AMBER Archive (2009)

Subject: Re: [AMBER] LYN again

From: FyD (fyd_at_q4md-forcefieldtools.org)
Date: Sun Apr 05 2009 - 14:24:27 CDT

Dear Marius,

> A few days ago I asked on the amber list about how to modify a neutral
> lysine in order to make another bond.

This is better to ask your questions to the q4md-fft or Amber mailing list.
With R.E.D. Server, we also provide a private assistance to each
registered user.

> The system that I study is something like this:
> O O
> || ||
> protein - Lys - N(NZ) - C - linker - C - N(NZ) - Lys - protein
> | |
> H H
>
> Basically the NZ atom of the lysine residue has one hydrogen attached to it
> and enters in a peptidic bond with the CO group of the linker.

If I understand you, your linker = NH-R-NH

> I've managed to get all the bonds in xleap, but now comes the big problem.
> First I was interested in determining the charge for the lysine residues,
> but since I've removed an hydrogen they are now -1. Unfortunately I don't
> have access to the JCC paper where the procedure of getting charges for
> amino acids is described (for example CYX).

I am not sure charge derivation for the CYX residue is described in
the original paper... The total charge of the CYX fragment is zero.
Consequently, the total charge of Cystine (disulfide bridge i.e.
CYX-CYX) is also zero.
I think this is exactly what you wish to achieve with your L-Lysine fragments.

> It would help me alot if someone could suggest a way on how to derive the
> charges for a charged amino acid and secoundly, should I constrain the
> charges on the CO moieties of the linker (I've seen that for almost all
> amino acids the atoms that enter a peptidic group have constrained charges).

Let's summarize the different cases:
1- charged NH3+ side chain: the LYS, NLYS & CLYS fragments are
available in the Amber force field topology database.
2- neutral NH2 side chain: the LYN, NLYN & CLYN fragments are not
available in the Amber FF Top.DB.
3- NH side chain: the LYH, NLYH & CLYH fragments are not available in
the Amber FF Top.DB. You want to get charges for the case 3-. Right ?

You have the choice of using R.E.D.-III.2 to derive the central,
N-term & C-term fragments in three independant R.E.D.-III.2 runs, or
to use R.E.D. Server (which interfaces R.E.D.-IV) where these three
fragments are generated in a single R.E.D. Server/R.E.D.-IV job.

All what you need is described in tutorials:
R.E.D.-III.x & a central fragment for a new amino acid:
http://q4md-forcefieldtools.org/Tutorial/Tutorial-1.php#10
as well as http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#15

R.E.D.-III.x & a terminal fragment for a new amino acid:
http://q4md-forcefieldtools.org/Tutorial/Tutorial-1.php#11
as well as http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#16
  & http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#17

R.E.D. Server & the three molecular fragments in a single step:
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#24

The three fragments corresponding to the "NH side chain" can be
obtained following a highly similar strategy than those presented in
the tutorials; i.e. using a dipeptide deriving from L-Lysine:
ACE-NHCH(R)CO-NME with R = (CH2)4NH-ACE (ACE = MeCO; NME = MeNH)
For the central fragment, you need to use three intra-molecular charge
constraints, each one set to zero; two for the two ACE groups + one
for the NME group.
For the terminal fragments, you need to use Acetate or Methylammonium
in the charge derivation, and to associate 2 intra- and 1
inter-molecular charge constraints.

A last difficulty in the case of L-Lysine is how you are going to
justify the conformations used in the charge derivations (the number
of possible conformations is large considering the long side chain of
L-Lysine)...

I hope this helps.

regards, Francois

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