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dc.contributor.authorYang, Ming
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 58-07, Section: B, page: 3515.;Advisors: Joel M. Friedman.
dc.description.abstractProtein dynamics include both equilibrium thermal fluctuations and non-equilibrium structural relaxation. This thesis both describes experiments that are designed to show how these two classes of protein dynamics influence ligand binding reactivity in hemoglobin and interprets these dynamics using a newly developed mathematical field dynamics model. This unified model reduces to several former models under appropriate limiting conditions.;Three distinct processes are observed for ligand recombination subsequent to photo dissociation of COHbA at ambient temperatures. Process I is the geminate rebinding (GR) phase S(t){dollar}\rm\sb{lcub}p{rcub}{dollar} persisting from tens to hundreds of nanoseconds, process II is the exponential R state solvent phase S(t){dollar}\rm\sb{lcub}e{rcub}{dollar} with a time scale of hundreds of microseconds and the slowest process III is the T state solvent phase S(t){dollar}\rm\sb{lcub}s{rcub},{dollar} which lasts beyond tens of milliseconds.;Temperature and viscosity effects on these processes are examined. The acceleration of the apparent GR rate upon reduction of the temperature from 300 to 200 K is the inverse GR temperature effect. This effect is caused by a slowing down of the tertiary relaxation in the photodissociated hemoglobin at lower temperature. The rebinding of both the R and T state solvent phases S(t){dollar}\rm\sb{lcub}e{rcub}{dollar} and S(t){dollar}\rm\sb{lcub}s{rcub}{dollar} exhibit normal viscosity effect, i.e., the bimolecular rebinding rates are slowed as the viscosity is increased. The reverse viscosity effect, discovered as an increase in the apparent rate, the yield and the duration of the geminate phase while increasing solvent viscosity, originate from a retardation of the tertiary relaxation in the photodissociated hemoglobin at higher viscosity solvent.;The conformational substrates in hemoglobin are organized in a hierarchical fashion as is their dynamics and associated ligand binding kinetics. The dynamics and conformational disorder in several sub populations of hemoglobin have been studied. For HbAO{dollar}\sb3{dollar} in a potassium phosphate buffer, the geminate phase of the rephotolyzed fraction contains a higher fraction of "fast" recombining molecules. These two GR components (fast and slow) are not conformationally averaged within 1.2 ns even at RT.;In aqueous buffer HbCO, the geminate phases of both populations are identical within 60 ns of the initial photo dissociative event, indicative of the protein being homogeneous on this time scale at room temperature with respect to the potential energy barrier controlling bond formation. At viscosity of 2650 cp and temperature of 280 K, with 60 ns delay the rephotolyzed fraction contains faster GR component when compared to the fully photolyzed population, indicating that the conformational substates are distributed along with an activation energy spectrum.
dc.publisherProQuest Dissertations & Theses
dc.subjectAnimal Physiology.
dc.titleDynamics and conformational disorder in hemeproteins

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