Computational Modeling of Lipoprotein Particles
|Kustantaja||Tampere University of Technology|
|Tila||Julkaistu - 4 huhtikuuta 2018|
|Nimi||Tampere University of Technology. Publication|
The ﬁrst key result of this thesis is the detailed structural model found for both HDL and LDL, showing that the previously proposed 2- and 3-layer models are inadequate for describing lipoprotein structure to a sufficient degree. It was found that the structural and dynamic properties of lipids hosted by lipoproteins depend significantly on their location and distance from the center of the particle. Second, this thesis work revealed the mechanism and the residues involved in anchoring CETP to the surface of lipoprotein particles. Also, the critical role of helix X as a door to the hydrophobic tunnel carrying the cargo lipids was clariﬁed. Third, based on BODIPY-simulations reported in this thesis one can conclude that BODIPY-labeled cholesteryl oleate is not a suitable probe for experimental cholesteryl oleate tracking studies in lipoprotein environments. It appears that a successful probe in a lipoprotein environment should have no signiﬁcant affinity for the hydrophilic surface region.
The ﬁndings give a solid grounds for further studies to explore the key initial steps associated with atherosclerosis and also the molecular-level events in the lipid exchange processes. For future purposes, this work demonstrates that the used simulation methods are particularly useful for studies of, e.g., the coupling between the lipid composition of lipoprotein particles and their structure and function.