Design of protein-protein interaction specificity using computational methods and experimental library screening
Name
783793039-MIT.pdf
Description
Full printable version
Size
15.21 MB
Format
Adobe PDF
Checksum (MD5)
68e3659ed83f41e80017a68bdbb5f7ba
Author(s)
Chen, Tsan-Chou Scott
Advisor(s)
Amy Keating.
Date Issued
2012
Publisher
Massachusetts Institute of Technology
Abstract
Computational design of protein-protein interaction specificity is a powerful tool to examine and expand our understanding about how protein sequence determines interaction specificity. It also has many applications in basic bioscience and biotechnology. One of the major challenges for design is that current scoring functions relying on general physical principles do not always make reliable predictions about interaction specificity. In this thesis I described application of two approaches to address this problem. The first approach sought to improve scoring functions with experimental interaction specificity data related to the protein family of design interest. I used this approach to design inhibitor peptides against the viral bZIP protein BZLF 1. Specificity against design self-interaction was considered in the study. The second approach exploited the power of experimental library screening to characterize a large number of designed sequences at once, increasing the overall probability of identifying successful designs. I presented a novel framework for such library design approach and applied it to the design of anti-apoptotic Bcl-2 proteins with novel interaction specificity toward BH3 peptides. Finally I proposed how these two approaches can be combined together to further enhance our design capabilities.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2012.
Cataloged from PDF version of thesis.
Includes bibliographical references.
Subjects
Biology.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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