AMBER Archive (2009)

Subject: Re: [AMBER] LYN again

From: Marius Retegan (marius.s.retegan_at_gmail.com)
Date: Mon Apr 06 2009 - 08:55:24 CDT

Hello,

On Sun, Apr 5, 2009 at 9:24 PM, FyD <fyd_at_q4md-forcefieldtools.org> wrote:

> 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
>

The above representation got messed up, so I'm going to explain it. The
linker has on both ends the C=O group, so what I called linker are just a
few carbon and nitrogen atoms. Between this C=O and the NZ-H of the lysine I
have a peptidic bond.

>
>
> 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.
>

Something similar. In my case I think I'm going to attach to the NZ atom of
the lysine a ACE group with a restrained charge.

>
> 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)...
>

Apparently, even for LYS residue, only two conformations where used for
deriving the charges in the original paper.

> I hope this helps.
>
> regards, Francois
>
>
Thank you.
Marius

>
>
> _______________________________________________
> AMBER mailing list
> AMBER_at_ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
_______________________________________________
AMBER mailing list
AMBER_at_ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber