Computational Prediction of the Agregated Structure of Denatured Lysozyme

Mis-folded proteins and their associated aggregates are a contributing factor in some human diseases. In this study we used the protein lysozyme as a model to define aggregation structures under denaturing conditions. Sasahara et al. (2007), Frare et al. (2009, 2006), and Rubin et al. (2008) observed conditions where heat denatured lysozyme formed fibril structures that were observed to be 8-17 nanometers in diameter under the electron microscope. Even though the crystal structure of lysozyme is known, the denatured form of this protein is still unknown. Therefore, we used Rosetta++ protein folding and blind docking software to create <i>in silico</i> models of the protein at denaturing temperatures and subsequently docked them into aggregates. Here we compare those structures and select forms consistent with the fibril structure from the previous papers. The next step is to be able to use the predicted models of the fibrilar forms of denatured lysozyme to help us understand the exact conformation of fibril structures. This will let us confirm the docking interactions during the fibril aggregation process. The ultimate goal is to use the validated denatured structures to model interactions with heat shock proteins during the dis-aggregation process.

Name thesis:degree_name

Master of Science

Discipline thesis:degree_discipline

Department of Biology

Year

2009

Author dc:creator

• Chotikasemsri, Pongsathorn

Contributors dc:contributor

• Dr. Claire Rinehart (Director),Dr. Sigrid Jacobshagen,Dr. Di Wu

• protein aggregation
• homodimer structures
• homotrimer structures
• Amino Acids, Peptides, and Proteins
• Biochemistry, Biophysics, and Structural Biology
• Cellular and Molecular Physiology
• Molecular Biology
• Molecular, Genetic, and Biochemical Nutrition

Repository record dc:identifier

https://digitalcommons.wku.edu/theses/120

OAI identifier oai:identifier

oai:digitalcommons.wku.edu:theses-1120