{"product_id":"ligand-binding-basics-isbn-9781119878421","title":"Ligand-Binding Basics","description":"\u003cp\u003e\u003cb\u003eA concise and accessible textbook covering ligand-binding theory in chemistry, biology, and drug development\u003c\/b\u003e \u003c\/p\u003e\u003cp\u003eIn \u003ci\u003eLigand-binding Basics: Evaluating Intermolecular Affinity, Specificity, Stoichiometry, and Cooperativity\u003c\/i\u003e, accomplished chemist Professor Jannette Carey introduces ligand binding in a thorough and practical way for those new to the topic, as well as anyone seeking a connection between theory and experiment. Using a minimum of mathematical formalism, this book offers analytical rigor while remaining accessible to non-specialist practitioners. It provides readers with the skills they need to analyze their own binding data or published results, helping them develop an intuitive grasp of ligand-binding phenomena integrated with structural and thermodynamic understanding. \u003c\/p\u003e\u003cp\u003eTopics covered include: \u003c\/p\u003e\u003cul\u003e\n\u003cli\u003eApplication of the principles of equilibrium, mass action, and mass balance to derive the basic equations that describe all binding processes\u003c\/li\u003e\n\u003cli\u003eRecommended approaches for plotting and graphical analysis of binding data\u003c\/li\u003e\n\u003cli\u003eStrategies for designing, analyzing, interpreting, and troubleshooting experiments from the perspective of ligand-binding theory\u003c\/li\u003e\n\u003cli\u003eReview of selected examples that illustrate integration of structural and thermodynamic analysis\u003c\/li\u003e\n\u003c\/ul\u003e \u003cp\u003ePerfect for students and educators in chemistry, biochemistry, molecular biology, and pharmaceutical science, \u003ci\u003eLigand-binding Basics\u003c\/i\u003e will also appeal to practitioners who aim to study ligand binding in any molecular system. \u003c\/p\u003e\u003cp\u003eAbout the Cover xi\u003c\/p\u003e \u003cp\u003eIntroduction xiii\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 The Biology of Molecules 1\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eWhy Study Intermolecular Interactions Quantitatively? 1\u003c\/p\u003e \u003cp\u003eEquilibrium and Kinetics 2\u003c\/p\u003e \u003cp\u003eThermodynamic Definitions of Affinity and Specificity 3\u003c\/p\u003e \u003cp\u003eThe Affinity\/Specificity Map 6\u003c\/p\u003e \u003cp\u003eBiology Requires Optimization of Affinity and Specificity 8\u003c\/p\u003e \u003cp\u003eThe Special Case of Protein-DNA Interactions 8\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 General Theory for Reversible Ligand Binding 10\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eDefinition of Ligand and Titration 10\u003c\/p\u003e \u003cp\u003eAffinity, Specificity, Stoichiometry, and Cooperativity 10\u003c\/p\u003e \u003cp\u003eLigand-binding Theory: Relationship to Experiment 13\u003c\/p\u003e \u003cp\u003eGeneral Theory for Reversible Ligand Binding: Rooted in Chemical Equilibrium 14\u003c\/p\u003e \u003cp\u003eGeneral Theory for Reversible Ligand Binding: Quantitative Treatment 14\u003c\/p\u003e \u003cp\u003eThe Case of 1:1 Binding 15\u003c\/p\u003e \u003cp\u003eGeneral Theory for Reversible Ligand Binding: Conservation of Mass 17\u003c\/p\u003e \u003cp\u003eDefinition of ν 18\u003c\/p\u003e \u003cp\u003eThe Basic Equation for 1:1 Binding 19\u003c\/p\u003e \u003cp\u003eThe Single Most Important Thing You Can Learn in This Book 20\u003c\/p\u003e \u003cp\u003eThe Example of Heme Binding to Apocytochrome c 21\u003c\/p\u003e \u003cp\u003eThe Rectangular Hyperbola 22\u003c\/p\u003e \u003cp\u003eThe Binding Isotherm 23\u003c\/p\u003e \u003cp\u003ePlot of ν vs. [Hf] 24\u003c\/p\u003e \u003cp\u003eGeneral Theory for Reversible Ligand Binding: Role of Mass Action 25\u003c\/p\u003e \u003cp\u003ePlot of [AH]vs.[Ht] with Fixed K 27\u003c\/p\u003e \u003cp\u003eDetermination of Kd from Experiment 28\u003c\/p\u003e \u003cp\u003ePlot of [AH]vs.[Ht] with Fixed [At] 29\u003c\/p\u003e \u003cp\u003eDetermining Molar Ratio from Experiment 29\u003c\/p\u003e \u003cp\u003eAbout Activity 31\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 Graphical Analysis 33\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eLimitations of Direct Plots 33\u003c\/p\u003e \u003cp\u003eThe Semi-log Plot 34\u003c\/p\u003e \u003cp\u003eBreadth of the Semi-log Plot 36\u003c\/p\u003e \u003cp\u003eMyoglobin and Hemoglobin 38\u003c\/p\u003e \u003cp\u003eAdvantages of the Direct and Semi-log Plots of Binding Data 40\u003c\/p\u003e \u003cp\u003eLinear Transforms of the Basic Binding Equation 40\u003c\/p\u003e \u003cp\u003eCommon Linearizations 41\u003c\/p\u003e \u003cp\u003eRequirements of the Linear Regression Model 41\u003c\/p\u003e \u003cp\u003eA Linear Model May Misrepresent the Physical Process 43\u003c\/p\u003e \u003cp\u003eDeviations from Linearity Are Hard to Detect or Interpret 44\u003c\/p\u003e \u003cp\u003eLinear Transforms Distort Data Completeness 44\u003c\/p\u003e \u003cp\u003eLinear Transforms Invite – Even Require – Extrapolation 46\u003c\/p\u003e \u003cp\u003eLinear Transforms Falsely Promise Both K and Molar Ratio from a Single Dataset 47\u003c\/p\u003e \u003cp\u003eSummary about Linear Treatments of Binding Data 47\u003c\/p\u003e \u003cp\u003eSimulation Is Just as Good as Fitting, Given Realistic Experimental Errors 50\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Binding of Multiple Ligands 52\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eConservation of Mass Outside the 1:1 Case 52\u003c\/p\u003e \u003cp\u003eRedefine ν to Accommodate Any Molar Ratio 53\u003c\/p\u003e \u003cp\u003eAccounting for the Definition of Molecule 54\u003c\/p\u003e \u003cp\u003eGeneralizing to Integer Multiples of 1:1 54\u003c\/p\u003e \u003cp\u003eThe Langmuir Equation for Any Molar Ratio with Sites of Identical Affinity and No Cooperativity 56\u003c\/p\u003e \u003cp\u003eAdair Equation for Any Number of Binding Events 57\u003c\/p\u003e \u003cp\u003eThe Langmuir Equation vs. the Adair Equation 60\u003c\/p\u003e \u003cp\u003eThermodynamic Linkage 61\u003c\/p\u003e \u003cp\u003eTwo Classes of Sites with Different Affinities 62\u003c\/p\u003e \u003cp\u003eBinding Isotherms for Multiple Sites with Different Affinities 62\u003c\/p\u003e \u003cp\u003eSummary 66\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 How to Determine Kd and Molar Ratio Experimentally 67\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eStoichiometric Titration First 68\u003c\/p\u003e \u003cp\u003eAmounts of Materials 69\u003c\/p\u003e \u003cp\u003eAssigning Partners 69\u003c\/p\u003e \u003cp\u003eChoice of Experimental Observables 70\u003c\/p\u003e \u003cp\u003eChoosing Solution Conditions 70\u003c\/p\u003e \u003cp\u003eHow Many Data Points? 71\u003c\/p\u003e \u003cp\u003eRange-Finding Stoichiometric Titration 72\u003c\/p\u003e \u003cp\u003eVisualizing Results 73\u003c\/p\u003e \u003cp\u003eRange-Finding Asymptotic Titration to Estimate Kd 74\u003c\/p\u003e \u003cp\u003eData Analysis 75\u003c\/p\u003e \u003cp\u003ePracticalities about Experimental Error 75\u003c\/p\u003e \u003cp\u003eStatistical Approaches to Estimate the Breakpoint 76\u003c\/p\u003e \u003cp\u003eRefined Asymptotic Titration 76\u003c\/p\u003e \u003cp\u003eDesigning an Experiment to Refine Kd 77\u003c\/p\u003e \u003cp\u003eCalculating Free Ligand Concentration 78\u003c\/p\u003e \u003cp\u003eRefining the Value of Molar Ratio 79\u003c\/p\u003e \u003cp\u003eExample of ArgR\/DNA Binding 79\u003c\/p\u003e \u003cp\u003ePlotting the Data 81\u003c\/p\u003e \u003cp\u003eDeriving Kd from the Data 81\u003c\/p\u003e \u003cp\u003eSummary 81\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 Cooperativity 83\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eFacilitated and Antagonized Binding 83\u003c\/p\u003e \u003cp\u003eFree Energy Definition of Cooperative Binding 84\u003c\/p\u003e \u003cp\u003eChemical Potential Diagram for Cooperative Binding 86\u003c\/p\u003e \u003cp\u003eCooperativity as Non-additivity 87\u003c\/p\u003e \u003cp\u003eReciprocity of Cooperative Effects 88\u003c\/p\u003e \u003cp\u003eLimitations of Linear Transforms for Cooperative Interactions 88\u003c\/p\u003e \u003cp\u003eMicroscopic View of Species Distribution 89\u003c\/p\u003e \u003cp\u003eHomotropic and Heterotropic Cooperativity 90\u003c\/p\u003e \u003cp\u003eCooperativity Affects Specificity as Well as Affinity 92\u003c\/p\u003e \u003cp\u003eCooperativity Is the Third Axis of the Affinity\/Specificity Map 94\u003c\/p\u003e \u003cp\u003eQuantifying Homotropic Cooperativity 95\u003c\/p\u003e \u003cp\u003eNegative Homotropic Cooperativity 95\u003c\/p\u003e \u003cp\u003eA Practical Advantage of Negative Cooperativity 97\u003c\/p\u003e \u003cp\u003ePositive Cooperativity and the Ligand Concentration Interval 97\u003c\/p\u003e \u003cp\u003eImportance of Individual-site Isotherms and Species Distribution 100\u003c\/p\u003e \u003cp\u003eSpecies Distributions by Specialized Experimental Methods 101\u003c\/p\u003e \u003cp\u003eThe Many Forms of Cooperativity 103\u003c\/p\u003e \u003cp\u003eEmergent Properties 103\u003c\/p\u003e \u003cp\u003eConnectivity and Search Entropy 104\u003c\/p\u003e \u003cp\u003eBreakdown of Additivity in Complex Systems 105\u003c\/p\u003e \u003cp\u003eStatistical Effects 107\u003c\/p\u003e \u003cp\u003eRelevance of Non-additivity for Analysis of Mutations 110\u003c\/p\u003e \u003cp\u003eUniversality and Promiscuity of Cooperativity 111\u003c\/p\u003e \u003cp\u003eProteins as Gestalt Objects 113\u003c\/p\u003e \u003cp\u003eSummary 115\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 Theoretical and Method-specific Troubleshooting 116\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eEquilibrium and Nonequilibrium Methods 116\u003c\/p\u003e \u003cp\u003eAccessible Concentration Ranges Limit Accessible Kd Values 116\u003c\/p\u003e \u003cp\u003eSignal from Ligand or Target? 118\u003c\/p\u003e \u003cp\u003eSeparation-based Methods 118\u003c\/p\u003e \u003cp\u003eFilter Binding 119\u003c\/p\u003e \u003cp\u003eGel Retardation or EMSA 120\u003c\/p\u003e \u003cp\u003eGel Filtration 121\u003c\/p\u003e \u003cp\u003eHummel and Dreyer Chromatography 121\u003c\/p\u003e \u003cp\u003eEquilibrium Dialysis 122\u003c\/p\u003e \u003cp\u003eUV Absorbance 123\u003c\/p\u003e \u003cp\u003eCD Spectroscopy 123\u003c\/p\u003e \u003cp\u003eFluorescence 124\u003c\/p\u003e \u003cp\u003eNMR 124\u003c\/p\u003e \u003cp\u003eITC 125\u003c\/p\u003e \u003cp\u003eAUC 129\u003c\/p\u003e \u003cp\u003eSPR 129\u003c\/p\u003e \u003cp\u003eMS 131\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 Allostery 133\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eAn Historical Overview 133\u003c\/p\u003e \u003cp\u003eFacilitated Binding 135\u003c\/p\u003e \u003cp\u003eElaboration of the MWC Model 136\u003c\/p\u003e \u003cp\u003eRelaxed Monomers and Tense Multimers 136\u003c\/p\u003e \u003cp\u003ePositive Homotropic Cooperativity Only 137\u003c\/p\u003e \u003cp\u003eArtifactual Origins of Affinity Heterogeneity 138\u003c\/p\u003e \u003cp\u003eRelaxation of Multimers by Ligand Binding 138\u003c\/p\u003e \u003cp\u003eKoshland’s Sequential (Asymmetric) Model 140\u003c\/p\u003e \u003cp\u003eG3Pase Was Heterogeneous, Not Negatively Cooperative 141\u003c\/p\u003e \u003cp\u003eMany Models Fit the Hemoglobin Data 142\u003c\/p\u003e \u003cp\u003eAdvantages of Negative Cooperativity for Molecular Insight 143\u003c\/p\u003e \u003cp\u003eBiology of Negative Cooperativity 145\u003c\/p\u003e \u003cp\u003eStructural Analysis Cannot Solve Allostery 146\u003c\/p\u003e \u003cp\u003eAllostery without Cooperativity 147\u003c\/p\u003e \u003cp\u003eSummary 148\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Lessons on Affinity and Specificity from Host\/Guest Chemistry 149\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e2D Representations of 3D Objects 149\u003c\/p\u003e \u003cp\u003eEarly Hosts Were Linear and Flexible 150\u003c\/p\u003e \u003cp\u003eDesign of Molecular Properties 151\u003c\/p\u003e \u003cp\u003eVery Weak Affinity and No Detectable Specificity 151\u003c\/p\u003e \u003cp\u003eLater Hosts Pre-organized in Bound Conformation 152\u003c\/p\u003e \u003cp\u003eEnormous Gains in Affinity and Specificity 152\u003c\/p\u003e \u003cp\u003eBonds between Host and Guest Are Identical 153\u003c\/p\u003e \u003cp\u003eLessons from the Host\/Guest Chemistry 153\u003c\/p\u003e \u003cp\u003eRational Design of Affinity and Specificity 153\u003c\/p\u003e \u003cp\u003eAffinity and Specificity Accrue in Parallel 155\u003c\/p\u003e \u003cp\u003eCryptic Contributions Can Dominate Binding 156\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Reconciling Structure and Thermodynamics in Molecular Interactions 157\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eThermodynamics of Molecular Interactions 158\u003c\/p\u003e \u003cp\u003eStructural Analysis of Bonding Does Not Predict Binding 160\u003c\/p\u003e \u003cp\u003eThe Goldilocks Region of Affinity\/Specificity Space 162\u003c\/p\u003e \u003cp\u003eConformational Rearrangement upon Binding Decouples Affinity and Specificity 163\u003c\/p\u003e \u003cp\u003eA Reservoir of Adaptability 164\u003c\/p\u003e \u003cp\u003eNo Simple Reconciliation of Structural and Energetic Views 165\u003c\/p\u003e \u003cp\u003eImplications for Drug Design 166\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 Applications in Modern Drug Development 167\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eBackground 167\u003c\/p\u003e \u003cp\u003eTechnological Developments 167\u003c\/p\u003e \u003cp\u003eCrystal Structures 168\u003c\/p\u003e \u003cp\u003eTrapped High-energy States 168\u003c\/p\u003e \u003cp\u003eAnother Example 171\u003c\/p\u003e \u003cp\u003eComputational Methods 175\u003c\/p\u003e \u003cp\u003eHigh-throughput Assays 177\u003c\/p\u003e \u003cp\u003eDruggability 178\u003c\/p\u003e \u003cp\u003eIrrational Drug Design 180\u003c\/p\u003e \u003cp\u003eA New Workflow 181\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix A Ligand-binding Study Questions 182\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix B Thought Experiments 195\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix C Derivations 197\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix D Simulation and Fitting 201\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eSimulation 201\u003c\/p\u003e \u003cp\u003eFitting 203\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix E About the Hill Equation 208\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eDeriving the Hill Equation 208\u003c\/p\u003e \u003cp\u003eThe Hill Equation as a Limit of the Adair Equation 209\u003c\/p\u003e \u003cp\u003eOn Applying the Hill Equation to Quantify Cooperativity 210\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix F Stereo Viewing 212\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003eBibliography 215\u003c\/p\u003e \u003cp\u003eIndex 227\u003c\/p\u003e  \u003cp\u003e\u003cb\u003eJannette Carey\u003c\/b\u003e has been a member of the Chemistry faculty at Princeton University for over thirty years, where she developed and teaches a two-term sequence in biophysical chemistry that is accessible to early graduate and advanced undergraduate students in a wide range of disciplines. Her biophysical research is focused on unifying the thermodynamic and structural basis for macromolecular interactions.   \u003c\/p\u003e\u003cp\u003e\u003cb\u003eA concise and accessible textbook covering ligand-binding theory in chemistry, biology, and drug development\u003c\/b\u003e \u003c\/p\u003e\u003cp\u003eIn \u003ci\u003eLigand-binding Basics: Evaluating Intermolecular Affinity, Specificity, Stoichiometry, and Cooperativity\u003c\/i\u003e, accomplished chemist Professor Jannette Carey introduces ligand binding in a thorough and practical way for those new to the topic, as well as anyone seeking a connection between theory and experiment. Using a minimum of mathematical formalism, this book offers analytical rigor while remaining accessible to non-specialist practitioners. It provides readers with the skills they need to analyze their own binding data or published results, helping them develop an intuitive grasp of ligand-binding phenomena integrated with structural and thermodynamic understanding. \u003c\/p\u003e\u003cp\u003eTopics covered include: \u003c\/p\u003e\u003cul\u003e\n\u003cli\u003eApplication of the principles of equilibrium, mass action, and mass balance to derive the basic equations that describe all binding processes\u003c\/li\u003e\n\u003cli\u003eRecommended approaches for plotting and graphical analysis of binding data\u003c\/li\u003e\n\u003cli\u003eStrategies for designing, analyzing, interpreting, and troubleshooting experiments from the perspective of ligand-binding theory\u003c\/li\u003e\n\u003cli\u003eReview of selected examples that illustrate integration of structural and thermodynamic analysis\u003c\/li\u003e\n\u003c\/ul\u003e \u003cp\u003ePerfect for students and educators in chemistry, biochemistry, molecular biology, and pharmaceutical science, \u003ci\u003eLigand-binding Basics\u003c\/i\u003e will also appeal to practitioners who aim to study ligand binding in any molecular system.\u003c\/p\u003e","brand":"Wiley","offers":[{"title":"Default Title","offer_id":47989529608421,"sku":"NP9781119878421","price":125.0,"currency_code":"USD","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1842\/7735\/files\/9781119878421.jpg?v=1761784475","url":"https:\/\/k12savings.com\/products\/ligand-binding-basics-isbn-9781119878421","provider":"K12savings","version":"1.0","type":"link"}