From: Jérôme Hénin (jhenin_at_ifr88.cnrs-mrs.fr)
Date: Thu Jul 05 2012 - 05:24:31 CDT
Hi Bob,
In an ideal world, you'd use a multiple-walker ABF formalism to
explore all these pathways at once, in parallel. It is documented in
principle (http://pubs.acs.org/doi/abs/10.1021/ct900524t) but there is
no implementation that is usable enough for your purpose.
Averaging data after the fact seems very legitimate to me. Just don't
average the PMFs, instead, compute a weighted average of the
gradients, and integrate the result. You can let the ABF code do that
for you: run a 0-step ABF simulation where you provide all of the
previous ABF outputs through the inputPrefix keyword. This will read
and combine the data properly and give you a single output.
Cheers,
Jerome
On 3 July 2012 20:47, Robert Johnson <robertjo_at_physics.upenn.edu> wrote:
> Hello Everyone,
> Are there any best practices for obtaining the average PMF from multiple
> runs? I am now using the RMSD to a reference structure as my collective
> variable. This has greatly improved the ability of my system to reach the
> desired endpoint. However, because DNA is very flexible there are many
> different pathways that can be taken to reach the final endpoint. As a
> result, each run results in a slightly different PMF with a different value
> of the free energy difference between my initial and final states. I have
> played around with the fullSamples and width parameters: right now I'm using
> fullSamples 1000 and width 0.005A. I think converging on a single PMF is
> just not possible in a single run with my system because it is so flexible.
> My current plan is to run the calculation several times to get an idea about
> the ensemble of PMFs that characterize the system and then just average them
> to get "the" PMF for the process. Does this sound like a good approach? Are
> there any other things to consider?
> Thanks,
> Bob
>
>
> On Thu, Jun 21, 2012 at 10:47 AM, Jérôme Hénin <jhenin_at_ifr88.cnrs-mrs.fr>
> wrote:
>>
>> Hi Bob,
>>
>> One caveat with the RMSD variable is to use small bins (smaller than
>> for a distance, typically). 0.05 A has worked for me in the past, but
>> in principle it depends on the ruggedness of the PMF.
>>
>> Cheers,
>> Jerome
>>
>>
>> On 20 June 2012 18:30, Robert Johnson <robertjo_at_physics.upenn.edu> wrote:
>> > Hi Jerome,
>> > Your idea of using the RMSD sounds like a good one to me. We don't
>> > expect to
>> > get a rigorous result for the PMF - we are more interested in
>> > qualitative
>> > results. I've never used the RMSD as a collective variable. I see there
>> > is
>> > documentation on how to do this here:
>> >
>> > http://www.ks.uiuc.edu/Research/namd/2.9/ug/node55.html#SECTION0001322150000000000000
>> >
>> > I also saw that there was some previous discussion on how to do this on
>> > the
>> > mailing list:
>> > http://www.ks.uiuc.edu/Research/namd/mailing_list/namd-l/12123.html
>> >
>> > The user mentions that he is following the tutorial for ubiquitin. I
>> > found a
>> > tutorial here: http://www.ks.uiuc.edu/Training/CaseStudies/pdfs/ubq.pdf
>> > However, it seems that the only colvar that is used is the end-to-end
>> > distance and not the RMSD. Is there another tutorial available?
>> >
>> > In the meantime we will try to follow the instructions in the user guide
>> > and
>> > perhaps we can get it to work on the first try. I'm just wondering if
>> > there
>> > are any other caveats that I need to worry about when using this type of
>> > colvar.
>> > Thanks,
>> > Bob
>> >
>> >
>> > On Wed, Jun 20, 2012 at 7:25 AM, Jérôme Hénin <jhenin_at_ifr88.cnrs-mrs.fr>
>> > wrote:
>> >>
>> >> Hi Bob,
>> >>
>> >> As you've noticed, the coordinate you used so far gives ambiguous
>> >> results because your system has a lot of flexibility, and will visit
>> >> basins that are not of interest to you. Now there are two kinds of
>> >> approaches to this problem:
>> >>
>> >> 1) add restraints that forbid visiting the unwanted states, but this
>> >> changes the meaning of the PMF you are calculating
>> >> 2) change your set of coordinates to describe the space of interest
>> >> more explicitly, and explore precisely that
>> >>
>> >> In many cases where you want mostly qualitative information on a
>> >> precise process, the first choice is the best one. Trying to extract a
>> >> PMF that is quantitative and meaningful and can yield real free energy
>> >> differences can be very demanding.
>> >>
>> >> Now about finding coordinates that describe the process: one simple
>> >> coordinate that would discriminate between the states that you mention
>> >> is the RMSD of the whole dimer with respect to the hybridized state.
>> >> Since the adsorbed state seems to be a deep and broad well, it doesn't
>> >> seem to need a very precise description to be visited in the
>> >> simulation.
>> >>
>> >> Caveat: finding good coordinates is difficult for us, because we don't
>> >> have the degree of physical intuition that you have about this system,
>> >> its degrees of freedom, and what type of motion is relevant or
>> >> irrelevant to your problem.
>> >>
>> >> Cheers,
>> >> Jerome
>> >>
>> >> On 19 June 2012 22:43, Robert Johnson <robertjo_at_physics.upenn.edu>
>> >> wrote:
>> >> > Hello All,
>> >> >
>> >> > I'm interested in determining how two complementary DNA strands can
>> >> > hybridize when they are both adsorbed to a carbon nanotube.
>> >> >
>> >> > I have already performed some ABF calculations to estimate the PMF
>> >> > for
>> >> > hybridization. My initial state is shown here:
>> >> > http://www.physics.upenn.edu/~robertjo/temp/InitialState.png
>> >> >
>> >> > My system consists of 2 DNA strands that are each 2 bases long - in
>> >> > this
>> >> > case each strand is GC. The blue bases are forming a G-C base pair.
>> >> > Over
>> >> > the
>> >> > course of the simulation I constrain the distances between the H-bond
>> >> > donors
>> >> > and acceptors for this base pair. Therefore, the blue base pair is
>> >> > present
>> >> > throughout the entire simulation.
>> >> >
>> >> > Then ABF is employed to force the two red bases to come together. The
>> >> > collective variable used is the distance between two atoms that share
>> >> > a
>> >> > H-bond when the red bases are paired (the orange atoms). Applying ABF
>> >> > causes
>> >> > (in most cases) the red bases to move toward each other and to form a
>> >> > base
>> >> > pair. The only way the red bases can hybridize is by lifting off the
>> >> > surface
>> >> > of the nanotube. The final state is is shown here:
>> >> > http://www.physics.upenn.edu/~robertjo/temp/Hybridized.png
>> >> >
>> >> > A graph of a representative PMF of this process is shown here:
>> >> > http://www.physics.upenn.edu/~robertjo/temp/RepresentativePMF.jpg
>> >> >
>> >> > The 2 strands initially start off in a deep energy minimum
>> >> > corresponding
>> >> > to
>> >> > adsorption to the nanotube. Forcing the two red bases to hybridize
>> >> > requires
>> >> > the system to surmount a large energy barrier. Then the system falls
>> >> > into a
>> >> > small energy minimum as the bases hybridize.
>> >> >
>> >> > About 60% of the time, I obtain a similar structure (and PMF) to that
>> >> > shown
>> >> > in the image(s). However, the rest of the time the bases come
>> >> > together
>> >> > in an
>> >> > orientation that does not favor hybridization. This makes it a little
>> >> > bit
>> >> > difficult to analyze the results since it is not known ahead of time
>> >> > what
>> >> > pathway the molecules will take.
>> >> >
>> >> > DNA is very flexible and I doubt that I will be able to fully sample
>> >> > all
>> >> > the
>> >> > different pathways that the DNA takes to reach the hybridized state.
>> >> > However, I would like a more reliable method for forcing the system
>> >> > to
>> >> > reach
>> >> > this hybridized state.
>> >> >
>> >> > Does anyone have ideas for better collective variables to use? Would
>> >> > a
>> >> > different method (i.e. metadynamics or steered MD) be a better
>> >> > choice?
>> >> > Since
>> >> > I'm interested in a very specific final state, I've also considered
>> >> > starting
>> >> > the simulation from the hybridized state and forcing the strands
>> >> > apart.
>> >> >
>> >> > I would appreciate any feedback you could give. Thanks!
>> >> > Bob
>> >> >
>> >> > --
>> >> > Bob Johnson, PhD
>> >> > Lab Coordinator & Lecturer
>> >> > Department of Physics and Astronomy
>> >> > University of Pennsylvania
>> >> > 209 S. 33rd St.
>> >> > Philadelphia, PA 19104
>> >> > Office: David Rittenhouse Laboratory 2C11
>> >> > Phone: 215-898-5111
>> >> > http://www.physics.upenn.edu/~robertjo
>> >
>> >
>> >
>> >
>> > --
>> > Bob Johnson, PhD
>> > Lab Coordinator & Lecturer
>> > Department of Physics and Astronomy
>> > University of Pennsylvania
>> > 209 S. 33rd St.
>> > Philadelphia, PA 19104
>> > Office: David Rittenhouse Laboratory 2C11
>> > Phone: 215-898-5111
>> > http://www.physics.upenn.edu/~robertjo
>
>
>
>
> --
> Bob Johnson, PhD
> Lab Coordinator & Lecturer
> Department of Physics and Astronomy
> University of Pennsylvania
> 209 S. 33rd St.
> Philadelphia, PA 19104
> Office: David Rittenhouse Laboratory 2C11
> Phone: 215-898-5111
> http://www.physics.upenn.edu/~robertjo
This archive was generated by hypermail 2.1.6 : Tue Dec 31 2013 - 23:22:12 CST
