As long as you morph pyrimidine into pyrimidine and purine into purine,
everything is fine, I'd say.
Morphing a pyrimidine into a purine is really problematic, cause you
have to morph the whole nucleoside. Until now I didn't find a
possibility to do that without perturbing all atoms of the base, which
leads to a very heavy perturbation and therefore a very "spiked" dG/dl.
Maik Goette, Dipl. Biol.
Max Planck Institute for Biophysical Chemistry
Theoretical & computational biophysics department
Am Fassberg 11
37077 Goettingen
Germany
Tel. : ++49 551 201 2310
Fax : ++49 551 201 2302
Email : mgoette[at]mpi-bpc.mpg.de
mgoette2[at]gwdg.de
WWW : http://www.mpibpc.gwdg.de/groups/grubmueller/
Robert Johnson wrote:
Thanks Maik for your advice. I think what I'm going to do is to look
at the relative binding free energy differences between the bases.
Thus, I will morph the bases into one another, leaving the sugar and
phosphate intact. Do you think this is a better strategy?
Thanks,
Bob
On 1/28/08, Maik Goette <[EMAIL PROTECTED]> wrote:
OK, forget my first reply and the mentioned topology splitting ;)
It MAY be a problem, that you switch off two charged molecules, but I
really dont know, if this is the problem.
Try some totally artificial process, where you build a neutral base and
use no counterion and morph the neutral base away.
From my experience with DNA I can tell you, that these huge
fluctuations are quite intrinsic due to the size of the perturbation.
Actually, I don't have an idea, how to get rid of them.
Trying to sample much longer could help to converge the system.
Furthermore, using more lambda-steps could help you in getting a better
total error and stuff.
Again, from my experience I can tell you, that calculating free energies
from letting nucleotides appear/disappear is really no fun.
If you come up with a solution yourself, I would be highly interested in it.
Regards
Maik Goette, Dipl. Biol.
Max Planck Institute for Biophysical Chemistry
Theoretical & computational biophysics department
Am Fassberg 11
37077 Goettingen
Germany
Tel. : ++49 551 201 2310
Fax : ++49 551 201 2302
Email : mgoette[at]mpi-bpc.mpg.de
mgoette2[at]gwdg.de
WWW : http://www.mpibpc.gwdg.de/groups/grubmueller/
Robert Johnson wrote:
Thanks David,
Since I'm turning off the VdW parameters as a second step, there
really isn't any reason to use the soft core potentials when turning
off the charges right? Thus, sc_alpha should be set to zero when
turning off charges?
Thanks,
Bob
On Jan 25, 2008 5:38 PM, David Mobley <[EMAIL PROTECTED]> wrote:
It will only be smooth if you don't use soft core (i.e. sc-alpha =0 ).
Best,
David Mobley
http://www.dillgroup.ucsf.edu/~dmobley
On Jan 25, 2008 12:40 PM, Robert Johnson <[EMAIL PROTECTED]> wrote:
Hello everyone,
As I mentioned in a previous post, I'm trying to compute the free
energy of binding of a DNA base on a carbon nanotube. My system
consists of a single DNA nucleotide (base, sugar, phosphate group) on
a rigid carbon nanotube in aqueous solution. A single Na+ counterion
is also included for charge neutralization. I'm proceeding with this
by computing the free energy associated with the following
transformations:
Water + Nanotube + DNA + Na+ -> Water + Nanotube + Nothing
Water + DNA + Na+ -> Water + Nothing
For each of these transformations I FIRST turn off the charges on the
base and counterion over a set of 5 lambda values (0.0, 0.25, 0.5,
0.75, 1.0). From literature and other posts on the GMX mailing list,
it seems like this small set of values should be adequate because
dG/dlambda tends to be pretty smooth for discharging the molecule.
Unfortunately, that doesn't seem to be the case in my system. Here is
a table of the dG/dlambda values I get from running 5 ns trajectories
of my system:
lambda <dG/dlambda>
0.0 6211.105
0.25 1055.254
0.5 1230.675
0.75 1128.359
1.0 756.2904
If you plot this you will see a large drop from lambda=0 to 0.25. Then
dG/dlambda increase slightly from lambda=0.25 to 0.5 and then smoothly
decreases after that. This seems like a pretty strange result. Also,
it seems that something weird is going on around lambda=0. If I
compute dG/dlambda for lambda=0.05, I get something around 1200-1300,
which is again a very sharp decrease from the value of 6211.105 I get
at lambda=0. Thus, it doesn't seem like simply adding more lambda
values is going to help me.
Here are the values I'm using for the free energy calculation:
free_energy = yes
init_lambda = 0.05
delta_lambda = 0
sc_alpha = 0.5
sc_power = 1
sc_sigma = 0.3
Also, here is an excerpt from my topology file:
[ atoms ]
1 P 1 DG P 1 1.1659 30.9700
P 0.0000 30.9700
2 O 1 DG O1P 1 -0.7761 16.0000
O 0.0000 16.0000
3 O 1 DG O2P 1 -0.7761 16.0000
O 0.0000 16.0000
I'm not perturbing any of the bonding interactions or VdW parameters -
I'm just turning off all charges on the molecule.
Does anyone have any ideas or suggestions about how this can be improved?
Thanks,
Bob Johnson
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