Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Applied Mathematics

Supervisor

Mikko Karttunen

Abstract

We have performed molecular modeling of membrane and peptide systems by employing the classical molecular dynamics method and force field parameterizations. In this thesis, our main interest is the interaction of sterols as well as peptides with membranes. The thesis consists of three related projects. The first project focuses on cholesterol (CHOL) and dehydroergosterol (DHE) interacting with palmitoyl-oleoyl phosphatidylcholine (POPC) lipid bilayers. We study the effects of both sterols on the bilayer and compare them with each other. We first study the condensing and ordering effect of these sterols. Then, we study their orientations within the bilayer and relate them to their interactions with the bilayer.In the second project, we study the interaction of a cell-penetrating-peptide, namely transportan, with dipalmitoyl phosphatidylcholine (DPPC) lipid bilayers with the aim of understanding the physical mechanism of the penetration process. By analyzing 10 simulations, we shed light on the behavior of the peptide and membrane when they are associated with each other. We also analyze four simulations in which the peptide is directly inserted in the bilayer core so as to study the behavior of the peptide when it is deep in the bilayer. By using umbrella sampling method and performing 41 biased simulations, we also try to find the free energy profile of the system as a function of the distance between the peptide and the center of mass of the bilayer.In the third project, we study the interaction of another cell-penetrating peptide, namely penetratin, with DPPC lipid bilayers. In this research, the spontaneous binding of a penetratin peptide as well as the role of different residues in binding are investigated. The behavior of penetratin is then compared with that of transportan and important differences are highlighted.

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