Assessing NMR-based Studies of Denatured Proteins using Non-random Structural Ensembles


Yue Zhang


Fitzkee, Nicholas C.

Committee Member

Lewis, Edwin A.

Committee Member

Emerson, Joseph P.

Date of Degree


Original embargo terms

MSU Only Indefinitely

Document Type

Graduate Thesis - Open Access

Degree Name

Master of Science


The random-coil model has been dominant for unfolded proteins since the 1950’s; however, some experiments showed that the unfolded proteins were biased toward specific conformations in conflict with the random-coil model. Recently, residual dipolar couplings (RDCs) and paramagnetic relaxation enhancement (PRE) were applied to obtain a large amount of structural information on unfolded proteins. Typically, these data were interpreted in a framework of random-coil ensembles with a good agreement between experimental data and theoretical predictions. In this thesis, it was tested whether locally organized nonrandom ensembles could describe this agreement equally as well. Using a complete set of RDC and PRE data for denatured ubiquitin, it was revealed that there was no distinguishable difference between random-coil ensembles and ensembles containing 50% native structure. Thus, while it is important to measure as many RDCs or PRE as possible, even the best datasets may be insensitive to local organization in unfolded proteins.



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