[gmx-users] Topology of a neutral single peptide

[Justin Lemkul]

On 5/30/16 10:42 AM, soumadwip ghosh wrote:
> Hi,
>      I am currently working on the interaction of single peptide chains
> with some ligands for which I need to keep all the carboxyl functional
> groups of a protein protonated, i.e, in the carboxylic acid form and
> thereby the peptide should be neutral. I obtained the PDB of Lysozyme at pH
> 6.8 and tried to make the protein topology. I did the following steps:
>
> 1. pdb2gmx -f lysozyme.pdb -o lysozyme.gro -ter -ignh
>
> When prompted I selected CHARMM 27 ff.
>
> Then it asked for the termini as follows:
>
> Linking CYS-6 SG-48 and CYS-127 SG-981...
> Linking CYS-30 SG-238 and CYS-115 SG-889...
> Linking CYS-64 SG-513 and CYS-80 SG-630...
> Linking CYS-76 SG-601 and CYS-94 SG-724...
> Select start terminus type for LYS-1
>  0: NH3+
>  1: NH2
>  2: None
>  I selected 1. Then
>
> Start terminus LYS-1: NH2
> Select end terminus type for LEU-129
>  0: COO-
>  1: COOH
>  2: CT2
>  3: CT3
>  4: None
> I again selected 1 but when the topology was created it showed : Total
> charge 9.000 e
>
> Where am I going wrong? Is there a way to obtain a completely neutral
> protein chain topology or is it strictly force field specific? Was there
> anything wrong with the command line? I am handling protein topology for
> the first time, so please excuse me if I am asking for much.
>

Choosing neutral termini is insufficient to obtain a neutral protein.  The 
constituent amino acid side chains of lysozyme yield a +8e charge at neutral pH. 
  If you want to alter all of these to be in their neutral forms (which would be 
a very strange state) you can do this with options in pdb2gmx, most likely 
-inter so you can choose the protonation states of everything interactively.

-Justin

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==================================================