From: Jérôme Hénin (jhenin_at_ifr88.cnrs-mrs.fr)
Date: Thu Jun 21 2012 - 09:47:28 CDT
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.
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:
> I also saw that there was some previous discussion on how to do this on the
> mailing list:
> 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
> On Wed, Jun 20, 2012 at 7:25 AM, Jérôme Hénin <jhenin_at_ifr88.cnrs-mrs.fr>
>> 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
>> 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.
>> 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
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