Dissertation

Protein folding with homologous sequences

DeFay, Thomas Robert

1996

Overview

The protein folding problem has been one of the most intractable problems facing science for almost 40 years. The problem is to predict the three-dimensional structure of a protein from its amino acid sequence. Early on, it was hoped that a simple pattern relating the amino acids would help solve this problem, much as the structure of DNA was solved. When this proved unsuccessful, efforts turned toward developing energy functions accurate enough to identify the native structure. In forty years this problem still has not yielded. Fortunately, a homologous family of sequences all fold to a similar three-dimensional structure. This fact can be exploited to increase the accuracy of structure predictions. The most straightforward way to use a homologous sequence is if that sequence already has an experimentally determined structure. In this case, the structure can be used as a template upon which to build a new structure, as we have done. We have also proposed a new method for predicting structure based upon an old technique, threading. When threading, the goal is to match a sequence with one of a set of known folds in a protein database. We have devised a new method which \"threads\" using the information from a set of homologous sequences.

• Publisher: ProQuest Dissertations & Theses
• Subject: Biophysics / Molecular biology / Organic chemistry / Pharmacology
• ISBN: 9798684698842