Is the linker involved in ligand binding? How long are the simulations? RMSF is very tricky to converge and you need to ensure you have adequate equilibration. In those plots (assuming black is an apo form), I don't see anything of real importance going on.

Thank you very much for the answer. The simulation contains 20 ns time. The black line indicates the RMSF of human topoisomerase I when it binds to anti-cancer agent topotecan. Linker domain is not involving in ligand binding. All ligands bind to the cleaved DNA binding site.

20 ns is not long enough to say anything conclusively about the linker dynamics in such a large protein (or any protein, for that matter). I assume by your use of the term "linker" you are referring to an unstructured/partially structured region connecting two folded domains. What you're observing is probably normal variability that occurs in simulations of such systems. A single trajectory is not definitive proof of anything regarding the protein's dynamics, and again your time frame is about an order of magnitude too short to conclude anything.

I agree with Justin, 20 ns is not long enough to predict any differences in linker dynamics in presence or absence of a ligand.

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Best,

Kalpana

Thank you everyone