[gmx-users] Free energy of transfer with accuracy

[David Mobley]

Eudes,

On Thu, Dec 11, 2008 at 8:27 AM, Eudes Fileti <fileti at ufabc.edu.br> wrote:
> Hello David, thanks for the reply!
> I am simulating the free energy of transfer of the C60, from ethanol to
> benzene.
> The softcore parameters, I used the are the same values of Tieleman et.al.
> (nature nanotechnology, 3, 363).
> At figure, each curve refers to a different solvent; one of them for ethanol
> and another for benzene.
> For lambda=0 I have the Coulomb and LJ parameters turn on and for lambda=1,
> turn off.
> I have found a large difference when simulating my system using sc_power=2.
> See in this link ( http://cromo.ufabc.edu.br/~fileti/web/dgdl-scpower.jpg )
> the comparison between
> plots from sc_power=1 and sc_power=2 for solute in benzene.
> Near 0 and 1, I believe that problem cancels out at difference, as can seen
> at
> ( http://cromo.ufabc.edu.br/~fileti/web/dgdl-transfer.jpg ) . Then the main
> problem, in my view,
> is in the intermediate region, where the plot presents a deep (-500 units)
> and noise minimum.
> Observe that in lambda=0, sc_power=2 reduce largely the derivative, but the
> critical region,
> one that makes the difference in calculation of the transfer free energy,
> remains the same,
> ie, the derivative still oscilates a lot and is not smooth.
> Are you believe that changing the value of alpha from 0.47 to 0.50 can
> resolve this?

OK, there are several issues here.
1) The "noisy" minimum in dV/dlambda
2) The overall shape of dV/dlambda
3) Other potential problems

On (1), the noisiness of the minimum you refer to really means there
are convergence problems for some reason -- probably correlation times
are particularly long there. This may be helped by using the soft core
parameters I mention, but I am not sure. See item #3.

On (2), in general, the overall shape of dV/dlambda seems to be
smoothest and best behaved with the particular soft core parameters I
mention. We did a lot of testing on this (i.e., many values of alpha
at each of several sc-power values).

On (3), there are other thing that can go wrong when using soft core.
See http://www.alchemistry.org/wiki/index.php/Best_Practices for some
discussion, and see rule #2 in particular. If you have any partial
charges on atoms in your C60 this could be a potential source of error
and noise. Also, if your C60 is hollow, I can imagine that it might
exclude solvent atoms from the inside, in which case you are going to
have a big convergence issue as solvent begins to interpenetrate with
the C60, which may lead to "noise" problems when this starts to
happen, whatever soft core functional form you use. This just means
you will need to run longer simulations in this regime.

Anyway, long story short, I suggest two things: (a) Make sure you turn
off partial charges on C60 (without using soft core) before turning
off the LJ using soft core, and (b) use the soft core functional form
I suggest.

David

> Please, ask me more details if you need.
> Thanks again.
> eef
>
> _______________________________________
> Eudes Eterno Fileti
> Centro de Ciências Naturais e Humanas
> Universidade Federal do ABC
> Rua Santa Adélia, 166 - Bloco B, Sala 1048
> 09210-170  Santo André - SP Brasil
> +55.11.4437-8408
> skype: eefileti
> http://cromo.ufabc.edu.br/~fileti/
>>
>>
>> ------------------------------
>>
>> Message: 4
>> Date: Thu, 11 Dec 2008 07:24:26 -0600
>> From: "David Mobley" <dmobley at gmail.com>
>> Subject: Re: [gmx-users] Free energy of transfer with accuracy
>> To: "Discussion list for GROMACS users" <gmx-users at gromacs.org>
>> Message-ID:
>>        <bc2c99750812110524r1aee080av4ac07eed79b4b0d2 at mail.gmail.com>
>> Content-Type: text/plain; charset=ISO-8859-1
>>
>> Hi,
>>
>> > Hi gmx-users,
>> > I have tried to calculate the free energy of transfer of
>> > a solute between two solvents by thermodynamic integration.
>> > However, the dgdl plot I have obtained is not smooth enough to ensure
>> > accuracy.
>> > I have used a non homogeneous spacing for lambda. The first is from 0.0
>> > to
>> > 0.4 (dl=0.04),
>> > the second is from 0.405 to 0.48 (dl=0.005) and the third is from 0.48
>> > to 1
>> > (dl=0.04).
>> > Overall, I was performed 40 simulations.
>> > As can be seen in the figure (
>> > http://cromo.ufabc.edu.br/~fileti/web/dgdl-transfer.jpg ),
>> > there is a large fluctuation in the region that goes from 0.40 to 0.48.
>> > Each simulation was carried out by 0.5ns preceded by 0.15ns of
>> > equilibration.
>> > I am using soft-core whose parameters are:
>> > ; Free energy control stuff
>> > free_energy              = yes
>> > init_lambda              = 0.00
>> > delta_lambda             = 0
>> > sc_alpha                 = 1.3
>> > sc-power                 = 1.0 (for this I also used 2).
>> > sc-sigma                 = 0.47
>> > In the example of the link sc-power=1, but I re-did the calculations
>> > with
>> > sc-power=1
>> > and I found the same behavior (although the format of the plot was a
>> > little
>> > different).
>>
>> > Can you suggest me a way to calculate this free energy difference with
>> > accuracy?
>> > The perturbation free energy method could give better results?
>> > Thank you
>> > EEF
>>
>> This does look alarming.
>>
>> I would make a couple comments here:
>> 1) Soft core parameters can be fairly sensitive. Michael Shirts and I
>> have both looked at these independently and we find that sc-power =
>> 1.0 with an alpha of 0.5 is typically substantially better than most
>> other options. Even alpha = 0.47 or 0.53 can be much worse than alpha
>> = 0.5. Your dV/dlambda curve looks to me like your soft core values
>> are far from ideal and that you are seeing a huge peak near lambda = 0
>> for this reason.
>> 2) Am I interpreting your e-mail correctly that lambda = 0 corresponds
>> to one solvent, and lambda = 1 corresponds to another? If so, I am
>> unclear on how exactly you're doing the transformation and could use
>> more detail on how you've set this up. A more straightforward (and
>> easier?) way to do this would be to transfer the solute to vacuum from
>> each solvent and then take the difference in the vacuum transfer free
>> energies. Please clarify which you're doing so we can help better.
>>
>>
>> David Mobley, Ph.D.
>> Assistant Professor of Chemistry
>> University of New Orleans
>> New Orleans, LA 70148
>> dlmobley at uno.edu
>> Office 504-280-6445
>> Fax 504-280-6860
>
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