Date of Award

Summer 8-21-2020

Level of Access Assigned by Author

Open-Access Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Advisor

Jayendran C Rasaiah

Second Committee Member

Francoi Amar

Third Committee Member

Scott Collins

Additional Committee Members

R Dean Astumian

Samuel Hess

Abstract

Proteins are the workhorses of biology and are essential to life as we know it. A protein’s function in the cell is intimately related to its three-dimensional structure. Thus, understanding structure formation in proteins has been an essential goal in molecular biology. Experiments indicate proteins start acquiring structure inside the ribosome—the cellular manufacturing plant of proteins—and the process is particularly important for membrane proteins. Therefore, the ribosome appears to play an active role in facilitating protein structure acquisition. However, how and when the ribosome accomplishes this task remains poorly understood. To better understand this process, we conducted molecular dynamics computer simulations of a model system. The model system is simple enough to extract general trends but complex enough to be relevant to real biological systems. In confirmation of earlier theoretical studies, we find that a tube of nanoscopic size can induce α-helix formation in proteins. However, we observe this confinement stabilization effect to be dependent on the type and sequence of amino acids within proteins. We surmised that water-mediated interactions would play a role in the sequence dependence and to quantify this effect we computed the difference in solvation free energies between α-helix and coil states for amino acids with polar and non-polar side chains while confined to polar or non-polar nanotubes. We find that nanotube confinement preferentially stabilizes hydrophobic protein sequences, which is consistent with experimental observations. We elaborate on these observations and discuss the relevance to the ribosome tunnel.

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