Table Of ContentErnst Schering Research Foundation Workshop 15
Computer Aided Drug Design in Industrial Research
Ernst Schering Research Foundation
Workshop 15
Computer Aided
Drug Design
in Industrial Research
E. C. Herrmann, R. Franke
Editors
With 51 Figures and 16 Tables
Springer-Verlag Berlin Heidelberg GmbH
ISBN 978-3-662-03143-8 ISBN 978-3-662-03141-4 (eBook)
DOI 10.1007/978-3-662-03141-4
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Preface
The Ernst Schering Research Foundation sponsored its 15th workshop
in Berlin on October 19-21, 1994. Leading scientists from Europe and
North America were invited to discuss computer-aided drug design in
industrial research.
Computer-aided drug design is a very exciting field and an intellec
tual challenge, like playing chess. But these reasons are no longer suf
ficient to justify using this method in industry, if they ever were.
Fig. 1. The participants of the workshop
VI Preface
Therefore, when we, together with Prof. Hoyer, started to think about
this workshop, our intentions quickly became clear.
We were not so much interested in the very latest developments of
methods or in computer-aided drug design itself - enough conferences
have dealt with these topics. However, we were very interested in the
usefulness and limitations of computer-aided drug design in the indu
strial research process.
A lot has changed in the pharmaceutical industry recently. These
changes are gaining momentum, so it is the right time to think about
the role of computer-aided drug design in this changing environment.
Just to mention two of these changes: First, most of us are faced with
severe cost reduction programs and computer-aided drug design has to
be judged by its possible impact on the bottom line; second, the signi
ficance of research is changing. Competition between pharmaceutical
companies is much more pronounced nowadays. This competition is
global and, even more importantly, it is competition by innovation. The
title of an article in a research management journal highlights this quite
clearly: '''Innovate or die' is the first rule of international industrial
competition" (de Pury 1994).
The issues of cost reduction and competition by innovation formed
the setting for our workshop, where we wanted to discuss the role of
computer-aided drug design in the overall quest for a new drug, ad
dressing topics such as how computer-aided drug design can be inte
grated in the overall research process to have the most impact, what
computer-aided drug design can contribute and where the pitfalls are,
and what factors favor or prohibit successful contributions from com
puter-aided drug design.
The goals set for this workshop were very ambitous, but we got
much more than we ever expected. Indeed, this is reflected in these
proceedings.
We gratefully acknowledge the contributions of the authors of the
chapters in this book and the assistance provided by the Ernst Schering
Research Foundation, in particular by Dr. Ursula-F. Habenicht.
E. C. Herrmann
R. Franke
Preface VII
Reference
de Pury D (1994) "Innovate or die" is the first rule of international industrial
competition. Research Technology Management 37(5):9-11
Table of Contents
Some Aspects of Computational Chemistry
G.-A. Hoyer ................ .
2 Computer-Aided Drug Design in Industrial Research
A Management Perspective
J. G. Topliss ........................ 11
3 Reflections on Collaborations of a Computational Chemist
with Medicinal Chemists and Other Scientists
1'. Connolly Martin . . . . . . . . . . . . . . . . . . . . .. 39
4 Structure-Based Ligand Design
K. Gubemator, C. Brager, D. Bur, D. M. Doran,
P. R. Gerber, K. Miiller, and T. M. Schaumann 61
5 Chances and Risks of Modeling in Industry
H. Koppen ................ . 79
6 The Advantages of Using Rational Drug Design
in Modem Drug Discovery: How to Integrate
Computer-Aided Drug Design and Modem Biotechnology
U. Norinder . . . . . . . . . . . . . . . . . . . . . . . .. 99
7 Screening Three-Dimensional Databases for Lead Finding
H. P. Weber. . . . . . . . . . . . . . . . . . . . . . . . .. III
x
Table of Contents
8 Optimization of Peptide Leads and Molecular Modeling
1. L Fauchere . . . . . . . . . . . . . . . . . . . . . . . .. 129
9 Quantitative Structure-Activity Relationships
and Crystallography in Industrial Drug Design
H. Kubinyi .................. ....... 163
10 The Role of Structure-Based Ligand Design
in Industrial Pharmaceutical Research
1. P. Tollenaere . . . . . . . . . . . . . . .. ....... 187
11 Drug Design Methods in Real-Life Situations:
Recent Examples and Future Opportunities
R. M. Hyde .......................... 207
12 Theoretical Chemistry as Part
of the Interdisciplinary Approach to Rational Drug Design
E. Eckle and N. Heinrich . . . . . . . . . . . . . . . . . . . 225
13 Computer-Aided Drug Design in Industry:
A Summary of Perspectives
R. Franke and E.G. Herrmann ................ 245
Subject Index ......................................... 251
Previous Volumes Published in this Series .................. 253
List of Contributors
C. Broger
Preclinical Pharmaceutical Research, Computational and Structural
Chemistry, F. Hoffmann-La Roche Ltd., 4002 Basel, Switzerland
D. Bur
Preclinical Pharmaceutical Research, Computational and Structural
Chemistry, F. Hoffmann-La Roche Ltd., 4002 Basel, Switzerland
D.M. Doran
Preclinical Pharmaceutical Research, Computational and Structural
Chemistry, F. Hoffmann-La Roche Ltd., 4002 Basel, Switzerland
E. Eckle
Institute of Physical Chemistry, Schering AG, MtillerstraBe 178,
13342 Berlin, Germany
J. L. Fauchere
Institut de Recherches SERVIER, 11, rue des Moulineaux,
92150 Suresnes-Paris, France
R. Franke
Consulting in Drug Design GbR, 16352 Basdorf, Germany
P. R. Gerber
Preclinical Pharmaceutical Research, Computational and Structural
Chemistry, F. Hoffmann-La Roche Ltd., 4002 Basel, Switzerland
XII List of Contributors
K. Gubernator
Preclinical Phannaceutical Research, Computational and Structural
Chemistry, F. Hoffmann-La Roche Ltd., 4002 Basel, Switzerland
N. Heinrich
Institute of Physical Chemistry, Schering AG, MiillerstraBe 178,
13342 Berlin, Germany
E. C. Herrmann
Institute of Physical Chemistry, Schering AG, MiillerstraBe 178,
13342 Berlin, Germany
G.-A. Hoyer
Institute of Physical Chemistry, Schering AG, MiillerstraBe 178,
13342 Berlin, Germany
R. M. Hyde
Department of Physical Sciences, Wellcome Research Laboratories,
Langley Court, Beckenharn, Kent BR3 3BS, UK
H. Koppen
Medicinal Chemistry Department, Boehringer Ingelheim KG,
55216 Ingelheim, Germany
H. Kubinyi
Drug Design, ZHB/w, A 30, BASF AG, 67056 Ludwigshafen, Germany
Y. C. Martin
Phannaceutical Products Division, Abbott Laboratories, Abbott Park,
IL 60064, USA
K. Muller
Preclinical Pharmaceutical Research, Computational and Structural
Chemistry, F. Hoffmann-La Roche Ltd., 4002 Basel, Switzerland
U. Norinder
Karo Bio AB, P.O.B. 4032, 14104 Huddinge, Sweden
T.M. Schaumann
Preclinical Phannaceutical Research, Computational and Structural
Chemistry, F. Hoffmann-La Roche Ltd., 4002 Basel, Switzerland
