Ligand Efficiency Indices for Drug Discovery

Ligand Efficiency Indices for Drug Discovery

Towards an Atlas-Guided Paradigm

1st Edition - January 15, 2013
This is the Latest Edition
  • Author: Celerino Abad-Zapatero
  • eBook ISBN: 9780124046825
  • Paperback ISBN: 9780124046351

Purchase options

Purchase options
DRM-free (Mobi, EPub, PDF)
Available
Sales tax will be calculated at check-out

Institutional Subscription

Free Global Shipping
No minimum order

Description

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, 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.

Key Features

  • 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

Readership

Researchers, new professionals and graduate students in medicinal chemistry, drug discovery and pharmaceutical sciences

Table of Contents

  • 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

Product details

  • No. of pages: 178
  • Language: English
  • Copyright: © Academic Press 2013
  • Published: January 15, 2013
  • Imprint: Academic Press
  • eBook ISBN: 9780124046825
  • Paperback ISBN: 9780124046351
  • About the Author

    Celerino Abad-Zapatero

    Affiliations and Expertise

    PhD, Adjunct Professor to the Graduate Faculty, Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL