SEAN EKINS, PHD, DSC, is an Adjunct Associate Professor in the Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy. Dr. Ekins is the author of more than seventy peer-reviewed papers and book chapters as well as several patents. He serves on editorial boards for the Journal of Pharmacological and Toxicological Methods, Drug Metabolism and Disposition, Drug Discovery Today, and Pharmaceutical Research.

• Preface xiAcknowledgments xiiiContributors xvPart I: Computers in Pharmaceutical Research And Development: a General Overview 11. History of Computers in Pharmaceutical Research and Development: A Narrative 3Donald B. Boyd and Max M. Marsh2. Computers as Data Analysis and Data Management Tools in Preclinical Development 51Weiyong Li and Kenneth Banks3. Statistical Modeling in Pharmaceutical Research and Development 67Andrea de Gaetano, Simona Panunzi, Benoit Beck, and Bruno Boulanger Copyrighted MaterialPart II: Understanding Diseases: Mining Complex Systems for Knowledge 1034. Drug Discovery from Historic Herbal Texts 105Eric J. Buenz5. Contextualizing the Impact of Bioinformatics on Preclinical Drug and Vaccine Discovery 121Darren R. Flower6. Systems Approaches for Pharmaceutical Research and Development 139Sean Ekins and Craig N. GirouxPart III: Scientific Information Handling and Enhancing Productivity 1677. Information Management—Biodata in Life Sciences 169Richard K. Scott and Anthony Parsons8. Chemoinformatics Techniques for Processing Chemical Structure Databases 187Valerie J. Gillet and Peter Willett9. Electronic Laboratory Notebooks 209Alfred Nehme and Robert A. Scoffin10. Strategies for Using Information Effectively in Early-Stage Drug Discovery 229David J. Wild11. Improving the Pharmaceutical R&D Process: How Simulation Can Support Management Decision Making 247Andrew Chadwick, Jonathan Moore, Maggie A.Z. Hupcey, and Robin PurshousePart IV: Computers in Drug Discovery 27512. Computers and Protein Crystallography 277David J. Edwards and Roderick E. Hubbard13. Computers, Cheminformatics, and the Medicinal Chemist 301Weifan Zheng and Michael Jones14. The Challenges of Making Useful Protein-Ligand Free Energy Predictions for Drug Discovery 321Jun Shimada15. Computer Algorithms for Selecting Molecule Libraries for Synthesis 353Konstantin V. Balakin, Nikolay P. Savchuk, and Alex Kiselyov16. Success Stories of Computer-Aided Design 377Hugo Kubinyi17. Pharmaceutical Research and Development Productivity: Can Software Help? 425Christophe G. Lambert and S. Stanley YoungPart V: Computers in Preclinical Development 44318. Computer Methods for Predicting Drug Metabolism 445Sean Ekins19. Computers in Toxicology and Risk Assessment 469John C. Dearden20. Computational Modeling of Drug Disposition 495Cheng Chang and Peter W. Swaan21. Computer Simulations in Pharmacokinetics and Pharmacodynamics: Rediscovering Systems Physiology in the 21st Century 513Paolo Vicini22. Predictive Models for Better Decisions: From Understanding Physiology to Optimizing Trial Design 529James R. Bosley, Jr.Part VI: Computers in Development Decision Making, Economics, and Market Analysis 55523. Making Pharmaceutical Development More Efficient 557Michael Rosenberg and Richard Farris24. Use of Interactive Software in Medical Decision Making 571Renée J. Goldberg ArnoldPart VII: Computers in Clinical Development 59125. Clinical Data Collection and Management 593Mazen Abdellatif26. Regulation of Computer Systems 633Sandy Weinberg27. A New Paradigm for Analyzing Adverse Drug Events 649Ana Szarfman, Jonathan G. Levine, and Joseph M. TonningPart VIII: Further Applications and Future Development 67728. Computers in Pharmaceutical Formulation 679Raymond C. Rowe and Elizabeth A. Colbourn29. Legal Protection of Innovative Uses of Computers in R&D 703Robert Harrison30. The Ethics of Computing in Pharmaceutical Research 715Matthew K. McGowan and Richard J. McGowan31. The UltraLink: An Expert System for Contextual Hyperlinking in Knowledge Management 729Martin Romacker, Nicolas Grandjean, Pierre Parisot, Olivier Kreim, Daniel Cronenberger, Thérèse Vachon, and Manuel C. Peitsch32. Powerful, Predictive, and Pervasive: The Future of Computers in the Pharmaceutical Industry 753Nick Davies, Heather Ahlborn, and Stuart HendersonIndex 775

"Computer Applications in Pharmaceutical Research and Development" is ideal for information technologists who want to understand the application of computers across the entire drug research and development process." (Journal of Clinical Research Best Practices, September 2008) "...a well-put-together volume with a lot of very interesting and timely information to convey...it would be a nice addition to individual, academic, and industrial libraries." (Journal of Medicinal Chemistry, December 28, 2006)"...strongly recommended both to the structural and medicinal chemistry community, and also to...computational chemists...the whole book is really very readable and enjoyable." (Structural Chemistry, December 2006)

SEAN EKINS, PHD, DSC, is an Adjunct Associate Professor in the Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy. Dr. Ekins is the author of more than seventy peer-reviewed papers and book chapters as well as several patents. He serves on editorial boards for the Journal of Pharmacological and Toxicological Methods, Drug Metabolism and Disposition, Drug Discovery Today, and Pharmaceutical Research.

• Preface xiAcknowledgments xiiiContributors xvPart I: Computers in Pharmaceutical Research And Development: a General Overview 11. History of Computers in Pharmaceutical Research and Development: A Narrative 3Donald B. Boyd and Max M. Marsh2. Computers as Data Analysis and Data Management Tools in Preclinical Development 51Weiyong Li and Kenneth Banks3. Statistical Modeling in Pharmaceutical Research and Development 67Andrea de Gaetano, Simona Panunzi, Benoit Beck, and Bruno Boulanger Copyrighted MaterialPart II: Understanding Diseases: Mining Complex Systems for Knowledge 1034. Drug Discovery from Historic Herbal Texts 105Eric J. Buenz5. Contextualizing the Impact of Bioinformatics on Preclinical Drug and Vaccine Discovery 121Darren R. Flower6. Systems Approaches for Pharmaceutical Research and Development 139Sean Ekins and Craig N. GirouxPart III: Scientific Information Handling and Enhancing Productivity 1677. Information Management—Biodata in Life Sciences 169Richard K. Scott and Anthony Parsons8. Chemoinformatics Techniques for Processing Chemical Structure Databases 187Valerie J. Gillet and Peter Willett9. Electronic Laboratory Notebooks 209Alfred Nehme and Robert A. Scoffin10. Strategies for Using Information Effectively in Early-Stage Drug Discovery 229David J. Wild11. Improving the Pharmaceutical R&D Process: How Simulation Can Support Management Decision Making 247Andrew Chadwick, Jonathan Moore, Maggie A.Z. Hupcey, and Robin PurshousePart IV: Computers in Drug Discovery 27512. Computers and Protein Crystallography 277David J. Edwards and Roderick E. Hubbard13. Computers, Cheminformatics, and the Medicinal Chemist 301Weifan Zheng and Michael Jones14. The Challenges of Making Useful Protein-Ligand Free Energy Predictions for Drug Discovery 321Jun Shimada15. Computer Algorithms for Selecting Molecule Libraries for Synthesis 353Konstantin V. Balakin, Nikolay P. Savchuk, and Alex Kiselyov16. Success Stories of Computer-Aided Design 377Hugo Kubinyi17. Pharmaceutical Research and Development Productivity: Can Software Help? 425Christophe G. Lambert and S. Stanley YoungPart V: Computers in Preclinical Development 44318. Computer Methods for Predicting Drug Metabolism 445Sean Ekins19. Computers in Toxicology and Risk Assessment 469John C. Dearden20. Computational Modeling of Drug Disposition 495Cheng Chang and Peter W. Swaan21. Computer Simulations in Pharmacokinetics and Pharmacodynamics: Rediscovering Systems Physiology in the 21st Century 513Paolo Vicini22. Predictive Models for Better Decisions: From Understanding Physiology to Optimizing Trial Design 529James R. Bosley, Jr.Part VI: Computers in Development Decision Making, Economics, and Market Analysis 55523. Making Pharmaceutical Development More Efficient 557Michael Rosenberg and Richard Farris24. Use of Interactive Software in Medical Decision Making 571Renée J. Goldberg ArnoldPart VII: Computers in Clinical Development 59125. Clinical Data Collection and Management 593Mazen Abdellatif26. Regulation of Computer Systems 633Sandy Weinberg27. A New Paradigm for Analyzing Adverse Drug Events 649Ana Szarfman, Jonathan G. Levine, and Joseph M. TonningPart VIII: Further Applications and Future Development 67728. Computers in Pharmaceutical Formulation 679Raymond C. Rowe and Elizabeth A. Colbourn29. Legal Protection of Innovative Uses of Computers in R&D 703Robert Harrison30. The Ethics of Computing in Pharmaceutical Research 715Matthew K. McGowan and Richard J. McGowan31. The UltraLink: An Expert System for Contextual Hyperlinking in Knowledge Management 729Martin Romacker, Nicolas Grandjean, Pierre Parisot, Olivier Kreim, Daniel Cronenberger, Thérèse Vachon, and Manuel C. Peitsch32. Powerful, Predictive, and Pervasive: The Future of Computers in the Pharmaceutical Industry 753Nick Davies, Heather Ahlborn, and Stuart HendersonIndex 775

"Computer Applications in Pharmaceutical Research and Development" is ideal for information technologists who want to understand the application of computers across the entire drug research and development process." (Journal of Clinical Research Best Practices, September 2008) "...a well-put-together volume with a lot of very interesting and timely information to convey...it would be a nice addition to individual, academic, and industrial libraries." (Journal of Medicinal Chemistry, December 28, 2006)"...strongly recommended both to the structural and medicinal chemistry community, and also to...computational chemists...the whole book is really very readable and enjoyable." (Structural Chemistry, December 2006)

SEAN EKINS, PHD, DSC, is an Adjunct Associate Professor in the Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy. Dr. Ekins is the author of more than seventy peer-reviewed papers and book chapters as well as several patents. He serves on editorial boards for the Journal of Pharmacological and Toxicological Methods, Drug Metabolism and Disposition, Drug Discovery Today, and Pharmaceutical Research.

• Preface xiAcknowledgments xiiiContributors xvPart I: Computers in Pharmaceutical Research And Development: a General Overview 11. History of Computers in Pharmaceutical Research and Development: A Narrative 3Donald B. Boyd and Max M. Marsh2. Computers as Data Analysis and Data Management Tools in Preclinical Development 51Weiyong Li and Kenneth Banks3. Statistical Modeling in Pharmaceutical Research and Development 67Andrea de Gaetano, Simona Panunzi, Benoit Beck, and Bruno Boulanger Copyrighted MaterialPart II: Understanding Diseases: Mining Complex Systems for Knowledge 1034. Drug Discovery from Historic Herbal Texts 105Eric J. Buenz5. Contextualizing the Impact of Bioinformatics on Preclinical Drug and Vaccine Discovery 121Darren R. Flower6. Systems Approaches for Pharmaceutical Research and Development 139Sean Ekins and Craig N. GirouxPart III: Scientific Information Handling and Enhancing Productivity 1677. Information Management—Biodata in Life Sciences 169Richard K. Scott and Anthony Parsons8. Chemoinformatics Techniques for Processing Chemical Structure Databases 187Valerie J. Gillet and Peter Willett9. Electronic Laboratory Notebooks 209Alfred Nehme and Robert A. Scoffin10. Strategies for Using Information Effectively in Early-Stage Drug Discovery 229David J. Wild11. Improving the Pharmaceutical R&D Process: How Simulation Can Support Management Decision Making 247Andrew Chadwick, Jonathan Moore, Maggie A.Z. Hupcey, and Robin PurshousePart IV: Computers in Drug Discovery 27512. Computers and Protein Crystallography 277David J. Edwards and Roderick E. Hubbard13. Computers, Cheminformatics, and the Medicinal Chemist 301Weifan Zheng and Michael Jones14. The Challenges of Making Useful Protein-Ligand Free Energy Predictions for Drug Discovery 321Jun Shimada15. Computer Algorithms for Selecting Molecule Libraries for Synthesis 353Konstantin V. Balakin, Nikolay P. Savchuk, and Alex Kiselyov16. Success Stories of Computer-Aided Design 377Hugo Kubinyi17. Pharmaceutical Research and Development Productivity: Can Software Help? 425Christophe G. Lambert and S. Stanley YoungPart V: Computers in Preclinical Development 44318. Computer Methods for Predicting Drug Metabolism 445Sean Ekins19. Computers in Toxicology and Risk Assessment 469John C. Dearden20. Computational Modeling of Drug Disposition 495Cheng Chang and Peter W. Swaan21. Computer Simulations in Pharmacokinetics and Pharmacodynamics: Rediscovering Systems Physiology in the 21st Century 513Paolo Vicini22. Predictive Models for Better Decisions: From Understanding Physiology to Optimizing Trial Design 529James R. Bosley, Jr.Part VI: Computers in Development Decision Making, Economics, and Market Analysis 55523. Making Pharmaceutical Development More Efficient 557Michael Rosenberg and Richard Farris24. Use of Interactive Software in Medical Decision Making 571Renée J. Goldberg ArnoldPart VII: Computers in Clinical Development 59125. Clinical Data Collection and Management 593Mazen Abdellatif26. Regulation of Computer Systems 633Sandy Weinberg27. A New Paradigm for Analyzing Adverse Drug Events 649Ana Szarfman, Jonathan G. Levine, and Joseph M. TonningPart VIII: Further Applications and Future Development 67728. Computers in Pharmaceutical Formulation 679Raymond C. Rowe and Elizabeth A. Colbourn29. Legal Protection of Innovative Uses of Computers in R&D 703Robert Harrison30. The Ethics of Computing in Pharmaceutical Research 715Matthew K. McGowan and Richard J. McGowan31. The UltraLink: An Expert System for Contextual Hyperlinking in Knowledge Management 729Martin Romacker, Nicolas Grandjean, Pierre Parisot, Olivier Kreim, Daniel Cronenberger, Thérèse Vachon, and Manuel C. Peitsch32. Powerful, Predictive, and Pervasive: The Future of Computers in the Pharmaceutical Industry 753Nick Davies, Heather Ahlborn, and Stuart HendersonIndex 775

"Computer Applications in Pharmaceutical Research and Development" is ideal for information technologists who want to understand the application of computers across the entire drug research and development process." (Journal of Clinical Research Best Practices, September 2008) "...a well-put-together volume with a lot of very interesting and timely information to convey...it would be a nice addition to individual, academic, and industrial libraries." (Journal of Medicinal Chemistry, December 28, 2006)"...strongly recommended both to the structural and medicinal chemistry community, and also to...computational chemists...the whole book is really very readable and enjoyable." (Structural Chemistry, December 2006)