Department

Chemistry

Program

Theory and Computation

Year

Master's 2nd Year

Supervisor Name

Mikko Karttunen

Supervisor Email

mkarttu@uwo.ca

Abstract Text

Saponins have been used as adjuvant agents for decades in vaccines and therapies, but none are as well studied or heavily used as QS-21. This achievement is notwithstanding the fact that QS-21 usage is limited by its stability, toxicity, and scarcity. These shortcomings have only pushed researchers to develop and experiment with artificial recreations of the saponin to harness its unique benefits. A considerable number of research hours have been poured into this topic, but like QS-21 there is a shortcoming here as well. The number of articles that look at QS-21 interactions with the bilayer or the conditions under which QS-21 will interact appeared as scarcely as QS-21 itself. In this work, we used molecular dynamic simulations to study how QS-21 interacts with the plasma membrane also known as the cell bilayer. To gain a proper understanding of the interactions, we created multiple systems designed to address a certain set of questions. Most of these systems are large lipid-cholesterol systems made from dipalmitoyl-phosphatidylcholine (DPPC), dioleoyl-phosphatidylcholine (DOPC), or distearoyl-phosphatidylcholine (DSPC) mixed with cholesterol with differing numbers of QS-21 molecules to investigate how the saponin interacts with the bilayer. Others were reference systems of QS-21 and counterions to understand QS-21 self-interactions. Lastly, some where designed for free energy difference calculations to quantify which bilayer composition was most favourable. We aim to provide an atomic-level understanding of QS-21 and bilayer interactions that can be used by experimentalists and theoreticians to develop better ways of studying QS-21 themselves by combining these results together.

In progress (data not fully collected)

Dietary Restrictions

I can't eat blue cheese and, while items touching it may not be a problem, I've been told to still avoid it. This has to do with my allergies to penicillin and cephalosporin. I've also ran into some problems with some mushrooms, but this is very sporadic.

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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Using Molecular Dynamics to Study QS21 Interactions and Penetration of Lipid-Cholesterol Bilayers

Saponins have been used as adjuvant agents for decades in vaccines and therapies, but none are as well studied or heavily used as QS-21. This achievement is notwithstanding the fact that QS-21 usage is limited by its stability, toxicity, and scarcity. These shortcomings have only pushed researchers to develop and experiment with artificial recreations of the saponin to harness its unique benefits. A considerable number of research hours have been poured into this topic, but like QS-21 there is a shortcoming here as well. The number of articles that look at QS-21 interactions with the bilayer or the conditions under which QS-21 will interact appeared as scarcely as QS-21 itself. In this work, we used molecular dynamic simulations to study how QS-21 interacts with the plasma membrane also known as the cell bilayer. To gain a proper understanding of the interactions, we created multiple systems designed to address a certain set of questions. Most of these systems are large lipid-cholesterol systems made from dipalmitoyl-phosphatidylcholine (DPPC), dioleoyl-phosphatidylcholine (DOPC), or distearoyl-phosphatidylcholine (DSPC) mixed with cholesterol with differing numbers of QS-21 molecules to investigate how the saponin interacts with the bilayer. Others were reference systems of QS-21 and counterions to understand QS-21 self-interactions. Lastly, some where designed for free energy difference calculations to quantify which bilayer composition was most favourable. We aim to provide an atomic-level understanding of QS-21 and bilayer interactions that can be used by experimentalists and theoreticians to develop better ways of studying QS-21 themselves by combining these results together.