This best-selling volume presents the principles and applications of physical chemistry as they are used to solve problems in biology and medicine. The First Law; the Second Law; free energy and chemical equilibria; free energy and physical Equilibria; molecular motion and transport properties; kinetics: rates of chemical reactions; enzyme kinetics; the theory and spectroscopy of molecular structures and interactions: molecular distributions and statistical thermodynamics; and macromolecular structure and X-ray diffraction. For anyone interested in physical chemistry as it relates to problems in biology and medicine.
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Ignacio Tinoco was an undergraduate at the University of New Mexico, a graduate student at the University of Wisconsin, and a postdoctoral fellow at Yale. He then went to the University of California, Berkeley, where he has remained. His research interest has been on the structures of nucleic acids, particularly RNA. He was chairman of the Department of Energy committee that recommended in 1987 a major initiative to sequence the human genome. His present research is on unfolding single RNA molecules by force.
Kenneth Sauer grew up in Cleveland, Ohio, and received his A.B. in chemistry from Oberlin College. Following his Ph.D. studies in gas-phase physical chemistry at Harvard, he spent three years teaching at the American University of Beirut, Lebanon. A postdoctoral opportunity to learn from Melvin Calvin about photosynthesis in plants led him to the University of California, Berkeley, where he has been since 1960. Teaching general chemistry and biophysical chemistry in the Chemistry Department has complemented research in the Physical Biosciences Division of the Lawrence Berkeley National Lab involving spectroscopic studies of photosynthetic light reactions and their role in water oxidation. His other activities include reading, renaissance and baroque choral music, canoeing, and exploring the Sierra Nevada with his family and friends.
James C. Wang was on the faculty of the University of California, Berkeley, from 1966 to 1977. He then joined the faculty of Harvard University, where he is presently Mallinckrodt Professor of Biochemistry and Molecular Biology. His research focuses on DNA and enzymes that act on DNA, especially a class of enzymes known as DNA topoisomerases. He has taught courses in biophysical chemistry and molecular biology and has published over 200 research articles. He is a member of Academia Sinica, the American Academy of Arts and Sciences, and the U.S. National Academy of Sciences.
Joseph Puglisi was born and raised in New Jersey. He received his B.A. in chemistry from The Johns Hopkins University in 1984 and his Ph.D. from the University of California, Berkeley, in 1989. He has studied and taught in Strasbourg, Boston, and Santa Cruz, and is currently professor of structural biology at Stanford University. His research interests are in the structure and mechanism of the ribosome and the use of NMR spectroscopy to study RNA structure. He has been a Dreyfus Scholar, Sloan Scholar, and Packard Fellow.
PREFACE
There is a deep sense of pleasure to be experienced when the patterns and symmetry of nature are revealed. Physical chemistry provides the methods to discover and understand these patterns. We think that not only is it important to learn and apply physical chemistry to biological problems, it may even be fun. In this book, we have tried to capture some of the excitement of making new discoveries and finding answers to fundamental questions.
This is not an encyclopedia of physical chemistry. Rather, we have written this text specifically with the life-science student in mind. We present a streamlined treatment that covers the core aspects of biophysical chemistry (thermodynamics and kinetics as well as quantum mechanics, spectroscopy, and X-ray diffraction), which are of great importance to students of biology and biochemistry. Essentially all applications of the concepts are to systems of interest to life-science students; nearly all the problems apply to life-science examples.
For this fourth edition we are joined by Joseph Puglisi, a new, young author who strengthens the structural biology content of the book. We have also tried to make the book more reader-friendly. In particular, we omit fewer steps in the explanations to make the material more understandable, and we have followed the many helpful and specific recommendations of our reviewers to improve the writing throughout. Important new topics, such as single-molecule thermodynamics, kinetics, and spectroscopy, are introduced. Subjects that have become less pertinent to current biophysical chemistry have been deleted or de-emphasized. Reference lists for each chapter have been updated. However, the format and organization of the book is essentially unchanged.
Chapter 1 introduces representative areas of active current research in biophysical chemistry and molecular biology: the human genome, the transfer of genetic information from DNA to RNA to protein, ion channels, and cell-to-cell communication. We encourage students to read the current literature to see how the vocabulary and concepts of physical chemistry are used in solving biological problems.
Chapters 2 through 5 cover the laws of thermodynamics and their applications to chemical reactions and physical processes. Essentially all of the examples and problems deal with biochemical and biological systems. For example, after defining work as a force multiplied by the distance moved (the displacement), we discuss the experimental measurement of the work necessary to stretch a single DNA molecule from its random-coiled form to an extended rod. Molecular interpretations of energies and entropies are emphasized in each of the chapters. Chapter 4, "Free Energy and Chemical Equilibria," now starts with the application of the chemical potential td chemical reactions. We think that this will make it easier to understand the logic relating activities and equilibrium constants to free energy. Binding of ligands and equilibria between phases are described in chapter 5, "Free Energy and Physical Equilibria." We discuss in detail the allosteric effect and the cooperative binding of oxygen by hemoglobin. We also describe the formation of lipid monolayers, lipid bilayers, and micelles, and their structures are compared to biological membranes.
Chapters 6 through 8 cover molecular motion and chemical kinetics. Chapter 6, "Molecular Motion and Transport Properties," starts with the Brownian motion on an aqueous surface of a single lipid molecule labeled with a fluorescent dye. The random motion of the molecule can be followed to test Einstein's equation relating average distance traveled by a single molecule to a bulk diffusion coefficient. Following this direct experimental demonstration of thermal motion of a molecule, we introduce the kinetic theory of gases and discuss transport properties (diffusion, sedimentation, and electrophoresis) of macromolecules. The next two chapters deal with general chemical kinetics and enzyme kinetics. New topics include Marcus's theory of charge-transfer reactions, allosteric effects in enzyme kinetics, and single-molecule enzyme kinetics.
Chapter 9, "Molecular Structures and Interactions: Theory," has been rearranged to begin with the origins of the quantum theory, continue through quantum mechanics of simple models, and, finally, discuss the semi-empirical methods applied to macromolecules. This logical progression should make it easier for students to understand and appreciate the applications of quantum mechanics to macromolecular structure. In chapter 10 we emphasize absorption, fluorescence, and nuclear magnetic resonance—the spectroscopic methods most used in structural biology.
In chapter 11, "Molecular Distributions and Statistical Thermodynamics," we present a detailed discussion of the effect of cooperativity or anticooperativity on the binding of successive ligands.
Chapter 12 discusses X-ray diffraction, electron microscopy, and scanning microscopies (such as atomic force microscopy), and emphasizes how structures are determined experimentally. We describe the many methods used to solve the phase problem in X-ray diffraction—including MAD, multi-wavelength anomalous diffraction.
The problems have been revised and checked for clarity and the answers in the back of the book and in the solutions manual have been checked for accuracy. We thank Christopher Ackerson, Ruben Gonzalez, Michael Sykes, and Anne Roberts for checking the problems.
We are gratified by the number of faculty who have elected to use this book over the many years since it was first published. We are also grateful for the many students and faculty who have given us their thoughts and impressions. Such feedback has helped improve the book from edition to edition. We are particularly grateful to those of our colleagues who commented on the third edition, reviewed the manuscript for this edition, and checked our manuscript for accuracy: Fritz Allen, University of Minnesota; Carey Bagdassarian, College of William and Mary; Wallace Brey, University of Florida; Mark Britt, Baylor University; Kuang Yu Chen, Rutgers University; Gerald S. Harbison, University of Nebraska-Lincoln; Roger Koeppel, University of Arkansas; Philip Reiger, Brown University; Gianluigi Veglia, University of Minnesota; and Danny Yeager, Texas A&M University.
We welcome your comments. Ignacio Tinoco, Jr.
INTinoco@lbl.gov
Kenneth Sauer
James C. Wang
Joseph D. Puglisi
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