197-202Familial amyloidotic polyneuropathy (FAP) is
strictly associated with point mutations of transthyretin (TTR) protein. The Tyr116->Ser (Y116S) mutant TTR is an important amyloidogenic variant responsible
for FAP. Structural dynamics of monomeric TTR and its mutant (Y116S) may give
some clue relating to amyloid formation. In this study, molecular dynamic
simulation at 310 K has been performed on wild-type and mutant (Y116S) TTR
monomer, which can provide the molecular insight of structural transition in
the inner and outer strand of the protein. Results show that mutation in the
H-strand (Tyr116->Ser) leads to disruption of secondary structure and H-bonding pattern of
some important parts of the inner DAGH-sheet of the protein. Especially, the
residues T106, A108, L110 of G-strand, S117 and T119 of H-strand are affected,
which are involved in the binding of thyroxin hormone. This unfolding of mutant
structure during dynamics may cause instability in the protein and thus induce
amyloidgenesis