3.8.4 Secondary structure changes during simulation
The average secondary structure transitions in each of the simulations
were monitored using Define Secondary Structure of Proteins (DSSP)
program 78. Simulations
started from residues in contact with the interface (DNA); these
residues include both the N- and C-termini of both the monomers of IRX4.
A scan be seen in Fig S8 and S9, the N-terminal region of the
homeodomain have attained quite a distinct secondary structure compare
to the mutants. Secondary structure analysis was used to identify the
extent of changes which helps in promoting the structural integrity of
the binding. Compared to the native structure, A149V after initial 50 ns
showed a robust helical propensity compared to other mutants. The
helical conformation amongst the other mutants were consistently altered
throughout the 200ns simulations involving turn structures.
Interestingly the smallest helix consisting of 9 amino acid (174-182)
didn’t show any major differences along the different mutants.
Examination of individual residue energy difference highlights the fact
there is reorientation of the protein from its initial orientation in
the mutants, highlighting the effect of the variants on DNA binding. The
final orientation and secondary structure in all the variants is
different, exhibiting loss of loss or gain in bending of the helix.