F409C

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Structure-based Mutation Analysis

Mapping onto crystal structure

Side chain properties

Figure 2: Structure of phenylalanine on position 409 in the wildtype protein
Figure 3: Structure of cysteine on position 409 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 phenylalanine on pos 409 in the wild type structure
Figure 5: Hydrogen Bonds for cysteine on pos 409 in the mutated type structure

The phenylalanine side chain in the wildtype protein does not participate in any hydrogen bonds (see Figure 4). The mutation to serine doesn't introduce new hydrogen bonding donors or acceptors, therefore the mutation has no effect on the hydrogen bonding network (see Figure 5).

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 401.00 433.33 32.33
relative 100% 108% 8%

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 -4358.528143 -1873.075388
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 2341.69 1600 6048.14 -9087.07
Angle 3597.89 240 594.267 -1309.54
Potential 4.68e+06 4.7e+06 7.12e+07 -2.85e+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 4.68e+06 -22020100
relative 100% 17% 83%

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

Conclusion

return to Structure-based mutation analysis