Chemoinformatics for Drug Discovery (eBook)

JÜRGEN BAJORATH, PhD, is Chair of Life Science Informatics at the University of Bonn and also an Affiliate Professor in the Department of Biological Structure at the University of Washington. In addition, he has more than 10 years' experience in drug disovery. His research focuses on the development of computational methods for medicinal chemistry and chemical biology. Dr. Bajorath holds 26 patents, has authored more than 400 scientific articles, and edited four books.

Preface vii

Contributors xiii

1 What Are Our Models Really Telling Us? A Practical Tutorial on
Avoiding Common Mistakes when Building Predictive Models 1

W. Patrick Walters

2 The Challenge of Creativity in Drug Design 33

Ajay N. Jain

3 A Rough Set Theory Approach to the Analysis of Gene Expression
Profiles 51

Joachim Petit, Nathalie Meurice, José Luis Medina-Franco,
and Gerald M. Maggiora

4 Bimodal Partial Least-Squares Approach and Its Application to
Chemogenomics Studies for Molecular Design 85

Kiyoshi Hasegawa and Kimito Funatsu

5 Stability in Molecular Fingerprint Comparison 97

Anthony Nicholls and Brian Kelley

6 C ritical Assessment of Virtual Screening for Hit
Identification 113

Dagmar Stumpfe and Jürgen Bajorath

7 Chemometric Applications of Naïve Bayesian Models in Drug
Discovery: Beyond Compound

Ranking 131

Eugen Lounkine, Peter S. Kutchukian, and Meir Glick

8 Chemoinformatics in Lead Optimization 149

Darren V. S. Green and Matthew Segall

9 Using Chemoinformatics Tools to Analyze Chemical Arrays in
Lead Optimization 179

George Papadatos, Valerie J. Gillet, Christopher N. Luscombe,
Iain M. McLay, Stephen D. Pickett, and Peter Willett

10 Exploration of Structure-Activity Relationships (SAR s)
and Transfer of Key Elements in Lead

Optimization 205

Hans Matter, Stefan Güssregen, Friedemann Schmidt, Gerhard
Hessler, Thorsten Naumann, and Karl-Heinz Baringhaus

11 Development and Applications of Global ADMET Models: In
Silico Prediction of Human Microsomal Lability 245

Karl-Heinz Baringhaus, Gerhard Hessler, Hans Matter, and
Friedemann Schmidt

12 Chemoinformatics and Beyond: Moving from Simple Models to
Complex Relationships in Pharmaceutical Computational Toxicology
267

Catrin Hasselgren, Daniel Muthas, Ernst Ahlberg, Samuel
Andersson, Lars Carlsson, Tobias Noeske, Jonna Stålring, and
Scott Boyer

13 Applications of Cheminformatics in Pharmaceutical Research:
Experiences at Boehringer Ingelheim in Germany 291

Bernd Beck, Michael Bieler, Peter Haebel, Andreas
Teckentrup, Alexander Weber, and Nils Weskamp

14 Lessons Learned from 30 Years of Developing Successful
Integrated Cheminformatic Systems 321

Michael S. Lajiness and Thomas R. Hagadone

15 Molecular Similarity Analysis 343

José L. Medina-Franco and Gerald M. Maggiora

Index 401

"Overall the book is well written, logically following the
larger storyline and most of the time offering high quality reviews
. . . Personally, I enjoyed reading this book and would recommend
it as a general introduction to the subject aimed especially for
post-graduate students and non-specialists working in the area of
drug design, but also for all of those who just want to update
their knowledge." (ChemMedChem, 1 June 2014)