From: George Patargias (gpat_at_bioacademy.gr)
Date: Fri Sep 19 2014 - 10:12:40 CDT
Hello Jerome,
Thanks for your reply.
I set up this calculation in 5 x 2 Ang windows with 2 ns ABF/MD in each.
>From the .count files, I noticed that, in all windows, the bins that
correspond to higher RMSD values are never visited, i.e the number of
collected samples is 0. Actually the first bin (towards the lower
boundary) has 7-8 times more samples than the rest.
This is probably why the RMSD values (from the .traj files) fluctuate
mostly around the lower RMSD value of every window.
Can this be caused by a too low or too high Nsamples value? I have set it
to 1000. Or maybe too low force constant for lower and upper boundary
values - I have set it to 100 Kcal/mol/Ang^2.
I copy/paste my colvars file used for the first window. Thanks again! George
colvar {
name RMSD
width 0.1 #Check again
lowerboundary 8.0
upperboundary 10.0
lowerwallconstant 100.0
upperwallconstant 100.0
outputAppliedForce on
rmsd {
atoms {
atomsfile equil2_Arp2Arp3CA.pdb
atomsCol B
atomsColValue 100.00
}
refPositionsFile Arp23_ac_min2_Arp2Arp3.pdb
refPositionsCol B
refPositionsColValue 100.00
}
}
abf { # Define an ABF bias on RMSD colvar
colvars RMSD
fullSamples 1000
> Hi George,
> Yes, it's definitely possible to run this in several windows.
> Be aware that RMSD coordinates have strong Jacobian terms - in short,
they
> have a strong tendency to drift to larger values in the absence of any
physical interactions. The ABF bias will compensate for that
automatically
> by applying significant negative biasing forces, especially at lower
values
> of the coordinate. In any case, there is a singularity around RMSD = 0,
where the PMF goes to infinity for purely geometric reasons.
> This might makes it a little less practical to work with RMSD
coordinates
> compared with more regular functions. At some point I experimented with
a
> logMSD coordinate which I expected to behave better, and wasn't totally
satisfied with the results.
> Best,
> Jerome
> On 17 September 2014 13:43, George Patargias <gpat_at_bioacademy.gr> wrote:
>> Hello,
>> As I have posted before, I am trying to study the conformational change
of
>> a protein using the RMSD colvar.
>> From a 10 ns TMD simulation (harmonic type of bias in the colvar
configuration file), I have a pretty good idea of the conformational pathway.
>> I would like now to extract a PMF for this conformational change using
the
>> ABF method.
>> From some test ABF/MD runs, the RMSD value drops from an initial value
of
>> 9.8 Ang (set as upperboundary) to 0.8 Ang (set as lowerboundary) within
400 ps and stays close to this value for the rest of the simulation. I
also tried to run a short ABF sim with 9.8 Ang (upperboundary) to 6.8 Ang
(lowerboundary) and with 100 kcal/mol/Ang^2 lower and upper wall constant
but the RMSD still becomes lower than the lowerboundary value. Is it
plausible to run ABF sims, let's say, for 3 windows (9.8 - 6.8, 6.8
>> - 3.8 and 3.8 - 0.8) with an initial RMSD value somewhere *between* the
range values of every window (like in the AmtB transporter tutorial)? Many
thanks in advance.
>> George
>> > The averaging of the ensemble of states of a single simulation is
done
>> by
>> > using the accumulated work flag itself (forces working in favor of
the
>> transformation or against it will be averaged simply by integrating
both).
>> > To average between multiple simulations, use the well known
>> Jarzynski's
>> > formula.
>> > You can define the same exact colvar but apply different methods to
it
>> and
>> > thus obtain different results, which should be equivalent in the
limit
>> of
>> > very long simulation time.
>> > You mentioned a 7-subunits protein, i.e. a very complex system, for
>> which
>> > you should anticipate that to obtain a reliable PMF won't be easy.
>> Doing
>> > preliminary tests such as a steered MD (aka a targeted MD in this
>> case)
>> to
>> > get an idea of the transformation pathway can be a good idea. Then
>> when
>> you know a bit about the transformation, use whichever free energy
calculation method you think most appropriate.
>> > Giacomo
>> >> Best wishes
>> >> George
>> >> > On Wed, Apr 16, 2014 at 6:14 AM, George Patargias
>> >> > <gpat_at_bioacademy.gr>wrote:
>> >> >> Hi Giacomo,
>> >> >> Sorry for the hassle; just one more question on this particular
>> ABF
>> >> calculation.
>> >> >> If I want to study the conformational transition A --> B and use
>> the
>> >> structure of B as a reference for the RMSD colvar, is the ABF bias
>> going
>> >> to "drive" the RMSD of A with respect to B from the upperboundary
>> value
>> (that I will calculate by superimposing A and B) to the
>> >> >> lowerboundary
>> >> >> value (a small one, like 0.1)?
>> >> >> George
>> >> >> > Yes, avoid using wrapAll in this case. Non covalently linked
>> >> protein
>> >> >> fragments would be wrapped individually, and mess up the
>> calculation
>> >> of
>> >> the
>> >> >> > RMSD.
>> >> >> > Giacomo
>> >> >> > On Tue, Apr 15, 2014 at 6:22 AM, George Patargias
>> >> >> > <gpat_at_bioacademy.gr>wrote:
>> >> >> >> Hello,
>> >> >> >> I am trying to set up an ABF calculation using the RMSD
colvar.
>> >> The
>> >> >> atom
>> >> >> >> block of the colvar configuration file contains all the
C-alpha
>> >> atoms
>> >> >> of
>> >> >> >> a
>> >> >> >> protein complex that consists of 7 (non covalently linked)
>> >> subunits.
>> >> >> I
>> >> >> am trying to decide whether I need to exclude the wrapAll option
>> (and
>> >> use only wrapWater) on the basis of the recommendations found here
>> http://www.ks.uiuc.edu/Research/namd/2.9/ug/node55.html#SECTION000132410000000000000
I would really appreciate any tips on this
>> >> >> >> Thanks!
>> >> >> >> Dr. George Patargias
>> >> >> >> Postdoctoral Research Fellow
>> >> >> >> Biomedical Research Foundation
>> >> >> >> Academy of Athens
>> >> >> >> 4, Soranou Ephessiou
>> >> >> >> 115 27
>> >> >> >> Athens
>> >> >> >> Greece
>> >> >> >> Office: +302106597568
>> >> >> Dr. George Patargias
>> >> >> Postdoctoral Research Fellow
>> >> >> Biomedical Research Foundation
>> >> >> Academy of Athens
>> >> >> 4, Soranou Ephessiou
>> >> >> 115 27
>> >> >> Athens
>> >> >> Greece
>> >> >> Office: +302106597568
>> >> Dr. George Patargias
>> >> Postdoctoral Research Fellow
>> >> Biomedical Research Foundation
>> >> Academy of Athens
>> >> 4, Soranou Ephessiou
>> >> 115 27
>> >> Athens
>> >> Greece
>> >> Office: +302106597568
>> Dr. George Patargias
>> Postdoctoral Research Fellow
>> Biomedical Research Foundation
>> Academy of Athens
>> 4, Soranou Ephessiou
>> 115 27
>> Athens
>> Greece
>> Office: +302106597568
Dr. George Patargias
Postdoctoral Research Fellow
Biomedical Research Foundation
Academy of Athens
4, Soranou Ephessiou
115 27
Athens
Greece
Office: +302106597568
This archive was generated by hypermail 2.1.6 : Wed Dec 31 2014 - 23:22:51 CST