Ligand Efficiency Indices for Drug Discovery
Towards an Atlas-Guided Paradigm
- 1st Edition - January 22, 2013
- Imprint: Academic Press
- Author: Celerino Abad-Zapatero
- Language: English
- Paperback ISBN:9 7 8 - 0 - 1 2 - 4 0 4 6 3 5 - 1
- eBook ISBN:9 7 8 - 0 - 1 2 - 4 0 4 6 8 2 - 5
The purpose of Ligand Efficiency Indices for Drug Discovery: Towards an Atlas-Guided Paradigm is to introduce in a concise and self-contained form the concepts, ideas, applicati… Read more
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Request a sales quoteThe purpose of Ligand Efficiency Indices for Drug Discovery: Towards an Atlas-Guided Paradigm is to introduce in a concise and self-contained form the concepts, ideas, applications and examples of efficiency-driven drug discovery to the biomedical community at large. The book emphasizes the use of 'new variables' and more objective numerical methods to drive drug discovery in an encompassing way. These 'new variables' are based on Ligand Efficiency Indices (LEIs) formulated in a way that permits mapping Chemico-Biological Space (CBS) in an Atlas-like representation. It provides a practical and timely discussion of the concepts, ideas, applications and examples of efficiency-driven drug discovery. This book emphasizes the use of a graphical representation and objective numerical methods to drive drug discovery more effectively. It presents the definition of LEIs and the corresponding efficiency planes within an atlas-like environment to provide a robust graphical and numerical framework for medicinal chemists and drug-discoverers.
- Provides a practical and timely discussion of the concepts, ideas, applications and examples of efficiency-driven drug discovery
- Emphasizes the use of ‘new variables’ and more objective numerical methods to drive quicker and more effective drug discovery
- Presents the definition of Ligand Efficiency Indices (LEIs) and the corresponding efficiency planes as key concepts to provide a graphical and numerical framework
Researchers, new professionals and graduate students in medicinal chemistry, drug discovery and pharmaceutical sciences
Dedication
Acknowledgments
Prologue
The Current Status of Drug Discovery
Introduction
Part 1: The Elements: Data, Variables, Concept, and the Server
Part I. The Elements: Data, Variables, Concept, and the Server
Chapter 1. Structure–Activity Databases for Medicinal Chemistry
1.1 PDB
1.2 PDBBind, MOAD
1.3 ChEMBL
1.4 WOMBAT
1.5 DrugBank
1.6 BindingDB
1.7 PubChem
1.8 Proprietary Databases
1.9 Perspective
1.10 Discussion
Chapter 2. The Variables: Definitions of Ligand Efficiency Indices
2.1 Ligand Efficiencies Based on Free Energy of Binding
2.2 Ligand Efficiencies Based on Physicochemical Properties
2.3 Ligand Efficiencies Based on Atomic Properties
2.4 A Formulation in Polar Coordinates
2.5 Refinements to the definitions of Ligand Efficiency (LE)
2.6 Discussion
Chapter 3. Variables and Data: The AtlasCBS Concept
3.1 The Vastness of Chemical Space
3.2 A Unified Formulation
3.3 The Concept of an Atlas-Like Representation
3.4 AtlasCBS vs. Other Navigation Tools in Medicinal Chemistry
3.5 Discussion
Chapter 4. The AtlasCBS Application
4.1 Basic Elements
4.2 Functionalities
4.3 Discussion
References for Part I
Part II: Conceptual Applications of the AtlasCBS: A New Paradigm
Part II. Conceptual Applications of the AtlasCBS: A New Paradigm
Personal Introduction
Chapter 5. Analysis of the Content of SAR Databases
5.1 Graphical Representation of Lipinski’s Guidelines (Ro5)
5.2 The Territory of Drugs vs. Nondrugs
5.3 Mapping of Bioactive Peptides
5.4 Discussion
Chapter 6. Fragment-Based Strategies
6.1 Analysis of the Content of Fragment Libraries
6.2 Deconvolution of Fragment Efficiencies
6.3 Discussion
Chapter 7. Navigating in Chemicobiological Space
7.1 Trajectories in Chemicobiological Space
7.2 The Search for Optimal Trajectories
7.3 Discussion
References for Part II
Part 3: Exploring CBS: Practical Examples Using the AtlasCBS Server
Part III. Exploring CBS: Practical Examples Using the AtlasCBS Server
Chapter 8. Sightseeing Chemicobiological Space
Introduction: Snapshots, Postcards, Vistas, and Navigational Charts of CBS
8.1 Getting Started: Neuraminidase
8.2 Panoramic View of HIV-LAND: HIV-1 Protease and Reverse Transcriptase
8.3 A Snapshot from Virtual Land: Mapping Calculated Efficiencies
8.4 Wetlands of Cancer—Kinase Inhibitors (Gleevec, Iressa)
8.5 Vistas from Neurotransmission: Acetylcholinesterase
8.6 Glimpses of Receptor Land: G Protein-Coupled Receptors
8.7 FB Lead Generation: Lactic Dehydrogenase A
8.8 A Window into the Future—Prospective Uses of AtlasCBS: Transthyretin
References for Part III
Epilogue
The Road Ahead
Appendix A. Algebraic Derivations
A.1 Derivation of the Relationship Between nBEI and NSEI and Related Variables in the Corresponding Efficiency Planes
Appendix B. Conversion Factors Among Various Ligand Efficiency Indices
B.1 BEI and LE
B.2 LE and NBEI
- Edition: 1
- Published: January 22, 2013
- No. of pages (Paperback): 178
- Imprint: Academic Press
- Language: English
- Paperback ISBN: 9780124046351
- eBook ISBN: 9780124046825
CA
Celerino Abad-Zapatero
Affiliations and expertise
PhD, Adjunct Professor to the Graduate Faculty, Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, ILRead Ligand Efficiency Indices for Drug Discovery on ScienceDirect