[gmx-users] Simulation parameter problem about protein unfolding

Chen amethyst0 at 126.com
Mon Oct 18 10:10:35 CEST 2010

>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.

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,

 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?

>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.

Hi, Itamar! Thanks for the reply! I didn't intend to make the
unfolding protein like a straight line. I just 'feel' the protein in 498K
should fluctuate a little larger. So I want to make sure I didn't make mistake
in MD parameters setting or water BOX preparing.

>-- 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!
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