BIOPHYSICAL THEORY AND MODELING |
Can an Atomic Force Microscope Sequence DNA using a Nanopore?
Shahid Qamar 1*, Philip Michael Williams 2 and Stuart Lindsay 3
1 Arizona State Univesity
2 University of Nottingham
3 Arizona State University
* To whom correspondence should be addressed. E-mail: shahid.qamar{at}asu.edu.
Submitted on March 13, 2007
Revised on June 8, 2007
Accepted on 14 September 2007
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Abstract |
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Bension has proposed that single molecules of DNA could be sequenced rapidly, in long sequential reads, by reading off the force required to pull a tightly fitting molecular ring over each base in turn using an Atomic Force Microscope (AFM). We present molecular dynamics simulations that indicate that pulling DNA very rapidly (m/s) could generate large force peaks as each base passed (ca. 1nN) with significant differences (ca. 0.5nN) between purines and pyrimidines. These speeds are six orders of magnitude faster that could be read out by a conventional AFM, and extending the calculations to accessible speeds using Kramers theory shows that thermal fluctuations dominate the process with the result that purines and pyrimidines cannot be distinguished by conventional AFM.
Key Words:
AFM, DNA Sequencing, Force Curve, Free Energy, Molecular Dynamics, Nanopore
