| Summary: | The transformation of cellular prion protein (PrPc) into pathogenic conformer (PrPSc) in transmissible spongiform encephalopathy is expedited by mutations in the prion protein. One recently reported novel mutation V176G is located in region of the protein known to cause Creutzfeldt-Jakob disease (CJD) but possess a unique neuropathological profile and spongiform alteration similar to Gerstmann–Sträussler–Scheinker syndrome (GSS). Using molecular dynamics simulations; the denaturation of the prion structure with V176G at 500K was studied to identify the dynamics in structural properties such as salt bridge, solvent accessibility, hydrogen bonds and hydrophobicity. The simulations revealed that the heat-induced unfolding caused destabilization of the native structure of PrP and affecting the ß-sheet region of the structure more than the a-helix. Unique salt bridge formation suggests conformational orientation that may be attributed to the V176G mutation. The mutation effects showed an increased fluctuation of the H1 region, gain of hydrogen bonds between H3 and H2 which may be part of the oligomerization pathway and determine the features of the PrPSc assemblies.
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