IDENTIFYING STRUCTURAL CHANGES IN EVOLVING VIRAL PROTEINS
Open Access
- Author:
- Roy, Sunando
- Graduate Program:
- Integrative Biosciences
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 24, 2011
- Committee Members:
- Mary Poss, Dissertation Advisor/Co-Advisor
Mary Poss, Committee Chair/Co-Chair
Francesca Chiaromonte, Committee Member
Ross Cameron Hardison, Committee Member
Philip C. Bevilacqua, Committee Member - Keywords:
- Protein
Structure
Evolution
Adaptation
Viruses
Multivariate Statistics - Abstract:
- Proteins are macromolecules that facilitate the basic biochemical functions of a cell. Proteins help organisms adapt to their new environment by changing their function, which in turn is often accompanied by changes in structure. When a virus moves from one host to another, the move is accompanied by changes in the sequence of the virus. These changes are studied using phylogenetic tools that identify sites in the genome, which are important for adaptation in the new host (positively selected sites). Studying how these changes in the genome sequence affects change in the structure of viral proteins is still very challenging, as a one-to-one relationship does not exist between changes in sequence and changes in structure. The primary structure of the protein is its amino acid sequence that determines the final tertiary structure of the protein. The rules that govern the folding of proteins starting from the linear amino acid sequence are still poorly understood. Over the last five decades progress has been made in predicting the secondary structure of proteins using robust computational tools. The secondary structure, which is an intermediate step (alpha helix, beta sheet, and coils) between primary and tertiary structure, is a property determined by a combination of amino acids. We have used six predicted secondary structural properties to construct a multivariate statistical pipeline that identifies differences in structure at amino acid positions between groups of related viral proteins (Human and Avian Metapneumovirus, HIV and SIV). This pipeline when used with phylogenetic analysis of linear sequence data adds value by predicting structural changes that arise in the course of viral adaptation to new host.