Simulating enzyme reactivity [E-Book] / editors: Inaki Tunon, Vicent Moliner.
Moliner, Vicent, (editor)
Tunon, Inaki, (editor)
Cambridge, UK : Royal Society of Chemistry, [2017]
1 online resource.
RSC theoretical & computational chemistry series
Full Text
Table of Contents:
  • 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?
  • 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
  • 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
  • 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
  • 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