1

Electric Transport and Coding Sequences of DNA Molecules

C. T. ShihDept. Phys., Tunghai University

計算科學專題 2

Outline

Introduction and Motivation Experimental Results The Coarse-Grained Tight-Binding

Model Sequence-Dependent Conductance

and the Gene-Coding Sequences Summary

計算科學專題 3

What is DNA? A Schematic View

計算科學專題 4

計算科學專題 5

Coding/Noncoding region Not all DNA codes correspond to gene

s (proteins) There are “junk” segments between

genes There are introns and exons in genes Only exons related to genetic codes In human genome, more than 98% co

des are junk and introns

計算科學專題 6

計算科學專題 7

Motivation: Is DNA a good conductor?

Interbase hybridization of z orbitals → Conductor? (Eley and Spivey, Trans. Faraday Soc. 58, 411, 1962)

計算科學專題 8

計算科學專題 9

Is DNA a molecular wire in biological system? Distance-independent charge transfer betw

een DNA-intercalated transition-metal complexes (Murphy et al., Science 262, 1025, 1993)

The conductance of DNA may related to the mechanism of healing of a thymine dimer defect (Hall et al., Nature 382, 731, 1996; Dandliker et al., Science 275, 1465, 1997)

計算科學專題 10

Thymine Dimer

How proteins (involved in repairing DNA defects) sense these defects?

計算科學專題 11

Do enzymes scan DNA using electric pulses?

"DNA-mediated charge transport for DNA repair" E.M. Boon, A.L. Livingston, N.H. Chmiel, S.S. David, and J.K. Barton, Proc. Nat. Acad. Sci. 100, 12543-12547 (2003).

MutY MutY

MutY MutY

Healthy DNA

Broken DNA

electron

Courtesy: R. A. Römer, Univ. Warwick

計算科學專題 12

Is DNA a building block in molecular electronics?

Sequence dependent Self-assembly Can be build as nanowires with compl

ex geometries and topologies As template of nanoelectronic devices

計算科學專題 13

Chen, J. and Seeman, N.C. (1991), Nature (London) 350, 631-633.

Zhang, Y. and Seeman, N.C. (1994), J. Am. Chem. Soc. 116, 1661-1669.

計算科學專題 14

計算科學專題 15

Experimental Results The results are controversial – almost cover all

possibilities (Endres et al., Rev. Mod. Phys. 76, 195, 2004) Anderson insulator (Zhang et al., PRL 89, 198102, 2

002) Band-gap insulator (Porath et al., Nature 403, 635,

2000) Activated hopping conductor (Tran et al., PRL 85, 1

564, 2000) Induced superconductor (Kasumov et al., Science 2

91, 280, 2000)

Score Now – Superconductor: Conductor: Semiconductor: Insulator = 1:5:5:7

計算科學專題 16

Experiment 1: Semiconductor D. Porath et al. Nature 403, 635

(2000) I-V curves Poly(G)-Poly(C) seq. (GC)15 Length: 10.4 nm Put the DNA between the electr

odes (space = 8nm) by electrostatic trapping

Several check to confirm that “1” DNA molecule between the electrodes

Measurement under air, vacuum, and several temperature

Maximum current ~ 100 nA ~ 1012 electrons/sec

Gap

計算科學專題 17

Higher T, larger gap

○: Sample #1 ＋ : Sample #2 ● and △:

Sample #3, cooling and heating measurements

計算科學專題 18

Experiment 2: Superconductivity? Yu. Kasumov et al. Science 291, 280 (2000) Sample: -DNA (bacteria phage), length=16m Substrate: Mica Electrode: Rhenium/Carbon (Re/C) → SC with Tc~ 1K, normal R ~

100 Slit R ~ 1 G, with DNA R ~ several Ks

計算科學專題 19

Results: Measurement: 1 nA, 30 Hz Ohmic behavior over the tem

perature range Power-law fit for the R-T curv

e for T>1K (Luttinger liquid behavior)

Exponent: -0.05, -0.03, -0.08 for DNA1, 2, and 3 respectively

At T~1K, R drops for DNA1, 2 Critical field: ~ 1Tesla Magnetoresistance: positive f

or DNA1 and 2, negative for 3

計算科學專題 20

Endres et al., Rev. Mod. Phys. 76, 195, 2004

計算科學專題 21

Reasons for Diversified Results

Contacts between electrode and DNA

Differences in the DNA molecules (length, sequence, number of chains…)

Effects of the environments (temperature, number of H2O, preparation and detection…)

計算科學專題 22

Effective Hamiltonian of the hole propagation

S. Roche, PRL 91, 108101 (2003) εn : hole energy for diff. base=8.24eV, 9.14eV, 8.87eV, a

nd 7.75eV for n=A,T,C,G, respectively

Zero temperature, t0=tm=1.eV, εm= εG

計算科學專題 23

Transmission Coefficient: Transfer Matrix Method

E: Energy of injected hole; T(E): Transmission coefficent

計算科學專題 24GCGCGC…… (60bps)

計算科學專題 25

Transmission Coefficient for Human Chromosome and Random Sequence

Main: Human Ch22 ChromosomeInset: Random Seq.

S. Roche et al., PRL 91, 228101 (2003)

計算科學專題 26

Transmission Analysis of Genomes

The lengths of complete genomic sequences are too long (in comparison with the electric propagation length) -> analyze subsequences instead

W: length (window size) of the subsequence which T(E) will be calculated

T(E,W,i): transmission coefficient of the subsequence from i-th to i+W-1-th base, with incident energy E

Integrate T(E,W,i) in the range E0→E0+E to get T(E0,E0+E,W,i)

Moving the window along the sequences and calculate T(E0,E0+E,W,i) for all i

計算科學專題 27

計算科學專題 28

Yeast 3

tDNA=1.0

tDNA=0.4

Randomized

Fitted by 0/w we Y3

R3

計算科學專題 29

Comparison between the Coding region and the Integrated Transmission

計算科學專題 30

t=1 eV

t=0.4 eV

計算科學專題 31

Overlap of T(W,i) and G(i) For particular W, both transmission a

nd coding (G(i)=1 if i is in the coding region, and =0 otherwise) are vectors in L-dimension (L: length of the seq.)

Normalize the two vectors Calculating the scalar product of the t

wo normalized vectors

計算科學專題 32

Overlap between T(W,i) and G(i) T(W,i)=(t1, t2....ti,....tN) The averaged transmission:

Let t’i=ti-<t>, and norm of t’:

t”i=t’i/|t’|, T”(W,i)=(t1”, t2”....ti”,.... t”N) Similarly, normalize G(i) → G”(i) Calc. the scalar product:

N

i itNt

1

1

N

i itt1

2''

i

iGiWTW )("),(")(

計算科學專題 33

Yeast ChIII (310kbps), tDNA=1eV

(MAX,wG)=(0.1,240)

計算科學專題 34

tDNA=1eV

tDNA=0.8eV

tDNA=0.6eV

tDNA=0.4eV

計算科學專題 35

Yeast Ch VIII (526kbps)

(MAX,wG)=(0.08,200)

計算科學專題 36

計算科學專題 37

(MAX,wG)=(-0.13,80)

計算科學專題 38

(MAX,wG)=(-0.08,50)

計算科學專題 39

計算科學專題 40

計算科學專題 47

Summary There are two parameters Max and wG which are characteris

tic values for different species The possible applications:

To locate the genes To understand the relation between transport properties and coding Relation to evolution and taxonomy DNA defect and repair

Future Works: Analysis for more genomes Finite-temperature effects – flexibility of the DNA chain, interaction

with phonons Ionization potential for bases is sequence-dependent More realistic (finer-grained) Hamiltonian Interaction of carriers – Hubbard U?