[gmx-users] Free energy of transfer with accuracy

Thu Dec 11 17:44:30 CET 2008

Hello David,
I use to follow the "rule 2" always.
However in all of these simulations, the carbon
atoms have no charge.

Well, I will do what you suggest:
Perform simulations with:

; Free energy control stuff
free_energy              = yes
init_lambda              = 0.00
delta_lambda             = 0
sc_alpha                 = 0.5
sc-power                 = 1.0
sc-sigma                 = 0.5

Also I will simulate longer times (say 1.5ns) for
lambdas ranging between 0.40 and 0.45 for 0005.

But first I would want to know two things.

1) The parameter sc-sigma of 0.5 is reasonable?
How this parameter affects the shape of dvdl plot?
You performed tests about it? I found little about
it in the forum.

2) In my tests, I realized that, simply changing the electrostatic
interactions
treatment (cut-off or PME), a large difference it was found at hydration
free energy.
With cutoff I have found 12.2kJ/mol while with PME, 24.0kJ/mol.
The accepted value must be around 20kJ/mol).
This to me was somewhat surprising, because, as mentioned above,
C60 does not have charge, so that effect should be minimized or zero.
In any case I assign it to the electrostatic of the solvent.
I suppose the PME result is more reliable, it's ok?
Do you know some work that explore the effect of the electrostatic of the
solvent
on the solvation free energy?
Thank you
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/

> Subject: Re: [gmx-users] Free energy of transfer with accuracy
> To: "Discussion list for GROMACS users" <gmx-users at gromacs.org>
> Message-ID:
>        <bc2c99750812110724tc388a77p1577e9c999a6dd2c at mail.gmail.com>
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>
> 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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