[gmx-users] Can g_wham support using different temperature for different windows?

Jianguo Li ljggmx at yahoo.com.sg
Wed Feb 23 14:49:26 CET 2011

Dear all,

Thank you all for your suggestions or comments to my problem. Now I am planning 
to extend my simulations or using REMD in those bad windows to get converged 

I have another question: if I extend the umbrellar simulation to 1 microsecond 
only in those problematic windows, while running shorter simulation (e.g., 100 
ns) in those windows far away from the membrane. Does g_wham accpet using 
diffrent simulation time for different windows?
Thank you in again,


From: XAvier Periole <x.periole at rug.nl>
To: Discussion list for GROMACS users <gmx-users at gromacs.org>
Sent: Wednesday, 23 February 2011 20:59:18
Subject: Re: [gmx-users] Can g_wham support using different temperature for 
different windows?

On Feb 23, 2011, at 3:21 AM, Jianguo Li wrote:

>Thank you  for the the useful information, XAvier.
>My peptide is highly positively charged, 18 AA with +12 charges. Other of my 
>group members told me their NMR experiment in water indicates the peptide 
>conformation is very dynamics. Actually I also did peptide refolding using REMD 
>in water, and I found it is flexible and has no stable structure in water, 
>except some instantaneously helical structures. In addition, my peptide consists 
>of two branches connected by unnatural peptide bond, so the backbone is 
>discontinuous, and also because of the high charges, I assume the peptide 
>doesn't form helcial structure in the negatively charged membrane. Therefore I 
>didn't put any constraints in the peptide to keep the secondary structure of the 
>peptide. I know there are assumptions in my model, but I have no other 
>information to increase the accuracy of the model.  In fact, when I am doing 
>REMD folding simulations using Gromos53a6 and CHARMM27 with cMap, I got 
>different results. But the common thing is that both results seems to indicate 
>the peptide is filexbile in water without stable secondary structure. Then I 
>used MARTINI FF with flexible structure, just to find some general features.
>I will try your suggestion, doing REMD in those bad windows.
>And the reference you mentioned is very useful, I will take a look at them :-)
>Another question: Suppose some other tools support using different temperatures 
>in different windows, as you mentioned, if 500K is too high to have a 
>significant contribution to the probability of 300K,  can I do a series of 
>simulation in a certain window with different temparatures (e.g. 300K, 350K, 
>400K,450K, 500K). In such cases, in each window, I need to do 5 simulations, 
>which will be much cheaper than doing REMD in that window. It would be 
>computationally cheaper but this is assuming that you'd get the info you are 
>looking for within these simulations and again the weight of the conformations 
>from 400/450/500 K at 300 K is questionable. Note also that the conformations 
>sampled at high temperature with position restrains on the lipids to avoid 
>deformation will be difficult to interpret! 

From: XAvier Periole <x.periole at rug.nl>
>To: Discussion list for GROMACS users <gmx-users at gromacs.org>
>Sent: Tuesday, 22 February 2011 21:18:12
>Subject: Re: [gmx-users] Can g_wham support using different temperature for 
>different windows?
>A few notes:
>- the original method (Kumar-JCC-1992) that inspired wham was actually 
>developed to mix different temperature simulations. It is however not clear 
>for the type of system you are simulating how much a 500K simulation 
>would be useful to improve the sampling at 300 K or so. The reason is 
>that the enthalpy difference between the two systems is so high that the 
>probability that a conformation from a 500K simulation would contribute
>to sampling at 300K is really low. It would much more efficient for systems 
>with implicit solvent for which the energy of the system does not vary so 
>much with the temperature. One could look at Chodera-JCTC-2007 
>and ref therein for a few examples.
>- I would think that a REMD simulation would be more useful. No need to
>run 30 replicas to very hight temperature! A bilayer at 500K might get funny.
>- Martini force field for flexible regions of protein should not be trusted ... 
>really interpreted with a lot of reserve. The "coil" definition is simply 
>flexible with absolutely no guaranty that it could be representing some thing 
>even close to reality, which we have only an approximate idea of what it is! 
>- A peptide in a bilayer has a very high chance to get into a helical 
>Do you think it is reasonable to keep it "flexible"? 
>- As noted by Justin and Chris, you definitely have a problem of convergence 
>I am not sure how many "converged" examples of PMFs of peptide crossing a
>bilayer are out in the literature (Justin?) but from our experience with 
>it does take an awful lot of time to really get convergence. For you system I 
>would expect at least a microsecond for the windows where sampling is an 
>issue. As an example, we saw significant differences on a PMF between two 
>simple helices up to 8 us ... and no charges were involved.
>This might be a lot pessimistic but you should not get fooled by a CG model.
>Martini is really good for a lot of things but other things should really but 
>looked at carefully. 

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