I made a model of a protein and want to study the effect of a mutation on a model structure via molecular dynamics simulation. I have two option:
1- produce mutation on native model structure and do MD simulation on native and mutated structures independently.
2- Do MD simulation on native model and then make mutation on final structure that obtained from native simulation and then perform MD simulation on this structure.
which option is better in your opinion?
We are following the 1st option for SNP (mutation) analysis.
At first we calculate RMSD and RMSF of wild type protein for different ns.
Than we mutate the wild protein (not simulated ) in a specific position and calculate RMSD & RMSF likewise.
Finally we compare the results of independent simulations.
If you simulate and then you mutate, you will have different levels of equilibration potentially. It is more controlled to mutate at t=0 and simulate.
OR, if you have an existing trajectory of the native structure, mutate the final frame and then simulate the native and mutated structure both for N additional steps.
Alternatively, and especially if you want to quantify the mutation effect, mutate (gradually) during the simulation (free energy perturbation).
The first option would be good but the second one would be better.
Martiniano Bello , what is the advantage of the second option, and if there is any, does it balance the loss of reproducibility? (The starting structure is one of one, the final structure is one of many).
Martin Klvana
Please share some more information on this "Alternatively, and especially if you want to quantify the mutation effect, mutate (gradually) during the simulation (free energy perturbation)."
Regards
Abu Turab Naqvi , using the free energy perturbation approach, one can change one amino acid into another and calculate the free energy difference between the two variants using the Zwanzig formula.
The second option in combination of cluster analysis would provide the most populated conformation, which in theory it would correspond with the thermodynamically more stabilized conformation in solution, and it can be used as starting conformer to perform mutations and new simulations.
- Badges
- Science topic