On Wed, Jan 26, 2005, Ilyas Yildirim wrote:
>
> 1. The transformation is from toluene -> nothing, and in order to do that,
> u do a 2-step MD simulation; one called as 'charging' and the other as
> 'disappearing'. For charging, the free energy difference is calculated as
> 2.35 kcal/mol, and for disappearing, the free energy difference is
> calculated as (for klambda=6) 2.7 kcal/mol. So, the total free energy
> difference of toluene -> nothing transformation is 2.35 + 2.7 = 5.05
> kcal/mol, am I right?
No. The signs of the two terms are opposite, so that the two terms nearly
cancel. I'll update the tutorial to make this clearer, but if you look at the
details, you can see that the vdW change is negative (for the direction
toluene -> nothing).
>
> 2. For the charging case, u are doing a 3-point Gaussian Integration,
> while for disappearing case, u are doing a 14-point Gaussian Integration.
> Is there any optimum number of lambda values for different structures at
> interest? For instance if I do a simple perturbation on the amino group of
> an RNA molecule, how can I decide how many lambda values I should use?
You can't necessarily know in advance how smooth the <dV/dl> vs. lambda curve
is. Experience is a help, but in principle you would need to investigate this
for each new type of perturbation.
>
> 3. For the disappearing case with klambda=6, you have chosen lambda values
> of 0.90, 0.92, 0.94, 0.96 and 0.98. Any reason for that?
The dV/dl curve is very steep near lambda=0.1, so I wanted to integrate that
region more carefully.
>
> 4. In the frcmod file which describes the parameters for the dummy atoms,
> you did not use zero values for harmonic force constants of the bonds and
> angles, and the barrier heights (PK). If the atoms are disappearing, why
> not choosing them as zero?
If you set the internal variables to zero, you end up with an ideal gas of
isolated atoms. This is very hard to sample over. Most people find it better
to keep the geometry mostly unchanged, and to assume that these internal free
energies will cancel in the water vs. vacuum simulations. But try some
experiments yourself, and see what you get.
....dac
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Received on Wed Jan 26 2005 - 17:53:01 PST
