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 D

Details

No. of pages:
178
Language:
English
Copyright:
© 2013
Published:
Imprint:
Academic Press
eBook ISBN:
9780124046825
Print 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

Reviews

"For those interested in a fresh interpretation of the utility of ligand efficiency indexes for drug discovery, this book serves as a nice introduction to a more modern, graphical approach to drug lead identification."--Doody.com, August 16, 2013
"Abad-Zapatero presents a novel approach to drug discovery that is based on the notion that a change of variables is necessary. The algebraic framework he proposes combines the affinity between ligands and targets with the physico-chemical properties of the ligands to construct a set of novel variables that can map chemico-biological space (CBS) and optimize the drug-discovery process."--Reference and Research Book News, August 2013