[gmx-users] Question about setting deprotonated cys in enzyme structure ....

Justin A. Lemkul jalemkul at vt.edu
Tue Apr 13 21:54:28 CEST 2010



Alberto Sergio Garay wrote:
> Dear all
> 
> I am preparing the topology for my enzyme molecule using pdb2gmx tool. 
> But first of all, I run a PROPKA program in order to assign the correct 
> protonation state for my molecule. As a result of this calculation I 
> obtained a pair of cysteines which should be deprotonated at pH 7 
> (fisiological pH), and others which should be protonated (the most of 
> them).

Should they be deprotonated such that they bear a net -1 charge, or connected 
via disulfide bond?

> 
> I have two questions: 1) Is it a correct aproximation to accept the 
> protonation state obtained by these kind of methods to assign the 
> charges of my enzyme's residues?
> 

I suppose that depends on the inherent approximations or limitations of the pKa 
calculation method.  Certainly considering pKa values makes for a more accurate 
model than blindly assuming certain protonation states, but probably the primary 
literature of the calculation method(s) will describe advantages, limitations, 
approximations, etc.  You can probably make an argument either way based on 
what's published.

> 2) How can I manage to select which cysteines are deprotonated and which 
> are not, using pdb2gmx tool?
> 

The first consideration is whether or not you want to use a force field for 
which parameters have been derived for this species.  As far as I know, only the 
AMBER force fields (by default) contain parameters for a cysteine that bears a 
net -1 charge.  There may be parameters out there for other force fields, 
though.  Using the AMBER force fields (after installing the ffamber ports) will 
require that you name the residues appropriately in the input coordinate file 
when running pdb2gmx.  That is, your deprotonated CYS would have to be named CYM 
to be interpreted correctly.

-Justin

> 
> Any help will appreciated.
> 

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

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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