Date of Graduation

5-2026

Document Type

Thesis

Degree Name

Bachelor of Science in Biology

Degree Level

Undergraduate

Department

Biological Sciences

Advisor/Mentor

Mahmoud Moradi

Committee Member

Michael Hoover

Second Committee Member

Dan Lessner

Third Committee Member

Oliver Lin

Abstract

P-Glycoprotein (Pgp) is a human efflux pump that belongs to the ABC transporter family. This protein consists of two transmembrane domains (TMD) that convert between inward to outward facing configurations to remove a wide variety of structurally different compounds from the intracellular membrane into the extracellular space using ATP.  This non-specific efflux of compounds has brought Pgp to scientific light as having a major role in multi-drug resistance of many diseases, and researchers are focused on developing a deeper understanding of the protein. To further this understanding, this study analyzed how the structure of Pgp is affected by a 10% concentration of cholesterol with 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) as the bulk lipid in the surrounding membrane. To examine the effects of 10% cholesterol in the surrounding membrane of the Pgp transporter, a simulation system was created in CHARMM-GUI and sent to the NAMD molecular dynamics simulation program to observe how the system would interact in real life conditions. Using these calculated trajectories, the data was run through a Root Mean Square Division (RMSD) and Root Mean Square Fluctuation (RMSF) equation. This study also connected data of the extracellular (EC) angle and the distance between the intracellular nucleotide binding domain (NBD) distance over the simulated time. Visual Molecular Dynamics (VMD) was used to visualize the inward-facing and outward-facing configurations of the protein.

Keywords

P-Glycoprotein; Molecular Dynamics; Computer Simulation; Multi-Drug Resistance; NAMD; CHARMM-GUI

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