Hydrogen exchange mass spectrometry of proteins : fundamentals, methods, and applications / edited by David D. Weis.

Format:

Book

Contributor:

Weis, David D., editor.

Language:

English

Subjects (All):

Proteins--Analysis.

Proteins.

Mass spectrometry.

Physical Description:

1 online resource (544 p.)

Edition:

1st ed.

Place of Publication:

Chichester, [England] : Wiley, 2016.

Language Note:

English

Summary:

Hydrogen exchange mass spectrometry is widely recognized for its ability to probe the structure and dynamics of proteins. The application of this technique is becoming widespread due to its versatility for providing structural information about challenging biological macromolecules such as antibodies, flexible proteins and glycoproteins. Although the technique has been around for 25 years, this is the first definitive book devoted entirely to the topic. Hydrogen Exchange Mass Spectrometry of Proteins: Fundamentals, Methods and Applications brings into one comprehensive volume the theory, instrumentation and applications of Hydrogen Exchange Mass Spectrometry (HX-MS) - a technique relevant to bioanalytical chemistry, protein science and pharmaceuticals. The book provides a solid foundation in the basics of the technique and data interpretation to inform readers of current research in the method, and provides illustrative examples of its use in bio- and pharmaceutical chemistry and biophysics In-depth chapters on the fundamental theory of hydrogen exchange, and tutorial chapters on measurement and data analysis provide the essential background for those ready to adopt HX-MS. Expert users may advance their current understanding through chapters on methods including membrane protein analysis, alternative proteases, millisecond hydrogen exchange, top-down mass spectrometry, histidine exchange and method validation. All readers can explore the diversity of HX-MS applications in areas such as ligand binding, membrane proteins, drug discovery, therapeutic protein formulation, biocomparability, and intrinsically disordered proteins.

Contents:

Title Page; Table of Contents; List of Contributors; Foreword; Preface; References; A Note about Nomenclature; References; 1 Hydrogen Exchange; 1.1 Isotopic Exchange and the Study of Protein Conformation and Dynamics; 1.2 Amide HX in Unstructured Polypeptides; 1.3 Amide HX in Folded Polypeptides; References; 2 Hydrogen Exchange Mass Spectrometry Experimental Design; 2.1 Application of HX-MS for Protein Dynamics; 2.2 Factors Governing HX; 2.3 HX-MS Workflow; 2.4 Centroids and Data Analysis; References; 3 Data Processing in Bottom-Up Hydrogen Exchange Mass Spectrometry; 3.1 Introduction

3.2 The Deuterated Isotopic Distribution3.3 Essential Elements of an HX-MS Data Processing Workflow; 3.4 Select Software Packages for Automation of Analysis; 3.5 Ongoing and Future Challenges; References; 4 Method Validation and Standards in Hydrogen Exchange Mass Spectrometry; 4.1 Introduction; 4.2 Rationale for a Reference Measurement System for HX-MS; 4.3 General Metrological Terminology; 4.4 Method Validation; 4.5 Standards: RM; 4.6 Summary: Maintaining Standards and Monitoring Performance; References; 5 Millisecond Hydrogen Exchange; 5.1 Introduction; 5.2 Instrumentation

5.3 Data Analysis5.4 Applications; 5.5 Conclusions and Outlook; References; 6 Proteases for Hydrogen Exchange Mass Spectrometry; 6.1 Introduction; 6.2 The Use of Pepsin in HX-MS; 6.3 The Use of Other Commercially Available Proteases; 6.4 The Use of Other Acidic Proteases After Expression or Extraction; References; 7 Extracting Information from Hydrogen Exchange Mass Spectrometry Data; 7.1 Introduction; 7.2 Basic Concepts in HX Data Analysis; 7.3 Algorithms for Extracting Rate Constants and Protection Factors; 7.4 Protein Dynamics Hidden in the Isotope Distributions

7.5 Concluding Remarks and Future ProspectsReferences; 8 Gas-Phase Fragmentation of Peptides to Increase the Spatial Resolution of the Hydrogen Exchange Mass Spectrometry Experiment; 8.1 Why Increase the Spatial Resolution in an HX Experiment Using MS/MS?; 8.2 H/D Scrambling in Peptides and How to Avoid It During MS/MS; 8.3 Integrating Gas-Phase Fragmentation Into the Classical Bottom-Up HX-MS Workflow; 8.4 Recent Applications of the Bottom-Up HX-MS/MS Workflow to Pinpoint the HX Properties of Proteins; 8.5 Future Directions; References; 9 Top-Down Hydrogen Exchange Mass Spectrometry

9.1 The Appeal of the Top-Down Scheme9.2 Top-Down HX-MS of Small Proteins: The Problem of Hydrogen Scrambling; 9.3 Conformer-Specific Characterization of Nonnative Protein States Using Top-Down HX ECD MS; 9.4 Convergence of Top-Down and Classical Schemes of HX-MS: Combination of Proteolytic and Gas-Phase Fragmentation without Chromatographic Separation; 9.5 The Road Ahead: Challenges and Future Directions; Acknowledgments; References; 10 Histidine Hydrogen Exchange for Analysis of Protein Folding, Structure, and Function; 10.1 Introduction; 10.2 Mechanism of Histidine Hydrogen Exchange

10.3 Historical Context

Notes:

Description based upon print version of record.

Includes bibliographical references at the end of each chapters.

Description based on print version record.

ISBN:

9781118703731

1118703731

9781118703748

111870374X

9781118703694

1118703693

OCLC:

908839035