Title page for ETD etd-11142003-223113

Type of Document

Dissertation

Author

Korostelev, Andrei Alexandrovich

Author's Email Address

korostel@chem.fsu.edu

URN

etd-11142003-223113

Title

Improving the Methods of Macromolecular Structure Determination

Degree

Doctor of Philosophy

Department

Chemistry and Biochemistry, Department of

Advisory Committee

Advisor Name	Title
Michael S. Chapman	Committee Chair
Donald L. D. Caspar	Committee Member
Naresh Dalal	Committee Member
Timothy A. Cross	Committee Member
Timothy M. Logan	Committee Member

Keywords

Electrostatics
Crystallography
Eectron Microscopy
Refinement
Hydrogen Bonds

Date of Defense

2003-10-16

Availability

unrestricted

Abstract

Atomic structures of biological systems can be obtained by several experimental methods, X-ray crystallography being one of the most widely used. Crystallography can provide a high resolution visualization (better than 1 A), but for macromolecules the resolution is often sample-limited, especially for large assemblies. Electron microscopy (EM) is applicable to large assemblies that may not be easy to crystallize, but imaging is at considerably lower resolution. Crystallography and electron microscopy, together or separately, are increasingly used to determine detailed structures of assemblies (ribosome, viruses) that have been challenging to characterize previously because of their size and complexity, or because of dynamic structural changes.
In this research, computational methods used in solving medium- and low-resolution structures were improved. Specifically, the focus was on refinement methods used to optimize the agreement between model and experimental data. Real-space refinement for crystallographic structure determination was further developed for optimally fitting models into experimental atomic electron density. Its application was extended to very low resolution for the building of atomic models of ribosomal complexes into electron density. Low-resolution refinements must be stereochemically restrained according to our prior knowledge of chemical geometry. New restraints were developed for hydrogen bonds and electrostatic interactions (using the Poisson-Boltzmann equation) and these have been shown to improve protein structure refinements at medium or low resolution.

Files

Filename		Size	Approximate Download Time (Hours:Minutes:Seconds)
Filename		Size	28.8 Modem	56K Modem	ISDN (64 Kb)	ISDN (128 Kb)	Higher-speed Access
	korostelev_disser.pdf	13.49 Mb	01:02:28	00:32:07	00:28:06	00:14:03	00:01:11