edited by Osman F. Güner
This book is a comprehensive look at pharmacophore history and use in drug design. The term "pharmacophore" was first used in the early 1900s, and since that time has become the underlying tenet of drug design. In principle, it is a simple idea, but in practice the large number of different methods, as well as the wide variety of problems to which these methodologies are applied, make this a very hard field to get started in - much of the information is not published anywhere, and there is no single complete source that includes information on all the different methods.
That is, until now.
If I had to describe this book in one word, it would be comprehensive. The most surprising thing about this book is that it hasn't already been written, for it fills a need in this community.
The 27 chapters in this volume describe not only the history of pharmacophore development, but the techniques and methods for developing pharmacophores from either a series of active compounds, or from a known receptor site. Included are quantitative and qualitative analysis methods, those that broke ground in the past, those considered state of the art today, and those recently developed methods that have not yet made it into commercial software.
This book is interesting on many levels. There is a historical perspective that describes how pharmacophores were described in the past, what types of approaches have been tried, and which ones worked best under what circumstances. For those just getting started in the field, would be excellent preliminary background reading, to be followed by a reading of the chapters that describe the particular applications/methods that will be used.
For those currently applying these methods to real world problems, this book contains a great review of currently available methods, and could be used to learn about unfamiliar pharmacophore mapping methodologies, to perhaps add some of these techniques into their own work. Many seemingly obvious but easily overlooked techniques, such as using protonated groups if appropriate for the pH you are modelling, and how to select a good training set (what size, what molecular characteristics), are explicitly listed.
For those developing new methods and applications, the descriptions of new techniques will prove most interesting. For all working in this field, the predictions of future directions and identification of current problems will prove useful, and hopefully inspirational in their own work. The level of detail given in most chapters is appropriate for those who are going to actually use the methods described. Many details normally omitted from journal articles are included here, such as typical ranges for various parameters, when should a number different from the default be used, for what types of structures and problems does this method work, and just as importantly, for what types of problems is it inappropriate.
The parts I found particularly fascinating were the reasons behind the decisions, and the limits of the various applications. Why was a particular method chosen? Why was a particular default setting used? What ranges of values are appropriate to try? What other ideas were tried, and found lacking? This information is rarely published, but is invaluable to those using the methods, or continuing their developement.
Most chapters are written by those who developed or commercialized the methods described. The author list includes most of the major players in the field, with just a few notable exceptions. As is to be expected, some authors are less critical of their own work, but overall the tone is excellent.
While the reference lists are not exhaustive, the combination of references and contact information for all chapter authors (including email addresses) provides ample starting points for those wanting more information on any topic. Similarly, the index is useful, but a more comprehensive one would improve the value as a reference volume. Since color is necessary to clearly illustrate the ideas presented, there is an insert of 20 pages of color plates, and one color table inserted elsewhere.
Much of the information in this volume can be directly applied to high throughput screening problems and combinatorial chemistry applications, areas of significant interest currently. These areas generate huge amounts of data, and are driving the need for more robust, more automated analysis methods. This comprehensive book reviewing current state of the art, will be a valuable resource for those continuing work in this area - new students and experienced researchers alike.
The book is divided into 5 major sections, containing a total of 27 chapters. Each chapter begins with an abstract, that summarizes the ideas and methods presented in that chapter, followed by an introductory section, to bring the uninitiated up to speed. Most chapters begin by describing the general strategy and methodology of the technique being discussed, then give explicit details, and finally end with examples of successful applications of the methods they describe. This is exceptionally useful in answering that often asked question "But do these methods really WORK?"
Part I is entitled "The Origins of Pharmacophore Research", and consists of a single chapter. This chaper is a historical overview of the "Evolution of the Pharmacophore Concept in Pharmaceutical Research", from man's earliest beginnings to the present time. This is an excellent orientation for those not familiar with the field, and a history lesson for those who are.
Part II deals with "Analog-Based Pharmacophores". An introductory chapter is included for those unfamilar with the area, followed by detailed chapters describing some of the main techniques in this area, written by the developers of those methods. It includes sections on "Automated Pharmacophore Development Systems", "Predictive Model Development - 3D QSAR" and "Applications in Drug Design". Some of these approaches are still being actively used and extended, others have fallen out of favor.
The chapters in this section are:
Part III is entitled "Receptor-Based Pharmacophores". These are more recently developed techniques, which have become possible as computer power and speed has increased.
Part IV deals with "New Algorithms in Pharmacophore Development". These chapters describe new ideas and algorithms, as well as improvements to existing algorithms.
Illustrated, hardcover, $109.95
560 p. Color ill. (IUL Biotechnology series)
ISBN: 0-9636817-6-1, published February 2000
Lisa M. Balbes, PhD, is a freelance consultant and technical writer. She specializes in the scientific software and bio/chemoinformatics industries, as Osiris Consultants.