The goal of the research was to develop a Protein-Specific Properties Evaluation (PSPE) framework that would aid in the statistical evaluation of variables for predicting ranges of and prior probability distributions for protein crystallization conditions. Development of such a framework is motivated by the rapid growth and evolution of the Protein Data Bank. Features of the framework that has been developed include (1) it is an instantiation of the scientific method for the framing and testing of hypotheses in an informatics setting, (2) the use of hidden variables, and (3) a negative result is still useful.
The hidden variables examined in this study are related to the estimated net charge (Q) of the proteins under consideration. The Q is a function of the amino acid composition, the solution pH, and the assumed pKa values for the titratable amino acid residues. The proteins size clearly has a significant impact on the magnitude of the Q. Therefore, two additional variables were introduced to mitigate this effect, the specific charge (Qbar) and the average surface charge density (sigma).
The principal observation is that proteins appear to crystallize at low values of Qbar and sigma. One problem with this observation is that low is a relative term and the frame of reference requires careful examination. The results are sufficiently weak that no prospective predictions appear possible although information of this type could be included with other weak predictors in a Bayesian predictor scheme. Additional work would be required to establish this; however that work is beyond the scope of the dissertation. Although many statistically significant correlations among Q-related quantities were noted, no evidence could be developed to suggest they were anything other than those expected from the additional information introduced with the hidden variables.
Thus, the principal conclusions of this PSPE analysis are that (1) Qbar/sigma and other Q-related variables are of limited value as prospective predictors of ranges of values of crystallization conditions. Although this is a negative result, it is still useful in that it allows attention to be directed into more productive avenues.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-10012007-171912 |
| Date | 04 January 2008 |
| Creators | Dougall, David Stephen |
| Contributors | Johh M. Rosenberg, Jerrold H. May, James Lyons-Weiler, Gregory F. Cooper, Vanathi Gopalakrishnan |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-10012007-171912/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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