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 PMF.
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, Cheers, Jianguo ________________________________ From: XAvier Periole <x.peri...@rug.nl> To: Discussion list for GROMACS users <gmx-users@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! >Cheers >Jianguo > > > > > ________________________________ From: XAvier Periole <x.peri...@rug.nl> >To: Discussion list for GROMACS users <gmx-users@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. > > >
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