Dear amber community,
I'd appreciate your advice on resolving an issue I'm having with TI
simulations. I'll first explain the attached system and the problem that
I have when I try to use single-topology for TI simulations.
System setup (setup.sh):
comp1.pdb and comp2.pdb each have a protein (:1-130) and a ligand
positioned at :102. They are combined in leap and the ligands are bonded
to the protein and the system is solvated. Next, the combined system is
tiMerged in parmed and the result is a protein :1-130 and two covalently
bonded ligands :131 and :132 (named 'lia' and 'lib' respectively). We
simply want to disappear :131.H321,H322,H323 to get to :132 in a TI
transformation (I've simplified things to focus on the issue).
The problem:
I equilibrate with "scmask1=':131.H321,H322,H323', scmask2=' ' " at
clambda=0.5 (see folder 1_equil_partial_sc). If you look at the movie
(step2.nc with topology merged.parm7), you'll see that the protein
becomes completely unstable which should not be happening. However, if I
equilibrate by transforming all of the ligand with "scmask1=':131',
scmask2=':132' ", the system is stable. My question is: what is wrong
with my first equilibration setup? Note that the problem doesn't seem to
be the equilibration process (slower heating etc doesn't help, I've
tried various scenarios) and since transforming the full ligand is
working, there seems to be something wrong with the TI setup which I
haven't been able to figure out. I should be getting the same results
when transforming only the three atoms compared to the full ligand.
I've gone through the tutorial and my setup is similar to the
"sidechain" section of the tutorial (single-topology) since I'm
transforming a covalently bonded ligand.
Here's the link to download the files:
https://drive.google.com/file/d/1WtHzJijXi_tleoSNbUa2bcOmMsxcX0J-/view?usp=sharing
Please let me know if any part is ambiguous and I'll explain further.
Thank you very much,
Ali Morshedifard
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Received on Thu Aug 04 2022 - 13:33:27 PDT
