Ligand-Binding Basics : Evaluating Intermolecular Affinity, Specificity, Stoichiometry, and Cooperativity

• Autore: Carey Jannette
• Pubblicazione: Newark : , : John Wiley & Sons, Incorporated, , 2025; ©2026
• Edizione: 1st ed.
• Descrizione fisica: 1 online resource (307 pages)
• Disciplina: 572.33
• Soggetto topico: Ligand binding (Biochemistry)
• Nota di contenuto: Cover -- Title Page -- Copyright -- Contents -- About the Cover -- Introduction -- Chapter 1 The Biology of Molecules -- Why Study Intermolecular Interactions Quantitatively? -- Equilibrium and Kinetics -- Thermodynamic Definitions of Affinity and Specificity -- The Affinity/Specificity Map -- Biology Requires Optimization of Affinity and Specificity -- The Special Case of Protein‐DNA Interactions -- Chapter 2 General Theory for Reversible Ligand Binding -- Definition of Ligand and Titration -- Affinity, Specificity, Stoichiometry, and Cooperativity -- Ligand‐binding Theory: Relationship to Experiment -- General Theory for Reversible Ligand Binding: Rooted in Chemical Equilibrium -- General Theory for Reversible Ligand Binding: Quantitative Treatment -- The Case of 1:1 Binding -- General Theory for Reversible Ligand Binding: Conservation of Mass -- Definition of ν‾ -- The Basic Equation for 1:1 Binding -- The Single Most Important Thing You Can Learn in This Book -- The Example of Heme Binding to Apocytochrome C -- The Rectangular Hyperbola -- The Binding Isotherm -- Plot of ν‾ vs. [Hf] -- General Theory for Reversible Ligand Binding: Role of Mass Action -- Plot of [AH] vs. [Ht] with Fixed K -- Determination of Kd from Experiment -- Plot of [AH] vs. [Ht] with Fixed [At] -- Determining Molar Ratio from Experiment -- About Activity -- Chapter 3 Graphical Analysis -- Limitations of Direct Plots -- The Semi‐log Plot -- Breadth of the Semi‐log Plot -- Myoglobin and Hemoglobin -- Advantages of the Direct and Semi‐log Plots of Binding Data -- Linear Transforms of the Basic Binding Equation -- Common Linearizations -- Requirements of the Linear Regression Model -- A Linear Model May Misrepresent the Physical Process -- Deviations from Linearity Are Hard to Detect or Interpret -- Linear Transforms Distort Data Completeness. ; Linear Transforms Invite - Even Require - Extrapolation -- Linear Transforms Falsely Promise Both K and Molar Ratio from a Single Dataset -- Summary about Linear Treatments of Binding Data -- Simulation Is Just as Good as Fitting, Given Realistic Experimental Errors -- Chapter 4 Binding of Multiple Ligands -- Conservation of Mass Outside the 1:1 Case -- Redefine ν< -- 3:mo 0:stretchy& -- equals -- "true" > -- ‾ to Accommodate Any Molar Ratio -- Accounting for the Definition of Molecule -- Generalizing to Integer Multiples of 1:1 -- The Langmuir Equation for Any Molar Ratio with Sites of Identical Affinity and No Cooperativity -- Adair Equation for Any Number of Binding Events -- The Langmuir Equation vs. the Adair Equation -- Thermodynamic Linkage -- Two Classes of Sites with Different Affinities -- Binding Isotherms for Multiple Sites with Different Affinities -- Summary -- Chapter 5 How to Determine Kd and Molar Ratio Experimentally -- Stoichiometric Titration First -- Amounts of Materials -- Assigning Partners -- Choice of Experimental Observables -- Choosing Solution Conditions -- How Many Data Points? -- Range‐Finding Stoichiometric Titration -- Visualizing Results -- Range‐Finding Asymptotic Titration to Estimate Kd -- Data Analysis -- Practicalities about Experimental Error -- Statistical Approaches to Estimate the Breakpoint -- Refined Asymptotic Titration -- Designing an Experiment to Refine Kd -- Calculating Free Ligand Concentration -- Refining the Value of Molar Ratio -- Example of ArgR/DNA Binding -- Plotting the Data -- Deriving Kd from the Data -- Summary -- Chapter 6 Cooperativity -- Facilitated and Antagonized Binding -- Free Energy Definition of Cooperative Binding -- Chemical Potential Diagram for Cooperative Binding -- Cooperativity as Non‐additivity -- Reciprocity of Cooperative Effects. ; Limitations of Linear Transforms for Cooperative Interactions -- Microscopic View of Species Distribution -- Homotropic and Heterotropic Cooperativity -- Cooperativity Affects Specificity as Well as Affinity -- Cooperativity Is the Third Axis of the Affinity/Specificity Map -- Quantifying Homotropic Cooperativity -- Negative Homotropic Cooperativity -- A Practical Advantage of Negative Cooperativity -- Positive Cooperativity and the Ligand Concentration Interval -- Importance of Individual‐site Isotherms and Species Distribution -- Species Distributions by Specialized Experimental Methods -- The Many Forms of Cooperativity -- Emergent Properties -- Connectivity and Search Entropy -- Breakdown of Additivity in Complex Systems -- Statistical Effects -- Relevance of Non-additivity for Analysis of Mutations -- Universality and Promiscuity of Cooperativity -- Proteins as Gestalt Objects -- Summary -- Chapter 7 Theoretical and Method‐specific Troubleshooting -- Equilibrium and Nonequilibrium Methods -- Accessible Concentration Ranges Limit Accessible Kd Values -- Signal from Ligand or Target? -- Separation‐based Methods -- Filter Binding -- Gel Retardation or EMSA -- Gel Filtration -- Hummel and Dreyer Chromatography -- Equilibrium Dialysis -- UV Absorbance -- CD Spectroscopy -- Fluorescence -- NMR -- ITC -- AUC -- SPR -- MS -- Chapter 8 Allostery -- An Historical Overview -- Facilitated Binding -- Elaboration of the MWC Model -- Relaxed Monomers and Tense Multimers -- Positive Homotropic Cooperativity Only -- Artifactual Origins of Affinity Heterogeneity -- Relaxation of Multimers by Ligand Binding -- Koshland's Sequential (Asymmetric) Model -- G3Pase Was Heterogeneous, Not Negatively Cooperative -- Many Models Fit the Hemoglobin Data -- Advantages of Negative Cooperativity for Molecular Insight -- Biology of Negative Cooperativity. ; Structural Analysis Cannot Solve Allostery -- Allostery without Cooperativity -- Summary -- Chapter 9 Lessons on Affinity and Specificity from Host/Guest Chemistry -- 2D Representations of 3D Objects -- Early Hosts Were Linear and Flexible -- Design of Molecular Properties -- Very Weak Affinity and No Detectable Specificity -- Later Hosts Pre‐organized in Bound Conformation -- Enormous Gains in Affinity and Specificity -- Bonds between Host and Guest Are Identical -- Lessons from the Host/Guest Chemistry -- Rational Design of Affinity and Specificity -- Affinity and Specificity Accrue in Parallel -- Cryptic Contributions Can Dominate Binding -- Chapter 10 Reconciling Structure and Thermodynamics in Molecular Interactions -- Thermodynamics of Molecular Interactions -- Structural Analysis of Bonding Does Not Predict Binding -- The Goldilocks Region of Affinity/Specificity Space -- Conformational Rearrangement upon Binding Decouples Affinity and Specificity -- A Reservoir of Adaptability -- No Simple Reconciliation of Structural and Energetic Views -- Implications for Drug Design -- Chapter 11 Applications in Modern Drug Development -- Background -- Technological Developments -- Crystal Structures -- Trapped High‐energy States -- Another Example -- Computational Methods -- High‐throughput Assays -- Druggability -- Irrational Drug Design -- A New Workflow -- Appendix A Ligand‐binding Study Questions -- Appendix B Thought Experiments -- Appendix C Derivations -- Appendix D Simulation and Fitting -- Simulation -- Fitting -- Appendix E About the Hill Equation -- Deriving the Hill Equation -- The Hill Equation as a Limit of the Adair Equation -- On Applying the Hill Equation to Quantify Cooperativity -- Appendix F Stereo Viewing -- Bibliography -- Index -- EULA.
• Sommario/riassunto: A concise and accessible textbook covering ligand-binding theory in chemistry, biology, and drug development In Ligand-binding Basics: Evaluating Intermolecular Affinity, Specificity, Stoichiometry, and Cooperativity , accomplished chemist Professor Jannette Carey introduces ligand binding in a thorough and practical way for those new.
• Titolo autorizzato: Ligand-Binding Basics
• ISBN: 1-394-34294-2; 1-119-87847-0
• Formato: Materiale a stampa
• Livello bibliografico: Monografia
• Lingua di pubblicazione: Inglese
• Record Nr.: 9911028670903321
• Lo trovi qui: Univ. Federico II