ABF/Steered MD for DNA Hybridization on Carbon Nanotubes

From: Robert Johnson (robertjo_at_physics.upenn.edu)
Date: Tue Jun 19 2012 - 15:43:26 CDT

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

I would appreciate any feedback you could give. Thanks!

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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