On Tue, Nov 15, 2011, Crystal.CHIA-YU Ku wrote:
>
> Here is my way to obtain the ligand from the crystal structure of
> ligand-receptor:
> 1. Download the ligand-receptor crystal structure file: 2HOM in PDB.
> The structure file has no hydrogen inside.
> 2. Copy atom coordinates of the ligand and their connectivity to
> another empty file, then store them as TPS.pdb.
> 3. Use Chimera to add hydrogen atoms to the ligand, and then save it
> as TPS_MD1.pdb which I already provided in the last email.
Basically, what you and Chimera did looks fine. You get the
doubly-deprotonated phosphate, which is likely to be what you really want,
but may be giving some problems.
>
> The only difference between original ligand information and the ligand
> processed by Chimera is that the hydrogen number of ligand handled by
> Chimera only provides 16 hydrogen, but the original ligand information
> says the ligand has 18 hydrogens. I cannot add two hydrogens to the
> phosphate group of my ligand by Chimera.
I tried neutralizing the phosphate (just added to hydrogens in xleap), then
antehcamber "ran", but the results are somewhat problematic: the structure
optimized to a conformation where one phosphate oxygen is only 1.95 Ang from
the sulfur, and the sulfur ends up then with a positive partial charge. I
suspect that the automatic am1-bcc procedure is not doing a good job here,
and you might want to see if thiamine or thiamine phosphate has been done in
the RED database. You will also want to read up about the ligand's
properties, in order to estimate what protonation state to use...I'm guessing
-1 overall for the ligand, especially if there is a metal atom nearby.
Attached is the tps.mol2 file I got from the following command:
antechamber -i tps3.pdb -fi pdb -o tps.mol2 -fo mol2 -c bcc -nc 1
where tps3.pdb is just modified from your structure by adding to protons to
the phosphate oxygens; I also pasted in the optimized structure from sqm, in
place of the original structure.
Not sure this "helps": some problems like this are quite tricky to deal with.
Here there are two obstacles to automated procedures:
a. The -1 charge state one expects in solution is hard to converge in the gas
phase.
b. Even if you get convergence by neutralizing the phosphate, the optimized gas
phase conformation is probably not a good one to derive a charge model from.
The "bottom line" is that the resp charge model is probably better than
AM1-bcc for this ligand. You should be able to use the mol2 file attached
(which comes from gaff), but use R.E.D. (or the resp options in antehcamber)
to try to get better charges....just edit them in place of the ones that are
there.
.....good luck....dac
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Received on Tue Nov 15 2011 - 18:00:03 PST
