[gmx-users] Re: FEP softcore problematics

Maik Goette mgoette at mpi-bpc.mpg.de
Fri Jun 23 14:30:23 CEST 2006

Welcome to the world of science...

But I thought exactly the same as you do and therefore give a +1 to your 


(BTW: Sorry, for this needless spam...)

Maik Goette, Dipl. Biol.
Max Planck Institute for Biophysical Chemistry
Theoretical & computational biophysics department
Am Fassberg 11
37077 Goettingen
Tel.  : ++49 551 201 2310
Fax   : ++49 551 201 2302
Email : mgoette[at]mpi-bpc.mpg.de
WWW   : http://www.mpibpc.gwdg.de/groups/grubmueller/

mernst at tricity.wsu.edu wrote:
>>Sorry about all of the confusion. Basically, the answer to this
>>depends on what exactly you're doing. (I should really write all of
>>this up in a tutorial soon). The way I think about it is that there
>>are two fundamental principles you need to keep in mind, and you can
>>do it any way you can cook up as long as you follow these two:
>>(1) Always use soft core when modifying vdW interactions
>>(2) Never leave charges on atoms for which you are turning off the vdW
>>The corollary is that you should generally not change charges and LJ
>>interactions at the same time, but this is more for efficiency reasons
>>than anything else.
>>So, if you can cook up a way to do what you want that doesn't violate
>>principles (1) or (2) and only involves two steps, great. For my
>>purposes, I'm doing absolute binding free energy calculations where I
>>don't mutate one thing into something else, so I can always do this --
>>I'm just disappearing atoms, so I first turn off teh charges, and then
>>second turn off the LJ interactions.
>>More generally, I suppose if you can think of a way to do the
>>transformation you want that only involves either (a) inserting atoms,
>>or (b) deleting atoms, but not both, you can do it in two steps. If it
>>only involves insertion, you first modify the LJ interactions to
>>"appear" some dummy atoms, and then turn on their charges. If it only
>>involves deletion, you first turn off the charges, then you turn off
>>the LJ interactions. If it involves both insertions and deletions,
>>maybe there is a way to do it in only two steps, but it isn't obvious
>>to me.
> 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!).
> 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.
> Again, thank you very much for your patient support and education that goes hand in hand
> with your excellent simulation software.
> Matt Ernst
> Washington State University
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