Large-Scale Quantum-Mechanical Enzymology

  • Greg Lever

Part of the Springer Theses book series (Springer Theses)

Table of contents

  1. Front Matter
    Pages i-xvii
  2. Greg Lever
    Pages 1-8
  3. Greg Lever
    Pages 19-77
  4. Greg Lever
    Pages 79-94
  5. Greg Lever
    Pages 143-148

About this book


This work establishes linear-scaling density-functional theory  (DFT) as a powerful tool for understanding enzyme catalysis, one that can complement quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics simulations. The thesis reviews benchmark studies demonstrating techniques capable of simulating entire enzymes at the ab initio quantum-mechanical level of accuracy. DFT has transformed the physical sciences by allowing researchers to perform parameter-free quantum-mechanical calculations to predict a broad range of physical and chemical properties of materials. In principle, similar methods could be applied to biological problems. However, even the simplest biological systems contain many thousands of atoms and are characterized by extremely complex configuration spaces associated with a vast number of degrees of freedom. The development of linear-scaling density-functional codes makes biological molecules accessible to quantum-mechanical calculation, but has yet to resolve the complexity of the phase space. Furthermore, these calculations on systems containing up to 2,000 atoms can capture contributions to the energy that are not accounted for in QM/MM methods (for which the Nobel prize in Chemistry was awarded in 2013), and the results presented here reveal profound shortcomings in said methods.


CHOMO-LUMO Gaps Density Functional Calculations for Enzyme Analysis Energetic structure of biomolecules Enzyme modelling Linear scaling DFT Modelling Enzyme Catalysis Protein modelling Spectra of biomolecules Structure of biomolecules Transition state searching Understanding enzyme catalysis Understanding enzyme catalysis

Authors and affiliations

  • Greg Lever
    • 1
  1. 1.Massachusetts Institute of TechnologyCambridgeUSA

Bibliographic information

  • DOI
  • Copyright Information Springer International Publishing Switzerland 2015
  • Publisher Name Springer, Cham
  • eBook Packages Physics and Astronomy
  • Print ISBN 978-3-319-19350-2
  • Online ISBN 978-3-319-19351-9
  • Series Print ISSN 2190-5053
  • Series Online ISSN 2190-5061
  • Buy this book on publisher's site
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