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Book Review Fundamental Principles of Molecular Modeling. Edited by W. Gans A. Amann and J. C. A

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New Light on Molecular Modeling
Since the early 1980s there have been
enormous developments in techniques for
simulating molecular properties to gain a
better understanding of macroscopic or
chemical phenomena, especially with a
view to “designing” new compounds for
particular applications (e.g., in pharmaceuticals, vaccines, or plastics), and
molecular modeling is now an important
and very active area of research. However, it is unfortunate that some researchers, and especially commercial organizations offering software for this
field, have raised quite unrealistic expectations by understating the complexity of
these methods. This has helped to create
the impression that anyone can now carry
out molecular modeling by using a system
as a “black box”, without needing to understand the chemical, physical, and
mathematical fundamentals. This eventually results in failure for many, if not the
majority, of molecular modeling projects,
which comes as no surprise to experts in
the field. That in turn has led to a widespread feeling in some circles that knowledge has not yet advanced far enough to
enable one to successfully model and design molecular properties. This is not so,
but in order to appreciate that one must
take the trouble to understand the principles of molecular modeling, so that one
can use the methods effectively, taking into account the present state of knowledge.
As can be seen from the titles of the three
books reviewed below, their authors have
set out to equip the reader with the necessary knowledge.
This section contains book reviews and a list of
new books received by the editor. Book reviews are
written by invitation from the editor. Suggestions
for books to be reviewed and for book reviewers
are welcome. Publishers should send brochures or
(better) books to the editorial office: Redaktion
Angewandte Chemie, Postfach 1011 61. D-69451
Weinheim, Germany. The editor reserves the right
of selecting which hooks will be reviewed. Uninvited books not chosen for review will not be returned.
Angew. Chem. Int. Ed. Engl. 1997, 36, No. 4
Guidebook on Molecular Modeling in
Drug Design. Edited by N . C. Cohen.
Academic Press, San Diego, 1996.
361 pp., hardcover $ 59.95.-ISBN
The editor of this book is an industrial
chemist, and consequently it is firmly orientated towards the applications of modeling techniques. The various aspects are
treated in seven chapters, and an eighth
chapter is a glossary with short explanations of terms commonly used in drug design and theoretical methods.
The first chapter, writtcn by the editor,
gives a general overview of modeling techniques used in the development of new
drugs. Cohen describes the history of such
techniques, and compares them with the
alternative of “chemical intuition”, citing
some examples.
In Chapter 2 Roderick Hubbard (University of York) describes the rapid development of computer graphics hardware,
which made it possible for the first time to
model molecular structures. Methods of
displaying molecules are also briefly discussed.
In Chapter 3 Tamara Gund (New
Jersey Institute of Technology) concentrates on the methods used for modeling
small molecules. Unfortunately there is
some overlapping here with the subject
matter of the previous two chapters. The
topics covered include the concept of the
pharmacophore, receptor mapping, docking, QSAR methods, molecular orbital
(MO) and molecular mechanics approaches, and some illustrative examples.
Chapter 4, by Akiko Itai and colleagues
(University of Tokyo), dcals with the design of new lead structures. The authors
discuss the different approaches that are
used, depending on whether or not one
knows the three-dimensional structure of
the target molecule (e.g., a receptor or an
enzyme). Much space is devoted to the
docking and “structure construction”
programs developed by the Tokyo group,
but others are treated only briefly and selectively.
In Chapter 5 John Priestle and Gregory
Paris (Ciba-Geigy) describe methods for
obtaining three-dimensional molecular
structures, some experimental results
s VCH Verlag,~ge.rellschaft
mhH. 0-69451 Weinheim,1997
from these methods in connection with interactions of proteins, and data banks
of 3D molecular structures for proteins
and compounds of low molecular mass.
They also discuss ways of extracting information from these sources. Lastly they explain the IUPAC nomenclature conventions for amino-acids, nucleic acids, and
sugars, a topic that seems rather out of
place in a book of this kind.
Chapter 6, by Peter Gund and coauthors (MSI), presents another viewpoint
on computeraided searching for active
agents. There is considerable overlapping
with material covered in the earlier chapters.
Finally, in Chapter 7, Konrad Koehler
and colleagues (Molecular Biology Research Institute, Rome) describe methods
for modeling drug-receptor interactions.
They also discuss interactions of proteins,
force-field techniques, and docking techniques, including receptor mapping. Various “drug targets” are also discussed.
A particular strength of the book is its
practically-orientated approach, with detailed descriptions of the techniques used
for modeling. However, the considerable
degree of overlapping between the chapters is annoying for the reader. Although
each chapter has its individual strengths,
since the authors emphasize different aspects of concern to the novice, the absence
of a unifying plan means that the book is
less useful than it could have been. It is
actually a collection of articles on drug
design methods seen from the different
viewpoints of the individual authors.
Considering all the chapters together, the
coverage of the field is fairly comprehensive. This book is of intercst to the reader
who is already working in a related field
and seeks detailed information about
specific topics; however, it does not constitute a systematic textbook-style introduction for the beginner.
Fundamental Principles of Molecular
Modeling. Edited by W. Gans, A .
Amann and J C. A . Boeyens. Plenum,
New York, 1996. 249 pp., hardcover
$79.50.-ISBN 0-306-45305-3
This book contains the proceedings of
an international workshop on the basic
0570-0833 97/3604-0413$ 15.00t.25/0
principles of molecular modeling, held in
Skukuza, in the Kruger National Park,
South Africa, in August 1995. It displays
both the strengths and the weaknesses
usually found in books of this kind. From
the negative standpoint, it is a rather arbitrary collection of articles from different
topic areas, and there is no attempt at a
comprehensive coverage of the subject.
On the other hand, such publications often contain excellent articles that are frequently cited later. It is not possible to
describe the book in just a few paragraphs, and therefore this review will concentrate on a few articles chosen from the
13 included in the book.
The introductory article by J. C. A.
Boeycns contains a very brief overview of
structure-fitting methods. The author
puts forward the unconventional view
that there is no experimental evidence to
indicate that molecules in the gas phase
have a clearly defined shape, expresses
reservations about the usual practice
based on the interpretation of X-ray diffraction data, and challenges the notion
that one can compute chemical structures
using quantum mechanics. Few chemists
arc likely to agree with these views at the
prcsent time. However, Sutcliffe of the
University of York also expresses reservations about the concept of molecular
structure within the quantum-mechanical
context. In several further chapters by different authors the concept of three-dimensional structures is discussed very thoroughly, mainly from the standpoint of the
quantum theoretician; the conclusions
they reach do not agree in all cases.
There is an abrupt change of subject in
the article by Frank H. Allen (Cambridge,
UK), who describes the setting up of the
Cambridge Crystallographic Data Bank
and explains its purposes. He shows how,
by comparing a large number of molecular structures, one can obtain information, such as the nature of noncovalent
interactions, that would not be accessible
by studying structures in isolation. The
following article by Gilli et al. (Ferrara)
discusscs the importance of hydrogenbonding interactions, in particular their
geomctry, in the context of molecular
Another chapter is concerned with the
determination of electrical properties
from diffraction data. This is followed by
a chapter in which Comba (Heidelberg)
discusses the modeling of structures and
spectroscopic properties of transition
mctal compounds, a topic that undoubtedly has enormous potential for future development. Some interesting examples of
applications in this area are described.
Another short chapter is devoted to theo414
retical predictions of crystal packing in
compounds of low molecular mass.
Lastly there are chapters on the molecular structures of special compounds, accompanied in some cases by tables of crystallographic data, atomic coordinates,
and bonding parameters; these chapters
are likely to be read only by those with a
particular interest in the compound classes treated.
To summarize, the book contains some
articles that are certainly worth reading in
view of the unconventional standpoints
adopted by the authors, so that one can
consider these and perhaps challenge
them. However, for the reader who wishes
to gain an understanding of the theoretical fundamentals and the background,
both experimental and theoretical, to
modern modeling methods, or perhaps
even to apply them, only about 10% of
the contents of this book is likely be of
practical value. Moreover, this material is
not particularly novel, and is therefore
available elsewhere in the many other
books published during the last 10-15
Modelling Molecular Structures. By
A . Hinchlijfe. Wiley, Chichester,
1996. 256 pp., paperback & 24.95.ISBN 0-471-95923-5
This book is a revised and considerably
extended version of the author’s Computational Quantum Chemistry, first published in 1988. Much of it is written in a
deliberately relaxed style, with bylines
such as “What on Earth is Chapter O?”,
and “Congratulations and welcome to the
text”. However, the
title of the book is
misleading. It is not
an introduction to
molecular modeling
in general, as one
would assume from
the title, nor does it
contain a survey of
the methods or
computer programs
used. Instead it consists mainly of an exposition of the quantum-mechanical
methods, accompanied by a short description of molecular mechanics methods
which, being only 16 pages long, is quite
inappropriate. There is also a half-page
paragraph on protein docking which
looks rather lost in this context.
The main part of the book is concerned
with topics such as the Born-Oppenheimer approximation, LCAO methods,
the hydrogen molecule, descriptions based
on the molecular orbital (MO) and valence
mbH, 0-69451 Wrinhrim,19Y7
bond (VB) methods, Slater orbitals, choice
of orbitals, electron correlation methods,
etc.-the range of topics usually covered
in books on quantum chemistry. In the
discussion of ab-initio and semi-empirical
methods, the former is given much more
attention. The MNDO method is covered
in exactly six lines with one literature reference, while the AM1 method (the most
modern one mentioned in the book) is
given ten lines and one reference. In contrast, an entire chapter is devoted to the
“Gaussian 92” suite of programs.
In the last quarter of the book the author deals with potential energy hypersurfaces, gives a very incomplete description
of optimization procedures in connection
with the multiple minima problem, and
discusses primary and induced properties
of molecules, from electric multipole moments to magnetic susceptibilities. The
last 20 pages are devoted to some applications, such as calculations of rotational
barriers, coupling constants, or crystal
lattice parameters, but the author fails to
do adequate justice here to the applied aspects of molecular modeling.
The book is accompanied by a diskette
containing a few exercises and solutions in
the forms of Wordperfect, Acrobat Reader. and Postscrint data files. There are also
programs in Basic, which provide demonstrations of some of the most common
quantum-mechanical calculations for the
hydrogen and water molecules using various MO methods, such as the determination of CNDO parameters, or Huckel calculations.
The question as to which readers can
benefit from this book is not easily answered. It deals with some selected topics
from the development of quantum chemistry during the past 30 years, but does not
treat any of these in great detail, and the
fascinating applications that have been
developed since the early 1970s are scarcely covered at all. Moreover, the compilations of results obtained using “Gaussian
92”, some of which extend over several
pages, also fail to redeem the book, as
very little interpretation is offered. Many
simple structural formulas are unnecessarily large, giving the impression that the
main aim was to fill some pages. If a high
school student were to be given the title of
this book as an essay topic, and handed in
this text, the comment at the end would
be: “misses the main point”.
0570-0833/97l3604-0414 $ 15.00+ .25/0
Dietmar Schomhurg
Institut fur Biochemie
der Universitat Koln
Cologne (Germany)
Angew. Chcm. In!. E d Enpl. 1997, 36, No. 4
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