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.