Martin Quantitative Drug Design

A Critical Introduction, Second Edition
2. Auflage 2010
ISBN: 978-1-4200-7100-9
Verlag: Taylor & Francis
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 292 Seiten

Since the publication of the first edition, the field has changed dramatically. Scientists can now explicitly consider 3D features in quantitative structure-activity relationship (QSAR) studies and often have the 3D structure of the macromolecular target to guide the 3D QSAR. Improvements in computer hardware and software have also made the methods more accessible to scientists. Taking these developments into account, Quantitative Drug Design: A Critical Introduction, Second Edition shows scientists how to apply QSAR techniques at a state-of-the-art level.
New to the Second Edition

- A new chapter on methods that identify the 3D conformations to use for 3D QSAR

- New discussions on partial least squares, multidimensional scaling, clustering, support vector machines, kNN potency prediction, and recursive partitioning

- Expanded case studies that include the results of data that has been re-analyzed using newer methods

- A new case study on the discovery of novel dopaminergics with pharmacophore mapping and CoMFA

- A new case study on the application of CoMFA to series in which the 3D structure of the ligand-protein complex is known

Based on the author’s four decades of experience in all areas of ligand-based computer-assisted drug design, this invaluable book describes how to transform ligand structure-activity relationships into models that predict the potency or activity/inactivity of new molecules. It will help you avoid traps when dealing with quantitative drug design.

Zielgruppe

Medicinal chemists; pharmaceutical chemists; computational chemists in the pharmaceutical or pesticide industries; graduate students in pharmacy, medicinal chemistry, and biochemistry; and scientists in federal agencies.

Autoren/Hrsg.

Martin, Yvonne C.

Fachgebiete

• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizinische Fachgebiete Pharmakologie, Toxikologie

Inhaltsverzeichnis

Overview of Quantitative Drug Design
Stages of Drug Discovery
Computer Descriptions of Changes in Structure Related to Changes in Properties of Molecules
Noncovalent Interactions in Biological Systems
Factors That Influence the Strength of an Interaction
The Importance of Water
Electrostatic Interactions
Hydrogen Bonds
Dispersion Interactions
Charge-Transfer Interactions
Hydrophobic Interactions
Steric Repulsion
Preparation of 3D Structures of Molecules for 3D QSAR
Preliminary Inspection of Molecules
Generating 3D Structures of Molecules
Strategies to Select the Conformation for 3D QSAR
Calculating Physical Properties of Molecules
The Electronic Properties of Molecules
The Hydrogen-Bonding Properties of Molecules
The Size of Substituents and Shape of Molecules
The Hydrophobic Properties of Molecules
Indicator or Substructure Variables
Composite Descriptors Calculated from 2D Structures
Properties Calculated from the 3D Structure of the Ligand-Macromolecule Complex
Organizing Molecular Properties for 3D QSAR
Biological Data
Consequences of Ligand-Biomolecule Interaction
Selection of Data for Analysis: Characteristics of an Ideal Biological Test
Calculation of Relative Potency
Choice of Classification Boundaries
Form of Equations Relating Potency and Physical Properties
Introduction to Model-Based Equations
Equation for an Equilibrium Model for Ionizable Compounds for Which Affinity Is a Function of Log P and Only the Neutral Form Binds
Equations for Equilibrium Models for Ionizable Compounds That Differ in Tautomeric or Conformational Distribution and Affinity Is a Function of Log P
Equations for Equilibrium Models for Which Affinity Depends on Steric or Electrostatic Properties in Addition to Log P
Equations for Models That Include Equilibria and the Rates of Biological Processes
Equations for Whole-Animal Tests for Wh

Über Autor(innen)

For more than forty years, Yvonne Connelly Martin worked in drug research at Abbott Laboratories. A long-time leader in computer-assisted drug design, she was a recipient of the Herman Skolnik award of the American Chemical Society in 2009 and the accomplishment award of the Society for Biomolecular Sciences in 2005. Dr. Martin is currently a member of the editorial advisory board and Perspectives editor of the Journal of Computer-Aided Molecular Design.