GROMACS version: 2023.2
GROMACS modification: No
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I tried to calculate free energy change of GLP-1 binding to GLP-1R.
I made membrane bilayer system using CHARMM-GUI and it went well for process of md simulation including energy minimization, nvt, npt equilibrium, and production.
I followed instruction for free energy calculation from the tutorial.
Absolute Binding Free Energy - Gromacs 2016 - AlchemistryWiki and completed ligand decoupling from complex and ligand decoupling from solution and calculated delta G using gmx_mpi bar -f *.xvg -o -oi -oh.
Lambdas for ligand decoupling from complex
bonded-lambdas = 0.0 0.01 0.025 0.05 0.075 0.1 0.2 0.35 0.5 0.75 1.0 1.00 1.0 1.00 1.0 1.00 1.0 1.0 1.0 1.0 1.0 1.0 1.00 1.0 1.00 1.0 1.00 1.0 1.00 1.0
coul-lambdas = 0.0 0.00 0.000 0.00 0.000 0.0 0.0 0.00 0.0 0.00 0.0 0.25 0.5 0.75 1.0 1.00 1.0 1.0 1.0 1.0 1.0 1.0 1.00 1.0 1.00 1.0 1.00 1.0 1.00 1.0
vdw-lambdas = 0.0 0.00 0.000 0.00 0.000 0.0 0.0 0.00 0.0 0.00 0.0 0.00 0.0 0.00 0.0 0.05 0.1 0.2 0.3 0.4 0.5 0.6 0.65 0.7 0.75 0.8 0.85 0.9 0.95 1.0
Lambdas for Ligand decoupling from solution
coul-lambdas = 0.0 0.25 0.5 0.75 1.0 1.00 1.0 1.0 1.0 1.0 1.0 1.0 1.00 1.0 1.00 1.0 1.00 1.0 1.00 1.0
vdw-lambdas = 0.0 0.00 0.0 0.00 0.0 0.05 0.1 0.2 0.3 0.4 0.5 0.6 0.65 0.7 0.75 0.8 0.85 0.9 0.95 1.0
When I see the results, coul-lambda changed much more significantly affected free energy while vdw-lambda didn’t much. It is also same in ligand decoupling.
And deltaG(complex) was =4214.92 kT and deltaG(ligand) was 4149.75 kT, which I am thinking too big.
I would like to get help regarding
- my results looks plausible
- Is there anything I need to check if there should be something wrong?