BOOK REVIEWS
J. Chem. Inf. Model., Vol. 46, No. 4, 2006 1877
BOOK REVIEWS Cheminformatics Developments. Edited by Jan H. Noordik. IOS Press: Amsterdam, 2004. 232 pp. ISBN 1-58603-450-2. Hardcover U.S.$175, EURO145, £96. In the preface, the editor, Jan H. Noordik says “This book seeks to document some key developments in computerized chemical information handling in the last two decades of the past century and to bridge to recent cheminformatics research by covering selected topics in the fields of organic synthesis, drug design, crystallography, modeling and chemistry teaching”. There are eight chapters. The first three cover the history of three centers: the Computer-aided Organic Synthesis/ Computer-aided Molecular Modeling (CAOS/CAMM) Center at Nijmegen in The Netherlands, the Chemical Database Service at Daresbury Laboratory in the United Kingdom, and the ComputerChemie-Centrum at Erlangen in Germany. The fourth, on cheminformatics in organic chemistry, surveys computer-assisted organic synthesis. The remaining four chapters discuss cheminformatics in drug design, crystallography, molecular modeling, and chemistry teaching, respectively. Noordik himself supplies the first chapter on the Dutch national academic facility for computer-assisted organic synthesis and molecular modeling, a center with which he was intimately involved until its metamorphosis into the local Nijmegen University bioinformatics research group, when cheminformatics fell out of favor with the funding bodies. Noordik surveys the contributions of the center in both services and research in computer-assisted organic synthesis and molecular modeling and its achievements in macromolecular sequence analysis, educational services, and chemistry teaching. In most respects, this chapter is an excellent historical account, but I have a few criticisms. In the section on substructure search, no mention is made of the fundamental contributions of the research teams at the University of Sheffield, and there are no references to the publications of Lynch, Willett, et al. The section on spectral data is cursory, essentially mentioning only McLafferty’s mass spectral software, an unspecified carbon-13 NMR system, and the SpecInfo system, all three used in the CAOS/CAMM Center at one time or another. On page 22, Noordik says “it is now safe to say that the [crystal] structural data of all compounds are ... in databases”. Sadly, this is by no means true, even today. The Nijmegen MOLDEN software is described in glowing terms on page 26, and on page 32 a “frequently cited paper” is mentioned, but ref 63 merely eulogizes about the number of users and the hotness of the publication, without citing the actual paper! Fortunately, a citation can be found by delving into another chapter in this book. No references or Web sites are given for GaussView, Gaussian, Cerius, SYBYL, GAMESS, and MOPAC. Chapter 2, by McMeeking and Fletcher, on the UK Chemical Database Service, is again largely historical, although it does conclude with a short section on future prospects. I particularly enjoyed this chapter, but I admit to a bias in that I have been involved with Daresbury Laboratory in a number of ways over many years. The specification and cost of the Service’s first VAX in 1984 is an eyeopener. The fight (in 1983) against “powerful skeptical elements within the UK chemical community who doubted the value of computer-based chemical information systems” reminded me of a PC-resistant, pharmaceutical industry manager of my acquaintance many years ago who insisted that he employed chemists “to make compounds not do the typing”. Chapter 3, by Gasteiger and Clark, is also enlivened by human touches, for example, the dead flies falling from the sun-heated roof, the ants creeping in from the pheromone laboratory, and the huge laser printer installed under a hood. Progress in cheminformatics has not come without a struggle. Martin Ott’s chapter is an excellent account of computer-assisted synthetic analysis (as opposed to reaction retrieval, which is covered
to some extent in Chapter 2). The programs discussed are further subdivided into synthesis design, reaction prediction, and mechanism elucidation programs. Nearly half the chapter relates to LHASA, but this is not surprising since LHASA is the software that has found widest usage and the author is still actively involved with it. Most practicing organic chemists make regular use of reaction retrieval systems, but few have sought advice from computer-assisted synthetic analysis software. Ott addresses this regrettable fact in his conclusion. Apart from a review by Gasteiger dated 2000, and a handful of references from the mid-1990s, most of the 106 literature references in this chapter are very old. In contrast, the small number of references in Chapter 5 is a disappointment, but this chapter, by Kelder, Wagener, and Timmers, is an exemplary exposition rather than a review of cheminformatics in drug design. It covers Organon’s Web tool, Monika, for assessing the “drug-likeness” of compounds, and the use of decision trees and recursive partitioning in lead optimization, in particular in the design of low molecular weight luteinizing hormone agonists. Motherwell’s chapter on crystallography devotes much more space to the use of the Cambridge Structural Database (and related software) than to its history and that of the Cambridge Crystallographic Data Center. The generalist reader interested in the history of cheminformatics might have liked more explanation of certain terms in this chapter (especially those related to symmetry), but there is no doubting the quality of the scientific content. The chapter is extensively referenced, but not one of the titles of the 248 articles is listed. This is particularly unfortunate since there are several errors and omissions in the references and in the way they are numbered. Verwer and Leusen’s chapter on molecular modeling is much more mathematical and specialized than the other chapters. All the references are to the work of the author, the editor, and their teams. The text briefly explains quantum mechanics, molecular mechanics, molecular dynamics, the Monte Carlo technique, conformational analysis, crystal lattices, and symmetry, but most of the chapter is devoted to applications of molecular modeling in crystallography. Prediction of crystal structures is an interesting and important field, but it would have been interesting to read about some applications in other fields. The book ends with a chapter on cheminformatics in chemistry teaching, mainly related to efforts at the CAOS/CAMM Center. This chapter is largely of historical interest. Some of the Web tools described are still relevant, but the world of education has changed since the end of 2003: webinars, the semantic Web, and tools such as blogs, wikis, and podcasts have emerged. New courses in cheminformatics (for example at Indiana University) and the European Vernetzes Studium Chemie (Network for Chemistry Education) project are also not mentioned. There is no index. It would also have been useful to have a glossary. There is, however, a list of referenced Web sites. This book was clearly a labor of love by Noordik and is remarkably free of the sort of errors that are usually found in multiauthored works. Unfortunately, I do not think that it will be widely read. It will be of interest to those of us who experienced the growth of cheminformatics in the 1980s and 1990s (I certainly enjoyed reading it), but $175 is a high price to pay for a trip down memory lane. Those who are seriously studying the history of cheminformatics may find the scope of this book too limited.
Wendy A. Warr Wendy Warr & Associates CI060130C 10.1021/ci060130c
