Novel methods in computational analysis and design of protein-protein interactions : applications to phosphoregulated interactions
Name
156998703-MIT.pdf
Description
Full printable version
Size
7.2 MB
Format
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Author(s)
Joughin, Brian Alan
Advisor(s)
Bruce Tidor and Michael B. Yaffe.
Date Issued
2007
Publisher
Massachusetts Institute of Technology
Abstract
This thesis presents a number of novel computational methods for the analysis and design of protein-protein complexes, and their application to the study of the interactions of phosphopeptides with phosphopeptide-binding domain interactions. A novel protein-protein interaction type, the action-at-a-distance interaction, is described in the complex of the TEM1 P-lactamase with the 3-lactamase inhibitor protein (BLIP). New action-at-a-distance interactions were designed on the surface of BLIP and computed to enhance the affinity of that complex. A new method is described for the characterization and prediction of protein ligand-binding sites. This method was used to analyze the phosphoresidue-contacting sites of known phosphopeptide-binding domains, and to predict the sites of phosphoresidue-contact on some protein domains for which the correct site was not known. The design of a library of variant WW domains that is predicted to be enriched in domains that might have specificity for "pS/pT-Q" peptide ligands is detailed. General methods for designing libraries of degenerate oligonucleotides for expressing protein libraries as accurately as possible are given, and applied to the described WW domain variant library.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2007.
Includes bibliographical references (p. 107-130).
Subjects
Biology.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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