[gmx-users] Re: forward and reverse free energy not consistant (Li Qiang)

David Mobley dmobley at gmail.com
Wed Jun 18 22:20:14 CEST 2008


Sorry to be slow to chime in here, but there are several reasons one
might run into hysteresis, even when not using "slow growth":

1) The aforementioned bug
2) Topology errors
3) Convergence problems.

Of 3), there could be many different types. A recurring source of
these problems is when people fail to use soft core potentials when
inserting/deleting atoms, or simply use wacky soft core parameters. Or
when they leave on electrostatic interactions on atoms that are being
removed using soft core. etc. Some discussion of these common issues
is at http://www.alchemistry.org and there are lots of relevant
references in the literature.

There are various other explanations for hysteresis too (though most
fall into subcategories of 3). I could imagine these might be a big
deal when doing something like changing chirality. Basically if you
are doing something where there is a conformational change (like in
chirality) there will be some intermediate region of your control
parameter where, to converge, the "system" (whatever that is) will
need to switch back and forth between conformations in order to
converge. Often, correlation times will be very long here and it can
be very hard to achieve convergence, hence you'll see hysteresis. You
should obviously invest more computational effort in this intermediate
region than everywhere else to try and blast through the sampling
problem -- or use an enhanced or biased sampling scheme that can help.

David


On Mon, Jun 16, 2008 at 12:01 PM, Justin A. Lemkul <jalemkul at vt.edu> wrote:
> The bug report can be found here:
>
> http://bugzilla.gromacs.org/show_bug.cgi?id=175
>
> The thread that gave rise to this report starts here:
>
> http://www.gromacs.org/pipermail/gmx-users/2007-November/030534.html
>
> -Justin
>
> Diana Lousa wrote:
>>
>> Hello,
>>
>> I'm having a similar problem, i.e. inconsistency between forward and
>> reverse  free energy calculations, in changing the chirality of a dihedral.
>> In my case it is unlikely that there is histeresis,  given that  I have  a
>>  long  simulation. Could you be more specific about the bug you're referring
>> to, I checked the reported known bugs and didn't find anything that was
>> likely to cause this strange results.
>>
>> Thanks
>>
>> Diana Lousa
>> Instituto de Tecnologia Química e Biológica
>> Universidade Nova de Lisboa
>> Av. da República – EAN,
>> 2780-157 Oeiras
>> PORTUGAL
>>
>>
>> ---------- Forwarded message ----------
>> From: Justin A. Lemkul <jalemkul at vt.edu <mailto:jalemkul at vt.edu>>
>> Date: 2008/6/16
>> Subject: Re: [gmx-users] Re: forward and reverse free energy not
>> consistant (Li  Qiang)
>> To: Discussion list for GROMACS users <gmx-users at gromacs.org
>> <mailto:gmx-users at gromacs.org>>
>>
>>
>> Which GMX version are you using?  There's a known bug in version 3.3.1
>> that has been fixed in 3.3.3. <http://3.3.3.>
>>
>> -Justin
>>
>> friendli wrote:
>> >
>> > Hi,
>> >
>> > I use thermodynamics integration. The protocol is 1000step energy
>> > minimization, 20 ps bond-constraint MD, and then 200ps MD for collecting
>> > dgdl.
>> >
>> > thanks
>> >
>> > Qiang
>> >
>> > Gerrit Groenhof wrote:
>> >>
>> >> Looks like hysteresis. Do you do slow growth, or discrete FEP?
>> >>
>> >> Gerrit
>> >>
>> >>
>> >>
>> >>> Dear all Gmxers,
>> >>>
>> >>> I am calculating a mutation free energy from L<->A for a five AA
>> >>> peptides using G96 53a6 force field.
>> >>> however, my dG_for and dG_rev is quite different.
>> >>> dG_for(lambda=0.00) = - 9.9 kJ/mol
>> >>> dG_rev(lambda=1.00) =   1.33 kJ/mol
>> >>>
>> >>> Is there anything wrong with setting up topologies?
>> >>>
>> >>> Here is the [atoms] part for morphed atoms. and I attached the full
>> >>> .top in the attachment.
>> >>> For L->A:
>> >>> [ atoms ]
>> >>>    17        CH2      2    LEU     CB      6          0     14.027
>> >>> CH3   0   15.035; qtot 1
>> >>>    18        CH1      2    LEU     CG      7          0     13.019
>> >>> DUM   0   13.019; qtot 1
>> >>>    19        CH3      2    LEU    CD1      7          0     15.035
>> >>> DUM   0   15.035; qtot 1
>> >>>    20        CH3      2    LEU    CD2      7          0     15.035
>> >>> DUM   0   15.035; qtot 1
>> >>>
>> >>>
>> >>> For A->L :
>> >>> [ atoms ]
>> >>>    17        CH3      2    ALA     CB      6          0     15.035
>> >>> CH2    0    14.027; qtot 1
>> >>>    60        DUM      6    DUM    DUM     24          0    13.019
>> >>> CH1    0    13.019
>> >>>    61        DUM      6    DUM    DUM     24          0    15.035
>> >>> CH3    0    15.035
>> >>>    62        DUM      6    DUM    DUM     24          0    15.035
>> >>> CH3    0    15.035
>> >>>
>> >>> thanks for help
>> >>>
>> >>> LQ
>> >>> -------------- next part --------------
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>> >>> Url :
>> >>> http://www.gromacs.org/pipermail/gmx-users/attachments/20080616/562fa99f/topol_A2L.bin
>> >>> -------------- next part --------------
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>> >>>
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>> --
>> ========================================
>>
>> Justin A. Lemkul
>> Graduate Research Assistant
>> Department of Biochemistry
>> Virginia Tech
>> Blacksburg, VA
>> jalemkul[at]vt.edu <http://vt.edu> | (540) 231-9080
>> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>>
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>
> --
> ========================================
>
> Justin A. Lemkul
> Graduate Research Assistant
> Department of Biochemistry
> Virginia Tech
> Blacksburg, VA
> jalemkul[at]vt.edu | (540) 231-9080
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>
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