Abstract
The large-scale conformation of DNA molecules plays a critical role in many basic elements of cellular functionality and viability. By targeting the structural properties of DNA, many cancer drugs, such as anthracyclines, effectively inhibit tumor growth but can also produce dangerous side effects. To enhance the development of innovative medications, rapid screening of structural changes to DNA can provide important insight into their mechanism of interaction. In this study, we report changes to circular DNA conformation from intercalation with ethidium bromide using all-atom molecular dynamics simulations and characterized experimentally by translocation through a silicon nitride solid-state nanopore. Our measurements reveal three distinct current blockade levels and a 6-fold increase in translocation times for ethidium bromide-treated circular DNA as compared to untreated circular DNA. We attribute these increases to changes in the supercoiled configuration hypothesized to be branched or looped structures formed in the circular DNA molecule. Further evidence of the conformational changes is demonstrated by qualitative atomic force microscopy analysis. These results expand the current methodology for predicting and characterizing DNA tertiary structure and advance nanopore technology as a platform for deciphering structural changes of other important biomolecules.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 8910-8917 |
| Number of pages | 8 |
| Journal | ACS Nano |
| Volume | 10 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 27 2016 |
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All Science Journal Classification (ASJC) codes
- Materials Science(all)
- Engineering(all)
- Physics and Astronomy(all)
Cite this
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Modeling and Analysis of Intercalant Effects on Circular DNA Conformation. / Krueger, Eric; Shim, Jiwook; Fathizadeh, Arman; Chang, Angela Nicole; Subei, Basheer; Yocham, Katie M.; Davis, Paul H.; Graugnard, Elton; Khalili-Araghi, Fatemeh; Bashir, Rashid; Estrada, David; Fologea, Daniel.
In: ACS Nano, Vol. 10, No. 9, 27.09.2016, p. 8910-8917.Research output: Contribution to journal › Article
TY - JOUR
T1 - Modeling and Analysis of Intercalant Effects on Circular DNA Conformation
AU - Krueger, Eric
AU - Shim, Jiwook
AU - Fathizadeh, Arman
AU - Chang, Angela Nicole
AU - Subei, Basheer
AU - Yocham, Katie M.
AU - Davis, Paul H.
AU - Graugnard, Elton
AU - Khalili-Araghi, Fatemeh
AU - Bashir, Rashid
AU - Estrada, David
AU - Fologea, Daniel
PY - 2016/9/27
Y1 - 2016/9/27
N2 - The large-scale conformation of DNA molecules plays a critical role in many basic elements of cellular functionality and viability. By targeting the structural properties of DNA, many cancer drugs, such as anthracyclines, effectively inhibit tumor growth but can also produce dangerous side effects. To enhance the development of innovative medications, rapid screening of structural changes to DNA can provide important insight into their mechanism of interaction. In this study, we report changes to circular DNA conformation from intercalation with ethidium bromide using all-atom molecular dynamics simulations and characterized experimentally by translocation through a silicon nitride solid-state nanopore. Our measurements reveal three distinct current blockade levels and a 6-fold increase in translocation times for ethidium bromide-treated circular DNA as compared to untreated circular DNA. We attribute these increases to changes in the supercoiled configuration hypothesized to be branched or looped structures formed in the circular DNA molecule. Further evidence of the conformational changes is demonstrated by qualitative atomic force microscopy analysis. These results expand the current methodology for predicting and characterizing DNA tertiary structure and advance nanopore technology as a platform for deciphering structural changes of other important biomolecules.
AB - The large-scale conformation of DNA molecules plays a critical role in many basic elements of cellular functionality and viability. By targeting the structural properties of DNA, many cancer drugs, such as anthracyclines, effectively inhibit tumor growth but can also produce dangerous side effects. To enhance the development of innovative medications, rapid screening of structural changes to DNA can provide important insight into their mechanism of interaction. In this study, we report changes to circular DNA conformation from intercalation with ethidium bromide using all-atom molecular dynamics simulations and characterized experimentally by translocation through a silicon nitride solid-state nanopore. Our measurements reveal three distinct current blockade levels and a 6-fold increase in translocation times for ethidium bromide-treated circular DNA as compared to untreated circular DNA. We attribute these increases to changes in the supercoiled configuration hypothesized to be branched or looped structures formed in the circular DNA molecule. Further evidence of the conformational changes is demonstrated by qualitative atomic force microscopy analysis. These results expand the current methodology for predicting and characterizing DNA tertiary structure and advance nanopore technology as a platform for deciphering structural changes of other important biomolecules.
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UR - http://www.scopus.com/inward/citedby.url?scp=84989181283&partnerID=8YFLogxK
U2 - 10.1021/acsnano.6b04876
DO - 10.1021/acsnano.6b04876
M3 - Article
C2 - 27559753
AN - SCOPUS:84989181283
VL - 10
SP - 8910
EP - 8917
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 9
ER -