{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/61792"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/61792","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Methods and applications in computational protein design","abstract":"In this thesis, we summarize our work on applications and methods for computational protein design. First, we apply computational protein design to address the problem of degradation in stored proteins. Specifically, we target cysteine, asparagine, glutamine, and methionine amino acid residues to reduce or eliminate a protein's susceptibility to degradation via aggregation, deamidation, and oxidation. We demonstrate this technique on a subset of degradation-prone amino acids in phosphotriesterase, an enzyme that hydrolyzes toxic organophosphates including pesticides and chemical warfare agents. Second, we introduce BroMAP/A*, an exhaustive branch-and- bound search technique with enumeration. We compare performance of BroMAP/A* to DEE/A*, the current standard for conformational search with enumeration in the protein design community. When limited computational resources are available, DEE/A* sometimes fails to find the global minimum energy conformation and/or enumerate the lowest-energy conformations for large designs. Given the same computational resources, we show how BroMAP/A* is able to solve large designs by efficiently dividing the search space into small, solvable subproblems.","abstract_html":"In this thesis, we summarize our work on applications and methods for computational protein design. First, we apply computational protein design to address the problem of degradation in stored proteins. Specifically, we target cysteine, asparagine, glutamine, and methionine amino acid residues to reduce or eliminate a protein's susceptibility to degradation via aggregation, deamidation, and oxidation. We demonstrate this technique on a subset of degradation-prone amino acids in phosphotriesterase, an enzyme that hydrolyzes toxic organophosphates including pesticides and chemical warfare agents. Second, we introduce BroMAP/A*, an exhaustive branch-and- bound search technique with enumeration. We compare performance of BroMAP/A* to DEE/A*, the current standard for conformational search with enumeration in the protein design community. When limited computational resources are available, DEE/A* sometimes fails to find the global minimum energy conformation and/or enumerate the lowest-energy conformations for large designs. Given the same computational resources, we show how BroMAP/A* is able to solve large designs by efficiently dividing the search space into small, solvable subproblems.","abstract_has_math":false,"creators":["Biddle, Jason Charles"],"institution":"Massachusetts Institute of Technology","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Computation for Design and Optimization Program.","school":null,"contributors":[],"advisors":["Bruce Tidor."],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010","date_published":"2010","updated_at":"2026-07-22T22:21:30Z","subjects":["Computation for Design and Optimization Program."],"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/1721.1/61792","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Bruce Tidor."]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. Computation for Design and Optimization Program."]},{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["Massachusetts Institute of Technology. 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The certified thesis is available in the Institute Archives and Special Collections.","Cataloged from student-submitted PDF version of thesis.","Includes bibliographical references (p. 107-111)."]},{"key":"dc:description.abstract","label":"Abstract","values":["In this thesis, we summarize our work on applications and methods for computational protein design. First, we apply computational protein design to address the problem of degradation in stored proteins. Specifically, we target cysteine, asparagine, glutamine, and methionine amino acid residues to reduce or eliminate a protein's susceptibility to degradation via aggregation, deamidation, and oxidation. We demonstrate this technique on a subset of degradation-prone amino acids in phosphotriesterase, an enzyme that hydrolyzes toxic organophosphates including pesticides and chemical warfare agents. Second, we introduce BroMAP/A*, an exhaustive branch-and- bound search technique with enumeration. We compare performance of BroMAP/A* to DEE/A*, the current standard for conformational search with enumeration in the protein design community. When limited computational resources are available, DEE/A* sometimes fails to find the global minimum energy conformation and/or enumerate the lowest-energy conformations for large designs. Given the same computational resources, we show how BroMAP/A* is able to solve large designs by efficiently dividing the search space into small, solvable subproblems."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["S.M."]},{"key":"dc:title","label":"Title","values":["Methods and applications in computational protein design"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bruce Tidor."],"dc:contributor.department":["Massachusetts Institute of Technology. Computation for Design and Optimization Program."],"dc:contributor.other":["Massachusetts Institute of Technology. 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