Date of Award

Spring 1-1-2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Computer Science

First Advisor

Debra Goldberg

Second Advisor

Richard Byrd

Third Advisor

Lawrence Hunter

Fourth Advisor

Deanne Sammond

Fifth Advisor

Robert Schnabel

Abstract

Proteins in vivo are not completely rigid molecules, and mobilities within their structure play a key role in protein function. We discuss a novel method for measuring two distinct types of protein fl exibility by comparing pairs of static protein structure coordinates. The measures focus on the mobility of a subset of atoms in the protein known as the backbone, and they quantify mobility or exibility at the level of the amino acids (or residues), which are the basic constituents of proteins. We validate our measures against a subset of proteins from the protein-protein docking benchmark, and against a number of individual proteins known to have mobility or exibility that is significant to their function. We also demonstrate the applicability of our methodology to several important biochemical topics including examples that apply to drug and enzyme design, and evaluation of computational protein structure prediction. We conclude with an analysis of protein structural and energetic terms showing which terms are associated with our exibility measures, and may therefore be useful within the context of protein modeling algorithms to predict the locality of exible regions.

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