Elucidating the Interplay Between Lipids and Membrane Proteins Using Multiscale Computer Simulations

Simple item page
dc.contributor.advisorTieleman, Dirk Peter
dc.contributor.authorSejdiu, Besian I.
dc.contributor.committeememberNg, Kenneth Kai Sing
dc.contributor.committeememberMacCallum, Justin L.
dc.contributor.committeememberLyman, Edward
dc.contributor.committeememberDerksen, Darren J.
dc.date2020-11
dc.date.accessioned2020-08-10T13:38:01Z
dc.date.available2020-08-10T13:38:01Z
dc.date.issued2020-07-30
dc.description.abstractBiological membranes are complex cellular structures formed by a large number of different lipid types, that also contain a variety of bound proteins, carbohydrates, and other molecules. The detailed orchestration of all these elements has been a major focus of scientific research during the last 5 decades. Computer-based methods, such as molecular dynamics (MD) simulations, have proven to be a valuable approach in addressing many of the details of lipid organization and membrane protein activity. I used MD simulations at both atomistic and coarse-grained level of detail to study the number of way lipids and proteins interact and their possible functional ramifications. In part of my work, I studied the interaction of G Protein-Coupled Receptors (GPCRs) with lipids at a family-wide level. Plenty of other computational studies had shown specific lipid-protein interactions for a handful of GPCRs but with quite different outcomes on their number, location, and lipid identity. In my work, I simulated 28 different GPCR structures and showed that they are distinguished by a unique interaction profile with membrane lipids. I provided a comprehensive analysis of simulation results with available crystallographic data. I also studied the lipid-protein interaction profile of AMPA receptors and cyclooxygenases (mainly COX-1), showing that they both form specific interactions with lipids, but do so in a quite different fashion. AMPA receptors interact specifically with diacylglycerol lipids, whereas COX-1 enzymes do so indiscriminately with glycerophospholipids, cholesterol, and fatty acids, but at different levels of interaction strength. Using atomistic simulations, we show the binding pathway of arachidonic acid to COX-1 and identify a series of arginine residues that guide it toward the hydrophobic cavity of the enzyme. As part of my work, I also developed a webserver that automates the analysis and visualization of lipid-protein interactions from MD simulations allowing for the creation of automated pipelines to study lipid-protein interactions in the future. Lastly, I provide a short review of some of the main challenges facing the field along with possible solutions going forward. My work expands our understanding of lipid-protein interactions.en_US
dc.identifier.citationSejdiu, B. I. (2020). Elucidating the Interplay Between Lipids and Membrane Proteins Using Multiscale Computer Simulations (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/38063
dc.identifier.urihttp://hdl.handle.net/1880/112372
dc.language.isoengen_US
dc.publisher.facultyScienceen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectmembrane proteinsen_US
dc.subjectcomputer simulationsen_US
dc.subjectmolecular dynamicsen_US
dc.subjectG Protein Coupled Receptorsen_US
dc.subjectlipid-protein interactionsen_US
dc.subject.classificationBiophysicsen_US
dc.subject.classificationBiochemistryen_US
dc.titleElucidating the Interplay Between Lipids and Membrane Proteins Using Multiscale Computer Simulationsen_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineBiological Sciencesen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrueen_US
Files
Original bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
ucalgary_2020_sejdiu_besian.pdf
Size:
12.09 MB
Format:
Adobe Portable Document Format
Description:
Thesis Document
Download
Thumbnail Image
Name:
ucalgary_2020_sejdiu_besian_supplementary_data.zip
Size:
23.35 MB
Format:
Zip files based on Chrome
Description:
Supplementary Data Files
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.62 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Open Theses and Dissertations