Hi,
I was trying to compute binding free energy using lambda dynamics approach in CHARMM. I found that the lambda variables were very stable during the simulation, and one of them was dominant throughout the simulation. I wonder what kind of reasons could account for this observation. IMHO, there could be a high free energy barrier between the ligands.
The output of lambda variables looks like below:
lam1 lam2 lam3 lam4 lam5
---------------------------------------------
1.000 0.003 0.013 0.002 0.982
1.000 0.001 0.025 0.005 0.969
1.000 0.001 0.022 0.008 0.968
1.000 0.005 0.005 0.008 0.983
1.000 0.004 0.000 0.010 0.986
1.000 0.002 0.004 0.017 0.977
1.000 0.001 0.004 0.007 0.988
1.000 0.001 0.001 0.003 0.995
1.000 0.004 0.000 0.000 0.996
1.000 0.007 0.000 0.000 0.993
1.000 0.011 0.001 0.001 0.987
1.000 0.015 0.001 0.001 0.983
1.000 0.012 0.000 0.002 0.986
1.000 0.010 0.000 0.001 0.989
Any suggestion is welcome.
