Chemoinformatics for Drug Discovery

Preface vii
Contributors xiii
1 What Are Our Models Really Telling Us? A Practical Tutorial onAvoiding 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 ExpressionProfiles 51
Joachim Petit, Nathalie Meurice, José Luis Medina-Franco,and Gerald M. Maggiora
4 Bimodal Partial Least-Squares Approach and Its Application toChemogenomics 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 HitIdentification 113
Dagmar Stumpfe and Jürgen Bajorath
7 Chemometric Applications of Naïve Bayesian Models in DrugDiscovery: 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 inLead 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, GerhardHessler, Thorsten Naumann, and Karl-Heinz Baringhaus
11 Development and Applications of Global ADMET Models: InSilico Prediction of Human Microsomal Lability 245
Karl-Heinz Baringhaus, Gerhard Hessler, Hans Matter, andFriedemann Schmidt
12 Chemoinformatics and Beyond: Moving from Simple Models toComplex Relationships in Pharmaceutical Computational Toxicology267
Catrin Hasselgren, Daniel Muthas, Ernst Ahlberg, SamuelAndersson, Lars Carlsson, Tobias Noeske, Jonna Stålring, andScott Boyer
13 Applications of Cheminformatics in Pharmaceutical Research:Experiences at Boehringer Ingelheim in Germany 291
Bernd Beck, Michael Bieler, Peter Haebel, AndreasTeckentrup, Alexander Weber, and Nils Weskamp
14 Lessons Learned from 30 Years of Developing SuccessfulIntegrated 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