| dc.description.abstract | The purpose of this project was to gain a better understanding of the means used to keep large proteins from becoming too stable. As globular proteins become larger, they bury a larger fraction of their side chains and peptide groups. Based on past research performed on forces stabilizing proteins, they should become much more stable as they become larger. However, this is not observed. This suggests that evolution has strategies to keep large proteins from becoming too stable. Theoretical and computational methods were used to compare and analyze the structure and stability of 8 globular proteins, ranging in size from 36 to 370 residues. For each of the proteins, computational methods were used to estimate the groups buried and the number of hydrogen bonds formed during folding. The estimated conformational stabilities were then able to be determined. The estimated stabilities were larger than the observed stabilities, and the difference increased with increasing size. The most surprising finding was that the burial of charged groups also increased with increasing size from less than 25% in the small proteins to over 50% in the larger proteins. This suggests that burying charged groups in the interior of the protein is the primary strategy used to fine tune protein stability. To confirm these findings, it is recommended that the computational methods used in this study be extended to a larger sample of proteins and that experimental methods be used to gain a better understanding of the cost of burying charged groups in protein folding. | en |
