Protein-protein complexes : analysis, modeling and drug design / edited by Martin Zacharias.

Format:

Book

Contributor:

Zacharias, Martin.

Language:

English

Subjects (All):

Protein-protein interactions.

Protein-protein interactions--Computer simulation.

Protein-protein interactions--Mathematical models.

Proteins--Structure.

Proteins.

Drugs--Design.

Drugs.

Physical Description:

1 online resource (400 p.)

Edition:

1st ed.

Place of Publication:

London : Imperial College Press, 2010.

Summary:

Given the immense progress achieved in elucidating protein-protein complex structures and in the field of protein interaction modeling, there is great demand for a book that gives interested researchers/students a comprehensive overview of the field. This book does just that. It focuses on what can be learned about protein-protein interactions from the analysis of protein-protein complex structures and interfaces. What are the driving forces for protein-protein association? How can we extract the mechanism of specific recognition from studying protein-protein interfaces? How can this knowledge be used to predict and design protein-protein interactions (interaction regions and complex structures)? What methods are currently employed to design protein-protein interactions, and how can we influence protein-protein interactions by mutagenesis and small-molecule drugs or peptide mimetics?The book consists of about 15 review chapters, written by experts, on the characterization of protein-protein interfaces, structure determination of protein complexes (by NMR and X-ray), theory of protein-protein binding, dynamics of protein interfaces, bioinformatics methods to predict interaction regions, and prediction of protein-protein complex structures (docking and homology modeling of complexes, etc.) and design of protein-protein interactions. It serves as a bridge between studying/analyzing protein-protein complex structures (interfaces), predicting interactions, and influencing/designing interactions.

Contents:

Intro

CONTENTS

Preface

1. X-ray Study of Protein-Protein Complexes and Analysis of Interfaces Joel Janin

1.1 Introduction

1.2 Preparing Proteins for Structural Studies

1.3 Preparing Protein-Protein Complexes and Multi-component Assemblies

1.4 Crystallization and X-ray Studies

1.5 The Geometric Analysis of Protein-Protein Interfaces

1.6 Types and Sizes of Protein-Protein Interfaces

1.7 Chemical and Physical Chemical Properties of the Interfaces

1.8 Atomic Packing and Interface Topology

1.9 Conclusions and Outlook

Acknowledgements

References

2. A Structural Perspective on Protein-Protein Interactions in Macromolecular Assemblies Ranjit P. Bahadur

2.1 Introduction

2.2 The Icosahedral Viruses

2.3 The Structure of the Icosahedral Virus Capsids

2.4 Structural and Chemical Features of the Protein-Protein Interfaces

2.4.1 Symmetry and Size of Interfaces

2.4.2 Chemical Composition and Hydrogen Bonds

2.4.3 Atomic Packing of the Interfaces

2.4.4 Interface Patches and Segments

2.4.5 Residue Conservation

2.5 Comparison with Binary Interfaces

2.6 Mechanism of the Capsid Assembly

2.7 Conclusions and Outlook

3. Energetics of Protein-Protein Interactions Ilian Jelesarov

3.1 Introduction

3.2 Thermodynamic Formalism Describing the Energetics of Binding Reactions

3.2.1 Determination of the Binding Affinity

3.2.1.1 Heterologous Binding

3.2.1.2 Homologous Binding (Self-association)

3.2.2 Free Energy, Enthalpy and Entropy of Association

3.2.3 Determination of Energetic Changes

3.3 Experimental Methods to Measure the Energetics of Protein- Protein Association

3.3.1 Methods utilising Physical Separation of Species

3.3.2 Indirect Spectroscopic Methods

3.3.3 Methods Based on Refractive Phenomena

3.3.4 Kinetic Approaches.

3.3.5 Isothermal Titration Calorimetry (ITC)

3.4 Energetics of Protein-Protein Interactions

3.4.1 Calculation of Binding Affinities

3.4.2 Structure-based Prediction of Binding Parameters

3.4.3 Understanding Binding: Are there Structure-Energy Relationships?

3.5 Conclusions and Outlook

4. Kinetics of Biomacromolecular Complex Formation: Theory and Experiment Georgi V. Pachov, Razif R. Gabdoulline and Rebecca C. Wade

4.1 Introduction

4.1.1 Bimolecular Association

4.1.1.1 Diffusional Encounter Complex

4.1.1.2 Bound Complex

4.1.2 Molecular Transport

4.1.2.1 Diffusion

4.1.2.2 Viscosity

4.1.3 Molecular Interactions

4.1.3.1 Electrostatics

4.1.3.2 Hydrodynamics

4.1.3.3 Hydrophobicity

4.1.4 Reaction Rates

4.2 Experimental Techniques

4.2.1 Crystallography

4.2.2 Nuclear Magnetic Resonance (NMR)

4.2.3 Stopped-flow Methods (SF)

4.2.4 Fluorescence Recovery After Photobleaching (FRAP)

4.2.5 Fluorescence Resonance Energy Transfer (FRET)

4.2.6 Fluorescence Correlation Spectroscopy (FCS)

4.2.7 Force Probe Methods

4.2.8 Electrophoresis

4.2.9 Surface Plasmon Resonance (SPR) Biosensor

4.3 Theoretical and Computational Approaches

4.3.1 Computation of Bimolecular Rate Constants

4.3.2 Estimation of Rate Enhancements due to Electrostatic Interactions

4.4 Recent Advances in Computational Approaches

4.4.1 Protein-Protein Interactions

4.4.1.1 Computation of Rates

4.4.1.2 Determinants of Binding

4.4.1.3 Encounter Complex Quantification

4.4.1.4 Induced Fit Phenomena

4.4.1.5 Crowding Phenomena

4.4.2 Protein-nucleic Acid Interactions

4.4.2.1 Computation of Rates

4.4.2.2 Specificity and Nonspecificity

4.4.2.3 Chromatin Models

4.5 Conclusions and Outlook

References.

5. Evolutionary Trace of Protein Functional Determinants Olivier Lichtarge

5.1 Introduction

5.2 Evolutionary Trace Basics: Which Amino Acids are Important in a Protein?

5.3 Validation Through Prospective Case Studies

5.3.1 Separation of Function

5.3.2 Rewiring Functions

5.3.3 Redirecting Protein Binding Specificity to DNA

5.3.4 Other Case Studies

5.4 Proteomics Properties of Evolutionary Important Residues

5.5 Molecular Determinants of GPCR Signal Transduction

5.6 Protein Function Prediction

6. Protein-Protein Docking Adrien Saladin and Chantal Prevost

6.1 Introduction

6.2 Definition and Goals of Macromolecular Docking

6.2.1 Protein-Protein Docking Terminology

6.2.2 Goals and Strategies

6.3 Protein-Protein Docking Methods

6.3.1 Systematic Search Methods

6.3.1.1 Discrete Sampling: The Correlation Methods

6.3.1.2 Geometric Surface Matching

6.3.2 Guided Search Methods

6.3.2.1 Example of a Guided Search Programme: ICM-DISCO

6.3.2.2 Speeding up the Calculation

6.3.2.3 Data-driven Methods

6.3.3 Refinement

6.3.3.1 Increasing the Resolution

6.3.3.2 Accounting for Side Chain Conformational Change

6.3.3.3 Explicit Solvation

6.3.3.4 Hierarchical Approaches

6.3.4 Scoring the Predictions

6.4 Evaluation of the Docking Methods

6.4.1 The CAPRI Experience

6.4.2 Docking Benchmarks

6.4.3 Challenges

6.5 Conclusions and Outlook

7. Data-driven Docking: Using External Information to Spark the Biomolecular Rendez-vous Adrien S.J. Melquiond and Alexandre M.J.J. Bonvin

7.1 Introduction

7.2 Stoichiometry and Composition

7.3 Shape of a Biomolecular Complex

7.4 Nature of the Interface: Which Residues are Engaged in a Date?

7.5 Orientation and Symmetry Problems.

7.6 Flexibility: How to Cope with Conformational Changes Occurring upon Complex Formation?

7.7 How to Implement Data-driven Docking, the HADDOCK Example

7.8 Conclusions and Outlook

8. High-resolution Protein-Protein Docking Nir London and Ora Schueler-Furman

8.1 Introduction

8.1.1 From Molecules to Networks: Making Sense of Large-scale Data, Starting from the Atomic Details of Protein-Protein Interactions

8.1.2 Docking - The Creation of Protein Complex Structures Starting from the Monomers

8.1.3 Explicit Modelling of the Atomic Details of the Protein-Protein Interface Allows Distinguishing the Correct from Alternative Conformations

8.1.4 The Scope of this Chapter

8.2 High-resolution Docking, as Defined by CAPRI

8.3 Accounting for Conformational Changes of Monomers is Crucial to High-resolution Modelling

8.3.1 Modelling Side Chain Flexibility

8.3.2 Taking it to the Next Step: Modelling Backbone Flexibility

8.3.2.1 Ensemble Docking

8.3.2.2 Refinement and Minimization

8.3.2.3 Modelling Hinge Motion

8.4 The High-resolution RosettaDock Protocol - Explicit Modelling of Full Side Chain Flexibility (and Beyond) Allows Accurate Modelling of Protein Complexes

8.4.1 Adding Backbone Conformational Flexibility to the RosettaDock Protocol

8.4.2 Ensemble Docking with RosettaDock

8.5 Additional High-resolution Docking Approaches

8.5.1 High-accuracy Modelling with Rigid Body Docking

8.5.2 A New Generation of Docking Protocols: Combining Successful Approaches of Low-resolution and High-resolution Searches

8.6 The Contribution of High-resolution Docking to the Understanding of Interactions of Biological Interest

8.6.1 Entry Mechanism of Anthrax Toxin

8.6.2 Antitumor Monoclonal Antibody 806 (mAb806) and the Epidermal Growth Factor Receptor (EGFR).

8.6.3 High-resolution Docking in the Service of Biochemistry

8.6.4 Applications of High-resolution Docking: Structure-based Prediction of Binding Specificity

8.7 Conclusions and Outlook

8.7.1 Impact of Docking on the Modelling Field

9. Scoring and Refinement of Predicted Protein-Protein Complexes Martin Zacharias

9.1 Introduction

9.2 Generation of Protein-Protein Complexes by Docking Methods

9.3 Protein-Protein Complexes Based on Homology to Known Complexes

9.4 Structural Refinement of Modelled Protein-Protein Complexes

9.4.1 Force Field Description of Proteins and Protein Complexes

9.4.2 Optimization Based on Energy Minimization

9.4.3 Accounting for Global Conformational Changes

9.4.4 Molecular Dynamics Simulation of Protein-Protein Complexes

9.4.5 Refinement of Docked Complexes by Molecular Dynamics Simulation

9.4.6 Monte Carlo and Brownian Dynamics Refinement of Docked Complexes

9.5 Scoring of Modelled Protein-Protein Complexes

9.5.1 Driving Forces for Molecular Association and the Scoring Problem

9.5.2 Scoring Based on Physical Force Fields

9.5.2.1 Scoring Based on Ensembles of Structures

9.5.3 Knowledge-based Scoring of Docked Complexes

9.5.3.1 Principles of Statistical Potentials to Score Predicted Complexes

9.5.3.2 Application of Statistical Potentials to Score Predicted Complexes

9.6 Conclusions and Outlook

10. Motif-mediated Protein Interactions and their Role in Disease Holger Dinkel and Heinrich Sticht

10.1 Introduction

10.2 Protein Interaction Domains

10.2.1 SH3 Domains

10.2.2 SH2 Domains

10.2.3 Signalling Adaptors: Proteins Containing Multiple Interaction Domains

10.3 Properties and Regulation of Motif-mediated Interactions

10.3.1 Inducible Interactions

10.3.2 Cooperative Effects.

10.3.3 Mutually Exclusive Interactions.

Notes:

Description based upon print version of record.

Includes bibliographical references and index.

ISBN:

9786612759840

9781282759848

1282759841

9781848163409

1848163401

OCLC:

670429689