{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/114000"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/114000","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"From metabolites to macromolecules: Computational models of the E. coli and H. sapiens cytoplasms","abstract":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-12-01","abstract_html":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-12-01","abstract_has_math":false,"creators":["Rickard, Meredith"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Gruebele, Martin H","Pogorelov, Taras V","Luthey-Schulten, Zaida","van der Donk, Wilfred"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-04-29T21:46:16Z","date_published":"2022-04-29T21:46:16Z","updated_at":"2026-07-22T22:24:54Z","subjects":["Chemistry"],"languages":["en","eng"],"rights":["Copyright 2021 Meredith Rickard"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/114000","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Gruebele, Martin H","Pogorelov, Taras V","Luthey-Schulten, Zaida","van der Donk, Wilfred"]},{"key":"dc:creator","label":"Author","values":["Rickard, Meredith"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-04-29T21:46:16Z","2024-04-29T21:47:53Z","2021-12","2021-12-03"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"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":["Chemistry"]}]},{"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 2021 Meredith Rickard"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/114000"]}]},{"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 2023-12-01","The student, Meredith Rickard, accepted the attached license on 2021-12-02 at 13:34.","The student, Meredith Rickard, submitted this Dissertation for approval on 2021-12-02 at 13:38.","This Dissertation was approved for publication on 2021-12-03 at 12:15.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17362 on 2022-04-06 at 17:17:42","Made available in DSpace on 2022-04-29T21:46:16Z (GMT). No. of bitstreams: 5 RICKARD-DISSERTATION-2021.pdf: 5737675 bytes, checksum: 28b6ac1123f9548bfbdfe446935fbc60 (MD5) Rickard_dissertation_supplementary_tables.xlsx: 16847 bytes, checksum: 5368a9acbf1b0811d28f544fb138d89e (MD5) Guin_permission.pdf: 217459 bytes, checksum: 5e9e885052a328f236f7aa8e54178267 (MD5) JPCL_permission.pdf: 211890 bytes, checksum: 045534551702a203324626e4115bf355 (MD5) LICENSE.txt: 4213 bytes, checksum: 541eeb98fea92027b0fda88c353bbe78 (MD5) Previous issue date: 2021-12-03","Embargo set by: Seth Robbins for item 123364 Lift date: 2024-04-29T21:46:25Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 123364 Lift date: 2024-04-29T21:47:53Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","U of I Only","In recent years, there has been an increasing emphasis on the impact of the cellular environment on biomolecular dynamics. In particular, there is growing evidence that the cell’s environment is finely tuned to modulate the stability, kinetics, binding, and activity of proteins within it. This thesis uses computational techniques to better understand the atomistic mechanisms underlying these impacts on protein dynamics. I begin by describing the motivation and challenges of simulating biomolecules in-cell. In Chapter 1, I discuss the in-cell environment and introduce crowding, sticking, and quinary interactions, the basic interactions that affect protein-dynamics in-cell. I briefly highlight several experimental studies that have demonstrated the impact of the cellular environment on protein dynamics over the last fifteen years. Then, I discuss the history and current landscape of simulating biomolecules in cellular conditions, including notable studies and ongoing challenges. In Chapter 2, I describe the design, construction, and simulation of my contribution to this landscape—several ~200,000 atom models that depict small sections of the E. coli and H. sapiens cytoplasm in atomistic detail. Then, I move into the results of these cytosolic simulations, including the effect of the cellular environment on ATP (Chapter 3), the partial folding of a small, fast-folding WW domain in the E. coli models (Chapter 4), and the nonspecific protein-protein sticking observed throughout my simulations (Chapter 5). Additionally, I present preliminary results from the H. sapiens cytoplasm simulations, including partial folding of another fast-folding construct and quinary interactions between two enzymes (Chapter 6). Finally, I describe the results of a collaboration between the Gruebele group, the Pogorelov group, Professor Stephen Taylor (UIUC Department of Music), Kurt Hebel, and Carla Scaletti (both of the sound design software company Symbolic Sound). Together, we have developed data sonification techniques to use sound as a teaching tool and data analysis aid in protein folding research (Chapter 7)."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["From metabolites to macromolecules: Computational models of the E. coli and H. sapiens cytoplasms"]}]}],"canonical_facts":{"dc:contributor":["Gruebele, Martin H","Pogorelov, Taras V","Luthey-Schulten, Zaida","van der Donk, Wilfred"],"dc:creator":["Rickard, Meredith"],"dc:date":["2022-04-29T21:46:16Z","2024-04-29T21:47:53Z","2021-12","2021-12-03"],"dc:description":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-12-01","The student, Meredith Rickard, accepted the attached license on 2021-12-02 at 13:34.","The student, Meredith Rickard, submitted this Dissertation for approval on 2021-12-02 at 13:38.","This Dissertation was approved for publication on 2021-12-03 at 12:15.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17362 on 2022-04-06 at 17:17:42","Made available in DSpace on 2022-04-29T21:46:16Z (GMT). No. of bitstreams: 5 RICKARD-DISSERTATION-2021.pdf: 5737675 bytes, checksum: 28b6ac1123f9548bfbdfe446935fbc60 (MD5) Rickard_dissertation_supplementary_tables.xlsx: 16847 bytes, checksum: 5368a9acbf1b0811d28f544fb138d89e (MD5) Guin_permission.pdf: 217459 bytes, checksum: 5e9e885052a328f236f7aa8e54178267 (MD5) JPCL_permission.pdf: 211890 bytes, checksum: 045534551702a203324626e4115bf355 (MD5) LICENSE.txt: 4213 bytes, checksum: 541eeb98fea92027b0fda88c353bbe78 (MD5) Previous issue date: 2021-12-03","Embargo set by: Seth Robbins for item 123364 Lift date: 2024-04-29T21:46:25Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 123364 Lift date: 2024-04-29T21:47:53Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","U of I Only","In recent years, there has been an increasing emphasis on the impact of the cellular environment on biomolecular dynamics. In particular, there is growing evidence that the cell’s environment is finely tuned to modulate the stability, kinetics, binding, and activity of proteins within it. This thesis uses computational techniques to better understand the atomistic mechanisms underlying these impacts on protein dynamics. I begin by describing the motivation and challenges of simulating biomolecules in-cell. In Chapter 1, I discuss the in-cell environment and introduce crowding, sticking, and quinary interactions, the basic interactions that affect protein-dynamics in-cell. I briefly highlight several experimental studies that have demonstrated the impact of the cellular environment on protein dynamics over the last fifteen years. Then, I discuss the history and current landscape of simulating biomolecules in cellular conditions, including notable studies and ongoing challenges. In Chapter 2, I describe the design, construction, and simulation of my contribution to this landscape—several ~200,000 atom models that depict small sections of the E. coli and H. sapiens cytoplasm in atomistic detail. Then, I move into the results of these cytosolic simulations, including the effect of the cellular environment on ATP (Chapter 3), the partial folding of a small, fast-folding WW domain in the E. coli models (Chapter 4), and the nonspecific protein-protein sticking observed throughout my simulations (Chapter 5). Additionally, I present preliminary results from the H. sapiens cytoplasm simulations, including partial folding of another fast-folding construct and quinary interactions between two enzymes (Chapter 6). Finally, I describe the results of a collaboration between the Gruebele group, the Pogorelov group, Professor Stephen Taylor (UIUC Department of Music), Kurt Hebel, and Carla Scaletti (both of the sound design software company Symbolic Sound). Together, we have developed data sonification techniques to use sound as a teaching tool and data analysis aid in protein folding research (Chapter 7)."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/114000"],"dc:language":["en","eng"],"dc:rights":["Copyright 2021 Meredith Rickard"],"dc:subject":["Chemistry"],"dc:title":["From metabolites to macromolecules: Computational models of the E. coli and H. sapiens cytoplasms"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:54Z"}