Alchemical Free Energy Perturbation

From: Jawahar Neelankatan (
Date: Sat Feb 25 2006 - 00:40:02 CST

 I had a few questions about alchemical free energy perturbation simulations.
I am getting strange and inconsistent results for an alchemical free energy perturbation simulation that I'm doing. I am transforming a K+ ion to an Na+ ion in a box of ~200 methanol molecules (solvent). So basically the only atoms involved in the transformation in the FEP simulation are K (initial state, vanishing) and Na (final state, appearing) and thus they are prevented from interacting with each other by a modification (exclusion list) I made in the !NNB (non-bonding) section of the psf file, using the alchemify program. The K and Na ions are however allowed to interact with the bulk solvent (methanol) molecules.
I also have a .fep file defined that contains the ~200 methanol molecules, K ion and Na ion. I wasn't sure whether to give both K and Na ions the exact same coordinates or not. I didn't think it'd make a difference since they aren't interacting to begin with. I went ahead and gave both of them the exact same coordinates in the .fep file. I then ran a 10000 step (2 fs per step) simulation with 5000 steps for equilibration and 5000 steps for sampling. I made delta_lambda = 0.025 to allow 40 windows for the growth of lambda from 0 to 1.
 The results I get don't bear much similarity to experimental results and in the .fepout output file, I'm seeing a few unrealistically large values (999999999) for the vdW(l+dl) i.e. the van der Waals energy for the lambda2 state in each window. Is this normal ? I modified the .fep file so that K and Na don't have the same coordinates (as they did in the first simulation) but then I get the 'constraint failure in RATTLE algorithm' error. However, I inserted a 'minimize 1000' command to minimize the system before equilibrating and subsequently sampling and that error doesn't occur anymore but I still get a few unrealistically large values for vdW(l+dl) and erroneous values for dG.
The configuration file and a small section of the .fep file are attached to this email. Does it matter that I'm using the OPLS force field ?
 Any suggestions are welcomed. Thanks.
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