Richard Swenson and Professor David Busath, PDBio
Importance of Project
In general, research of the function of proteins involved in harmful diseases helps researchers who are investigating these diseases better understand part of their puzzle to be able to find solutions to these problems and often opens doors for new treatments of other disorders. For example, to reduce wrinkles, doctors inject patients with Botulinum Neurotoxin(BoTox). I would like to add to the world’s understanding of BoTox so that new procedures can be developed and the harmful effects of botulism can be reduced. My research of Phospholipase A-2 (sPLA2) will likewise add to knowledge of the function of this and other similar proteins. sPLA2 is thought to play a role in atherosclerosis, gall stones, inflammatory diseases, and other disorders.
Botulinum Neurotoxin
I worked with a masters student at BYU named Brad Strongin to create a hypothesis about the quaternary structure of the botulinum toxin as it forms channels. We concluded that the botulinuum toxin forms a tetramer that inserts into the bilayer before creating a pore through which the toxic part can translocate.
Phospholipase A2
The main focus of my work was to examine the different forces involved in the extraction of lipids into the active site of phospholipase A2. This project specifically used molecular dynamics simulations to model a gel liquid lipid interface. Many unforeseen obstacles greatly impeded the progress of this project. However, as we have overcome these obstacles, we have learned much that will help future researchers in similar research. To our knowledge, we are the first to model a lipid domain interface of this type. The biggest problem in this type of modeling is the amount of computational power needed. I was able to work with the department computer support to install the needed software onto the university’s supercomputer. This will enable future students at BYU to conduct similar experiments. Another obstacle we had to address was what parameter to use for surface tension. In learning about this parameter, future students will be able to more quickly set up viable simulations.
The results of my experiments are inconclusive because of the number of ambiguous parameters among the field. However, my simulations were successful in doing what I was going to do. We hope that the results of this research will inspire others to conduct similar experiments to help refine the knowledge of the parameters necessary to ultimately answer questions of bilayer structure using computational techniques. This project has proved difficult, yet possible. I have recently applied to the Master’s program in the PDBio department. If accepted, I will continue refining the parameters of this project in hopes to gain conclusive results that reveal valuable information about the function of lipid rafts in bilayer membranes.