Construction of a synaptic membrane for in silico endocannabinoid investigations

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Kimberly M. Zorn (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Patricia Reggio

Abstract: The mechanism of a chemical reaction cannot be assumed prior to identifying the solvent, thus to accurately model membrane-bound cannabinoid receptors, details of the lipid bilayer must be considered as well. Traditionally thought of as a permeable barrier, the membrane also serves as a medium for hydrophobic ligand delivery; the Reggio group has published on the entry of sn-2-arachidonoylglycerol into the cannabinoid CB2 receptor through the trans-membrane region. Currently receptor and ligand trajectories are calculated in a single-phospholipid bilayer, however biological membranes are comprised of many lipid species. Herein nanosecond timescale molecular dynamics studies of various membrane compositions are reported, culminating to a final model mimicking a synaptic plasma membrane in phospholipid composition. Structural changes to phospholipids in increasingly heterogeneous compositions are discussed, along with interactions between endocannabinoid N-arachidonoylglycine (NAGly) and membrane components. The final model provides a significant contrast to a pure phosphatidylcholine bilayer, in addition to proposing new investigations of ligand diffusion, phospholipid clustering, and similar hydrogen bonding studies.

Additional Information

Publication
Thesis
Language: English
Date: 2016
Keywords
Membrane, Molecular dynamics
Subjects
Biological transport
G proteins $x Receptors
Cannabinoids $x Receptors
Ligands (Biochemistry)

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