Detecting SNPs using a synthetic nanopore

被引:108
作者
Zhao, Q. [1 ]
Sigalov, G. [1 ]
Dimitrov, V. [1 ]
Dorvel, B. [1 ]
Mirsaidov, U. [1 ]
Sligar, S. [1 ]
Aksimentiev, A. [1 ]
Timp, G. [1 ]
机构
[1] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA
关键词
D O I
10.1021/nl070668c
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We have discovered a voltage threshold for permeation through a synthetic nanopore of dsDNA bound to a restriction enzyme that depends on the sequence. Molecular dynamic simulations reveal that the threshold is associated with a nanonewton force required to rupture the DNA-protein complex. A single mutation in the recognition site for the restriction enzyme, i.e., a single nucleotide polymorphism (SNP), can easily be detected as a change in the threshold voltage. Consequently, by measuring the threshold voltage in a synthetic nanopore, it may be possible to discriminate between two variants of the same gene (alleles) that differ in one base.
引用
收藏
页码:1680 / 1685
页数:6
相关论文
共 22 条
[1]   Microscopic kinetics of DNA translocation through synthetic nanopores [J].
Aksimentiev, A ;
Heng, JB ;
Timp, G ;
Schulten, K .
BIOPHYSICAL JOURNAL, 2004, 87 (03) :2086-2097
[2]   Optimized particle-mesh Ewald/multiple-time step integration for molecular dynamics simulations [J].
Batcho, PF ;
Case, DA ;
Schlick, T .
JOURNAL OF CHEMICAL PHYSICS, 2001, 115 (09) :4003-4018
[3]  
BRUNGER AT, 1992, X PLOR VERSION 3 1 S
[4]   DNA-mediated fluctuations in ionic current through silicon oxide nanopore channels [J].
Chang, H ;
Kosari, F ;
Andreadakis, G ;
Alam, MA ;
Vasmatzis, G ;
Bashir, R .
NANO LETTERS, 2004, 4 (08) :1551-1556
[5]   Probing single DNA molecule transport using fabricated nanopores [J].
Chen, P ;
Gu, JJ ;
Brandin, E ;
Kim, YR ;
Wang, Q ;
Branton, D .
NANO LETTERS, 2004, 4 (11) :2293-2298
[6]   Ligand binding: Molecular mechanics calculation of the streptavidin biotin rupture force [J].
Grubmuller, H ;
Heymann, B ;
Tavan, P .
SCIENCE, 1996, 271 (5251) :997-999
[7]   The electromechanics of DNA in a synthetic nanopore [J].
Heng, JB ;
Aksimentiev, A ;
Ho, C ;
Marks, P ;
Grinkova, YV ;
Sligar, S ;
Schulten, K ;
Timp, G .
BIOPHYSICAL JOURNAL, 2006, 90 (03) :1098-1106
[8]   Stretching DNA using the electric field in a synthetic nanopore [J].
Heng, JB ;
Aksimentiev, A ;
Ho, C ;
Marks, P ;
Grinkova, YV ;
Sligar, S ;
Schulten, K ;
Timp, G .
NANO LETTERS, 2005, 5 (10) :1883-1888
[9]   Sizing DNA using a nanometer-diameter pore [J].
Heng, JB ;
Ho, C ;
Kim, T ;
Timp, R ;
Aksimentiev, A ;
Grinkova, YV ;
Sligar, S ;
Schulten, K ;
Timp, G .
BIOPHYSICAL JOURNAL, 2004, 87 (04) :2905-2911
[10]   Electrolytic transport through a synthetic nanometer-diameter pore [J].
Ho, C ;
Qiao, R ;
Heng, JB ;
Chatterjee, A ;
Timp, RJ ;
Aluru, NR ;
Timp, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (30) :10445-10450