{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/38630"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/38630","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Novel methods in computational analysis and design of protein-protein interactions : applications to phosphoregulated interactions","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Joughin, Brian Alan"],"institution":"Massachusetts Institute of Technology","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Dept. of Biology.","school":null,"contributors":[],"advisors":["Bruce Tidor and Michael B. Yaffe."],"committee_chairs":[],"committee_members":[],"year":2007,"date_issued":"2007","date_published":"2007","updated_at":"2026-07-22T22:21:58Z","subjects":["Biology."],"languages":["eng"],"rights":["M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission."],"rights_urls":["http://dspace.mit.edu/handle/1721.1/7582"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1721.1/38630","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Bruce Tidor and Michael B. Yaffe."]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. Dept. of Biology."]},{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["Massachusetts Institute of Technology. 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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."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["Novel methods in computational analysis and design of protein-protein interactions : applications to phosphoregulated interactions"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bruce Tidor and Michael B. Yaffe."],"dc:contributor.department":["Massachusetts Institute of Technology. Dept. of Biology."],"dc:contributor.other":["Massachusetts Institute of Technology. Dept. of Biology."],"dc:creator":["Joughin, Brian Alan"],"dc:date.accessioned":["2007-08-29T20:37:35Z"],"dc:date.available":["2007-08-29T20:37:35Z"],"dc:date.issued":["2007"],"dc:description":["Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2007.","Includes bibliographical references (p. 107-130)."],"dc:description.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). 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