2026-09-20T08:11:34Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/132648 2026-03-24 col_2142_5131 col_2142_14828 com_2142_5130 com_2142_14827 com_2142_14793 com_2142_8903

application/pdf en text 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 Computational investigation of membrane proteins across species and functional classes Hasdemir, Hale Siir 2025-11-24 Tajkhorshid, Emad Tajkhorshid, Emad Das, Aditi Shukla, Diwakar Pogorelov, Taras 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 eng 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. 2025-12 Thesis https://hdl.handle.net/2142/132648 Copyright 2025 Hale Siir Hasdemir School of Molecular & Cell Bio Biophysics & Quant Biology University of Illinois Urbana-Champaign Ph.D. Dissertation