AMBER Archive (2008)

Subject: Re: AMBER: AMBER file preparation for protein-carbohydrate complex

From: Karl Kirschner (
Date: Sun May 25 2008 - 04:25:35 CDT

Hi Neha,

        If I understand correctly, there are a few separate problems here
that need to be solved before you can perform a simulation that is
trustworthy. I will assume that you are using Glycam06.

1) Atom Type. You will have to create and add new atom types that are
not present in Glycam. This will require understanding and modifying
the leaprc.Glycam06 (atom types) and Glycam_06d.dat (parameters such
as atomic weight, nonbonded parameters, etc.) appropriately.
Alternatively, you can create your own leaprc and parameter.dat files.

2) Prep File. If you have computed RESP partial atomic charges for
sulfated IdoA and GlcNS6S, then I assume you have separate quantum
minimized structures, that are "capped" at the C1 position with -OH
or -OCH3, which can be used as input into Antechamber. (These charges
should have been developed using HF/6-31G*//HF/6-31G* theory for MEP
and a restraint weight of 0.0005 on QM minimized structures. Ideally,
you would have an ensemble average charge set.) Antechamber can
provide you with a prep file that uses z-matrix or cartesian
coordinates. a) You will have to remove the "capped" group, and the
hydrogen from the linkage oxygen, from the resulting prep file, in
order to leave these position open for binding to another residues.
b) You will have to alter the atom types to those of Glycam and those
that you added in step 1. c) Modify the three letter residue
abbreviation in the resulting prep file to that which is used in your
2HYU.pdb file. This will likely take some time, and will require a
very good understanding of the details concerning prep files and how
they are implemented by Leap.

3) Parameters. Be careful when you are Frankensteining parameters.
Mixing parameters that were developed using different methods can
result in poor physical/energetic behavior of your system in
minimizations and simulations. It can be done, but the resulting
mixed parameter set has to be benchmarked first to ensure that the
correct physics are captured. This will be important for the sulfated
carbohydrates since the ring conformations are important and the
sulfur parameters that you add will likely effect this. This is
potentially the hardest and more important issue that you have to
think about. One could develop parameters for this system that are
compatible using the procedure that we outline in our Glycam06 paper
(J. Comput. Chem. 29 (2008) 622-655), which would be the safest thing
to do.

I hope this helps you out.

Karl N. Kirschner, Ph.D.
Center for Molecular Design, Co-Director
Visiting Assistant Professor
Hamilton College, Clinton NY 13323

On May 25, 2008, at 9:17 AM, wrote:

> Thank you very much for posting your reply. You are right but the
> issue is the pdb is a heparin fragment which has sulfated IdoA and
> GlcNS6S.
> Building AMBER input files with carbohydrates is easy and it can done
> through glycam website. But I am working with gags. I assigned glycam
> atom type and residue to it and sulfate parameters from Altona's paper
> but glycam residue type doesnot have sulfates included in it. Hence,
> AMBER cannot identify the atom type or residue name for my molecule
> which has sulfates.
> For example you can extract heparin from 2HYU file and try to prepare
> input files for AMBER.
> How do I prepare pdb file for this sulfated molecules? I have
> obviously calculated RESP charges.
> Regards,
> Neha
> On 5/23/08, Lachele Foley (Lists) <> wrote:
>> Tell me if I understand you. You want to assign charges to the
>> carbohydrate, but you want to use different charges from those
>> provided by GLYCAM. Is that right? If so, it might be simplest to
>> make a separate set of prep files by copying over the relevant GLYCAM
>> residues and changing the charges in the new file(s).
>> However, it is not generally recommended that you alter the GLYCAM
>> charge set. Why not use the charges from GLYCAM? Also, is your pdb
>> file being generated using GLYCAM residues, or was it generated
>> elsewhere?
>> There is discussion of a similar issue in the AmberTools manual, by
>> the way (page 61, section If you have not already, you
>> might find it useful to read through that.
>> On Thu, May 22, 2008 at 10:31 AM, Neha Gandhi
>> <> wrote:
>>> Hi All,
>>> I am working on protein-charged carbohydrate complex and I want
>>> to perform
>>> MD simulations. The ligand has charged groups. PDB file format
>>> allows easy
>>> assignment of charges for the protein based on 3 letter amino
>>> acid code
>>> but
>>> how this format is not useful for charged ligands. I am using
>>> RESP charged
>>> and GLYCAM forcefield for the carbohydrate.
>>> Mol2 file format is also not helpful as it ll work for only a single
>>> residue
>>> in AMBER. How I prepare the input file for ligand-receptor
>>> complex for
>>> in this case?
>>> Again, the other issue will be the amino acid name will be
>>> truncated in
>>> case
>>> of ligand when I run ambpdb. In this case, the carbohydrate
>>> residue has
>>> nomenclature based on glycam.
>>> Your help is appreciated.
>>> --
>>> Regards,
>>> Neha Gandhi
>> --
>> :-) Lachele
>> Lachele Foley
>> 2-0263
>> ---------------------------------------------------------------------
>> --
> --
> Regards,
> Neha Gandhi

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