880 J. Chem. Inf. Comput. Sci., Vol. 40, No. 3, 2000
BOOK REVIEWS
BOOK REVIEWS Comparative QSAR. Edited by James Devillers. Taylor & Francis, Washington, D.C. 1998. ix + 371 pp. ISBN 1-56032716-2. $135.00. The eight chapters are written by experts in their fields, and the editor states in his preface that no attempt has been made to enforce a consensus view. Nonetheless, the reader will find that there is, however, a consensus, namely, that the field of quantiative structure-activity relationships (QSAR) has reached a maturity enabling it to address both the billion-dollar drug design industry and the molecular mechanisms governing chemical and biological interactions. The first two chapters deal with QSAR involving aquatic organisms. J. Devillers, D. Domine, S. Bintein, and W. Karcher present in their chapter (Comparison between Fish Bioconcentration Models) extensive tables for hundreds of compounds on bioconcentration factors in fish, discussing in depth modeling based on lipophilicity and comparing nine equations in terms of log P (five linear and four nonlinear dependences). The results are of interest both as scientific results and in terms of forthcoming possible regulations of the European Union in the aquatic environment. T. W. Schultz, G. D. Sinks, and A. P. Bearden then present a mechanism of action (MOA) approach concerning aquatic toxicity to a gram-negative prokariotic bacterium, a ciliate single-celled eukariotic protozoan (in both cases static tests were performed), and a fish species under a flow-through system (fathead minnow). Again, comprehensive tabulated data are presented, and the molecular descriptors are limited to hydrophobicity and the calculated super-delocalizability. Whereas some corrrelations are excellent, this chapter also includes numerical and graphical data for regression analyses (e.g. for nitrobenzene derivatives) which show no correlation and could have been dispensed with in words rather than figures. The conclusion of the authors is that there is some similarity between the protozoan and fish species, but extrapolation of ecotoxicity data from in Vitro studies with simpler organisms to vertebrates is risky, unless the toxicity mechanism is perfectly understood. R. L. Compadre, C. Byrd, and C. M. Compadre describe in their chapter (Comparative QSAR and 3D-QSAR Analysis of Mutagenicity of Nitroaromatic Compounds) an approach which involves on one hand “classic” description by means of steric, electronic, and hydrophobic parameters contrasted on the other hand with the comparative molecular field analysis (CoMFA) which describes better the steric factors. Whereas it is well-established that the mechanism involves reduction of nitro compounds to nucleophilic species which attack the polynucleotides, the Ames test does not identify which enzymes and chemical species (nitro anion-radical, hydroxylamine radical, or superoxide radical) are responsible for the mutagenic action. A table with about 260 nitro derivatives and the corresponding equations indicates general agreement between the two approaches, separately or combined, with more detail provided by the elaborate CoMFA calculations. The following four chapters deal with separate, non-overlapping topics. Thus, P. S. Magee presents some novel approaches to modeling transdermal penetration and reactivity with epidermal proteins. Allergic contact dermatitis and the skin permeation rate are mechanistically determined by lipophilicity (log P, which can be partitioned between lipophilic and hydrophilic factors) and by molecular size, modeled by the molar refraction. Data for about 400 compounds are presented with the various approaches for QSAR. The author then hypothesizes on the thermodynamic properties of haptens and ends by declaring that he would welcome cooperative efforts to fill in the many blanks in the field of hapten-protein reactivity. An interesting discussion about structure-odor relationships for musk fragrance is presented by D. Zakarya and M. Chastrette. The authors offer a concise presentation of the various hypotheses, empirical rules, and QSAR studies concerning structure-musk odor relationships. The most comprehensive study, mentioned in the bibliography of the chapter, involved 230 musks and 132 non-musks with structures related to musks. The three main classes of synthetic musks are monocyclic benzenoid nitromusks, indanes, and tetralins. Subtle steric factors change
appreciably the fragrance. High-throughput molecular modeling techniques used in pharmacology are yet to be applied in this area. K. N. Reddy, F. E. Dayan, and S. O. Duke present in their chapter a QSAR analysis of protoporphyrinogen oxidase (protox) inhibitors. These are among the most potent herbicides of the past decade. The protox enzyme converts protoporphyrinogen IX into protoporphyrin IX, which is a precursor both for heme and for chlorophyll, and whose accumulation in the plasma membrane induces the formation of the lethal singlet oxygen. An intriguing variety of 10 chemical classes of structures able to inhibit protox is reviewed accordingly, but since the enzyme structure is not yet known, unifying properties derived from QSAR analysis have yet to be discovered. The authors agree with Hansch and Leo that QSAR is useful for lead optimization, but not for generating new leads. The bactericidal activity of sulfa drugs is known to be due to their similarity to p-aminobenzoic acid involved in the synthesis of folic acid, which is a vitamin for humans. Tetrahydrofolic acid mediates one-carbon transport. Methotrexate owes its anticancer activity to its similarity with folic acid. The inhibitors of dihydrofolate reductase (DHFR) are reviewed by C. D. Selasssie and T. E. Klein. QSAR in this area is of long date, and although molecular graphics analysis can be successfully used in this case when the enzyme structure is known, differences between DHFR isolated from various bacterial or animal species can also be understood on the basis of the corresponding dependency on electrostatic or hydrophobic parameters in QSAR. The most extensive, and, in the reviewer’s opinion, the most fascinating of all chapters, is authored by Corwin Hansch, the “father” of QSAR since his 1962 study, and his co-workers, H. Gao and D. Hoekman. This chapter should become a citation classic, since it opens many “doors of perception” and has many paragraphs and data worthy of being quoted. In brief, the authors describe how their database of about 10 000 QSAR data (of which one-third are for biological systems) can be put to use in understanding the chemistry of living cells and thus in devising better drugs or pesticides. Together with the reviews published by Hansch in Chem. ReV., this chapter can become a gold mine for medicinal chemists and pharmacologists, if they know how to read it and how to use the database. A few quotes from this last chapter are in order: “(T)he advent of ... ‘sexy’ 3-D pictures of ligands bound to enzymes of established structure captured researchers’s attention the way that the Lorelei of old entranced the sailors on the Rhein. Mechanism based on physical organic chemistry was forgotten.... Can SAR problems be solved de noVo with 3-D pictures? Our belief is that mechanistic physical organic chemistry is on the verge of an exciting new venture in helping to elucidate chemico-biological interactions that will do vastly more than simply justify its existence to make only incremental advances in our study of the chemistry of life.” What the authors of this chaper do is first let the reader know how to mine the rich database for relevant, meaningful, and manageable information. Then they show by example what one can learn from such data. By grouping together QSAR equations in trems of electronic and/ or lipophilicy parameters, it becomes possible to gain insight into mechanisms of enzymatic reactions. Thus, the signs and Values of the slopes and intercepts in such equations are powerful indicators about similarity or dissimilarity between complicated biochemical reactions and simple reactions that are well-understood mechanistically. Because biological QSARs are more difficult and expensive, and frequently less precise and with smaller numbers of data, than physical-organic QSARs, “lateral” support by the latter ones can add confidence in the results of the former studies. Bridges must be built between these two strictly compartmentalized areas of research. Numerous examples are presented and discussed, connecting this last chapter with several previous ones. On this basis, several suggestions for plausible mechanisms and for promising classes of new drugs are made in this chapter. It is fitting to conclude this book review with a few other quotations from this chapter: “The rather abstract, ‘boring’, multivariate equations
BOOK REVIEWS
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have left many who stopped to think of the enormous complexity of the problem of formulating QSAR from a set of chemicals perturbing a cell or a mouse with the feeling that they were watching a con game.... The 3-D graphics distracted many from trying to relate biological QSAR to the much better understood mechanistic studies from the fields of physical organic and biochemistry. But the enormous driving force to understand how chemicals react with the various forms of life (and its constituent parts) and the economic prospects in terms of designing the billion-dollar drug as well as understanding toxicology, have been relentless encouragement for more and more researchers to attempt what some still regard as impossible.... Because there are virtually an unlimited number of organic chemicals and a huge number of biological systems (DNA, enzymes, organelles, cells, and whole organisms) with which they can intercact, we must develop generalizations, limited as they may be, to be used in the planning stage of synthesis of the myriad chemicals we seem to need to facilitate our existence.... Our present system is a small start on the problem of the design and construction of a computerized means of keeping account of what has been done and how it can be used, but we are confident that it will grow rapidly.” This book will be useful and inspiring for chemists, biochemists, medicinal chemists, and pharmacologists, in addition to the “hard-core” professionals involved in drug design, such as computational chemists who devise high-throughput synthesis and screening of combinatorial libraries.
Alexandru T. Balaban Polytechnic UniVersity Bucharest, Romania
book describes recent developments in automated gene characterization. It does not address mature, well-documented technology such as fluorescence-based sequencing or flow cytometry, but focuses on newer evolving technologies. The areas covered are quite diverse, including, for example, atomic force microscopy, miniaturized systems, robotics and robotics software, electronic notebooks, data handling, and data analysis. The book is divided into four sections. The first four chapters cover laboratory automation: robotics, software, modular equipment, and machine vision. The second section discusses control systems which can integrate and coordinate the operation of different components. This is followed by a series of chapters describing new technologies for DNA and RNA sequencing. The final section describes ways to acquire, analyze, and manage the mountains of data which are generated by large-scale genome projects. The editor has assembled an interesting discussion of the problems posed by the Human Genome Project and other large-scale sequencing efforts. He has illustrated clearly the broad range of-disciplines which must work together to generate and use genomic information. This book will likely be more interesting to those involved in generating the data than to the end-users of the data, but the end-users might be interested to see the many different tools which are involved in wrestling the data from a string of nucleic acids.
D. Eric Walters Finch UniVersity of Health Sciences/ The Chicago Medical School CI000342O
CI0003404
10.1021/ci000342o
10.1021/ci0003404
Named Organic Reactions. By Thomas Laue and Andreas Plagens. John Wiley & Sons: Chichester, U.K., 1998. 288 pp. ISBN 0-471-97142-1. $69.95.
The Physics of Laser-Atom Interactions. By Dieter Suter. Cambridge Studies in Modern Optics. Cambridge University Press: Cambridge, U.K. 1997. 457 pp. ISBN 0-521-46239-8. $100.00
Organic students and chemists know the importance of named reactions to their field, and Named Organic Reactions aims to fill an information gap in this area. The authors assert that the book is “suitable for easy reading and learning, as well as for revision [sic] for an exam in organic chemistry.” However, the text is dense and includes a level of detail that may prove difficult for some beginning organic students. Laue and Plagens describe over 100 reactions judged to be the most important in preparative organic chemistry and organic classes. They do not include reactions whose mechanisms are straightforward enough to be deduced easily. Ample references include citations to the original literature, review articles, and recent works. As compared to Organic Syntheses Based on Name Reactions and Unnamed Reactions (Pergamon, 1994), Named Organic Reactions provides a more in-depth description for each reaction, although its coverage is only 30% of reactions in the older title. The Laue and Plagens book has only a subject index. Organic Syntheses, on the other hand, provides four indexes including the named reactions, reagents, types of reactions, and synthesis of functional groups. This book would be a good supplemental reference; however, it is not recommended to be the sole source for named reactions.
This book is joined by several other titles in the series “Cambridge Studies in Modern Optics”, with P. L. Knight and A. Miller serving as series editors. This is an international series which contains books on all aspects of theoretical and applied modem optics at levels ranging from advanced textbooks to monographs. The book under review provides a thorough introduction to the interaction of atoms and atomic ions with optical and magnetic fields. Particular emphasis is placed on multilevel effects, where more than two atomic states participate in the interaction. Atomic vapors can exhibit anisotropic behavior under these conditions, giving rise to a wide range of interesting phenomena. The book is divided into 11 chapters. The Introductory chapter is followed by those on Two-Level Atoms, Three-Level Effects, Internal Degrees of Freedom, Optical Pumping, Optically Anisotropic Vapors, Coherent Raman Processes, Sublevel Dynamics, Two-Dimensional Spectroscopy, Nonlinear Dynamics, and Mechanical Effects of Light. With a full and theoretical coverage, and over 250 illustrations, the book will be of great interest to graduate students of laser spectroscopy, quantum electronics, and quantum optics and to researchers in these fields. The book has an extensive list of references and a well-structured index.
Sarah George Indiana UniVersity
Venkat K. Raman Chemical Abstracts SerVice
CI000341W
CI0003451
10.1021/ci000341w
10.1021/ci0003451
Automation Technologies for Genome Characterization. Edited by Tony J. Beugelsdijk. Wiley-Interscience: New York. 1997. 306 pp. ISBN 0-471-12806-6. $69.95.
Data Compression in Digital Systems. By Roy Hoffman. Digital Multimedia Standards Series. International Thomson Publishing/Chapman & Hall: New York. 1996. 415 pp. ISBN 0-412-08551-8. $64.95.
Once, not long ago, genes were discovered one at a time, with a great deal of manual effort. Now, the Human Genome Project (and genome projects for other organisms) has turned genomics into a highly automated process. This process has, at the same time, become much more multidisciplinary because automation has brought in robotics and has created a need for data handling on an unprecedented scale. This
Data compression is a very dynamic field, with applications for compression of speech, audio, image, and video data. As part of the Digital Multimedia Standards Series, the book is about compressing data to make digital systems work more efficiently. The exciting technology and its importance for current and future digital systems
882 J. Chem. Inf. Comput. Sci., Vol. 40, No. 3, 2000 are explained in easy-to-understand terms. With a well-written overview, the material is organized in four parts: Marketplace, Algorithms, Applications, and Digital Systems. Marketplace explores the user requirements for data compression and the marketplace constraints and rules that effect its application. The chapter on algorithms provides the background needed to understand how the most important data compression algorithms operate; these include algorithms for diffuse data and symbolic data. A comprehensive industry-by-industry guide to modern data compression applications is presented in the chapter on applications. The final chapter on digital systems describes important decisions and techniques for incorporating data compression in current and future digital information-handling systems. The book has a short list of abbreviations and acronyms and an extensive list of references. This easy-to-read book is an invaluable reference and presents a unique blend of introductory material on what data compression is and how it operates, combined with an in-depth look at how the technology is used in real-world applications. The book covers data available only at the time of writing (1996), lacking information on more-recent developments in the fast-paced world of consumer electronics.
Venkat K. Raman Chemical Abstracts SerVice CI000343G 10.1021/ci000343g
Handbook of Computational Quantum Chemistry. By David B. Cook. Oxford University Press: New York. 1998. 743 pp. ISBN 0-19-850114-5. $140.00. Quantum chemistry forms the basis of molecular modeling, a tool widely used to obtain important chemical information and visual images of molecular systems. Advances in computing have meant that there have been considerable developments in molecular modeling, and these developments have lead to significant achievements in the design and synthesis of, for example, drugs and catalysts. The modern and thorough text provides an accessible introduction to the theory of the main streams of quantum chemical ideas. Throughout the book, the practical implementation of the main areas of quantum chemistry accompanies the theoretical explanation. The author presents this in a straightforward and accessible manner, leading to the use of modem “Literate Programming” software tools (D. E. Knuth’s WEB system). The book is divided into 34 well-written chapters, including Mechanics and Molecules, the Hartree-Fock Method, The Matrix SCF Equations, A Special Case: Closed Shells, Implementation of the Closed-shell Case, Tools and Methods, Molecular Integrals, Repulsion Integral Storage, Virtual Orbitals, Population Analysis, The General MO Functional, Molecular Symmetry, The Orthogonal VB model, etc. A separate chapter is devoted to a compilation of resource materials for additional reading and materials available for downloading from the Internet; several of the URL’s have, however, already changed. The book provides an up-to-date account of a subject which has expanded enormously over the past decade both in theoretical methods and areas of application. This informative text will be of interest to graduate students, academic faculty, and industrial research and development staff in the chemical and pharmaceutical fields.
Venkat K. Raman Chemical Abstracts SerVice CI0003449 10.1021/ci0003449
Fundamentals of Chemistry (3rd ed.). By Ralph A. Burns. Prentice-Hall: Upper Saddle River, NJ. 1999. 744 pp. ISBN 0-13-918665-4. $77.75. First, the content: This is a sound, well-written textbook for introductory college chemistry. The material is organized logically and presented in a clear and engaging writing style. Principles are illustrated with numerous real world examples to which students can relate.
BOOK REVIEWS Diagrams and illustrations are great. There are hundreds of workedout problems. You could not go wrong selecting this textbook. But my favorite part of the book comes before chapter 1. There is a letter from Ralph Burns to the chemistry student which explains exactly how to learn chemistry. I particularly like the way he addresses that question which plagues every professor: “What should I memorize for the exam?” Professor Burns, could I please copy those three paragraphs and distribute them to my biochemistry students?
D. Eric Walters Finch UniVersity of Health Sciences/ The Chicago Medical School CI000346T 10.1021/ci000346t
Process Design Principles: Synthesis, Analysis, and Evaluation. By Warren D. Seider, J. D. Seader, and Daniel R. Lewin. Wiley: New York. 1999. 824 pp. ISBN 0-471-243124. $99.95. The courseware for the design of chemical processes is addressed to senior undergraduates. It is a textbook accompanied by a multimedia CD-ROM that contains more than 500 Mb using ASPEN PLUS, HYSYS, and DYNAPLUS; other programs (CHEMCAD, PRO/II) are to be added in the near future. The course is organized in five parts (15 chapters, 550 pages) plus 12 appendices (263 pages), followed by author and subject indexes. Part 1 (Process InventionsHeuristics and Analysis) has the following four chapters: The Design Process, Process Creation, Simulation To Assist in Process Creation, and Heuristics for Process Synthesis. Part 2 (Detailed Process SynthesissAlgorithmic Methods) contains the following three chapters: Synthesis of Separation Trains, Second Law Analysis, and Heat and Power Integration. Part 3 (Detailed Design, Equipment Sizing, Economics, and Optimization) has four chapters: Heat Exchanger Design, Capital Cost Estimation, Profitability Analysis, and Optimization of Process Flowsheets. Part 4 (Plantwide Controllability Assessment) has three chapters: Interaction of Process Design and Process Control, Flowsheet Controllability Analysis, and Dynamic Simulation of Process Flowsheets. Part 5 (Design Report) is a single chapter addressing written process design reports and oral presentation. The appendices describe software for process design (ASPEN PLUS, HYSYS), for dynamic simulation (DYNAPLUS), or for algebraic modeling systems (GAMS); phase equilibria and process unit models; physical property estimation, solids handling, and electrolytes. Appendix 8 contains problem statements for 31 design projects, each prepared by chemical engineers in Pennsylvania companies for design teams of three students; the design is to be completed during one semester, with advice from faculty and industrial consultants. A striking feature of this textbook is the continuous use of realworld problems, lavish use of illustrations, diagrams, tables, and simulation flowsheets provided by computer programs, as well as numerous exercises at the end of each chapter. The presentation of case studies enhances the interest of students and provides a background for seminar discussions. A few leading bibliographic references are provided at the beginning and at the end of most chapters. Environmental protection, safety considerations, and engineering ethics are discussed in the first chapter, but these aspects are encountered throughout the course. Half of the problem statements in Appendix 8 involve environmental tasks. Economics analysis (gross profit) for alternative reaction paths, along with technical/safety/environmental considerations, determines the ultimate feasibility of a project. Practical use of computer-aided design tools gives confidence to students. In conclusion, this is an excellent and highly recommended courseware for undergraduate and postgraduate chemical engineering students.
Alexandru T. Balaban Polytechnic UniVersity of Bucharest, Romania CI000347L 10.1021/ci0003471
BOOK REVIEWS
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Contemporary Instrumental Analysis. By Kenneth A. Rubinson and Judith Faye Rubinson. Prentice-Hall: Upper Saddle River, NJ. 2000. 840 pp. ISBN 0-13-790726-5. $110. Instrumental analysis using physical methods such as electrochemical methods, electronic absorption and emission spectra, vibrational spectra (infrared and Raman), nuclear magnetic resonance spectra, and mass spectra have changed the paradigms of chemistry, particularly organic chemistry. Coupled with various chromatographic and electrophoretic methods, both the identification of natural products and the organic synthesis are now based heavily on such post-WWII techniques. The present textbook mirrors the analytical chemist’s interest and approach, starting with sampling techniques and statistical treatment of data, following with principles and intricacies of instruments, and ending with applications of the various methods enumerated above. It is a book of analytical chemists, by analytical chemists, and for analytical chemists. The 18 chapters are well-illustrated with clear figures and numerous tables, case studies, cross-references, suggestions for further reading, problems, and exercises. Several appendices, answers to exercises, and an index conclude the book. The authors mentioned radioimmunoassay and neutron activation analysis but did not include some of the other radiochemical techniques, such as Mo¨ssbauer spectra and radioisotope dilution analysis; however, they did discuss isotope dilution analysis in the framework of mass spectrometry. X-ray diffraction analysis was also left out. Carbon-13 NMR spectra are reported to require either highly concentrated samples, 13C-enriched samples, or long data collection times (days)sbut this is no longer true with present-day high-field Fourier transform instruments. No 13C-NMR exercises are provided, only figures with 1H-NMR spectra are among the exercises. A list of available software for analytical chemistry would have been welcome. This is, however, an excellent textbook, different from the books on physical methods familiar to organic chemists. It is highly recommended both for analytical and for organic chemistry undergraduate and graduate students.
Alexandru T. Balaban Polytechnic UniVersity Bucharest, Romania CI000348D 10.1021/ci000348d
Reviews in Computational Chemistry, Volume 13. Edited by Kenny B. Lipkowitz and Donald B. Boyd. Wiley-VCH: New York. 1999. 426 pp. ISBN 0-471-33135-X. $135. The latest volume in this series continues to provide excellent reviews for theoretical and computational chemists. The preface by the two editors discusses (on the basis of data provided by the Institute of Scientific Information for the most cited chemists) the major contributions due to practitioners of computational chemistry: from the top 50 authors, a quarter are computational chemists, and from the top 1000 authors, a tenth are in computational chemistry. Many of these mostcited computational chemists have contributed a chapter to ReViews in Computational Chemistry. The preface also presents personal views on the contributions of Professors Norman L. Allinger and Michael J. S. Dewar. The first chapter by Bally and Borden is entitled “Calculations on Open-Shell Molecules: A Beginner’s Guide”; it provides, as the title says, a survey of methods for computing wave functions for radicals, radical-ions, and diradicals. Such open-shell species have gained importance after the discovery that many reactions previously believed to involve movements of electron pairs actually occur by singleelectron-transfer steps. The restricted open-shell Hartree-Fock (HF) method does not include spin polarization; hence, it is unable to predict spin densities, whereas the unrestricted Hartree-Fock wave functions do not yield pure spin states because they introduce the artifact of spin contamination. A possible remedy is to use the CASSCF (complete active space self-consistent field) and other procedures. An attractive alternative is provided by density functional theory (DFT), which is able to make calculations for most radicals and radical-ions as easy
and reliable as the restricted HF (RHF) methods for closed-shell molecules. Caveats in the use of DFT methods are discussed; it is believed that the B3LYP (Becke-Lee-Yang-Parr) ab initio method is the method of choice. Examples are provided to warn the reader that for open-shell molecules symmetry should never be taken for granted. For diradicals, three cases are discussed in detail: twisted ethene, square cyclobutadiene, and trimethylenemethane. Various properties can be predicted by such calculations: rotation barriers and other kinetic or thermodynamic parameters, vibrational and electronic spectra, and ESR spectra. A glossary of acronyms completes this chapter. Chapter 2 by Kestner and Combariza, entitled “Basis Set Superposition Errors: Theory and Practice”, discusses the artifact caused by the lowering of energy of a molecule by the electron density of molecules in its neighborhood. The full counterpoise correction method is able to solve this problem. An appendix provides a sample input deck for counterpoise corrections using Gaussian 92 or 94. The third chapter by Anderson, entitled “Quantum Monte Carlo: Atoms, Molecules, Clusters, Liquids, and Solids”, reviews techniquess such as variational, diffusion, Green’s function, and path integralsapplied to the increasingly complex systems presented in the chapter’s title. The chapter starts with a quotation from I. N. Levine’s book on quantum chemistry: “If you learn enough abbreviations you can convince some people that you know quantum chemistry.” There are three main branches of the quantum chemistry’s family tree: density functional theory (DFT), quantum Monte Carlo (QMC), and Rayleigh-Ritz variational theory (RRV). Many additional branches follow, and they are illustrated in a diagram. Although the Monte Carlo computer programs are less user friendly than those based on the Hartree-Fock approach, and although the Monte Carlo method has not been as widely used as other ways for solving the Schro¨dinger equation, the power of such calculations consists of their applicability to very large systems. However, even for systems with few electrons, QMC methods are sometimes superior to other approaches. A sampling of applications concludes this chapter, starting with the potential energy surface for the reaction of a hydrogen atom with a hydrogen molecule, and including metallic lithium or liquid water. “Molecular Models of Water: Derivation and Description” is the title of the next chapter by Wallqvist and Mountain. Aqueous solutions have a tremendous importance in chemistry and life sciences; therefore, many calculations on such systems have been published involving both QMC and molecular dynamics computer simulations with a few thousand water molecules at liquid density. The results reflect the accuracy of the potential functions. The intermolecular interactions between water molecules involve attractive electrostatic, polarization and dispersion forces as well as exchange repulsion. The authors provide a guide for those who wish to use available computer programs. They indicate that the simple point charge (SPC/E) model is probably the model of choice, followed by the transferable intermolecular four-site potential model (TIP4P, with a CPU time load almost twice as high as SPC/E). Chapter 5 by Briggs and Antosiewicz is entitled “Simulation of pHDependent Properties of Proteins Using Mesoscopic Models”. Steering substrates of enzymes toward the active site, protein stability and folding, or binding of ligands are among the pH-dependent properties of proteins. Molecular dynamics simulations, such as the finite difference Poisson-Boltzmann (FDPB) method reported by Bashford and Karplus in 1990, were followed by developments which included the authors’ own calculations based on the Monte Carlo technique. A computationally-efficient three-step algorithm is presented. Protonation equilibria of proteins are discussed assuming that the solvent and the solute can be treated as continuous dielectric media. Alternative microscopic simulations based on the protein dipole-Langevin dipole (PDLD) model are extremely time intensive. The experimental and theoretical approaches for determining pKa values and pH-dependent properties of proteins are presented and are followed by sample applications such as the total charge of the bovine pancreas trypsin inhibitor, the binding of inhibitors by HIV protease, and the dipole moments of proteins. The sixth and last chapter, entitled “Structure Diagram Generation”, was written by Helson. Nowadays all chemical journals expect two-
884 J. Chem. Inf. Comput. Sci., Vol. 40, No. 3, 2000 dimensional chemical structures to be provided using commercially available programs such as ChemDraw, ChemWindow, or ISIS/Draw. The effort to produce such software during the past 2 decades is reviewed, without burdening the reader by specialist jargon (and a glossary plus list of acronyms assists the less initiated). One should be aware that years of effort and tens of thousands of lines of code are needed for such software; some of the programs are available free for the asking. All chapters are accompanied by many bibliographic references, and the volume has an author and an extensive subject index, reflecting the editors’ care to produce yet another high-quality review volume.
Alexandru T. Balaban Polytechnic UniVersity of Bucharest, Romania CI0003496 10.1021/ci0003496
Molecular Mechanics and Conformational Analysis in Drug Design. By Gyorgy Keseru and Istvan Kolossvary. Blackwell Science Ltd.: Oxford, U.K. 1999. 168 pp. ISBN 0-632-05289-9. $120. The aim of this book is to introduce the basic concepts of molecular mechanics and conformational analysis to the nonspecialist. Since desktop modeling is becoming widespread in the workplace, computational chemistry tools are routinely used by many nonspecialists as an aid to their research. The present book provides a useful introduction to the theory behind the computational algorithms. The material is presented in sufficient detail to allow the nonspecialist to make informed decisions about force field parameters, solvation models, and completeness of a conformational search, for example, so that the modeling software can be used as more than a calculational “black box”.
BOOK REVIEWS Chapter 1 presents the concepts behind the molecular mechanics method, while Chapter 2 describes and compares the factors which determine the performance of the most commonly used force fields. Both chapters end with a useful summary section. Chapter 3 describes how various force fields were parametrized and concludes with a practical guide on how to derive parameters for applications not covered by the chosen force field. Chapter 4 focuses on solvation. Discrete solvent models are very briefly discussed. Continuum solvation models are evaluated, and suggestions are made for the appropriate application of each. Chapter 5 describes energy minimization techniques with the goal of providing sufficient information to allow the nonspecialist user to select the appropriate technique for a particular application. Two cases are used as benchmarks for the various minimization routines: minimization of a small protein and minimization of a molecular complex. In addition, special attention is given to how to locate transition states on a potential energy surface. Chapter 6 describes the various methods of conformational analysis and their application to location of a global energy minimum, treatment of macrocyclic structures, and docking of a ligand in a protein. Chapter 7 describes various techniques for calculating binding free energy with particular attention paid to the MINTA technique developed by one of the authors. Chapter 8 presents a case study in biomolecular modeling based on the example of ligand binding to cytochrome P-450. The book contains 18 color plates illustrating various molecular structures, properties, and complexes. It is a very readable introduction to the concepts and applications of molecular mechanics for the specialist and nonspecialist alike.
Bruce Slutsky and Carol A. Venanzi New Jersey Institute of Technology CI0003505 10.1021/ci003505
