Re: [AMBER] looking for parameters for DHFR substrates and inhibitors... [one more try]

From: FyD <>
Date: Wed, 02 Dec 2009 09:19:00 +0100

Dear Sidney,

May-be you should think developing your own parameters ;-)

After looking in Wikipedia:
it looks like these molecules derive all from L-glutamic acid. Right ?
You could easily imagine a building block approach based on a common
fragment L-glutamic acid and with various aromatic counterpart(s).

You could use R.E.D.-III.3 for that (or may-be R.E.D. Server/R.E.D.-IV
if you want to develop the FF libraries of all these molecules +
analogs in a single approach).

You will need to build a C-terminal fragment for L-glutamic acid
  & a central fragment in same time
or you can use the fragment CGLU (if charged) from the Amber force
field topology database

Then, either you split your aromatic counterparts in two using
additional constraints (inter-molecular charge constraint) during the
charge fit or you keep all in a single block. Once again, if a common
group is found in the aromatic part I would split the system in twos:
common & variable. You can find examples of such approaches in
R.E.DD.B. I think you can find answers of such charge constraints in
the last R.E.DD.B. projects:
In these two projects, you will find "connections" between various
building blocks of different natures.

Following a similar approach, my feeling is that you can easily
generate a project with various common & variable parts/blocks for all
your molecules & many analogs you might be interested in the future.

Advantage of the building block approach:
- you fully control the conformation(s) of the building blocks used &
- you can build FF library for the molecules you are interested and
for many analogs (variable parts).

In your case as you have an amino-acid, I would use the ff99SB force
field; similarly as what is done in the "F-85" R.E.DD.B. project.

If you are interested in starting such a work (quite quick since the
different building blocks are small), do not hesitate to ask questions
in the amber or q4md-fft mailing list.

regards, Francois

> There have been quite a few computational studies of DHFR, and I was
> surprised that I couldn't find any published parameters for the substrates
> and inhibitors readily available. Anyone have any insights into where I
> could find them? Using standard parameters for these ligands would be
> preferable to reinventing the wheel and doing my own parameterization.
> Thank you in advance for your help.
> Sid
> On Sat, Nov 21, 2009 at 8:47 PM, Sidney Elmer <> wrote:
>> Hi all,
>> Does anyone know where I could find parameters for methotrexate,
>> dihydrofolate, and tetrahydrofolate? I was unable to find anything on
>> google. I also checked on REDDB but couldn't find any there, either. Any
>> leads would be very helpful. Thanks.
>> Sid

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Received on Wed Dec 02 2009 - 00:30:02 PST
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