Outer membrane proteins (OMPs) perform a range of important functions in the cell biology of Gram-negative bacteria, mitochondria and chloroplasts. These functions include biogenesis, virulence, signal transduction, nutrient transport and apoptosis. In contrast to their inner membrane counterparts, OMPs have been more difficult to study due to the relative paucity of crystal structures. Although outer membrane proteins have been characterized and studied extensively by various structural and biophysical methods, our understanding of their folding, insertion and oligomerization is far behind that of inner membrane proteins. The goal of this study is to elucidate the folding and insertion mechanism of these transmembrane β-barrel proteins (TMBs) and ultimately to provide guidelines for computationally designing OMP sequences that fold and insert efficiently. Using a subset of amino acids from thirty-five outer membrane proteins from Gram-negative bacteria and mitochondria, a propensity vs depth in membrane profile for each residue was derived. Although results indicate similar trends between amino acids of inner and outer membrane proteins, there are also differences that can be explained by differences in factors such as environment, secondary structural preferences, and folding/insertion pathway. The propensity profiles were converted into energies of insertion as a function of depth from the center of the membrane. This thesis explores the many ways of using the statistical potential to answer questions about OMP folding, insertion and oligomerization that could not have been framed due to the experimental limitations. We conclude with a discussion of ways to improve our potential, including the assumption of asymmetry of the lipid bilayer as well as incorporating homology model building.
Subject (authority = RUETD)
Topic
Computational Biology and Molecular Biophysics
Subject (authority = ETD-LCSH)
Topic
Bacterial proteins
Subject (authority = ETD-LCSH)
Topic
Mitochondria--Formation
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Rutgers University Electronic Theses and Dissertations
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Rutgers University. Graduate School - New Brunswick
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