[gmx-users] Simulation parameter problem about protein unfolding

Itamar Kass itamar.kass at monash.edu
Mon Oct 18 07:06:50 CEST 2010


If I can add to this discussion, I think that your results are very 
reasonable. Proteins in solution are not straight lines, but fold to 
some extent. If you wish to have en elongated protein you have to pull 
it like it is being done in AFM experiments.


On 18/10/10 3:56 PM, 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.
> -- original message --
> Hi All,
> I met a problem when I try to unfold a protein using Gromacs, It 
> seemed the protein cannot be totally unfolded!
> The simulated system has one Engrailed Homeodomain (En) protein (a 
> three helix bundle protein with 54 residues, 629 atoms), total 4848 
> spce waters, and 7 Cl- used to neutralize the system in a 5.752(nm)^3 
> water BOX. I use the NTP ensemble with T=498K and P=26atm. The system 
> has 1nm thick water in each side of the En protein, and the density of 
> the system has been adjusted to0.829 g/cm3.
> The simulation lasted 24ns. The helixes disappeared at about 4ns. And 
> after that some beta sheet formed in the N terminal of the protein. 
> However, the protein kept in a compact state during the 24ns 
> simulation. The radius of gyration of the protein fluctuated around 
> 1.1nm during the simulation.
> I've also noticed similar simulation done by others. For example, 
> David Becka and Valerie Daggett reviewed their En protein unfolding in 
> paper "Methods for molecular dynamics simulations of protein 
> folding/unfolding in solution. Methods 34 (2004) 112¨C120". The 
> simulations were performed with ENCAD and ilmm, and used an 0.8nm 
> cutoff range. And the ensemble they used is NVE as I know. A stretched 
> unfolding state occurred at about 5ns in their 60ns simulation in 
> 498K, with little helix structure.
> I was wondering whether the difference is caused by using different MD 
> software and force field, or by some wrong parameters in my .mdp file. 
> I've also conducted another 18ns simulation, and the result is almost 
> the same. I list he mdp file below. Any comment is appreciated!


"In theory, there is no difference between theory and practice. But, in practice, there is." - Jan L.A. van de Snepscheut

| Itamar Kass, Ph.D.
| Postdoctoral Research Fellow
| Department of Biochemistry and Molecular Biology
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