Simulating enzyme reactivity : computational methods in enzyme catalysis Exploring the theories methodologies and applications in simulations of enzymatic reactions this book is a great resource for postgraduate students and researchers 1.5 Conclusions and PerspectivesAcknowledgments; References; Section I: Theory; Chapter 2 Fundamentals of Enzyme Catalysis: Determination of Rate Constants; 2.1 Introduction; 2.2 The Elements of Enzyme Kinetics in Particular Rate Constants; 2.2.1 Rate Constants Experimentally Determined; 2.2.2 Comparison of Experimental Rate Constants with Theoretically Computed Values; 2.2.3 A Note on Other Approaches; 2.3 Typical Components of a Simulation Study of Enzyme Catalysis; 2.3.1 Structural and Other Background; 2.3.2 Selection of QM and MM Regions and Methods Cover; Contents; Chapter 1 Perspective on Computer Modelling of Enzymatic Reactions; 1.1 Introduction; 1.2 Defining and Calculating the Catalytic Effect; 1.2.1 Using a Logical and Useful Definition; 1.2.2 Evaluating Reliable Activation Free Energies by Computational Approaches; 1.2.3 Electrostatic Transition State Stabilisation (TSS); 1.3 What was Found by Reliable Computational Studies; 1.3.1 General Findings; 1.3.2 Quantifying the Source of Electrostatic Contributions to Catalysis; 1.4 What are the Problems with Other Proposals 2.3.3 The Border of the QM Region and its Embedding in the MM Region2.3.4 Establishing the Potential energy Surface; 2.3.5 Establishing the Reaction Path or Swath; 2.3.6 Development of a Free energy Surface; 2.3.7 Calculation of Rate Constants; 2.4 Analytical Expressions for Rate Constants; 2.4.1 The Stable States Picture11 12; 2.4.2 Variational Transition state Theory; 2.4.3 Hammes Schiffer et al. and Klinman et al.; 2.5 An Instructive Example: Rate Constants from the Multiconfigurational Molecular Mechanics Approach QM MM MCMM; 2.5.1 Elements of the QM MM MCMM Approach 1.4.1 Ground state Destabilisation by Steric Strain Does Not Provide a Large Catalytic Effect1.4.2 Dynamical Effects Do Not Contribute Significantly to Enzyme Catalysis; 1.4.3 Correlated Modes Clearly Exist in Proteins but They Also Exist in Solution; 1.4.4 Problems with the Generalised Compression Idea; 1.4.5 RSD by Desolvation Effects Does Not Provide Large Catalytic Effects; 1.4.6 Entropy Contributions of Bringing the Reactants Together are Unlikely to Account for Large Catalytic Effects; 1.4.7 Allosteric Control of Catalytic Activity is Also Associated with Electrostatic Effects 2.5.2 The Empirical Valence bond Technique for the QM Region2.5.3 The Case of the Resonance Integral; 2.5.4 Identification and Characterisation of Stationary Points; 2.5.5 Minimum energy Pathways; 2.5.6 Toward Good Cheap Hessians; 2.6 Good Hessians Give Good Rate Constants; Acknowledgments; References; Chapter 3 A Transition State Theory Perspective for Enzymatic Reactions: Fundamentals and Applications; 3.1 Introduction; 3.2 TST and Allied Theories for Enzyme Reactions; 3.2.1 Assumptions and Structure of TST; 3.2.2 TS Surface Recrossing Corrections to TST; 3.3 Classical Enzyme Reactions