# Why did ligand leave the binding pocket? **URL:** \ **Category:** User discussions\ **Tags:** forcefield\ **Created:** [January 4, 2022, 12:42pm UTC](https://gromacs.bioexcel.eu/t/why-did-ligand-leave-the-binding-pocket/3398 "2022-01-04T12:42:34Z")\ **Posts on this page:** 2\ **Page:** 1
**Author:** ![NicoleDH](https://avatars.discourse-cdn.com/v4/letter/n/7feea3/32.png) [@NicoleDH](https://gromacs.bioexcel.eu/u/NicoleDH)\ **Post date:** [January 4, 2022, 12:42pm UTC](https://gromacs.bioexcel.eu/t/why-did-ligand-leave-the-binding-pocket/3398/1 "2022-01-04T12:42:34Z")
GROMACS version: 2018.8 GROMACS modification: No forefield: charmm36-feb2021 obtain ligand topology from CGenFF Hi, everyone! I am working on a protein-ligand complex system, during pre- equilibrium phase, I add position restraints to ligand and release it during production MD. The total simulation time is 1 us. The start complex structure is from crystal structure. During the first 400 ns, the protein adopts a ‘closed’ pose, and there are little changes according to the RMSD-time plot. And ligand binds to the binding pocket perfectly. After 600 ns, the system reaches equilibrium state, and the protein adopts a ‘open’ pose, namely the binding pocket opens. And the ligand moves to one side of the binding pocket because the pocket is too larger for it now. Why does it happen? If I simulate longer, can the ligand go back and the protein restore the ‘close’ conformation? And will it work if I try other forcefield like Amber99SB-ILDN? Any suggestion will be appreciate! Thanks. ---
**Author:** ![Jeancolar11](https://avatars.discourse-cdn.com/v4/letter/j/278dde/32.png) [@Jeancolar11](https://gromacs.bioexcel.eu/u/Jeancolar11)\ **Post date:** [December 6, 2022, 4:52am UTC](https://gromacs.bioexcel.eu/t/why-did-ligand-leave-the-binding-pocket/3398/2 "2022-12-06T04:52:01Z")
> [@NicoleDH](#): > > ggestion will b hello, Did you solve the problem