Molecular Modeling

Hans-Dieter Höltje is director of the Institute of Pharmaceutical Chemistry at the Heinrich-Heine-Universität Düsseldorf (Germany) where he also holds the chair of Medicinal Chemistry. His main interest is the molecular mechanism of drug action.
 
Wolfgang Sippl is Professor of Pharmaceutical Chemistry at the Martin-Luther-University of Halle-Wittenberg (Germany). He is interested in 3D QSAR, molecular docking and molecular dynamics, and their applications in drug design and pharmacokinetics.
 
Didier Rognan leads the Drug Bioinformatics Group at the Laboratory for Molecular Pharmacochemistry in Illkirch (France). He is mainly interested in all aspects (method development, applications) of protein-based drug design and virtual screening.
 
Gerd Folkers is Professor of Pharmaceutical Chemistry at the ETH Zürich (Switzerland). The focus of his research is the molecular interation between drugs and their binding sites.

Umfassend und präzise, besonders für Anfänger gut verständlich: Dieser Band erklärt die Grundlagen der Molekülmodellierung kompetent und nachvollziehbar. Ausführlichen Informationen zur Modellierung von kleinen Molekülen und Proteinen folgen durchgearbeitete Beispiele, die dem Leser den Weg zum ersten eigenen Experiment ebnen. Neu in dieser dritten Auflage ist ein Kapitel zur Chemogenomik, das (gemeinsam mit dem überarbeiteten und erweiterten Beispiel zur Behandlung komplizierterer Biomoleküle) den gegenwärtigen Trend zur "chemischen Biologie" widerspiegelt.
Die Autoren, erfahrene Dozenten in diesem Themenbereich, garantieren die Praxistauglichkeit des Bandes als Begleiter einschlägiger Vorlesungen. Für Fachleute interessant: Als einziges gegenwärtig erhältliches Werk enthält das Buch einen systematischen Vergleich der Möglichkeiten und Grenzen moderner MM-Verfahren und entsprechender Software-Pakete.

Ideal for beginners, this book explains the basics of modeling in a competent yet easily understandable way. Following complete sections on the modeling of small molecules, protein modeling and chemogenomics, completely worked-out examples show the way to the reader s first modeling experiment.

Introduction
 
Small Molecules
- Generation of 3D-Coordinates
- Computational Tools for Geometry Optimization
- Conformational Analysis
- Determination of Molecular Interaction Potentials
- Pharmacophore Identification
- 3D QSAR Methods
 
A Case Study for Small Molecule Modeling: Dopamine D3 Receptor Antagonists
- Building a Pharmacophore Model
- 3D QSAR Analysis
 
Introduction to Comparative Protein Modeling
- Where and How to get Information on Proteins
- Terminology and Principles of Protein Structure
- Comparative Protein Modeling
- Optimization Procedures - Model Refinement - Molecular Dynamics
- Validation of Protein Models
- Properties of Proteins
 
Virtual Screening and Docking
- Preparation of the Partners
- Docking Algorithms
- Scoring Functions
- Postfiltering Virtual Screening Results
- Comparison of Different Docking and Scoring Methods
- Examples of successful Virtual Screening Studies
 
Scope and Limits of Molecular Docking
- Docking in the Polar Active Site that Contains Water
- Including Cofactor in Docking? (NEW)
- Impact of Tautomerism on Docking (NEW)
 
Chemogenomic Approaches to Rational Drug Design (NEW)
- Description of Ligand and Target Spaces
- Ligand-based Chemogenomic Approaches
- Targed-based Chemogenomic Approaches
- Target-Ligand Based Chemogenomic Approaches
 
A Case Study for Protein Modeling: the Nuclear Hormone Receptor CAR as an Example for Comparative Modeling and the Analysis of Protein-Ligand Complexes (NEW)
- The Biochemical and Pharmacological Description of the Problem
- Comparative Modeling of the Human Nuclear Hormone Receptor CAR
- Analysis of the Models that Emerged from MD Simulations
- Analysis of CAR Mutants
- Modeling of CAR-Ligand Complexes
- The CAR X-Ray Structure Comes into Play
- Virtual Screening for Novel CAR Activators