Quantum Tunnelling in Enzyme-Catalysed Reactions

Introduction. Preface: Beyond the Historical Perspective on Hydrogen and Electron Transfers. Chapter 1: The Transition State Theory Description of Enzyme Catalysis for Classically Activated Reactions: Introduction Quantifying the Catalytic Activity of Enzymes Free Energy Analysis of Enzyme Catalysis Transition State Stabilisation or Ground State Destabilisation? Selective Stabilisation of Transition Structures by Enzymes Enzyme Flexibility and Dynamics. Chapter 2: Introduction to Quantum Behavior - A Primer: Introduction Classical Mechanics Quantum Mechanics Heisenberg Uncertainty Principle The Schr/dinger Equation Electronic Structure Calculations Born-Oppenheimer Approximation Hartree-Fock Theory Basis sets Zero-point Energy Density Functional Theory DFT Calculations of Free Energies of Activation of Enzyme Models DFT Calculations of Kinetic Isotope Effects Quantum Mechanics/Molecular Mechanics Methods Summary and Outlook. Chapter 3: Quantum Catalysis in Enzymes: Introduction Theory Variational Transition State Theory The Transmission Coefficient One-Dimensional Tunneling Multidimensional Tunneling Ensemble Averaging Examples Liver Alcohol Dehydrogenase Dihydrofolate Reductase Soybean-Lipoxygenase-1 and Methylmalonyl-CoA Mutase Other Systems and Perspectives Concluding Remarks. Chapter 4: Selected Theoretical Models and Computational Methods for Enzymatic Tunneling: Introduction Vibronically Nonadiabatic Reactions: Proton-coupled Electron Transfer Theory Application to Lipoxygenase Predominantly Adiabatic Reactions: Proton and Hydride Transfer Theory Application to Dihydrofolate Reductase Emerging Concepts About Enzyme Catalysis. Chapter 5: Kinetic Isotope Effects from Hybrid Classical and Quantum Path Integral Computations: Introduction Theoretical Background Path Integral Quantum Transition State Theory Centroid Path Integral Simulations Kinetic Isotope Effects Sequential Centroid Path Integral and Umbrella Sampling (PI/UM) The PI-FEP/UM Method Kleinert's Variational Perturbation (KP) Theory Potential Energy Surface Combined QM/MM Potentials The MOVB Potential Computational Details Illustrative Examples Proton Transfer between Viscosity Multiple Reactive Configurations and a Place for Single-Molecule Measurements. Chapter 10. Computational Simulations of Tunnelling Reactions in Enzymes Introduction Molecular Mechanical Methods Quantum Mechanical Methods Combined Quantum Mechanical/Molecular Mechanical Methods Improving Semiempirical QM Calculations Calculation of Potential Energy Surfaces and Free Energy Surfaces Simulation of the H-tunnelling Event Calculation of H-tunnelling Rates and Kinetic Isotope Effects Analysing Molecular Dynamics Trajectories A Case Study: Aromatic Amine Dehydrogenase (AADH) Preparation of the System Analysis of the H-tunnelling Step in AADH Analysis of the Role of Promoting Motions in Driving Tunnelling Comparison of Short-range Motions in AADH with Long Range Motions in Dihydrofolate Reductase Summary. Chapter 11. Tunneling Does Not Contribute Significantly to Enzyme Catalysis, But Studying Temperature Dependence of Isotope Effects is Useful Introduction Methods Simulating Temperature Dependence of KIEs in Enzymes Concluding Remarks. Chapter 12: The Use of X-Ray Crystallography to Study Enzymic H-Tunnelling Introduction X-Ray Crystallography: A Brief Overview Accuracy of X-Ray Diffraction Structures Dynamic Information from X-Ray Crystallography Examples of H-tunnelling Systems Studied by Crystallography Crystallographic Studies of AADH Catalytic Mechanism Crystallographic Studies of MR Conclusions. Chapter 13: The Strengths and Weaknesses of Model Reactions for the Assessment of Tunneling in Enzymic Reactions Model Reactions for Biochemical Processes Model Reactions Relevant to Enzymic Tunneling Isotope Effect Temperature Dependences and the Configurational-Search Framework (CSF) for their Interpretation The Traditionally Dependent Category The Underdependent Tunneling Category The Overdependent Tunneling Category Example 1. Hydride Transfer in a Thermophilic Alcohol Dehydrogenase The Kirby-Walwyn Intramolecular Model Reaction The Powell-Bruice Tunneling Model Reaction Enzymic Tunneling in Alcohol Dehydrogenases Model Reactions and the Catalytic Power of Alcohol Dehydrogenase Example 2. Hydrogen-atom Transfer in Methylmalonyl Coenzyme A Mutase (MCM) Non-enzymic Tunneling in the Finke Model Reactions for MCM Enzymic Tunneling in MCM Model Reactions and MCM Catalytic Power The Roles of Theory in the Comparison of Model and Enzymic Reactions Model Reactions, Enzymic Accelerations, and Quantum Tunneling. Chapter 14: Long-Distance Electron Tunneling in Proteins: Introduction Electronic Coupling and Tunneling Pathways Direct Method Avoided Crossing Application of Koopmans' Theorem Generalized Mulliken-Hush Method The Propagator Method Protein Pruning Tunneling Pathways The Method of Tunneling Currents General Relations Many-Electron Picture Calculation of Current Density. Hartree-Fock Approximation Interatomic Tunneling Currents Many-Electron Aspects One Tunneling Orbital (OTO) Approximation and Polarization Effects The Limitation of the SCF Description of Many-Electron Tunneling Correlation Effects. Polarization Cloud Dynamics. Beyond Hartree-Fock Methods Quantum Interference Effects. Quantized Vertices Electron Transfer or Hole Transfer? Exchange Effects Dynamical Aspects.Chapter 15. Proton-coupled Electron Transfer: The Engine that Drives Radical Transport and Catalysis in Biology Introduction PCET Model Systems Unidirectional PCET Networks Bidirectional PCET Networks PCET Biocatalysis PCET in Enzymes: A Study of Ribonucleotide Reductase The PCET Pathway in RNR PCET in the ?2 Subunit of RNR PCET in ?2 Subunit of RNR: PhotoRNRs A Model for PCET in RNR Concluding Remarks.