Date of Award

1-1-2012

Document Type

Campus Access Dissertation

Department

Computer Science and Engineering

First Advisor

Homayoun Valafar

Abstract

Protein folding is the one of the most important topics of research in Biochemistry. The understanding of how a protein folds into its three dimensional shape from its amino acid sequence is of extreme importance in medicine today because proteins play important roles in diseases such as sickle cell anemia, Alzheimer's disease, and Parkinson's disease to name a few. Current protein force fields such as those implemented in CHARMM, AMBER, NAMD, and Xplor-NIH have many individual force terms that include bonded and non-bonded energies. While deemed complete, the use of these traditional force fields in ab initio approaches to protein structure determination has been unsuccessful. In this report, we introduce the software package SCOPE and its utility in evaluating and extending the currently existing force fields. SCOPE is unique in a number of ways, including its examination of protein structure in rotamer space, which leads to a reduction in dimensionality of the energy landscape and elimination of the bonded energy terms. The latest version of SCOPE includes an exclusive hydrogen bond energy term, and is also capable of producing a hydrogen bond profile that is substantially more informative than a single hydrogen bond energy value. SCOPE also includes a hydrophobicity score and profile. Furthermore the energy profile produced by SCOPE is incorporated into an artificial neural network based approach to predict the backbone root mean square deviation of a given protein structure to that of the native structure based on its potential energy alone. This method has been shown to help with refinement of protein structures from around 7.0 Å to approximately 2.0 Å

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