[gmx-users] Simulation parameter problem about protein unfolding

[chris.neale at utoronto.ca]

Chen,

to answer this, please see David's post and my reply. To answer if  
your unfolded state ensemble is accurate, you will need to know some  
experimentally evaluated quantities of the state that you are trying  
to reproduce: 498K, 26 atm, a certain amount of salt, etc, (but not  
including the forcefield model or cutoffs, which are obviously  
intrinsically part of the model).

Then, if your data does not match this, then you can conclude that the  
simulation time was too short or the parameters were not valid. Also,  
I guarantee it was... you'll probably need something more like 10 ms -  
10 s (what is the unfolding rate under these conditions?), which is  
rather difficult to obtain).

Comparing a temperature denatured state to an AFM denatured state, one  
does not expect them to match. The point here was to ask: are you sure  
that your ensemble of conformations is incorrect given the conditions?

Chris.

-- original message --

> At 2010-10-18 12:56:31£¬chris.neale at utoronto.ca wrote:
> Generally, forcefields are not parameterized for temperatures other   
> than 298K, so simulations are not expected to reproduce the expected  
>  properties (like boiling water and the correct temperature   
> denaturation of proteins).
>
> There's almost certainly other issues here (including the fact that   
> I'm entirely sure that you can get a lot more than 24 ns of  
> simulation  on a 54 aa protein; and 26 atom of pressure seems pretty  
> arbitrary)  but it will come down to this eventually.
>
> Just because you found a paper in which they get a denatured state   
> does not imply that they got the correct denatured state.
>
> Chris.
>

Hi, Chris! Thanks for the reply! I have not conducted unfolding
before, so I compared my result with other's to make sure it is reasonable in
some extend. The 26 atm pressure comes from experiment result (Haar et al.,
1984) mentioned in some MD related papers (e.g. 'J. Mol. Biol. (2000) 296,
1257-1282').

  I've searched the maillist
and noticed some issues about High temperature simulations. I'm not sure
whether the 'ilmm' force field has been optimized for high temperature
simulation. I also noticed some users asked about MD parameters in  
'unfolding a
protein'. And the parameters they used are different from ours' (e.g. the
'rlist', 'rcoulomb' and 'temperature or pressure couple algorithm').

  I just want to make sure I
didn't make mistakes in these parameters which maybe cause the protein keeping
in a compact state! The radius of gyration of the protein fluctuated around
1.1nm (never bigger than 1.4nm) during our 30ns simulation now. If the MD
parameters I chose have no problem, then I could keep going. Any comment?