[gmx-users] Re: Counterions: influence on protein dynamics.

[Maxim Fedorov]

> ------------------------------
> 
> Message: 7
> Date: Mon, 27 Feb 2006 09:11:14 +0100
> From: David van der Spoel <spoel at xray.bmc.uu.se>
> Subject: Re: [gmx-users] Counterions: influence on protein dynamics.
> To: Discussion list for GROMACS users <gmx-users at gromacs.org>
> Message-ID: <4402B422.9060405 at xray.bmc.uu.se>
> Content-Type: text/plain; charset=windows-1252; format=flowed
> 
> Maxim Fedorov wrote:
> > Dear all,
> > 
> > I am doing MD simulations of some polypeptide chains. These 
> > polypeptides have non-zero net charge; therefore, I should add 
> some 
> > counterions into the box to use the PME.
> > I am wondering ? is there an elegant way to reduce influence of 
> these 
> > counterions on polypeptide dynamics?
> > Until now I see only two options for that:
> > 1)	Constrain ions somewhere far from the solute ? but is doesn?t 
> > seem a good idea because the solute can move, and, therefore, 
> contact 
> > the ions with time.
> > 2)	Make a ?quasimolecule? - solute +  ions and constrain the bond 
> > distances between solute and ions.
> > Option 2) was proposed by Anton in some of his respond to the 
> users of 
> > the mail-list. It looks better than opt. 1). But ? I am a bit 
> worrying 
> > about the difference between dynamics of such ?quasimolecule? 
> > and ?natural? dynamics of my polypeptide chain (a hypothetical 
> case 
> > without ions).
> > Could it help if I equal to zero the ion masses in opt 2)?
> > Thank you all in advance.
> You just want a big box, many ions and long simulation times. 
> Anything 
> else will make referees frown.
> 
Dear David,

Thank you for your message, but ...
It doesn't seem to answer for my particular question -
probably I should go in more details.
I am investigating the charge-driven unfolding of protonated polypetides
like poly-L-Lysine and other compbinations of
charged/neutral residials.
The  poly-L-Lysine with ambient conditions (pH~7) is protonated,
therefore, it is quickly unfolds from an initial helical structure 
(which it has with pH >10) due to repelling of the side-chain positive
charges 
I am intersting in the final conformation and unfolding dynamics of such
system.

But ...
If I add some counterions into the box and allow them to approach 
my polypeptide they screen the charges and it stabilises the initial
conformation. This effect of ion stabilisation is well known and it is
an intersting topic, but in this particular case I don't need this - I
want to unfold my structure as it happens in experiment (our
experimentators have some unpublished data and there several classical
papers of Sheraga and others about the pH driven unfolding of
poly-L-Lysine, which were published in 70ths).

So, I want to get rid of this screening effect by placing the ions
somethere far from the solute. But I would like to take it in some smart
way, to reduce some possible artefacts (see the points 1) and 2) in my
previous letter.
> > 1)	Constrain ions somewhere far from the solute -  but is doesn't
seem a good idea because the solute can move, and, therefore, contact
the ions with time.
> > 2)	Make a 'quasimolecule' - solute +  ions and constrain the
bond.But I am a bit worrying about the difference between dynamics of
such 'quasimolecule?' and 'natural' dynamics of my polypeptide chain (a
hypothetical case without ions).

It woiuld be great to recieve a hint from a person who is more
experienced with such kind of things.

Regarding the size/simulation time -

As a standart I am using 24 ns for equilibration (~1200(7 residials)
-1700 water SPC molecules (21 residials), number of ions variates from 7
to 21 correspondingly).

Then I collect statistics from 20 ns productive run.

The system seems to be well (say, more or less :-)) equilibrated - I
checked several geometrical and energetical properties they are fine.
And it doesn't want to unfold even for 50 ns - due to the charge
screening by ions. And it is not because the simulation time is still
too short - I made a good sampling of the phase space 
with some Replica - Exchange run - in case of ions
the system has a global minumum in folded conformation.
In case of cut-off and absence of ions it doesn't have even local
minimum in the folded conformation - which correspond to the
experimental reslults and #common sense'.
If I don't use the ions and PME (simply using the cut-off) - the results
are more close to experiment - it quickly unfolds as it should be. 
But I have to use the PME because for more comples systems the cut-off 
doesn't suit our tasks.

Thank you in advance,

Maxim.