GROMACS version: 2020.2
GROMACS modification: No
In four separate 200-ns simulations of homologous protein-ligand complexes, I have found that the RMSD values all show continuous gradual increases across time:
I was just curious, is this any cause for concern with regards to the stability of the protein? Or is this general increase in RMSD across time to be expected?
Any thoughts would be greatly appreciated!
The RMSD tell you how much your simulated structures deviate from the starting structure or from the experimental structure (if you have calculated your RMSD using as reference the experimental structure). This is not necessary a measurament of the stability of your protein.
You may have many flexible loops in your protein that oscillate differently and contribute differently to RMSD values. You can calculate RMSD only for the more rigid part of your system (e.i excluding flexible loop region and focusing only on backbone atoms) to better compare the deviations respect the reference structure.
You can find several posts in the forum on protein and “RMSD” that may help on understanding your results.
Thank you very much for your response.
I now understand that RMSD tells how much the simulated structure deviates from the starting structure. However, my question remains: is the continuous gradual increase in RMSD across the four simulations expected? Or is this a cause for concern?
All the best,
There is no way for us to answer this question. RMSD is a degenerate metric; it has many interpretations. You have to watch your trajectories to see what is going on. Maybe loops are just flexing and nothing else. But don’t over-interpret RMSD. It’s only a first indicator of relative stability of a structure and should be followed up with more careful analysis.