Data di Pubblicazione:
2008
Citazione:
IN SILICO STUDIES ON MODELS OF SYNTHETIC HDL / A. Guerini Rocco ; Cesare Sirtori, Guido Franceschini. DIPARTIMENTO DI SCIENZE FARMACOLOGICHE, 2008. 21. ciclo, Anno Accademico 2007/2008.
Abstract:
The major protein components of high-density lipoproteins (HDL) are apolipoprotein
(apo) A-I and apoA-II. Sixty-three different mutations of apoA-I
are known. Among them, apoA-IMilano (IM) and apoA-IParis (IP) are characterized
by an R-C substitution, leading to the formation of disulfide-linked
homodimers and of heterodimers with apoA-II. From observations in humans
and in animal models apoA-IM and apoA-IP behave as molecules with
an intrinsic antiatherogenic activity. No experimental structure at atomic
resolution of lipid-bound apoA-I is available. In this thesis I present four
molecular models of synthetic HDL containing a lipidic core of palmitoyloleoyl-
phosphatidylcholine and either two molecules of wild type apoA-I, or
one apoA-IM homodimer, or one apoA-IP homodimer, or two molecules of
apoA-IM–apoA-II heterodimer. On all the systems I computed molecular
dynamics simulations to obtain reliable data about the behavior of apoA-I
in a lipidic environment and to sharpen the understanding of its molecular
functions in regulating cholesterol homeostasis. In all the four models of s-
HDL the increase with time in the number of favorable interactions between
apoA-I and phospholipids was the driving force for the structural reorganization
and stabilization of s-HDL. I found a strong correspondence between
computed and experimental properties, which supports the reliability of my
results.
Tipologia IRIS:
13 - Tesi di dottorato discussa entro ottobre 2010
Elenco autori:
A. GUERINI ROCCO
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