Figure 9: Average free energy of binding per nucleotide in the DNA for all variants. Graph showing energy difference amongst the native and mutant proteins with respect the DNA nucleotide sequence.
3.9.2 Energy landscape per amino acid in the homeodomain
Multi-dimensional energy plots, attributed to each amino acid in the homeodomain were generated to analyze the change in energy landscape across the sequence. As depicted in Fig S10 and S11, energy plots for both monomers show a variation in the energy dynamics of the protein structure after simulations. The changes in the C-terminal domain of the protein can be seen in all the variants compared to the WT protein. Interestingly, the amino acid residues interacting with DNA showed a decreased in binding potential in all the mutants. The N- terminal residues K147, N148, A149 and Y169 showed a decrease in binding energy in the variants. The highlight were the C-terminal residue mutants which changed the overall binding potential of the protein, affecting the flexibility of the helix and decreasing the potential of IRX4 to bind DNA.