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dc.rights.licenseUsers may download and share copies with attribution in accordance with a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. No commercial use or derivatives are permitted without the explicit approval of the author.
dc.contributorMakhatadze, George I.
dc.contributorGarcía, Angel E.
dc.contributorRoyer, Catherine Ann
dc.contributorBarquera, Blanca L.
dc.contributor.authorChen, Calvin Rong-sen
dc.date.accessioned2021-11-03T08:54:14Z
dc.date.available2021-11-03T08:54:14Z
dc.date.created2017-11-10T13:04:56Z
dc.date.issued2017-08
dc.identifier.urihttps://hdl.handle.net/20.500.13015/2071
dc.descriptionAugust 2017
dc.descriptionSchool of Science
dc.description.abstractPiezophiles are extremophilic organisms that have evolved to survive at high hydrostatic pressures. They can be found at ocean depths of 11,000 meters where pressures reach 1,100 atmospheres and can even survive deep within in the Earth’s crust. Multitudes of thermophilic and piezophilic organisms thrive around hydrothermal vents where temperatures and pressures reach up to 400°C and 250 atm.
dc.description.abstractThe work presented here demonstrates the possibility of quantitative calculation of the individual volumetric properties of proteins, nucleic acids, and their changes upon unfolding. It opens the possibility for a proteome-wide analysis of pressure-stable proteins to better understand the underlying volumetric and structural characteristics that lead to pressure stability. It also reveals the potential strategies for engineering increased pressure stability in proteins by positively increasing ΔVTot and Δα through the increase of non-polar surface area upon unfolding and/or improvement of the protein packing efficiency.
dc.description.abstractIn the following chapters, we detail the steps taken to resolve this discrepancy through the creation of a geometric volume calculator for 3D structures (Chapter 2), the formulation of a rigorous volume decomposition scheme and calculation model for proteins, and the parameterization of the volumetric effects of hydration (Chapter 3). This resulted in excellent quantitative agreement with experimental ΔVTot values and resolution of the Protein Volume Paradox. We then extend the volumetric calculation model to encompass a temperature range of 280-340K to investigate the molecular determinants behind the positive temperature dependence of ΔVTot (Chapter 4), revealing that hydration volume is the primary contributor to protein expansivity and change in protein expansivity. Finally, we apply the volumetric decomposition scheme and calculation methodology to nucleic acids (Chapter 5). We obtain quantitative agreement of ΔVTot values with experiment, demonstrating the robustness and generalizability of the volume decomposition and calculation method previously used for proteins.
dc.description.abstractThe effect of pressure on macromolecular stability is directly related to the change in volume upon unfolding of a macromolecule, ΔVTot = (∂ΔGu/∂P)T. Experimentally, this value can range from -4 to +1% for proteins, indicating that pressure can either stabilize or destabilize proteins. The molecular details behind the magnitude and sign of volume changes upon unfolding have so far been unresolved. In addition, there exists a large discrepancy between the expected theoretical ΔVTot and the values observed from experiment, termed the “Protein Volume Paradox”. These are obstacles to obtaining a quantitative understanding of the volumetric changes that occur upon protein folding, denying insights into the strategies for imparting pressure stability to proteins.
dc.description.abstractThe existence of organisms at these extreme conditions is remarkable as the building blocks of life, proteins and nucleic acids, require a specific native three-dimensional structure to be functional, whereas environmental stressors like high pressure can denature these molecules and prevent organisms from growing at these conditions. Therefore, piezophiles must possess special adaptations in their macromolecules to handle these extreme conditions. To characterize these possible adaptations, we must first understand the relationship between pressure stability and properties of the macromolecule.
dc.language.isoENG
dc.publisherRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofRensselaer Theses and Dissertations Online Collection
dc.subjectBiology
dc.titleMolecular determinants of the effects of hydrostatic pressure on proteins and nucleic acids and their temperature dependence
dc.typeElectronic thesis
dc.typeThesis
dc.digitool.pid178623
dc.digitool.pid178624
dc.digitool.pid178625
dc.rights.holderThis electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
dc.description.degreePhD
dc.relation.departmentDept. of Biological Sciences


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