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Can an Atomic Force Microscope Sequence DNA Using a Nanopore?

Shahid Qamar ^*, Phil M. Williams  and S. M. Lindsay ^*

^* Center for Single Molecule Biophysics, The Biodesign Institute, Arizona State University, Tempe, Arizona 85287; and Laboratory of Biophysics and Surface Analysis School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, United Kingdom

Correspondence: Address reprint requests to Shahid Qamar, Center for Single Molecule Biophysics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287. E-mail: shahid.qamar{at}asu.edu.

R. 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 is passed (1 nN) with significant differences (0.5 nN) between purine and pyrimidine. These speeds are six orders of magnitude faster than 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 purine and pyrimidine cannot be distinguished with the pulling speeds attained by current AFM technology.