Master of Science
The saponin QS21 has been used and studied for years as an adjuvant agent to improve vaccines for both humans and animals. However, how the saponin interacts with the membrane and itself remains poorly understood. We studied the QS21-A majority isomer using all-atom classical molecular dynamics simulations in model bilayers composed of cholesterol and either DOPC or DPPC. As this is one of the few computational studies on QS21-A, we had very few resources to compare our results to. Nevertheless, we were able to gain insight into possible configurations that QS21-A takes after penetration, the effect of the bilayer on QS21-A micelle formation, as well as hydrogen bonding and radius of gyration. We hope that our results will help with the development of better drugs and vaccines, but more work is needed to verify these results and understand both isomers.
Summary for Lay Audience
Vaccines are used to protect cells from various ailments with the most common one being viral in nature. To improve these vaccines, compounds called adjuvant agents are used. Saponins are a family of molecules known for creating soap-like foam in water that have been used to fulfil this role. The most studied saponin is a molecule called QS21, which has been used since its discovery. Despite its power, the use of QS21 is limited since we lack a full understanding on how it works, the limited supply, storage issues, and noted toxicity of the molecule. We do not even know if there is a difference between the two types of QS21. Due to this, we employed a computer-based method known as molecule dynamics to study the more common type of QS21 to gain insight to how it works with the bilayer. Using bilayers made from cholesterol and phosphatidylcholines, we looked at the shape and structure a group of QS21 molecules take as well as how the molecule bonded with the bilayer. We learnt about the structure that the QS21 molecules took, how the bilayer possibly changed the interactions QS21 made, and a possible method of how QS21 penetrates the bilayer. We hope that this information will help the development of better drugs and vaccines, but studies with the molecule must continue to gain a deeper understanding of QS21 and to verify these results.
Guerrero, Sarai, "Saponin Penetration and Interactions with Membranes" (2019). Electronic Thesis and Dissertation Repository. 6675.
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