Transmissible Spongiform Encephalopathies are fatal neurological disorders caused by a proteinaceous infectious particle (PrPSC). The PrPSC transforms the normal prion isoform (PrPC) to the infective conformation by a mechanism which remains unknown. In previous work we identified a set of anti-prion compounds with EC50 in the range 1�10 nM in a mouse cellular model, however, the target(s) of these compounds is unknown. In this project, we describe an in silico protocol for target prediction using inverse docking. A set of 333 differentially expressed genes involved in the transformation and identified using microarray analysis were collected from the literature; 168 corresponding structures were downloaded from the PDB; and a diverse set of five anti-prion compounds were docked to the proteins using GOLD. From the results, we have identified a set of putative targets shared by the compounds. Next, we aim to corroborate the results through a proteomics analysis.

Searching putative targets in silico for anti–prion compounds

243rd National Meeting (2012)

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