GROMACS version:2023.3
GROMACS modification: Yes/No
Hello everyone,
I performed 200 ns protein ligand simulation. Out of three replicates, the ligand stays inside the pocket in two replicates and in one of the replicates it moves out of the pocket into the solvent around 100 ns. What does it mean? How do you interpret this result? Any suggestions or feedback will be appreciated. Thanks
Pawan
The binding of a ligand to a protein is a reversible process. It will leave and bind again if you simulate long enough. If the binding is very favourable, or the binding is in a buried site, it may take a long time for the ligand to leave, whereas if it is a weakly binding ligand in an exposed binding site it may not stay as long.
Not much can be said about the ligand leaving the binding site in one out of three simulations. Do you have any experimental data about the binding process? To get more knowledge I would recommend a few more simulations and possibly slightly longer as well.
It is also possible that the binding is not optimal in the simulations. Are there any bridging water molecules involved in the binding? Are they modeled correctly? Is the protonation state of the ligand and the residues in the binding site correct?