{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/116027"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/116027","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Simulating atomic-level interactions in the coagulation cascade","abstract":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-08-01","abstract_html":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-08-01","abstract_has_math":false,"creators":["Muller, Melanie P."],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biophysics & Computnl Biology","degree_department":null,"school":null,"contributors":["Tajkhorshid, Emad","Shukla, Diwkar","Morrissey, James H","Rienstra, Chad"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-08","date_published":"2022-08","updated_at":"2026-07-22T22:24:55Z","subjects":["extrinsic complex","factor X","factor VII","protein-lipid interactions"],"languages":["en","eng"],"rights":["Copyright 2022 Melanie P. Muller"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/116027","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Tajkhorshid, Emad","Shukla, Diwkar","Morrissey, James H","Rienstra, Chad"]},{"key":"dc:creator","label":"Author","values":["Muller, Melanie P."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-08","2022-07-05"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biophysics & Computnl Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["extrinsic complex","factor X","factor VII","protein-lipid interactions"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2022 Melanie P. Muller"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/116027"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-08-01","The student, Melanie Muller, accepted the attached license on 2022-06-27 at 19:10.","The student, Melanie Muller, submitted this Dissertation for approval on 2022-06-27 at 19:38.","This Dissertation was approved for publication on 2022-07-05 at 09:58.","DSpace SAF Submission Ingestion Package generated from Vireo submission #18056 on 2022-11-15 at 19:16:16","The reactions that take place within the coagulation cascade are essential for formation of clots. They are critical for wound healing when activated properly, and when improperly activated can result in devastating health consequences. The biochemical reactions that make up the cascade have been extensively mapped experimentally, but the detailed mechanisms of coagulation modulation and protease activation have remained elusive. This is partly due to the atomic-level nature of the highly specific interaction between coagulation proteins and membrane phospholipids which allow spontaneous binding from plasma for a number of coagulation proteins at the initiation of clotting. Several important coagulation proteins are also highly flexible, which has made experimental characterization of their complete structures at atomic resolution prohibitively difficult. Computational methodologies provide a unique means of investigating atomic-level interactions of the blood coagulation cascade that are out of reach with experimental methods. Here, we present our findings probing protein-lipid interactions and complex formation of blood coagulation proteins using computational means. Molecular dynamics simulations have been used to model spontaneous membrane binding and protein-lipid interactions of the membrane binding domains of factor X, factor VII, and factor IX at an atomic level. Building on these simulations, we developed an atomic-level, membrane-bound model of the ternary extrinsic complex of blood coagulation using a novel computational methodology combining nonequilibrium molecular dynamics, specialized membrane bilayer representations, and protein-protein docking. Finally, we will present our atomic-level model of tissue factor:factor VIIa bound to XK1, a tissue factor protease inhibitor and factor X hybrid molecule, and discuss potential for future approaches combining experimental and computational methodologies to probe interactions in the coagulation cascade."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Simulating atomic-level interactions in the coagulation cascade"]}]}],"canonical_facts":{"dc:contributor":["Tajkhorshid, Emad","Shukla, Diwkar","Morrissey, James H","Rienstra, Chad"],"dc:creator":["Muller, Melanie P."],"dc:date":["2022-08","2022-07-05"],"dc:description":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-08-01","The student, Melanie Muller, accepted the attached license on 2022-06-27 at 19:10.","The student, Melanie Muller, submitted this Dissertation for approval on 2022-06-27 at 19:38.","This Dissertation was approved for publication on 2022-07-05 at 09:58.","DSpace SAF Submission Ingestion Package generated from Vireo submission #18056 on 2022-11-15 at 19:16:16","The reactions that take place within the coagulation cascade are essential for formation of clots. They are critical for wound healing when activated properly, and when improperly activated can result in devastating health consequences. The biochemical reactions that make up the cascade have been extensively mapped experimentally, but the detailed mechanisms of coagulation modulation and protease activation have remained elusive. This is partly due to the atomic-level nature of the highly specific interaction between coagulation proteins and membrane phospholipids which allow spontaneous binding from plasma for a number of coagulation proteins at the initiation of clotting. Several important coagulation proteins are also highly flexible, which has made experimental characterization of their complete structures at atomic resolution prohibitively difficult. Computational methodologies provide a unique means of investigating atomic-level interactions of the blood coagulation cascade that are out of reach with experimental methods. Here, we present our findings probing protein-lipid interactions and complex formation of blood coagulation proteins using computational means. Molecular dynamics simulations have been used to model spontaneous membrane binding and protein-lipid interactions of the membrane binding domains of factor X, factor VII, and factor IX at an atomic level. Building on these simulations, we developed an atomic-level, membrane-bound model of the ternary extrinsic complex of blood coagulation using a novel computational methodology combining nonequilibrium molecular dynamics, specialized membrane bilayer representations, and protein-protein docking. Finally, we will present our atomic-level model of tissue factor:factor VIIa bound to XK1, a tissue factor protease inhibitor and factor X hybrid molecule, and discuss potential for future approaches combining experimental and computational methodologies to probe interactions in the coagulation cascade."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/116027"],"dc:language":["en","eng"],"dc:rights":["Copyright 2022 Melanie P. Muller"],"dc:subject":["extrinsic complex","factor X","factor VII","protein-lipid interactions"],"dc:title":["Simulating atomic-level interactions in the coagulation cascade"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Biophysics & Computnl Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:55Z"}