Re: ABF/Steered MD for DNA Hybridization on Carbon Nanotubes

From: Jérôme Hénin (
Date: Wed Jun 20 2012 - 06:25:36 CDT

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 <> 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:
> 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:
> A graph of a representative PMF of this process is shown here:
> 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

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