[gmx-users] Re: FEP softcore problematics

David Mobley dmobley at gmail.com
Mon Jun 26 18:24:12 CEST 2006


> Thank you very much for the clarification. None of my calculations have involved
> combined insertion/deletion. I have always picked the state that has more atoms for my
> starting state, then mutated toward the state with fewer atoms. This means that I don't
> have to re-do recent simulations (hurray!) but I'm still not sure why some of them give
> the results they do (boo!).

If you want (on or off-list) to give some more particulars about what
exactly you're doing and how, I might be able to give some suggestions
for things to look at. (i.e., particular molecule(s) you're working
on, and maybe a pdb code/file or two, along with some lambda values,
simulation lengths, etc).

> I am amazed what I have learned about free energy calculations from this list and from
> papers suggested on it (Michael Shirts' recent work in particular, even if I don't need
> as much accuracy and precision as he achieved). The documentation for most packages that
> support free energy simulations is almost criminally simple in its description of the
> process. When I first started investigating thermodynamic perturbation/integration, it
> seemed like it would be fairly straightforward to use. I thought maybe it would increase
> setup time by about 50% and simulation time tenfold. Now it seems like it's practically
> a discipline unto itself. Review articles and original papers from 10-15 years ago also
> made me think the process would be much simpler than it actually turns out to be. Even
> books from the last 5 years haven't given me nearly so much useful information as
> references and suggestions from this list have. There's a big gap between getting
> roughly plausible results and getting reliable quantitative information, and it seems
> that most published material I've seen never crosses that gap.

Agreed. I had pretty much the same experience when I started off
beginning about a year and a half ago, although I spent most of the
time figuring out stuff for  myself for a while.

Michael Shirts and I and a couple others are hoping to put together a
"best practices" review paper for free energy calculations in the
relatively near future, as this seems to be something rather badly


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