Cheung, Margaret S.2019-09-10December 22018-12December 2https://hdl.handle.net/10657/4409Proteins are essential to supporting life in every living being. The three-dimensional shape of proteins is fundamental to their ability to function properly. The functional conformation is reached through a process known as protein folding. Most of the knowledge about protein folding was obtained from studies in dilute conditions; thus, it is necessary to understand how they fold in the cellular environment. Among the different interactions that a protein experiences inside the cell, there are two interactions: hydrodynamic interactions (HI) and macromolecular crowding. In this work, I used coarse-grained computational models of two-state proteins to study these interactions separately. First, I studied the impact of HI on the folding reaction of two proteins: chymotrypsin inhibitor 2 (CI2) and α-spectrin Src-homology 3 domain (SH3). I found that the dynamic effect of HI is temperature dependent relative to that in the absence of HI. This result implies the existence of a “crossover behavior” close to the folding temperature. I discovered that the acceleration due to HI for CI2 is greater than that for SH3, suggesting that the magnitude of the acceleration of a folding reaction is related to the protein topology. Furthermore, I investigated the factors that modulate the shape of the urea-unfolded ensemble of apoazurin in the presence of dextran 20, a synthetic crowder. Experiments discovered that dextran 20 increases the size of the unfolded apoazurin conformations. I demonstrated that crowder models with spherical and rod-like shapes using only steric repulsive interactions cannot explain this experimental finding. I found that the existence of attractive interactions between the protein and rod-like crowder models and the arrangement of these crowders in the vicinity of the protein could resemble the experimental observations.application/pdfengThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).Protein foldingHydrodynamic interactionsMacromolecular crowdingCoarse-grained molecular simulations2019-09-10Thesisborn digital