**From:** Jérôme Hénin (*jerome.henin_at_ibpc.fr*)

**Date:** Fri Sep 19 2014 - 10:46:45 CDT

**Next message:**Douglas Houston: "Re: Using nodelist file causes namd to hang"**Previous message:**George Patargias: "Re: ABF with the RMSD colvar"**In reply to:**George Patargias: "Re: ABF with the RMSD colvar"**Next in thread:**George Patargias: "Re: ABF with the RMSD colvar"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

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
*

*>
*

*>
*

*>
*

*>
*

*>
*

*>
*

*>
*

**Next message:**Douglas Houston: "Re: Using nodelist file causes namd to hang"**Previous message:**George Patargias: "Re: ABF with the RMSD colvar"**In reply to:**George Patargias: "Re: ABF with the RMSD colvar"**Next in thread:**George Patargias: "Re: ABF with the RMSD colvar"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

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