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.
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