Applied biophysics for drug discovery

Content: Title Page 
 Copyright Page
 Contents
 List of Contributors
 Chapter 1 Introduction
 References
 Chapter 2 Thermodynamics in Drug Discovery 
 2.1 Introduction
 2.2 Methods for Measuring Thermodynamics of Biomolecular Interactions
 2.2.1 Direct Method: Isothermal Titration Calorimetry
 2.2.2 Indirect Methods: van\'t Hoff Analysis
 2.2.2.1 Enthalpy Measurement Using van\'t Hoff Analysis
 2.3 Thermodynamic-Driven Lead Optimization 
 2.3.1 The Thermodynamic Rules of Thumb
 2.3.2 Enthalpy-Entropy Compensation
 2.3.3 Enthalpy-Entropy Transduction
 2.3.4 The Role of Water 2.4 Enthalpy as a Probe for Binding2.4.1 Thermodynamics in Fragment-Based Drug Design (FBDD) 
 2.4.2 Experimental Considerations and Limitations When Working with Fragments
 2.4.3 Enthalpic Screening
 2.5 Enthalpy as a Tool for Studying Complex Interactions
 2.5.1 Identifying and Handling Complexity
 2.6 Current and Future Prospects for Thermodynamics in Decision-Making Processes 
 References
 Chapter 3 Tailoring Hit Identification and Qualification Methods for Targeting Protein-Protein Interactions 
 3.1 Introduction
 3.2 Structural Characteristics of PPI Interfaces 3.3 Screening Library Properties3.3.1 Standard/Targeted Libraries/DOS
 3.3.2 Fragment Libraries
 3.3.3 Macrocyclic and Constrained Peptides
 3.3.4 DNA-Encoded Libraries 
 3.4 Hit-Finding Strategies 
 3.4.1 Small-Molecule Approaches 
 3.4.2 Peptide-Based Approaches 
 3.4.3 In Silico Approaches
 3.5 Druggability Assessment
 3.5.1 Small Molecule: Ligand-Based Approaches 
 3.5.2 Small Molecule: Protein Structure-Based Approaches 
 3.6 Allosteric Inhibition of PPIs
 3.7 Stabilization of PPIs
 3.8 Case Studies
 3.8.1 Primary Peptide Epitopes
 3.8.1.1 Bromodomains
 3.8.2 Secondary Structure Epitopes 3.8.2.1 Bcl-2 3.8.2.2 p53/MDM2
 3.8.3 Tertiary Structure Epitopes
 3.8.3.1 CD80-CD28
 3.8.3.2 IL-17A 
 3.9 Summary
 References
 Chapter 4 Hydrogen-Deuterium Exchange Mass Spectrometry in Drug Discovery --
Theory, Practice and Future 
 4.1 General Principles
 4.2 Parameters Affecting Deuterium Incorporation
 4.2.1 Primary Sequence
 4.2.2 Intramolecular Hydrogen Bonding
 4.2.3 Solvent Accessibility
 4.2.4 pH Value
 4.3 Utilization of HDX MS
 4.3.1 Binding Site and Structural Changes Characterization upon Ligand Binding
 4.3.1.1 Protein Stability --
Biosimilar Characterization 4.4 Practical Aspects of HDX MS4.4.1 Labeling
 4.4.1.1 Deuterium Oxide and Protein Concentration
 4.4.1.2 Ligand/Protein Ratio
 4.4.1.3 Incubation-Labeling Time
 4.4.1.4 Careful Preparation of the Control Sample
 4.4.2 Sample Analysis
 4.4.3 Data Analysis
 4.5 Advantages of HDX MS
 4.6 Perspectives and Future Application of HDX MS
 References
 Chapter 5 Microscale Thermophoresis in Drug Discovery 
 5.1 Microscale Thermophoresis
 5.1.1 Theoretical Background
 5.1.2 Added Values for Small-Molecule Interaction Studies
 5.1.2.1 Size-Change Independent Binding Signals