An ab Initio Study of Biological Systems

A dissertation submitted for the degree of Doctor of Philosophy at the
University of Cambridge

Matthew Segall

Clare Hall, Cambridge

June 1997

• Contents
• List of Figures
• List of Tables
• Introduction
  • Molecular Simulations in the Biological Sciences
  • Ab Initio versus Conventional Simulations
  • Outline of Thesis
• The Total Energy Pseudopotential Method
  • Introduction
  • The Many-Body Schrödinger Equation
  • Density Functional Theory
  • The Exchange-Correlation Term
  • The Choice of a Basis Set - Plane Waves
  • Pseudopotentials
  • Non-linear Core Corrections
  • Direct Minimisation
  • Parallel versus Serial Implementations
  • Nuclear Degrees of Freedom
  • Charged Molecules
  • Summary
• Population Analysis
  • Introduction
  • Methods
  • Application to Simple Molecules
  • Practical Example
  • Bonding in Bulk Crystals.
  • Overlap Population as a Measure of Bond
    Modulus
    • NaCl Structure Crystals
    • Zincblende Structure Crystals
    • Simple Molecules
    • Analysis
  • Spin Population Analysis
    • Diatomic Molecules
    • Bulk Systems
  • Summary
• Acetylcholine: A Validation Study
  • Introduction
  • Methods
  • Results and Discussion
    • Conformation Energy Maps
    • The Ground State Conformation
  • Summary
• Understanding Cytochrome P450 - Ligand Interactions
  • Introduction
  • Cytochromes P450
    • History and Background
    • The P450 Catalytic Cycle
    • Physical Properties of P450
    • Substrates, Substrate Analogues and Inhibitors
  • Computational Approach
  • Results and Discussion
    • Ground State Spin Calculations
    • The Rôle of the Iron-coordinated Water
  • Summary
• Conclusion
  • Summary of Thesis
  • Further Work
• Implementation of Population Analysis
  • Techniques
  • Computational Methods
  • Orbital FT Kernels
• Constraining the Central Dihedral Angles in Acetylcholine
• References
• About this document ...