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.