[gmx-users] Simulation parameter problem about protein unfolding

David van der Spoel spoel at xray.bmc.uu.se
Mon Oct 18 10:38:30 CEST 2010

On 2010-10-18 06.56, 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.
There is no correct denatured state. There are infinitely many. Check 
out recent work on NMR of "unfolded" proteins.

> 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!

David van der Spoel, Ph.D., Professor of Biology
Dept. of Cell & Molec. Biol., Uppsala University.
Box 596, 75124 Uppsala, Sweden. Phone:	+46184714205.
spoel at xray.bmc.uu.se    http://folding.bmc.uu.se

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