I have performed 300ns simulation of my protein ligand complex , my motive behind the simulation is that I want the dissociation of protein chains after reaching or attachment of ligand to single fragment of protein or at Interface.
My protein has 2 fragments or chains attached to gather , I have docked the compound with given method in literature and then make a complex of best pose , finally perform MD simulation by using specific parameters mentioned literature for the system here just ligand is different .
My ligand has ability to do confirmation change in proteins making them unavailable to attachment with others .
So in order to validate the results I perform simulation, during the start of simulation the ligand protein complex shows stable rmsd value till 50ns after 50ns it suddenly hits 50A repeatedly for protein and ligand rmsd increase to very high value .
In order to check what is happening I remove the pbc effect and center the protein but again the rmsd remain same.
Further when I analyze the trajectory at frames where the rmsd of protein and ligand is high , I found that during that frame the snaps shots shows that when the ligand binds to interface or even approaching at Interface or binding any part of fragment A which is needed in my case , I causes the separation of two fragments , and then in between 100-150ns is goes towards Fragment B and remain attached there for course of time but there were no major chain in Rmsd of protein means complex remain stable although the ligand leaves the pocket and bind to another part , and at last it again.come back to the interface and the rmsd become high of protein approx 8-10A and remain attached there till end of simulation .
So my question is that I didn’t perform the simulation for stability of protein I just want to check that any level the ligand binding to only fragment A indues the separation or increasing the distance between fragments.
And binding to chain B doesn’t produce such effect.
I also validate it by calculating the distance between the amino acids residues of both fragments that are important for stabilization but they show very high distance approx 140A when ligand is approaching them .
In conclusion I want anyone to comment on my story that how I interpret it .
I also perform the MD simulation of apo system they show Rmsd of less than 4A mentioned in literature and also the fluctuations are very less of important residues no of hydrogen bonds are high.
But with ligand the fluctuations of residues hit to 12A.
Because my ligand rmsd is very high the experts don’t accepting it , but my main point I don’t want stability here I just want to proof that binding of ligand to any region causes the separation of fragments even when ligand is approaching or wandering or at the pocket.
Kindly post detail comments.
I will share the images upon answer.
Thanks