- Tytuł:
- Computational studies of TTR related amyloidosis: exploration of conformational space through petri net-based algorithm
- Autorzy:
-
Jakubowski, R.
Gogolińska, A.
Pepłowski, Ł.
Skrzyniarz, P.
Nowak, W. - Powiązania:
- https://bibliotekanauki.pl/articles/1954249.pdf
- Data publikacji:
- 2022-02-01
- Wydawca:
- Politechnika Gdańska
- Tematy:
-
transthyretin amyloidosis
molecular dynamics
Petri nets
clustering
conformational space
graphs
dynamika molekularna
sieci Petriego grupowanie
konformacyjne miejsca
wykresy - Opis:
- Amyloidosis, a serious and widespread disease with a genetic background , manifests itself through the formation of dangerous fibrils in various organs. Apart from the polluted environment and an unhealthy lifestyle, genetic factors may accelerate this process leading in some cases to lethal damages to the body. Recently, a growing interest in amyloidogenic protein research has been observed. Transthyretin (TTR) is a tetrameric protein that transports thyroid hormone thyroxine and retinol binding protein in plasma and the cerebral fluid. Sometimes TTR breaks apart and forms fibrils. Several single point mutations, having de stabilizing impact on the TTR complex, are involved in the amyloidogenic TTR cascade. Problems with the TTR tetramer stability and conformational space characteristics of the protein have not been addressed computationally before. We present selected results of our molecular dynamics (MD, ∼ 2000ns) and steered MD simulations ( SMD ) of three variants of TTR : Wild Type ( WT ), V 30 M and L 55 P . SMD has been used to enforce the dissociation of TTR . Conformational spaces of WT TTR and its amyloidogenic variants have been investigated using a novel “ One Place One Conformation ” ( OPOC ) algorithm based on a graph technique called Petrinet (PN) formalism. While the PN approach alone does not permit a direct identification of protein regions with reduced stability, it gives quite a useful tool for an effective compari son of complex protein energy landscapes explored during classical and/or SMD steered molecular dynamics simulations.
- Źródło:
-
TASK Quarterly. Scientific Bulletin of Academic Computer Centre in Gdansk; 2014, 18, 3; 289--300
1428-6394 - Pojawia się w:
- TASK Quarterly. Scientific Bulletin of Academic Computer Centre in Gdansk
- Dostawca treści:
- Biblioteka Nauki
Artykuł