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

XAvier Periole x.periole at rug.nl
Wed Feb 23 13:59:18 CET 2011

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!
> Cheers
> Jianguo
> 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 ... or
> really interpreted with a lot of reserve. The "coil" definition is  
> simply something
> 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 conformation.
> 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 Martini
> 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.
> XAvier.
> 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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