Contents

• Contents
• Preface
• Introduction to theoretical chemistry
  • Overview of the methods
  • Introduction: Potential Energy
    • Quantum Mechanics
    • Molecular Mechanics
    • Hybrid methods
    • Derivatives of the potential energy
  • Introduction: Optimization Methods
    • Common issues: convergence criteria and step length
    • Non derivative methods
    • First derivatives methods
    • Second derivative methods
    • Reaction path
    • Cartesian, internal and redundant coordinates
    • Second order methods for large systems
  • Introduction: Molecular Dynamics
    • Basic equations and algorithms
    • Thermostats and barostats
    • Constraints
    • Langevin Dynamics and Stochastic Dynamics
  • Introduction: Statistical Mechanics
    • Free energy calculations
    • Potential of mean force
    • Chemical kinetics: Transition state theory
  • Enzymatic reaction simulations
• Mandelate Racemase enzyme
  • Introduction: experimental results
    • Racemases and the aim of their study
    • Presentation of Mandelate Racemase enzyme
  • Introduction: Previous theoretical studies
  • Modulation of substrate activity
    • Methods and strategies
    • Reaction mechanism of propargylglycolate substrate
    • Reaction mechanism of mandelate substrate
    • Comparison with experimental kinetics
    • Inhibition by propargylglycolate substrate
    • Discussion
    • Conclusions
    • Tables of results
  • Gas phase calculations
    • Semiempirical calculations
    • DFT calculations
    • Some short conclusions and perspectives
• Optimization of big systems
  • Optimization in QM/MM surfaces
    • Equations and its implementation
    • Tests on model systems
    • Conclusions
  • Micro-iterative method
    • Strategies and its implementation
    • Tests on Mandelate Racemase
    • Conclusions
  • How important is an accurate optimization
    • Procedure
    • Comparison between Mandelate Racemase mechanism structures
    • Conclusions
  • Avoiding the memory problem
    • Initial hessians, sparsity and storage
    • General scheme for the strategy
    • Results and discussion
• Molecular Dynamics and Free Energy
  • Model and setup
    • Potential Energy Surface
    • Molecular Dynamics
    • Potential of Mean Force
  • PMF on different reaction coordinates
    • Selection of a reaction coordinate
    • Combining two bond distances
    • Combining four bond distances
    • Reactivity for the mutant N197A
  • Discussion and conclusions
• Final Conclusions
• Computer resources and informatics
  • An example of numerical computation
• Source Code
• Acronyms
• Bibliography
• Bibliography
• About this document ...