The Science and Business of Drug Discovery is written for those who want to learn about the biopharmaceutical industry and its products whatever their level of technical knowledge. Its aim is to demystify the jargon used in drug development, but in a way that avoids over simplification and the resulting loss of key information. Each of the twenty chapters is illustrated with figures and tables which clarify some of the more technical points being made. Also included is a drug discovery case history which draws the relevant material together into a single chapter. In recognizing that it is difficult to navigate through the many external resources dealing with drug development, the book has been written to guide the reader towards the most appropriate information sources, including those listed in the two appendices. The following topics are covered: Different types of drugs: from small molecules to stem cells Background to chemistry of small and large molecules Historical background to drug discovery, pharmacology and biotechnology The drug discovery pipeline: from target discovery to marketed medicine Commercial aspects of drug discovery Challenges to the biopharmaceutical industry and its responses Material of specific interest to technology transfer executives, recruiters and pharmaceutical translators

Quantum Systems in Chemistry and Physics contains a refereed selection of the papers presented at the first European Workshop on this subject, held at San Miniato, near Pisa, Italy, in April 1996. The Workshop brought together leading experts in theoretical chemistry and molecular physics with an interest in the quantum mechanical many-body problem. This volume provides an insight into the latest research in this increasingly important field. Throughout the Workshop, the emphasis was on innovative theory and conceptual developments rather than on computational implementation. The various contributions presented reflect this emphasis and embrace topics such as density matrices and density functional theory, relativistic formulations, electron correlation, valence theory, nuclear motion, response theory, condensed matter, and chemical reactions. Audience: The volume will be of interest to those working in the molecular sciences and to theoretical chemists and molecular physicists in particular.

This book describes atomic orbitals at a level suitable for undergraduates in chemistry. The mathematical treatment is brought to life by many illustrations rendered from mathematical functions (no artists' impressions), including three-dimensional plots of angular functions, showing orbital phase, and contour plots of the wavefunctions that result from orbital hybridisation.Orbitals extends the key fundamental quantum properties to many-electron atoms, linear combinations of atomic orbitals, simple molecules, delocalised systems and atomic spectroscopy. By focusing on simple model systems, use of analogies and avoiding group theory the results are obtained from initial postulates without the need for sophisticated mathematics.

This unique volume offers a clear perspective of the relevant methodology relating to the chemical theory of the next generation beyond the Born-Oppenheimer paradigm. It bridges the gap between cutting-edge technology of attosecond laser science and the theory of chemical reactivity. The essence of this book lies in the method of nonadiabatic electron wavepacket dynamic, which will set a new foundation for theoretical chemistry.In light of the great progress of molecular electronic structure theory (quantum chemistry), the authors show a new direction towards nonadiabatic electron dynamics, in which quantum wavepackets have been theoretically and experimentally revealed to bifurcate into pieces due to the strong kinematic interactions between electrons and nuclei.The applications range from nonadiabatic chemical reactions in photochemical dynamics to chemistry in densely quasi-degenerated electronic states that largely fluctuate through their mutual nonadiabatic couplings. The latter is termed as "chemistry without the potential energy surfaces" and thereby virtually no theoretical approach has been made yet.Restarting from such a novel foundation of theoretical chemistry, the authors cast new light even on the traditional chemical notions such as the Pauling resonance theory, proton transfer, singlet biradical reactions, and so on.

This monograph develops a new way of justifying the claims made by science about phenomenon not directly observable by humans, such as atoms and black holes. It details a way of making inferences to the existence and properties of unobservable entities and states of affairs that can be given a probabilistic justification. The inferences used to establish realist claims are not a form of, and neither do they rely on, inference to the best explanation. Scientific Realism maintains that scientific theories and hypotheses refer to real entities, forces, and relations, even if one cannot examine them. But, there are those who doubt these claims. The author develops a novel way of defending Scientific Realism against a range of influential attacks. He argues that in some cases, at least, we can make probabilistically justifiable inferences from observed data to claims about unobservable, theoretical entities. He shows how this enables us to place some scientific realist claims on a firmer epistemological footing than has previously been the case. This also makes it possible to give a unified set of replies to the most common objections to Scientific Realism. The final chapters apply the developed conceptual apparatus to key cases from the history of science and from recent science. One example concerns realism with respect to atoms. Another looks at inferences from recent astronomical data to conclusions about the size and shape of those parts of the universe lying beyond that which we can observe.

The Latest Developments on the Role of Dynamics in Protein Functions Computational Approaches to Protein Dynamics: From Quantum to Coarse-Grained Methods presents modern biomolecular computational techniques that address protein flexibility/dynamics at all levels of theory. An international contingent of leading researchers in chemistry, physics, and biology show how these advanced methods provide insights into dynamic aspects of biochemical processes. A particular focus is on intrinsically disordered proteins (IDPs), which lack a well-defined three-dimensional structure and function as dynamic ensembles. The book covers a wide spectrum of dynamics, from electronic structure-based to coarse-grained techniques via multiscaling at different levels. After an introduction to dynamics and historical overview of basic methodologies, the book addresses the following issues: Is there a quantitative relationship between enzymatic catalysis and protein dynamics? Which are the functionally relevant motions of proteins? How can structural properties and partner recognition mechanisms of IDPs be simulated? How can we speed up molecular dynamics? How can we describe conformational ensembles by the synergistic effort of computations and experiments? While dynamics is now considered essential for interpreting protein action, it is not yet an integral component in establishing structure-function relationships of proteins. Helping to reshape this classical view in biochemistry, this groundbreaking book explores advances in computational methodology and contributes to the new, ensemble way of studying proteins.

"Astrochemistry and Astrobiology" is the debut volume in the new series "Physical Chemistry in Action." Aimed at both the novice and experienced researcher, this volume outlines the physico-chemical principles which underpin our attempts to understand astrochemistry and predict astrobiology. An introductory chapter includes fundamental aspects of physical chemistry required for understanding the field. Eight further chapters address specific topics, encompassing basic theory and models, up-to-date research and an outlook on future work. The last chapter examines each of the topics again but addressed from a different angle. Written and edited by international experts, this text is accessible for those entering the field of astrochemistry and astrobiology, while it still remains interesting for more experienced researchers.

"It was sheer chance that I encountered David Bohm's writing in 1958 ... I knew nothing about him. What struck me about his work and prompted my initial letter was his underlying effort to seek for some larger sense of reality, which seemed a very humanized search." - Charles Biederman, from the foreword of the book
This book marks the beginning of a four thousand page correspondence between Charles Biederman, founder of Constructivism in the 1930s, and David Bohm the prestigious physicist known for his interpretation of quantum theory. Available for the first time, we are given a rare opportunity to read through and engage in a remarkable transatlantic, intellectual discussion on art and science, creativity and theory.

Organic materials with extraordinary magnetic properties promise a wide range of light, flexible, and inexpensive alternatives to familiar metal-based magnets. Individual organic molecules with high magnetic moments will be the foundation for design and fabrication of these materials.This book provides a systematic understanding of the structure and properties of organic magnetic molecules. After a summary of the phenomenon of magnetism at the molecular level, it presents a survey of the challenges to theoretical description and evaluation of the magnetic character of open-shell molecules, and an overview of recently developed methods and their successes and shortfalls. Several fields of application, including very strong organic molecular magnets and photo-magnetic switches, are surveyed. Finally, discussions on metal-based materials and simultaneously semiconducting and ferromagnetic extended systems and solids point the way toward future advances.The reader will find a comprehensive discourse on current understanding of magnetic molecules, a thorough survey of computational methods of characterizing known and imagined molecules, simple rules for design of larger magnetic systems, and a guide to opportunities for progress toward organic magnets.

"Ideas of Quantum Chemistry" shows how quantum mechanics is applied to chemistry to give it a theoretical foundation. From the Schroedinger equation to electronic and nuclear motion to intermolecular interactions, this book covers the primary quantum underpinnings of chemical systems. The structure of the book (a TREE-form) emphasizes the logical relationships among various topics, facts and methods. It shows the reader which parts of the text are needed for understanding specific aspects of the subject matter. Interspersed throughout the text are short biographies of key scientists and their contributions to the development of the field.

"Ideas of Quantum Chemistry" has both textbook and reference work aspects. Like a textbook, the material is organized into digestible sections with each chapter following the same structure. It answers frequently asked questions and highlights the most important conclusions and the essential mathematical formulae in the text. In its reference aspects, it has a broader range than traditional quantum chemistry books and reviews virtually all of the pertinent literature. It is useful both for beginners as well as specialists in advanced topics of quantum chemistry. An appendix on the Internet supplements this book.
Presents the widest range of quantum chemical problems covered in one book Unique structure allows material to be tailored to the specific needs of the reader Informal language facilitates the understanding of difficult topics

This is a comprehensive overview of state-of-the-art computational methods based on orbital-free formulation of density functional theory completed by the most recent developments concerning the exact properties, approximations, and interpretations of the relevant quantities in density functional theory. The book is a compilation of contributions stemming from a series of workshops which had been taking place since 2002. It not only chronicles many of the latest developments but also summarises some of the more significant ones. The chapters are mainly reviews of sub-domains but also include original research.

This open access book brings out the state of the art on how informatics-based tools are used and expected to be used in nanomaterials research. There has been great progress in the area in which "big-data" generated by experiments or computations are fully utilized to accelerate discovery of new materials, key factors, and design rules. Data-intensive approaches play indispensable roles in advanced materials characterization. "Materials informatics" is the central paradigm in the new trend. "Nanoinformatics" is its essential subset, which focuses on nanostructures of materials such as surfaces, interfaces, dopants, and point defects, playing a critical role in determining materials properties. There have been significant advances in experimental and computational techniques to characterize individual atoms in nanostructures and to gain quantitative information. The collaboration of researchers in materials science and information science is growing actively and is creating a new trend in materials science and engineering.

Special numerical techniques are already needed to deal with nxn matrices for large n.Tensor data are of size nxnx...xn=n DEGREESd, where n DEGREESd exceeds the computer memory by far. They appear for problems of high spatial dimensions. Since standard methods fail, a particular tensor calculus is needed to treat such problems. The monograph describes the methods how tensors can be practically treated and how numerical operations can be performed. Applications are problems from quantum chemistry, approximation of multivariate functions, solution of pde, e.g., with stochastic coefficie

In Monte Carlo Methods in Chemical Physics: An Introduction to the Monte Carlo Method for Particle Simulations J. Ilja Siepmann Random Number Generators for Parallel Applications Ashok Srinivasan, David M. Ceperley and Michael Mascagni Between Classical and Quantum Monte Carlo Methods: "Variational" QMC Dario Bressanini and Peter J. Reynolds Monte Carlo Eigenvalue Methods in Quantum Mechanics and Statistical Mechanics M. P. Nightingale and C.J. Umrigar Adaptive Path-Integral Monte Carlo Methods for Accurate Computation of Molecular Thermodynamic Properties Robert Q. Topper Monte Carlo Sampling for Classical Trajectory Simulations Gilles H. Peslherbe Haobin Wang and William L. Hase Monte Carlo Approaches to the Protein Folding Problem Jeffrey Skolnick and Andrzej Kolinski Entropy Sampling Monte Carlo for Polypeptides and Proteins Harold A. Scheraga and Minh-Hong Hao Macrostate Dissection of Thermodynamic Monte Carlo Integrals Bruce W. Church, Alex Ulitsky, and David Shalloway Simulated Annealing-Optimal Histogram Methods David M. Ferguson and David G. Garrett Monte Carlo Methods for Polymeric Systems Juan J. de Pablo and Fernando A. Escobedo Thermodynamic-Scaling Methods in Monte Carlo and Their Application to Phase Equilibria John Valleau Semigrand Canonical Monte Carlo Simulation: Integration Along Coexistence Lines David A. Kofke Monte Carlo Methods for Simulating Phase Equilibria of Complex Fluids J. Ilja Siepmann Reactive Canonical Monte Carlo J. Karl Johnson New Monte Carlo Algorithms for Classical Spin Systems G. T. Barkema and M.E.J. Newman

This textbook presents basic numerical methods and applies them to a large variety of physical models in multiple computer experiments. Classical algorithms and more recent methods are explained. Partial differential equations are treated generally comparing important methods, and equations of motion are solved by a large number of simple as well as more sophisticated methods. Several modern algorithms for quantum wavepacket motion are compared. The first part of the book discusses the basic numerical methods, while the second part simulates classical and quantum systems. Simple but non-trivial examples from a broad range of physical topics offer readers insights into the numerical treatment but also the simulated problems. Rotational motion is studied in detail, as are simple quantum systems. A two-level system in an external field demonstrates elementary principles from quantum optics and simulation of a quantum bit. Principles of molecular dynamics are shown. Modern boundary element methods are presented in addition to standard methods, and waves and diffusion processes are simulated comparing the stability and efficiency of different methods. A large number of computer experiments is provided, which can be tried out even by readers with no programming skills. Exercises in the applets complete the pedagogical treatment in the book. In the third edition Monte Carlo methods and random number generation have been updated taking recent developments into account. Krylov-space methods for eigenvalue problems are discussed in much more detail. Short time Fourier transformation and wavelet transformation have been included as tools for time-frequency analysis. Lastly, elementary quantum many-body problems demonstrate the application of variational and Monte-Carlo methods.

This book is a presentation of a qualitative theory of chemical bonding, stressing the physical processes which occur on bond formation. It differs from most (if not all) other books in that it does not seek to "rationalise" the phenomena of bonding by a series of mnemonic rules. A principal feature is a unified and consistent treatment across all types of bonding in organic, inorganic, and physical chemistry. Each chapter has an Assignment Section containing "problems" which might be usefully attempted to improve the understanding of the new material in that chapter. The new edition has had several appendices added which give support to concepts which, if included in the main text, would have hindered the main thrust of the presentation. These new appendices are an attempt to clarify oversights and errors which have been tacitly ignored and which have now become part of the conventional wisdom.

This detailed book collects modern and established computer-based methods aimed at addressing the drug discovery challenge from disparate perspectives by exploiting information on ligand-protein recognition. Beginning with methods that allow for the exploration of specific areas of chemical space and the designing of virtual libraries, the volume continues with sections on methods based on docking, quantitative models, and molecular dynamics simulations, which are employed for ligand discovery or development, as well as methods exploiting an ensemble of protein structures for the identification of potential protein targets. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Protein-Ligand Interactions and Drug Design provides detailed practical procedures of solid computer-aided drug design methodologies employed to rationalize and optimize protein-ligand interactions, for experienced researchers and novices alike.

The Schroedinger equation is the master equation of quantum chemistry. The founders of quantum mechanics realised how this equation underpins essentially the whole of chemistry. However, they recognised that its exact application was much too complicated to be solvable at the time. More than two generations of researchers were left to work out how to achieve this ambitious goal for molecular systems of ever-increasing size. This book focuses on non-mainstream methods to solve the molecular electronic Schroedinger equation. Each method is based on a set of core ideas and this volume aims to explain these ideas clearly so that they become more accessible. By bringing together these non-standard methods, the book intends to inspire graduate students, postdoctoral researchers and academics to think of novel approaches. Is there a method out there that we have not thought of yet? Can we design a new method that combines the best of all worlds?

The composition of the most remote objects brought into view by the Hubble telescope can no longer be reconciled with the nucleogenesis of standard cosmology and the alternative explanation, in terms of the Λ-Cold-Dark-Matter model, has no recognizable chemical basis. A more rational scheme, based on the chemistry and periodicity of atomic matter, opens up an exciting new interpretation of the cosmos in terms of projective geometry and general relativity.

The response of atomic structure to environmental pressure predicts non-Doppler cosmical redshifts and equilibrium nucleogenesis by α--particle addition, in accord with observed periodic variation of nuclear abundance.

Inferred cosmic self similarity elucidates the Bode -Titius law, general commensurability in the solar system and the occurrence of quantum phenomena on a cosmic scale.

The generalized periodic function involves both matter and anti-matter in an involuted mapping to a closed projective plane. This topology ensures the same symmetrical balance in a chiral universe, wrapped around an achiral vacuum interface, without singularities.

A new cosmology emerges, based on the theory of projective relativ-ity, presented here as a translation of Veblen's original German text. Not only does it provide a unification of gravity, electromagnetism and quantum theory, through gauge invariance, but also supports the solution of the gravitational field equations, obtained by Godel for a rotating universe.

The appearance of an Einstein-Rosen bridge as outlet from a black hole, into conjugate anti-space, accounts for globular clusters, quasars, cosmic radiation, γ-ray bursters, pulsars, radio sources and other re-gions of plasma activity.

The effects of a multiply-connected space-time manifold on observa-tions in an Euclidean tangent space are unpredictable and a complete re-assessment of the size and structure of the universe is indicated.

The target readership includes scientists, as well as non-scientists - everybody with a scientific or philosophical interest in cosmology and, especially those cosmologists and mathematicians with the ability to recast the crude ideas presented here into appropriate mathematical models.

This book is a stop-gap contribution to the science and technology of carbon plasmas and carbon vapors. It strives to cover two strongly related fields: the molecular quantum theory of carbon plasmas and carbon nanostructures; and the molecular and atomic spectroscopy of such plasmas and vapors. These two fields of research are strongly intertwined and thus reinforce one another.

Even though the use of carbon nanostructures is increasing by the day and their practical uses are emerging, there is no modern review on carbon plasmas, especially from molecular theoretical and spectroscopic viewpoints. The importance of the present book is therefore great from both educational and practical aspects. This review might be the first step towards bringing such textbooks into existence for university education. Similarly, for applied and engineering works in carbon nanostructures, the book provides a theoretical salient point for technologists in the field.

Metallic systems are ubiquitous in daily life. They play key roles, for example, in the chemistry of many biomolecules, ionic solutions, nanoparticles, and catalytic processes. They may be in solid, liquid, or gaseous form. The interactions of other molecules with metal surfaces are of considerable importance. Each of these topics is addressed in Metallic Systems. As we have entered the age where theoretical approaches are sufficiently mature to complement and guide experiments in many areas, an understanding of the theoretical tools and approaches to studying metallic systems is essential. Metallic Systems is concerned with enhancing our understanding of the diverse chemistry of metals and metal-containing systems and the applicability of modern quantum chemistry methodologies to study them. Metallic Systems presents brief overviews of most of the popular approaches to quantum chemical treatments and computations of chemical systems that include metals. Attention is given to the potentialities and limitations of first principles Density Functional Theory and dynamics methods (e.g. QM/MM approaches). The book emphasizes the importance of using methods that take into account crucial physical features such as explicit solvation, temperature and dynamics of metal-containing systems. It emphasizes first principles calculations in providing reliable and detailed information concerning electronic structures, mechanisms, and reaction energetics. Accessible to newcomers to the field, Metallic Systems overviews theory underpinning current methodologies. It presents a practical set of modalities for studying metallic systems, assesses current technological barriers, and examines future challenges and topics of exploration.

This new volume is devoted to molecular chemistry and its applications to the fields of biology. It looks at the integration of molecular chemistry with biomolecular engineering, with the goal of creating new biological or physical properties to address scientific or societal challenges. It takes a both multidisciplinary and interdisciplinary perspective on the interface between molecular biology, biophysical chemistry, and chemical engineering. Molecular Chemistry and Biomolecular Engineering: Integrating Theory and Research with Practice provides effective support for the development of the laboratory and data analysis skills that researchers will draw on time and again for the practical aspects and also gives a solid grounding in the broader transferable skills.

This book explores novel computational strategies for simulating excess energy dissipation alongside transient structural changes in photoexcited molecules, and accompanying solvent rearrangements. It also demonstrates in detail the synergy between theoretical modelling and ultrafast experiments in unravelling various aspects of the reaction dynamics of solvated photocatalytic metal complexes. Transition metal complexes play an important role as photocatalysts in solar energy conversion, and the rational design of metal-based photocatalytic systems with improved efficiency hinges on the fundamental understanding of the mechanisms behind light-induced chemical reactions in solution. Theory and atomistic modelling hold the key to uncovering these ultrafast processes. Linking atomistic simulations and modern X-ray scattering experiments with femtosecond time resolution, the book highlights previously unexplored dynamical changes in molecules, and discusses the development of theoretical and computational frameworks capable of interpreting the underlying ultrafast phenomena.

The theoretical methods of quantum chemistry have matured to the point that accurate predictions can be made and experiments can be understood for a wide range of important gas-phase phenomena. A large part of this success can be attributed to the maturation of hierarchies of approximation, which allow one to approach very high accuracy, provided that sufficient computational resources are available. Until recently, these hierarchies have not been available in condensed-phase chemistry, but recent advances in the field have now led to a group of methods that are capable of reaching this goal.

Accurate Condensed-Phase Quantum Chemistry addresses these new methods and the problems to which they can be applied. The book begins with an overview of periodic treatments of electron correlation, with an emphasis on the algorithmic features responsible for their computational efficiency. The first section of the book:

• Describes the Laplace-transform approach to periodic second-order perturbation theory (MP2)
• Examines local and density fitted schemes for MP2 in crystalline systems
• Presents test calculations for a variety of systems with small and medium-sized unit cells

The next section focuses on methods based on treatment of the periodic solid in terms of fragments. This part of the book:

• Explores the incremental many-body scheme for electron correlation in solids, and describes progress towards metals and molecules on surfaces
• Describes the hierarchical method as an alternative fragment-based approach to electron correlation in crystalline solids, using conventional molecular electronic structure methods
• Examines electrostatically embedded many-body expansion for large systems, with an emphasis on molecular clusters and molecular liquids
• Explores delocalized and localized orbital approaches to the electronic structures of periodic and non-periodic solids

Lastly, the book describes a practical method by which conventional molecular electronic structure theory can be applied to molecular liquids and solids. Along with the methodology, it presents results on small to medium water clusters as well as on liquid water.

The principal focus of this volume is to illustrate the level of accuracy currently achievable by "ab initio" quantum chemical calculations. While new developments in theory are discussed to some extent, the major emphasis is on a comparison of calculated properties with experiments. This focus is similar to the one taken in the book, "Comparison of Ab Initio Quantum Chemistry with Experiment for Small Molecules", edited by Rodney Bartlett (Reidel, 1984). However, the phenomenal improvement in both theoretical methods and computer architecture have made it possible to obtain accurate results for rather large molecular systems. For example, the electronic spectra of the nucleic acid base monomer structures shown on the front cover have been obtained using a fully correlated "ab initio" study. This text is intended for researchers, teachers and students in chemistry and physics.