AMBER Archive (2008)

Subject: RE: AMBER: Problems simulating a protein-ligand complex

From: Ross Walker (ross_at_rosswalker.co.uk)
Date: Fri Jun 06 2008 - 18:34:39 CDT

Hi Sasha,

 

Can you post the output file from the minimization? You probably have two atoms sitting on top of each other or very close.

 

All the best

Ross

 

From: owner-amber_at_scripps.edu [mailto:owner-amber_at_scripps.edu] On Behalf Of Sasha Buzko
Sent: Friday, June 06, 2008 4:13 PM
To: amber_at_scripps.edu
Subject: RE: AMBER: Problems simulating a protein-ligand complex

 

Hi Ross,
thank you for the detailed instructions (although I'm trying to use GB and avoid having to add explicit solvent).

I did get a complex with the correct position of the ligand (used Sirius to check the prmtop/inpcrd). But at the stage of minimization I run into NaN values for all energies after about 100 steps (in the minimization out file). Not sure whether it's missing parameters or something else.. frcmod file had the following:

IMPROPER
c3-cc-na-cc 1.1 180.0 2.0 Using default value
h5-na-cc-nd 1.1 180.0 2.0 Using default value
c -cc-cd-nd 1.1 180.0 2.0 Using default value
cd-nc-c -o 10.5 180.0 2.0 General improper torsional angle (2 general atom types)
na-nc-cd-nh 1.1 180.0 2.0 Using default value
cd-hn-nh-hn 1.1 180.0 2.0 Using default value
cc-cd-na-hn 1.1 180.0 2.0 General improper torsional angle (2 general atom types)
cd-na-cc-na 1.1 180.0 2.0 Using default value

But again, I'm not sure what could cause the issue with NaN values. Since the ligand is a triphosphate, I set its charge to -3 (using -nc -3 flag for antechamber). In any event, I'm a bit low on possible causes..
Can you think of anything in this regard?

Thanks again

Sasha

On Fri, 2008-06-06 at 15:55 -0700, Ross Walker wrote:

 
Hi Sasha,
 
I would do something along the lines of the following:
 
1) open protein pdb in a text editor and remove the END (at the end) and just make sure there is a ter card there. Also remove any connectivity data.
 
2) open the ligand pdb file and remove anything prior to the first atom definition. Go to the end and remove everything past the last atom definition and just add an END card.
 
3) cp protein pdb to complex.pdb
   Cat ligand pdb >> complex.pdb
 
4) load leap
   Source leaprc.ff99SB
   Source leaprc.gaff
   Loadamberprep ligand.prep
   Loadamberparams ligand.frcmod
   Foo = loadpdb complex.pdb
   Solvateoct foo TIP3PBOX 10.0
   Saveamberparm foo prmtop inpcrd
 
I hope that makes sense and is what you actually want to do I.e make a prmtop and inpcrd for the solvated complex.
 
All the best
Ross
 
 
 
From: owner-amber_at_scripps.edu [mailto:owner-amber_at_scripps.edu] On Behalf Of Sasha Buzko
Sent: Friday, June 06, 2008 3:16 PM
To: amber_at_scripps.edu
Subject: Re: AMBER: Problems simulating a protein-ligand complex
 
Thank you, David.
 
With hydrogens added in another application, the antechamber part worked.
 
But another issue appears when I combine the protein structure with the antechamber output in xleap. The ligand is loaded as a prepin file, followed by its frcmod with missing parameters. Then I load the pdb file of the protein and use complex = combine { protein GNP }, where GNP is the name of the residue assigned to the ligand. However, the ligand ends up being shifted in space far from the protein, even though the initial coordinates corresponded to the complex.. I assume that it's the result of the intermediate operations.. but is there a way to combine the two entities into the original complex?
 
Thanks for any advice
 
Sasha
 
 
 
 
On Fri, 2008-06-06 at 11:59 -0700, David A. Case wrote:
 
On Fri, Jun 06, 2008, Sasha Buzko wrote:
>
> The structure has correct connectivity and came directly from a PDB
> file. Since the ligand PDB file is not that large, I'm pasting it below.
> Thank you for any suggestions.
 
You don't have any hydrogen atoms in your input structure. Antechamber
doesn't know how to add hydrogens...you need to draw them in by hand, or
use some other model building program to add all of the hydrogens.
 
...hope this helps...dac
 
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