Book, Software, and Web Site Reviews
Bioinformatics: Sequence and Ge-
nome Analysis, 2nd ed. David W.
Mount. Cold Spring Harbor, NY:
Cold Spring Harbor Laboratory
Press, 2004, 692 pp., $75.00, paper-
back. ISBN 0-87969-712-1.
The production of a good introduc-
tion to the field of bioinformatics has
been a very difficult task because of
the duality of the target audience. A
text that is appropriate for the com-
puter scientist is typically not good
for the biologist, and vice versa. Pro-
ducing a primer that is suitable for
both has been a target of numerous
authors in the past few years. One
of the most successful has been the
first edition of David Mount’s book,
and so it was that I received this
second edition with no little sense
of anticipation. Would this be a
successful upgrade, or would the
changes be merely cosmetic? Fur-
thermore, would the third class
of bioinformatics students be well
served; namely, those many bio-
science workers who graduated long
before bioinformatics became a stan-
dard part of the curriculum and who
now find that their skills need to be
updated to keep up with the times?
This second edition is a qualified
success. Every chapter in the second
edition appears to be rewritten ex-
tensively, and three useful new chap-
ters have been added. As a result, the
new edition tops out at 692 pages,
and many of the problems with the very popular and powerful PSI-
first edition have been rectified. BLAST program.
This is designed to be a textbook. Overall, this second edition is a
There are problem sets at the back of considerable improvement over the
the chapters as well as separate chap- first and will be popular on the desks
ter guides for biologists and com- of many scientists as well as many
puter scientists that make the notori- students. If you work in one particu-
ous bioinformatics learning curve a lar branch of bioinformatics, you
bit more gentle. Working scientists would do better to get a specialized
will particularly appreciate the ex- book in that one field. If you find that
tensive glossary of terms at the be- you need a reference that covers the
ginning of each chapter. Considering entire breadth of bioinformatics, you
the fact that, for many, bioinformat- need to buy this book.
ics appears to be an endless string
of incomprehensible buzzwords, this Martin Gollery
section alone may justify the cost
of the book. Numerous flowcharts Center for Bioinformatics
serve to explain algorithms in a way University of Nevada at Reno
that is greatly superior to a series of Department of Biochemistry
long-winded explanations. Several Reno, NV 89557
chapters have a page with web ad-
dresses to appropriate and useful DOI: 10.1373/clinchem.2005.053850
sites.
One of the new chapters, and in-
deed, a very important one, is the Evaluation of Enzyme Inhibitors in
introduction to the probability and Drug Discovery: A Guide for Medic-
statistics of sequence alignments. inal Chemists and Pharmacologists.
Unfortunately, this will not provide a Robert A. Copeland. Hoboken, NJ:
simple answer to the questions that John Wiley & Sons, Inc., 2005, 271 pp.,
most people will have with these $84.95, hardcover. ISBN 0-471-68696-4.
types of problems—what is meant by (Book web site http://www.chipsbooks.
the terms E value, P score, and Z com/evalenz.htm)
score, how they are calculated, and a
few examples. For readers who really
need to dig into the statistics, this
chapter is great, but for many it will
be overkill.
The chapter on Perl is a welcome
addition; I have long maintained that
it is shameful that biology students
graduate without some introduction
to Perl. Not only is Perl uniquely
suited to the analysis of sequences,
output files, and databases that are
becoming so common, but many of
the standard functions are already
written and debugged as BioPerl
modules. You will not become a pro-
grammer by reading this section, but
it will teach you how to get started
with Perl, BioPerl, and the various
modules. Beyond that, you should
take a look at the O’Reilly books on
Perl for bioinformatics.
I would like to see more emphasis
on the more commonly used tech-
niques; for example, Mount spends a Many drugs produce their pharma-
good deal of time on the Bayes block cologic effects by inhibiting enzymes,
aligner and much less time on the and the importance of this class of
Clinical Chemistry 51, No. 11, 2005 2219
2220
therapeutic agents has increased
with the mapping of the human ge-
nome, which facilitates identification
of novel enzyme targets. To produce
a successful drug, however, it is es-
sential that selective inhibitors be
identified, which requires that each
candidate be evaluated for potency
against a plethora of potential tar-
gets. This analysis has fallen on the
shoulders of the experts in enzyme
kinetics in the pharmaceutical indus-
try. With the increase in drug-related
research in academia and with the
need for medicinal chemists and phar-
macologists to understand enzyme ki-
netics to facilitate drug discovery, a
useful compendium of enzyme kinetic
theory, applications, and practical ex-
amples has been needed. This rela-
tively short book by a highly success-
ful practitioner in the pharmaceutical
industry does an excellent job of filling
this need.
The book is organized in eight
chapters: Why Enzymes as Drug Tar-
gets?; Enzyme Reaction Mechanisms;
Reversible Modes of Inhibitor Inter-
actions with Enzymes; Assay Con-
siderations for Compound Library
Screening; Lead Optimization and
Structure-Activity Relationships for
Reversible Inhibitors; Slow Binding
Inhibitors; Tight Binding Inhibitors;
and Irreversible Enzyme Inactiva-
tors. The chapters are organized
around key concepts presented as
study guides, and the concepts are
explained extensively in English and
with the use of multiple practical
examples. Virtually every type of ki-
netic problem one encounters in
drug discovery and evaluation is il-
lustrated and explained in this book.
Each chapter contains enough math-
ematical description of the key ki-
netic concept under discussion that
the reader can easily get an idea of
the fundamentals, but the emphasis
is on how data are obtained, in-
terpreted, and used in drug develop-
ment. For those desiring more math-
ematical background, the bibliography
contains many excellent references to
the landmark papers and reviews.
This book serves as an extremely valu-
able starting point for anyone who
needs to acquire and/or interpret
good kinetic data for enzyme inhibi-
Book, Software, and Web Site Reviews
tion. I highly recommend it to those
contemplating entry into the field.
As one might expect for an attempt
to condense a vast field into a small
book, some topics and references
have been omitted. For example, al-
though the citations for enzyme ki-
netic methods are excellent and ac-
knowledge the primary authors of
the key papers, the citations to me-
dicinal chemistry discoveries are not
good. Too many citations to impor-
tant medicinal chemistry discoveries
refer to a medicinal chemistry text-
book co-authored by Dr. Copeland. It
is unfortunate that the seminal syn-
thetic and enzyme kinetic work of
Miguel Ondetti and Dave Cushman
or the works of Art Patchett and his
coworkers—studies that gave rise to
captopril and enalapril and the mod-
ern protease inhibitor field—are not
cited by name. I would hope that this
oversight will be corrected in future
editions of the book.
Daniel H. Rich
School of Pharmacy
University of Wisconsin
Madison, WI 53705
DOI: 10.1373/clinchem.2005.051946
Proteins: Structure and Function.
David Whitford. Chichester, West
Sussex, England: John Wiley & Sons
Ltd., 2005, 542 pp., paperback,
$65.00. ISBN 0-471-49894-7.
Back in the early 1970s, when I was a
guest at the National Institutes of
Health, a protein biochemist la-
mented that there was no future in
studying proteins—interest had
shifted to nucleic acids. It was be-
coming easier to learn the amino acid
sequence of a protein by sequencing
its cDNA bases than by the classic
techniques of protein chemistry.
Now, however, the pendulum has
swung, and proteins are recognized
to be the active molecules that the
vast DNA libraries encode; pro-
teomes are surpassing genomes.
Cloning has allowed preparation of
almost any desired modification of a
protein, and combinatorial tech-
niques have shown interactions of
proteins with each other and with
smaller molecules. There is great in-
terest in how extended peptide
chains fold to native configurations
and how proteins are degraded, as
well as how they are synthesized.
This book is described as introduc-
tory yet extensive, aimed at directing
students “to the amazing beauty and
complexity of protein systems”. It is
designed to be a basic text for under-
graduates or as a review and update
source for graduates. Chapter sub-
jects include amino acids, 3-dimen-
sional structure, fibrous proteins,
membrane proteins, proteomics and
protein evolution, enzyme function,
protein metabolism, cloning and iso-
lation methods, physical chemical
analytical techniques, protein fold-
ing, and the disease implications of
protein mutations and conforma-
tional changes. The Preface and In-
troduction give credit to “scientific
‘giants’” in our past; it was hearten-
ing to see the late Christian B. Anfin-
sen, my thesis professor and a Nobel
Prize winner, cited among these,
along with Mulder, Sumner, Sanger,
and Pauling.
This book includes considerable
detail of metabolic pathways related
to proteins: the citric acid cycle, bio-
synthesis of proteins, degradation of
proteins via proteasomes, and fold-
ing inside GroEC-GroES barrels, for
example; it thus goes well beyond
protein chemistry. There are many
fine structural diagrams, in ribbon
form, wire-frame, space-filling, and

3-dimensional reconstructions; the
models of ribosome action are partic-
ularly informative.
Two chapters on purification and
physical chemical studies are com-
prehensive without involving highly
technical aspects. They cover cloning
and the common steps in isolation—
salting out, centrifugation, electro-
phoresis, ultrafiltration, chromatog-
raphy, Western blotting, and affinity
chromatography. The increasingly
popular technique of mass spectrom-
etry is described, along with 5 types
of preionization; ESI (electrospray
ionization) and MALDI (matrix-as-
sisted laser desorption/ionization)
are widely used, with TOF (time-of-
flight) detection, and precision is at-
tained to 6 figures.
X-Ray crystallographic theory is
made understandable, as are the
Clinical Chemistry 51, No. 12, 2005
techniques of circular dichroism,
electron spin resonance, and optical,
fluorescence, infrared, and Raman
spectroscopy. The reader learns of
the growing application of NMR (nu-
clear magnetic resonance) to the
study of protein structure, with its 3
pulse schemes, COSY (correlation
spectroscopy), TOCSY (total correla-
tion spectroscopy), and NOESY (nu-
clear Overhauser effect spectros-
copy). The final chapter, on the
involvement of protein structure in
medicine, gives as examples sickle
cell anemia, HIV, cholera toxin ac-
tion, influenza, the p53 proteins in
relation to malignancy, antitrypsin
deficiency, and the role of protein
misfolding in neurodegenerative dis-
eases.
This reviewer found one point of
disagreement. The color generated in
2221
the biuret reaction (Chapter 2, page
33) is said to arise from reduction of
Cu(II) to Cu(I), whereas this color is
generally considered to result from
complexation of Cu(II) by peptide
nitrogens.
This book fulfills its goal as a
worthwhile investment for the be-
ginning student or for the advanced
scientist seeking a better grasp of
protein chemistry, including both
structural and metabolic aspects.
Theodore Peters
Bassett Research Institute
Cooperstown, NY 13326-1038
DOI: 10.1373/clinchem.2005.057588