Protein-ligand interactions. (2012)

• Record Type: Book
• Further Information: Note: Edited by Holger Gohlke.
• Other Names: Gohlke, Holger
• Contents: PREFACE; ; PART I: Binding Thermodynamics; ; STATISTICAL THERMODYNAMICS OF BINDING AND MOLECULAR RECOGNITION MODELS; Introductory Remarks; The Binding Constant and Free Energy; A Statistical Mechanical Treatment of Binding; Strategies for Calculating Binding Free Energies; ; SOME PRACTICAL RULES FOR THE THERMODYNAMIC OPTIMIZATION; OF DRUG CANDIDATES; Engineering Binding Contributions; Eliminating Unfavorable Enthalpy; Improving Binding Enthalpy; Improving Binding Affinity; Improving Selectivity; Thermodynamic Optimization Plot; ; ENTHALPY?ENTROPY COMPENSATION AS DEDUCED FROM MEASUREMENTS; OF TEMPERATURE DEPENDENCE; Introduction; The Current Status of Enthalpy?Entropy Compensation; Measurement of the Entropy and Enthalpy of Activation; An Example; The Compensation Temperature; Effect of High Correlation on Estimates of Entropy and Enthalpy; Evolutionary Considerations; Textbooks; ; PART II: Learning from Biophysical Experiments; ; INTERACTION KINETIC DATA GENERATED BY SURFACE PLASMON RESONANCE BIOSENSORS AND THE USE OF KINETIC RATE CONSTANTS IN LEAD GENERATION AND OPTIMIZATION; Background; SPR Biosensor Technology; From Interaction Models to Kinetic Rate Constants and Affinity; Affinity versus Kinetic Rate Constants for Evaluation of Interactions; From Models to Mechanisms; Structural Information; The Use of Kinetic Rate Constants in Lead Generation and Optimization; Designing Compounds with Optimal Properties; Conclusions; ; NMR METHODS FOR THE DETERMINATION OF PROTEIN?LIGAND INTERACTIONS; Experimental Parameters from NMR; Aspects of Protein?Ligand Interactions That Can Be Addressed by NMR; Ligand-Induced Conformational Changes of a Cyclic Nucleotide Binding Domain; Ligand Binding to GABARAP Binding Site and Affinity Mapping; Transient Binding of Peptide Ligands to Membrane Proteins; ; PART III: Modeling Protein?Ligand Interactions; ; POLARIZABLE FORCE FIELDS FOR SCORING PROTEIN?LIGAND INTERACTIONS; Introduction and Overview; AMOEBA Polarizable Potential Energy Model; AMOEBA Explicit Water Simulation Applications; Implicit Solvent Calculation Using AMOEBA Polarizable Force Field; Conclusions and Future Directions; ; QUANTUM MECHANICS IN STRUCTURE-BASED LIGAND DESIGN; Introduction; Three MM-Based Methods; QM-Based Force Fields; QM Calculations of Ligand Binding Sites; QM/MM Calculations; QM Calculations of Entire Proteins; Concluding Remarks; ; HYDROPHOBIC ASSOCIATION AND VOLUME-CONFINED WATER MOLECULES; Introduction; Water as a Whole in Hydrophobic Association; Confined Water Molecules in Protein?Ligand Binding; ; IMPLICIT SOLVENT MODELS AND ELECTROSTATICS IN MOLECULAR RECOGNITION; Introduction; Poisson?Boltzmann Methods; The Generalized Born Model; Reference Interaction Site Model of Molecular Solvation; Applications; ; LIGAND AND RECEPTOR CONFORMATIONAL ENERGIES; The Treatment of Ligand and Receptor Conformational Energy in Various Theoretical Formulations of Binding; Computational Results on Ligand Conformational Energy; Computational Results on Receptor Conformational Energy; Concluding Remarks; ; FREE ENERGY CALCULATIONS IN DRUG LEAD OPTIMIZATION; Modern Drug Design; Free Energy Calculations; Example Protocols and Applications; Discussion; ; SCORING FUNCTIONS FOR PROTEIN?LIGAND INTERACTIONS; Introduction; Scoring Protein?Ligand Interactions: What for and How to?; Application of Scoring Functions: What Is Possible and What Is Not?; Thermodynamic Contributions and Intermolecular Interactions: Which Are Accounted for and Which Are Not?; Conclusions or What Remains to be Done and What Can be Expected?; ; PART IV: Challenges in Molecular Recognition; ; DRUGGABILITY PREDICTION; Introduction; Druggability: Ligand Properties; Druggability: Ligand Binding; Druggability Prediction by Protein Class; Druggability Predictions: Experimental Methods; Druggability Predictions: Computational Methods; A Test Case: PTP1B; Outlook and Concluding Remarks; ; EMBRACING PROTEIN PLASTICITY IN LIGAND DOCKING; Introduction; Docking by Sampling Internal Coordinates; Fast Docking to Multiple Receptor Conformations; Single Receptor Conformation; Multiple Receptor Conformations; Improving Poor Homology Models of the Binding Pocket; State of the Art: GPCR Dock 2010 Modeling and Docking Assessment; Conclusions and Outlook; ; PROSPECTS OF MODULATING PROTEIN?PROTEIN INTERACTIONS; Introduction; Thermodynamics of Protein?Protein Interactions; CADD Methods for the Identification and Optimization of Small-Molecule Inhibitors of PPIs; Examples of CADD Applied to PPIs; Summary;
• Publisher Details: Place of publication not identified : Wiley-VCH
• Publication Date: 2012
• Extent: 1 online resource (359 pages)
• Subjects: 615.19; Proteins; Ligands (Biochemistry); Ligand binding (Biochemistry); Drugs -- Structure-activity relationships
• Languages: English
• ISBNs: 9783527645961
• Access Rights: Legal Deposit; Only available on premises controlled by the deposit library and to one user at any one time; The Legal Deposit Libraries (Non-Print Works) Regulations (UK).
• Access Usage: Restricted: Printing from this resource is governed by The Legal Deposit Libraries (Non-Print Works) Regulations (UK) and UK copyright law currently in force.