[gmx-developers] Re: Coulomb decoupling?

[David Mobley]

Berk (and all),


On Thu, May 2, 2013 at 12:54 PM, Berk Hess <hess at kth.se> wrote:

>  This is all describes in the manual, AFAIK.
>
> Sorry there was some overlap. I hadn't found the discussion I'll cite
below yet.


>  On 05/02/2013 09:44 PM, David Mobley wrote:
>
> Right, what I'm asking about is
> A) how exactly is this end result achieved? (The system is periodic, so
> how is the periodicity removed for the end state?)
>
> The periodicity of intra-molecular interactions is always removed.
> These interactions are excluded from PME and added directly as listed
> pairs.
>

The manual says this: "All intra-molecular non-bonded interactions for
moleculetype couple-moltype are replaced by exclusions and explicit pair
interactions. In this manner the decou- pled state of the molecule
corresponds to the proper vacuum state without periodicity effects. "

Does this apply to BOTH the A and B states? Your answer "the periodicity of
intra-molecular interactions is always removed" suggests you're saying that
the solute is never allowed (in either A or B state) to interact with
copies of itself. Doesn't this mean that that (considering the case of a
small molecule in solution being decoupled) the A state has periodic
interactions between all of the solvent molecules, and between solvent and
solute, but no periodic interactions between solute and solute? (If so,
won't this tend to leave the solvent box with a net dipole moment for PME
purposes?)

>
>  B) how was it validated that it is working as it should be?
>
> I checked this and it works.
>

What I'm asking is, "checked how", and "works for what"? Specifically I'm
trying to figure out whether this can be expected to always yield the same
results as annihilation (assuming simulations are converged), even for
larger/flexible/more polar molecules. To that end I'm trying to understand
whether there are any limitations in the formalism, and exactly how it's
been tested.

>
>  C) when you say, "without cutoffs", is this referring to just Coulomb
> cutoffs or also LJ? I'm assuming just coulomb. If so, then there are
> internal LJ interactions in the gas phase which are missing outside the LJ
> cutoff (assuming the molecule is larger than the cutoff). While these are
> also missing in solution, they are generally captured well by the
> dispersion correction. In vacuum that is not the case, so neglect of these
> could adversely affect solvation estimates, it seems to me. Has this been
> tested? How?
>
> LJ is treated as Coulomb, plain LJ, no cut-off.
>
> OK, thanks.

>  D) how will the use of decoupling affect dispersion corrections to the
> energy and pressure? (Will the dispersion corrections still give the
> correct free energy contribution in decoupling?) how has this been tested,
> if at all?
>
> This is the only complicating factor.
> There is no correct way of using dispersion correction with decoupling.
> As the intra-molecular interactions are excluded, these do not end up the
> average C6
> and they do not end up in the pair count for dispersion correction.
>

So, are you saying dispersion corrections should be turned off when using
decoupling? Dispersion corrections tend to contribute substantially to free
energies unless one runs with a large cutoff, which would suggest this is a
bad idea. It seems like I probably need to know exactly how the dispersion
correction contribution to the free energy is computed in the case of
decoupling, so I can estimate how wrong this will be due to the pair
count/average C6 being wrong.

Probably this also raises the question of whether GROMACS should not allow
the user to run decoupling with the dispersion correction (since it's not
correct) or whether it instead should issue a warning and provide some
guidance as to how to fix things (if we have any such guidance to offer).

Thanks,
David


On Thu, May 2, 2013 at 12:54 PM, Berk Hess <hess at kth.se> wrote:

>  This is all describes in the manual, AFAIK.
>
>
> On 05/02/2013 09:44 PM, David Mobley wrote:
>
> Right, what I'm asking about is
> A) how exactly is this end result achieved? (The system is periodic, so
> how is the periodicity removed for the end state?)
>
> The periodicity of intra-molecular interactions is always removed.
> These interactions are excluded from PME and added directly as listed
> pairs.
>
>  B) how was it validated that it is working as it should be?
>
> I checked this and it works.
>
>  C) when you say, "without cutoffs", is this referring to just Coulomb
> cutoffs or also LJ? I'm assuming just coulomb. If so, then there are
> internal LJ interactions in the gas phase which are missing outside the LJ
> cutoff (assuming the molecule is larger than the cutoff). While these are
> also missing in solution, they are generally captured well by the
> dispersion correction. In vacuum that is not the case, so neglect of these
> could adversely affect solvation estimates, it seems to me. Has this been
> tested? How?
>
> LJ is treated as Coulomb, plain LJ, no cut-off.
>
>  D) how will the use of decoupling affect dispersion corrections to the
> energy and pressure? (Will the dispersion corrections still give the
> correct free energy contribution in decoupling?) how has this been tested,
> if at all?
>
> This is the only complicating factor.
> There is no correct way of using dispersion correction with decoupling.
> As the intra-molecular interactions are excluded, these do not end up the
> average C6
> and they do not end up in the pair count for dispersion correction.
>
> Cheers.
>
> Berk
>
>
>  Thanks!
>
> On Thursday, May 2, 2013, Berk Hess wrote:
>
>>  Hi,
>>
>> You didn't explain exactly what you are doing.
>> The decouple mdp options decouple the molecule to a vacuum state, i.e.
>> pure Coulomb without cut-off's.
>>
>> Cheers,
>>
>> Berk
>>
>> On 05/02/2013 07:10 PM, David Mobley wrote:
>>
>> Could I get some input on this?
>>
>> I have a couple of cases for rather polar molecules where decoupling and
>> annihilation give me statistical significant differences in hydration free
>> energies. The differences are not that large, but significant. I'm trying
>> to find out what's already been done to validate so I know how much
>> time/effort to spend testing to try and figure out if there is a problem
>> here.
>>
>> Thanks.
>>
>>
>> On Tue, Apr 30, 2013 at 1:25 PM, David van der Spoel <
>> spoel at xray.bmc.uu.se> wrote:
>>
>> On 2013-04-30 18:02, David Mobley wrote:
>>
>> Hi,
>>
>> In GROMACS 4.6 and later, there's now a new feature available to allow
>> decoupling of solute molecules in free energy calculations. I wanted to
>> inquire as to how Coulomb decoupling works, as I'm not clear.
>>
>> Specifically, imagine I'm running a calculation of the hydration free
>> energy of a small molecule in water, and I decouple it (LJ and Coulomb)
>> from its surroundings. What is the final reference state for the small
>> molecule? Is it the small molecule interacting with periodic copies of
>> itself in the gas phase (bad)? Or is it not interacting with periodic
>> copies of itself either? If the latter, how is this achieved?
>>
>>  Good question, also one would like to be able to decouple a molecule
>> only in the central box and not in the surrounding boxes. This does not
>> make a difference for liquids but it does for crystals.
>>
>>
>> Since I'm not familiar with the Coulomb decoupling aspect and it is
>> conceptually more complicated than LJ decoupling, I want to make sure I
>> understand how it's supposed to be working.
>>
>> Thanks!
>> David
>>
>>
>> --
>> David Mobley
>>  dmobley at gmail.com <mailto:dmobley at gmail.com>
>> 949-385-2436
>>
>>
>>
>>
>> --
>> David van der Spoel, Ph.D., Professor of Biology
>> Dept. of Cell & Molec. Biol., Uppsala University.
>> Box 596, 75124 Uppsala, Sweden. Phone:  +46184714205.
>> spoel at xray.bmc.uu.se    http://folding.bmc.uu.se
>> --
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>>
>>
>>
>> --
>> David Mobley
>>
>>
>
> --
> Sent from my mobile device. Please pardon any unusual brevity or typos.
>
>
>
>
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-- 
David Mobley
dmobley at gmail.com
949-385-2436
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