Protein-Ligand Interactions

Holger Gohlke

John Wiley & Sons, May 21, 2012 - Medical - 359 pages

Innovative and forward-looking, this volume focuses on recent achievements in this rapidly progressing field and looks at future potential for
development.
The first part provides a basic understanding of the factors governing protein-ligand interactions, followed by a comparison of key experimental methods (calorimetry, surface plasmon resonance, NMR) used in generating interaction data. The second half of the book is devoted to insilico methods of modeling and predicting molecular recognition and binding, ranging from first principles-based to approximate ones. Here,
as elsewhere in the book, emphasis is placed on novel approaches and recent improvements to established methods. The final part looks at
unresolved challenges, and the strategies to address them.
With the content relevant for all drug classes and therapeutic fields, this is an inspiring and often-consulted guide to the complexity of
protein-ligand interaction modeling and analysis for both novices and experts.

Contents

• Some Practical Rules for the Thermodynamic Optimization: 23
• EnthalpyEntropy Compensation as Deduced from Measurements: 33
• Learning from Biophysical Experiments: 45
• NMR Methods for the Determination of ProteinLigand Interactions: 71
• Modeling ProteinLigand Interactions: 99
• Quantum Mechanics in StructureBased Ligand Design: 121
• Hydrophobic Association and VolumeConfined: 145
• Implicit Solvent Models and Electrostatics in Molecular Recognition: 171
• Ligand and Receptor Conformational Energies: 191
• Free Energy Calculations in Drug Lead Optimization: 207
• References: 227
• Scoring Functions for ProteinLigand Interactions: 237
• Challenges in Molecular Recognition: 265
• Embracing Protein Plasticity in Ligand Docking: 283
• Prospects of Modulating ProteinProtein Interactions: 295
• Index: 331

About the author

Holger Gohlke is Professor of Pharmaceutical and Medicinal Chemistry at the Heinrich-Heine-University, Dusseldorf, Germany. He obtained his diploma in chemistry from the Technical University of Darmstadt and his PhD from Philipps-University, Marburg, working with Gerhard Klebe, where he developed the DrugScore and AFMoC approaches. He then did postdoctoral research at The Scripps Research Institute, La Jolla, USA, working with David Case on developing and evaluating computational biophysical methods to predict protein-protein interactions. After appointments as Assistant Professor at Goethe University Frankfurt and Professor at Christian-Albrechts-University, Kiel, he moved to Dusseldorf in 2009.
He was awarded the 'Innovationspreis in Medizinischer und Pharmazeutischer Chemie' from the Gesellschaft Deutscher Chemiker and the Deutsche Pharmazeutische Gesellschaft, and the Hansch Award of the Cheminformatics and QSAR Society.
His current research focuses on the understanding, prediction, and modulation of interactions involving biological macromolecules from a theoretical perspective. His group applies and develops techniques grounded in bioinformatics, computational biology, and computational biophysics.

Bibliographic information

• Title: Protein-Ligand Interactions; Volume 53 of Methods and Principles in Medicinal Chemistry
• Editor: Holger Gohlke
• Contributors: Raimund Mannhold, Hugo Kubinyi, Gerd Folkers
• Edition: illustrated
• Publisher: John Wiley & Sons, 2012
• ISBN: 3527329668, 9783527329663
• Length: 359 pages
• Subjects: Medical / Pharmacology; Science / Chemistry / General