[gmx-users] Creation of a Non-Standard Residue

Justin A. Lemkul jalemkul at vt.edu
Fri Jun 4 03:52:43 CEST 2010

Mark Zottola wrote:
> Let me clarify.
> I have no problem determining the bond stretching or angle bending 
> parameters for HCN.  This was a very straightforward task.  Unit 
> conversion to get those values in a gromacs force field was also a 
> non-issue.
> The problems I am having are:
> 1) How do I specify a POLAR hydrogen on a carbon atom?  There are polar 
> hydrogens (or so it seems) in the gromacs forcei field, but ostensibly 
> they are on heteroatoms such as nitrogen or oxyen.  Is there a way to 
> force gromacs to let a polar hydrogen on a carbon?

You can specify whatever you want in the topology, as long as you can justify 
that it is consistent with the underlying force field model.  For instance, 
aromatic C-H pairs are represented by explicit hydrogens in the Gromos force fields.

> 2) I AM looking for advice on the van der Waals parameters.  Yes, I can 
> guess and tweak until the cows come home, but obviously there are 
> recommendations which I do not know.  So... any suggestions on this.

This is a tough task.  Much of the Gromos derivation relies on empirical fitting 
and tweaking to reproduce condensed-phase behavior.  You could start with a few 
existing atom types, simulating a box of HCN, and revising based on the results 
you get (densities, heat of vaporization, etc).  The primary literature on the 
derivation of these parameter sets is a bit sparse, but you should be able to 
get started.

> 3)  The problem is quite simple, I want to develop parameters for HCN so 
> I can use it as both ligand AND as a component n a solvent box.  I do 
> have the formula (4 or 5 steps from the web) to create my solvent box, 
> but I need to have HCN properly parameterized. 

As is the case for any small molecule :)

> 4)  I am asking for this as I cannot use the Dundee server to make the 
> appropriate topology file.
> The warning blurb was good at saying "Parameter development is done by 
> professionals, so please do not try this at home."  I am asking for help 
> in the above issues as I am new to GROMACS but NOT other MD programs.

I would estimate that 95% of the parameterization questions asked on the list 
are posted by people in way over their heads, so it is good to know your 
experience level.  I would say that the best approach is (unfortunately) 
somewhat empirical, but such is the nature of the beast with Gromos force 
fields.  Some simple QM might give you a start for calculating charges, but as I 
understand it, QM was used in the Gromos derivations only to get relative 
electron densities around all of the atoms, after which charges were assigned 
(empirically) and revised to fit condensed-phase behavior.


> Thanks again for any help. 
> On Thu, Jun 3, 2010 at 7:30 PM, Mark Abraham <mark.abraham at anu.edu.au 
> <mailto:mark.abraham at anu.edu.au>> wrote:
>     ----- Original Message -----
>     From: Mark Zottola <mzottola at gmail.com <mailto:mzottola at gmail.com>>
>     Date: Friday, June 4, 2010 1:55
>     Subject: [gmx-users] Creation of a Non-Standard Residue
>     To: Discussion list for GROMACS users <gmx-users at gromacs.org
>     <mailto:gmx-users at gromacs.org>>
>      > I am trying to to create a non-standard residue - HCN.  This
>     cannot be done by the Dundee PRODRG server as it subsumes the polar
>     hydrogen into the carbon.  This results in a diatomic molecule that
>     the program cannot handle.
>      >  
>      > I do mind creating a new drug by hand, but a search through the
>     email list has been less than fruitful.  I have
>     done parameter/non-standard residue formation in AMBER, I believe I
>     understand the process.  Yet, there is no clear delineation of how
>     one does charges.  The best I found was the proper suggestion
>     that CHELPG charges from a QM calculation should be employed.  This
>     is to be expected, but WHICH method should one use:  hf/6-31g*,
>     MNDO, something else?
>     The standard advice is here
>     http://www.gromacs.org/Documentation/How-tos/Parameterization. For
>     starters, choose a force field you want to parameterize HCN to work
>     *with*.
>      > I know I will have to augment my parameter file to include the
>     new atom types and parameters.  But as HCN has a polar hydrogen "on
>     a carbon" how do I ensure that this is explicitly maintained?  If I
>     lie and call the hydrogen on carbon "H", the designation for an atom
>     bonded to Nitrogen, is this enough to keep that hydrogen explicit?
>      I also want to make a solvent box of HCN (cheaper and safer than
>     trying this experimentally!!).  I am assuming that simple
>     electrostatics balanced against Van der Waals interactions will
>     dictate the proximity of hydrogen bond donor to acceptor in this
>     forcefield. 
>     You seem to be creating problems for yourself by not having a clear
>     objective - or at least not expressing it here!
>      > Finally, I assume a kluge of non-bonded parameters (van derWaals)
>     is reasonable or is there a preferred way of determining an L-J
>     potential?
>     Guessing values randomly is likely to get random results.
>     Parameterization and validation of parameters are difficult topics
>     to work on, and not encouraged for newcomers.
>      > If I totally missed the answers to these questions, a hint on
>     better keywords or a good reference encompassing these issues would
>     be welcome.
>     Mark
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Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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