A few examples of what is not ignored to gain "elegance":- DNA exists as triple and quadruple strands - Watson-Crick complementary bases have mismatches - There can be more than four bases in DNA - There are more than sixty-four codons - There may be more that twenty amino acids in proteins While Emergent Computation emphasizes bioinformatics applications, the last chapter studies mathematical linguistics applied to areas such as languages found in birds, insects, medical applications, anthropology, etc.Emergent Computation tries to avoid unnecessary mathematical abstraction while still being rigorous. The demands made upon the knowledge of chemistry or mathematics is minimized as well. The collected technical references are valuable in itself for additional reading.

Makes connections between diseases, drugs and signaling in those chapters not specifically devoted to pathogens. Reviews background in first 5 chapters then offers chapters on cancers and apoptosis and on bacteria and viruses. Signaling in the immune, endocrine (hormonal) and nervous systems covered along with cancer, apoptosis and gene regulation. Each chapter ends with a problem section to facilitate discussion.

An ultimate goal of modern biology is to understand how the genetic blueprint of cells(genotype)determinesthestructure,function,andbehaviorofalivingorganism (phenotype). At the center of this scienti?c endeavor is characterizing the bioch- ical and cellular roles of proteins, the working molecules of the machinery of life. A key to understanding of functional proteins is the knowledge of their folded str- tures in a cell, as the structures provide the basis for studying proteins’ functions and functional mechanisms at the molecular level. Researchers working on structure determination have traditionally selected - dividual proteins due to their functional importance in a biological process or pa- way of particular interest. Major research organizations often have their own protein X-ray crystallographic or/and nuclear magnetic resonance facilities for structure - termination, which have been conducted at a rate of a few to dozens of structures a year. Realizing the widening gap between the rates of protein identi?cation (through DNA sequencing and identi?cation of potential genes through bioinformatics an- ysis) and the determination of protein structures, a number of large scienti?c init- tives have been launched in the past few years by government funding agencies in the United States, Europe, and Japan, with the intention to solve protein structures en masse, an effort called structural genomics. A number of structural genomics centers (factory-like facilities) have been established that promise to produce solved protein structures in a similar fashion to DNA sequencing.

Volume Two of this two-volume sequence presents a comprehensive overview of protein structure prediction methods and includes protein threading, De novo methods, applications to membrane proteins and protein complexes, structure-based drug design, as well as structure prediction as a systems problem. A series of appendices review the biological and chemical basics related to protein structure, computer science for structural informatics, and prerequisite mathematics and statistics.

Ion channels are biological nanotubes that are formed by membrane proteins. Because ion channels regulate all electrical activities in living cells, understanding their mechanisms at a molecular level is a fundamental problem in biology. This book deals with recent breakthroughs in ion-channel research that have been brought about by the combined effort of experimental biophysicists and computational physicists, who together are beginning to unravel the story of these exquisitely designed biomolecules. With chapters by leading experts, the book is aimed at researchers in nanodevices and biosensors, as well as advanced undergraduate and graduate students in biology and the physical sciences. Key FeaturesPresents the latest information on the molecular mechanisms of ion permeation through membrane ion channelsUses schematic diagrams to illustrate important concepts in biophysicsWritten by leading researchers in the area of ion channel investigations