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.
• Języki publikacji: EN

Abstrakty

EN

Amyloidosis, a serious and widespread disease with a genetic background , manifests itself through the formation of dangerous fibrils in various organs. Apart from th e polluted environment and an unhealthy lifestyle, genetic factors may acceler ate this process leading in some cases to lethal damages to the body. Recently, a growing interest i n 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 cerebr al 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 Petri net ( PN ) formalism. While the PN approach alone does not permit a direct identification of protein regions wi th 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.

Słowa kluczowe

EN

transthyretin amyloidosis; molecular dynamics; Petri nets; clustering; conformational space; graphs

PL

transthyretin amyloidosis; dynamika molekularna; sieci Petriego grupowanie; konformacyjne miejsca; wykresy

• Wydawca: Politechnika Gdańska
• Czasopismo: TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk
• Rocznik: 2014
• Tom: Vol. 18, No 3
• Strony: 289--300
• Opis fizyczny: Bibliogr. 21 poz., rys., tab., wykr.

Twórcy

autor

Jakubowski R.

• Institute of Physics, Faculty of Physics, Astronomy and Inf ormatics Nicolaus Copernicus University Grudziadzka 5, 87-100 Torun, Poland

autor

Gogolińska A.

• Institute of Physics, Faculty of Physics, Astronomy and Inf ormatics Nicolaus Copernicus University Grudziadzka 5, 87-100 Torun, Poland
• Faculty of Mathematics and Computer Science, Nicolaus Copern icus University Chopina 12/18, 87-100 Torun, Poland

autor

Pepłowski Ł.

• Institute of Physics, Faculty of Physics, Astronomy and Inf ormatics Nicolaus Copernicus University Grudziadzka 5, 87-100 Torun, Poland

autor

Skrzyniarz P.

• Institute of Physics, Faculty of Physics, Astronomy and Inf ormatics Nicolaus Copernicus University Grudziadzka 5, 87-100 Torun, Poland

autor

Nowak W.

• Institute of Physics, Faculty of Physics, Astronomy and Inf ormatics Nicolaus Copernicus University Grudziadzka 5, 87-100 Torun, Poland

Bibliografia

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