Jianguo Li wrote:
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?
Theoretically, but if you are going to discard any of the initial time (that is,
equilibration in each window) by using the -b option, you'll have to make sure
that you don't eliminate windows by doing so, i.e. 100 ns in some windows and 1
us in others, using g_wham -b 200000 would completely neglect any windows with
shorter time and basically make the PMF curve useless.
-Justin
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 <mailto:x.peri...@rug.nl>>
*To:* Discussion list for GROMACS users <gmx-users@gromacs.org
<mailto: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.
--
========================================
Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
========================================
--
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
