From: Jérôme Hénin (jerome.henin_at_ibpc.fr)
Date: Fri Sep 19 2014 - 10:46:45 CDT
Hi George,
Try plotting the PMF calculated by ABF (even unconverged) and -RT
log(samples per bin), and see how those two compare. The log sampling
should be significantly flatter than the PMF.
The accumulation at one side could depend from non-equilibrium effects, and
depend on the history of the system. Was nonequilibrium pulling involved at
some point? Did it have time to relax? What happens if you start a free
simulation instead of ABF?
Best,
Jerome
On 19 September 2014 17:12, George Patargias <gpat_at_bioacademy.gr> wrote:
> 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
>
>
>
>
>
>
>
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