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dc.contributor.advisorScholtz, J. Martin
dc.creatorSchell, David Andrew
dc.date.accessioned2005-02-17T21:04:14Z
dc.date.available2005-02-17T21:04:14Z
dc.date.created2003-12
dc.date.issued2005-02-17
dc.identifier.urihttp://hdl.handle.net/1969.1/1526
dc.description.abstractProperly folded proteins are necessary for all living organisms. Incorrectly folded proteins can lead to a variety of diseases such as Alzheimer’s Disease or Bovine Spongiform Encephalitis (Mad Cow Disease). Understanding the forces involved in protein folding is essential to the understanding and treatment of protein misfolding diseases. When proteins fold, a significant amount of surface area is buried in the protein interior. It has long been known that burial of hydrophobic surface area was important to the stability of the folded structure. However, the impact of burying polar surface area is not well understood. Theoretical results suggest that burying polar groups decreases the stability, but experimental evidence supports the belief that polar group burial increases the stability. Studies of tyrosine to phenylalanine mutations have shown the removal of the tyrosine OH group generally decreases stability. Through computational investigations into the effect of buried tyrosine on protein stability, favorable van der Waals interactions are shown to correlate with the change in stability caused by replacing the tyrosine with phenylalanine to remove the polar OH group. Two large-scale studies on nearly 1000 high-resolution x-ray structures are presented. The first investigates the electrostatic and van der Waals interactions, analyzing the energetics of burying various atom groups in the protein interior. The second large-scale study analyzes the packing differences in the interior of the protein and shows that hydrogen bonding increases packing, decreasing the volume of a hydrogen bonded backbone by about 1.5 Å3 per hydrogen bond. Finally, a structural comparison between RNase Sa and a variant in which five lysines replaced five acidic groups to reverse the net charge is presented. It is shown that these mutations have a marginal impact on the structure, with only small changes in some loop regions.en
dc.format.extent5545232 bytesen
dc.format.mediumelectronicen
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherTexas A&M University
dc.subjectprotein foldingen
dc.subjectpackingen
dc.subjectRNaseen
dc.subjecthydrogen bondingen
dc.subjectpolar group burialen
dc.titleComputational and experimental investigations of forces in protein foldingen
dc.typeBooken
dc.typeThesisen
thesis.degree.departmentBiochemistry and Biophysicsen
thesis.degree.disciplineBiochemistryen
thesis.degree.grantorTexas A&M Universityen
thesis.degree.nameDoctor of Philosophyen
thesis.degree.levelDoctoralen
dc.contributor.committeeMemberLiWang, Andy
dc.contributor.committeeMemberPace, C. Nick
dc.contributor.committeeMemberKunkel, Gary
dc.type.genreElectronic Dissertationen
dc.type.materialtexten
dc.format.digitalOriginborn digitalen


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