Re: ABF with the RMSD colvar

From: Jérôme Hénin (jerome.henin_at_ibpc.fr)
Date: Wed Sep 17 2014 - 07:13:05 CDT

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
>
>
>
>
>
>
>
>
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>
>
>
>
>
>

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