{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/132648"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/132648","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Computational investigation of membrane proteins across species and functional classes","abstract":"Membrane proteins play central roles in cellular communication, metabolism, and homeostasis, yet experimental characterization of their dynamic interactions with membranes remains highly challenging. In this dissertation, I implement advanced molecular dynamics (MD) simulation workflows to investigate the conformational dynamics, substrate recognition, and lipid-mediated regulatory mechanisms of a diverse set of membrane-associated proteins across species and functional classes, spanning both peripheral and integral membrane proteins. I characterize the membrane-binding mechanism of human beta-2-glycoprotein I, revealing key electrostatic and hydrophobic interactions that drive anionic lipid recognition and identifying a previously unreported lipid-interaction site within its membrane-binding domain. I then explore substrate binding in human cytochrome P450 2J2 using molecular docking, MD simulations, and free energy perturbation calculations, elucidating structural determinants governing regioselective cannabinoid metabolism. Next, I examine lipid-dependent stabilization of the ATP-binding cassette transporter BmrCD from Bacillus subtilis, showing how specific membrane interactions contribute to efflux function and multidrug resistance mechanisms in Gram-positive bacteria. Finally, I investigate LetAB from Escherichia coli, a recently identified lipid transporter that spans the bacterial cell envelope, using atomistic simulations to define a putative phospholipid translocation pathway and establish the functional role of LetA in intermembrane lipid trafficking. Together, these studies demonstrate how computational biophysics can overcome long-standing barriers in membrane protein research by enabling atomic-scale resolution of lipid–protein coupling, rare conformational transitions, and catalytic processes inaccessible to experiment alone, ultimately advancing our understanding of membrane-associated protein function and informing therapeutic and antimicrobial strategies targeting these essential systems.","abstract_html":"Membrane proteins play central roles in cellular communication, metabolism, and homeostasis, yet experimental characterization of their dynamic interactions with membranes remains highly challenging. In this dissertation, I implement advanced molecular dynamics (MD) simulation workflows to investigate the conformational dynamics, substrate recognition, and lipid-mediated regulatory mechanisms of a diverse set of membrane-associated proteins across species and functional classes, spanning both peripheral and integral membrane proteins. I characterize the membrane-binding mechanism of human beta-2-glycoprotein I, revealing key electrostatic and hydrophobic interactions that drive anionic lipid recognition and identifying a previously unreported lipid-interaction site within its membrane-binding domain. I then explore substrate binding in human cytochrome P450 2J2 using molecular docking, MD simulations, and free energy perturbation calculations, elucidating structural determinants governing regioselective cannabinoid metabolism. Next, I examine lipid-dependent stabilization of the ATP-binding cassette transporter BmrCD from Bacillus subtilis, showing how specific membrane interactions contribute to efflux function and multidrug resistance mechanisms in Gram-positive bacteria. Finally, I investigate LetAB from Escherichia coli, a recently identified lipid transporter that spans the bacterial cell envelope, using atomistic simulations to define a putative phospholipid translocation pathway and establish the functional role of LetA in intermembrane lipid trafficking. Together, these studies demonstrate how computational biophysics can overcome long-standing barriers in membrane protein research by enabling atomic-scale resolution of lipid–protein coupling, rare conformational transitions, and catalytic processes inaccessible to experiment alone, ultimately advancing our understanding of membrane-associated protein function and informing therapeutic and antimicrobial strategies targeting these essential systems.","abstract_has_math":false,"creators":["Hasdemir, Hale Siir"],"institution":"University of Illinois Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biophysics & Quant Biology","degree_department":null,"school":null,"contributors":["Tajkhorshid, Emad","Das, Aditi","Shukla, Diwakar","Pogorelov, Taras"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-12","date_published":"2025-12","updated_at":"2026-07-22T22:25:07Z","subjects":["Membrane","Membrane protein","Molecular dynamics","Lipid–protein interactions","Peripheral membrane protein","Integral membrane protein","Beta-2-glycoprotein I","Antiphospholipid syndrome","Cytochrome P450","Cannabinoid metabolism","Free energy perturbation","ABC transporter","BmrCD","Multidrug resistance","LetAB","Lipid transport","Phospholipid translocation","Computational biophysics"],"languages":["en"],"rights":["Copyright 2025 Hale Siir Hasdemir"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/132648","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Tajkhorshid, Emad","Das, Aditi","Shukla, Diwakar","Pogorelov, Taras"]},{"key":"dc:creator","label":"Author","values":["Hasdemir, Hale Siir"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-12","2025-11-24"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biophysics & Quant 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 Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Membrane","Membrane protein","Molecular dynamics","Lipid–protein interactions","Peripheral membrane protein","Integral membrane protein","Beta-2-glycoprotein I","Antiphospholipid syndrome","Cytochrome P450","Cannabinoid metabolism","Free energy perturbation","ABC transporter","BmrCD","Multidrug resistance","LetAB","Lipid transport","Phospholipid translocation","Computational biophysics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2025 Hale Siir Hasdemir"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/132648"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Membrane proteins play central roles in cellular communication, metabolism, and homeostasis, yet experimental characterization of their dynamic interactions with membranes remains highly challenging. In this dissertation, I implement advanced molecular dynamics (MD) simulation workflows to investigate the conformational dynamics, substrate recognition, and lipid-mediated regulatory mechanisms of a diverse set of membrane-associated proteins across species and functional classes, spanning both peripheral and integral membrane proteins. I characterize the membrane-binding mechanism of human beta-2-glycoprotein I, revealing key electrostatic and hydrophobic interactions that drive anionic lipid recognition and identifying a previously unreported lipid-interaction site within its membrane-binding domain. I then explore substrate binding in human cytochrome P450 2J2 using molecular docking, MD simulations, and free energy perturbation calculations, elucidating structural determinants governing regioselective cannabinoid metabolism. Next, I examine lipid-dependent stabilization of the ATP-binding cassette transporter BmrCD from Bacillus subtilis, showing how specific membrane interactions contribute to efflux function and multidrug resistance mechanisms in Gram-positive bacteria. Finally, I investigate LetAB from Escherichia coli, a recently identified lipid transporter that spans the bacterial cell envelope, using atomistic simulations to define a putative phospholipid translocation pathway and establish the functional role of LetA in intermembrane lipid trafficking. Together, these studies demonstrate how computational biophysics can overcome long-standing barriers in membrane protein research by enabling atomic-scale resolution of lipid–protein coupling, rare conformational transitions, and catalytic processes inaccessible to experiment alone, ultimately advancing our understanding of membrane-associated protein function and informing therapeutic and antimicrobial strategies targeting these essential systems.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2027-12-01","The student, Hale Hasdemir, accepted the attached license on 2025-11-20 at 13:19.","The student, Hale Hasdemir, submitted this Dissertation for approval on 2025-11-20 at 13:39.","This Dissertation was approved for publication on 2025-11-24 at 13:47.","DSpace SAF Submission Ingestion Package generated from Vireo submission #22914 on 2026-02-19 at 18:45:49"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Computational investigation of membrane proteins across species and functional classes"]}]}],"canonical_facts":{"dc:contributor":["Tajkhorshid, Emad","Das, Aditi","Shukla, Diwakar","Pogorelov, Taras"],"dc:creator":["Hasdemir, Hale Siir"],"dc:date":["2025-12","2025-11-24"],"dc:description":["Membrane proteins play central roles in cellular communication, metabolism, and homeostasis, yet experimental characterization of their dynamic interactions with membranes remains highly challenging. In this dissertation, I implement advanced molecular dynamics (MD) simulation workflows to investigate the conformational dynamics, substrate recognition, and lipid-mediated regulatory mechanisms of a diverse set of membrane-associated proteins across species and functional classes, spanning both peripheral and integral membrane proteins. I characterize the membrane-binding mechanism of human beta-2-glycoprotein I, revealing key electrostatic and hydrophobic interactions that drive anionic lipid recognition and identifying a previously unreported lipid-interaction site within its membrane-binding domain. I then explore substrate binding in human cytochrome P450 2J2 using molecular docking, MD simulations, and free energy perturbation calculations, elucidating structural determinants governing regioselective cannabinoid metabolism. Next, I examine lipid-dependent stabilization of the ATP-binding cassette transporter BmrCD from Bacillus subtilis, showing how specific membrane interactions contribute to efflux function and multidrug resistance mechanisms in Gram-positive bacteria. Finally, I investigate LetAB from Escherichia coli, a recently identified lipid transporter that spans the bacterial cell envelope, using atomistic simulations to define a putative phospholipid translocation pathway and establish the functional role of LetA in intermembrane lipid trafficking. Together, these studies demonstrate how computational biophysics can overcome long-standing barriers in membrane protein research by enabling atomic-scale resolution of lipid–protein coupling, rare conformational transitions, and catalytic processes inaccessible to experiment alone, ultimately advancing our understanding of membrane-associated protein function and informing therapeutic and antimicrobial strategies targeting these essential systems.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2027-12-01","The student, Hale Hasdemir, accepted the attached license on 2025-11-20 at 13:19.","The student, Hale Hasdemir, submitted this Dissertation for approval on 2025-11-20 at 13:39.","This Dissertation was approved for publication on 2025-11-24 at 13:47.","DSpace SAF Submission Ingestion Package generated from Vireo submission #22914 on 2026-02-19 at 18:45:49"],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/132648"],"dc:language":["en"],"dc:rights":["Copyright 2025 Hale Siir Hasdemir"],"dc:subject":["Membrane","Membrane protein","Molecular dynamics","Lipid–protein interactions","Peripheral membrane protein","Integral membrane protein","Beta-2-glycoprotein I","Antiphospholipid syndrome","Cytochrome P450","Cannabinoid metabolism","Free energy perturbation","ABC transporter","BmrCD","Multidrug resistance","LetAB","Lipid transport","Phospholipid translocation","Computational biophysics"],"dc:title":["Computational investigation of membrane proteins across species and functional classes"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Biophysics & Quant Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:07Z"}