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.
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:
-------------------------------------------------------------------------
--
gmx-users mailing list gmx-users@gromacs.org
http://lists.gromacs.org/mailman/listinfo/gmx-users
Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search
before posting!
Please don't post (un)subscribe requests to the list. Use the
www interface or send it to gmx-users-requ...@gromacs.org.
Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
--
gmx-users mailing list gmx-users@gromacs.org
http://lists.gromacs.org/mailman/listinfo/gmx-users
Please search the archive at
http://www.gromacs.org/Support/Mailing_Lists/Search before posting!
Please don't post (un)subscribe requests to the list. Use the
www interface or send it to gmx-users-requ...@gromacs.org.
Can't post? Read http://www.gromacs.org/Support/Mailing_Lists