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

[Mark Abraham]

Maxim Fedorov wrote:

> 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 experimentators have some unpublished data and there several classical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).

Charge separation is expensive energetically. Even though the unfolding 
may be charge-driven, it simply isn't going to be true that there are no 
counter-ions around in an experiment. Thus to have a realistic 
simulation you need to have some counter-ions (preferably at a realistic 
ionic strength)... but you say that "some counter-ions" stabilize the 
initial conformation. If you were adding charges to neutralize the 
system, you could try adding fewer counter-ions as a compromise.

> 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.

Whatever you do to change the system is going to be a non-physical 
system. You say the physically realistic simulation doesn't follow 
experiment. Perhaps you should have a look at your simulation protocol, 
particularly the electrostatics treatment, to see if the fault might be 
there, rather than assume it's only the charge-screening effect. MM 
force fields are a model of reality, often applied in MD using further 
approximations to real physics, so there are multiple sources of problems.

> 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.

How long does the experimental system take to unfold?

Mark