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Septop tutorial inquiry #315

@priscilladuggan4

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@priscilladuggan4

Hello,
I was working through the SepTop tutorial (openmm_septop/septop_tutorial.ipynb) with the example Tyk2 structures (ejm 31 --> 42), followed by simulation of the ERa system (with ligands 3b and 2e and aux paper setup). I ran triplicates of each system, but free energy results I received for were quite noisy for both:

Tyk2:
Run 1: 0.769 kcal/mol
Run 2: 1.540 kcal/mol
Run 3: 0.3927 kcal/mol

ERa:
Run 1 = -3.37 kcal/mol
Run 2 = -0.72 kcal/mol
Run 3 = -4.29 kcal/mol

I ran through the tutorial as is, which I think is meant to replicate the publication (https://pubs.acs.org/doi/10.1021/acs.jctc.3c00282) parameters. I was hoping you might be able to provide some insight as to whether there is something I am missing that might have caused the precision noise, as I was expecting higher precision for this specific transformation (referencing the paper). I checked the overlap matrices and they look fine, but the simulations were clearly not converged.
Happy to provide further details if needed. Thank you!

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