Front Cover; Computational Approaches for Studying Enzyme Mechanism Part A; Copyright; Contents; Contributors; Preface; Chapter One: The Role of Molecular Dynamics Potential of Mean Force Calculations in the Investigation of Enzyme Catalysis; 1. Introduction; 2. Method; 2.1. Umbrella Sampling; 2.2. Steered MD; 3. Applications; 3.1. Protein Farnesyltransferase; 3.1.1. Understanding the Conformational Activation of FPP; 3.1.2. Identification of the Mg2+ Binding Site in FTase; 3.1.3. Simulating the Farnesylation Reaction; 3.2. Aromatic Prenyltransferase NphB

3.2.1. Identifying the Product Regioselectivity Associated with NphB Catalysis3.2.2. Elucidating the Reaction Mechanism with QM/MM PMF Simulations; 3.3. Aspergillus Fumigatus Prenyltransferase; 3.3.1. Regioselectivity of WT FtmPT1; 3.3.2. Regioselectivity of G115T Mutant; 3.4. Cytochrome P450s; 4. Summary; Acknowledgments; References; Chapter Two: Empirical Force Fields for Mechanistic Studies of Chemical Reactions in Proteins; 1. Introduction; 2. Computational Approaches; 2.1. Adiabatic Reactive Molecular Dynamics; 2.2. Multisurface ARMD; 2.3. Empirical Valence Bond; 3. Applications

3.1. Rebinding Dynamics in MbNO3.2. NO Detoxification Reaction in trHbN; 3.3. Competitive Ligand Binding in trHbN; 4. Outlook; Acknowledgments; References; Chapter Three: Generalized Ensemble Sampling of Enzyme Reaction Free Energy Pathways; 1. Introduction; 2. Collective Variable and Reaction Order Parameter; 3. Traditional Importance Sampling vs GE Sampling; 4. Dimensionality Limit; 5. One of the First Metadynamics-Based Enzyme Reaction Studies; 6. GE-Based String Optimization: The OTPRW Method; 7. OTPRW Study of a Substrate-Assisted Glycosylation Reaction; 8. Final Remarks; Acknowledgments

2.1. The Pseudobond Approach to Describe the QM/MM Boundary Across Covalent Bonds2.2. A Dual Focal aiQM/MM-PME Potential with the Periodic Boundary Condition; 2.3. Microiterative Optimization and Reaction Coordinate Driving; 2.4. Born-Oppenheimer aiQM/MM-MD with Umbrella Sampling; 2.5. Implementation; 3. Examples; 3.1. Dissociation of tert-Butyl Chloride in Water; 3.2. First Step of Acylation Reaction for a Serine Protease; 4. Enzyme Simulation Protocol; 5. Conclusion; Acknowledgments; References; Chapter Six: QM/MM Calculations on Proteins; 1. Introduction; 2. Methods; 2.1. QM Methods