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theses

We present a broad effort at the development of crystal simulation methodology and its application to benefit both macromolecular crystallography and molecular dynamics methods. Crystallography is the current method of choice for structural determination of biomolecules, but it is hampered by the inherently time and space-averaged nature of the experiment as well as methodological limitations that do not sufficiently account for the heterogeneous and dynamic nature of crystals. Molecular dynamics has proven itself as a method capable of probing the physics and chemistry of biomolecules on an atomic scale, but requires continued development of the underlying force field parameters to more accurately reproduce observables. Our effort has focused on developing the framework for molecular dynamics simulations of biomolecular crystals. We first present our methodology for performing crystal simulations and show how it is applied first to simple peptide crystals and then to increasingly complex biomolecular systems. We demonstrate the the utility of crystal simulations for validation of molecular dynamics. Then we show the improvement to crystallographic methods that can be gained by incorporating molecular dynamics methods. Our work is of significant benefit to both the molecular dynamics and macromolecular crystallography communities and proposes specific approaches to integrate the two fields for the benefit of both.

ETD_6644

Ph.D.

Includes bibliographical references

by Paul A. Janowski

doi:10.7282/T39G5PS6

ETD doctoral

The author owns the copyright to this work.