Y438N

Structure-based Mutation Analysis

Side chain properties

Figure 2: Structure of tyrosine on position 82 in the wildtype protein

Figure 3: Structure of asparagine on position 82 in the mutated protein

Hydrogen Bonding network

The following figures show the hydrogen bonds between the wildtype residue and its environment compared to the formation of hydrogen bonds when the corresponding residue is mutated.

Figure 4: Hydrogen Bonds for tyrosine on pos 438 in the wild type structure

Figure 5: Hydrogen Bonds for asparagine on pos 438 in the mutated type structure

The hydrogen bond donor property of the amino acid on position 438 is maintained but the bond seems to be between different sidechains now (Compare Figure 4 and 5). This substitution also disturbs the hydrogen bonding network of our protein.

foldX Energy Comparison

We used the foldX tool to compare the energy of the wildtype protein and the mutated structure. The following table shows the calculated energy values as well as the percentage of difference, to compare the energy calculations with other tools:

Energy	wildtype energy	total energy of mutated protein	difference
absolute	401.00	431.56	30.56
relative	100%	107%	7%

The total energy of the mutated structure is a little bit higher than the energy of the wildtype protein structure. As protein energies should be low for a stable protein, the increasing energy leads to the assumption that this mutation might be damaging for the protein structure.

minimise Energy Comparison

Next we used the minimise tool to compare the energy of the wildtype protein and the mutated structure. The following table shows the calculated energy values as well as the percentage of difference, to compare the energy calculations with other tools:

Energy	wildtype energy	total energy of mutated protein	difference
absolute	-2485.452755	-4339.778964	-1854.326209
relative	100%	57%	43%

The mutated structure has an energy that is much smaller than the wildtype

gromacs Energy comparison

The Gromacs energy comparison was conducted using the AMBER03 force field. The following table shows the calculated energies for the wildtype protein structure.

Energy	Average	Err.Est	RMSD	Tot-Drift (kJ/mol)
Bond	3072.83	2200	-nan	-13100.2
Angle	3616.97	230	-nan	-1295.57
Potential	2.67001e+07	2.6e+07	-nan	-1.60382e+08

Here are the results for the mutated protein structure.

Energy	Average	Err.Est	RMSD	Tot-Drift (kJ/mol)
Bond	3141.2	2300	-nan	-13216.1
Angle	3672.66	290	-nan	-1550.04
Potential	8.33e+06	8.1e+06	-nan	-4.94e+07

As we want to compare the Gromacs energies with the other tools, we calculate the ratio of difference considering the potential energy:

Energy	wildtype energy	total energy of mutated protein	difference
absolute	2.67001e+07	5.16e+06	-18370100
relative	100%	19%	81%

The calculated energy for the mutated structure is much smaller than for the wildtype structure.

Conclusion

return to Structure-based mutation analysis