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

Jianguo Li ljggmx at yahoo.com.sg
Wed Feb 23 03:21:05 CET 2011

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. 


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 be
looked at carefully. 


On Feb 22, 2011, at 9:12 AM, Jianguo Li wrote:

Sorry I forgot to attach my mdp files. 
>Here is the mdp file for pulling simulaition:

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