DNA Computing and Robotics:
Engineering (Science?), Fun, and Applications
Milan N. Stojanovic
NSF Center for Molecular Cybernetics
Department of Medicine
Columbia University
Suppose we have a set of primitives:
Sensor primitives:
Computing primitives:
Moving primitives:
?
?
?
?
?
?
Recipe for Computing Primitives:
1. Take Recognition Regions,
A T
GC
A T
G
A CG
A
G
T
T
A
ACA
T
A
A
C
C
Beacons (Tyagi and Kramer)
2. Take Nucleic acid catalysts,
S2
+
E
+
+
E
S
+
S1
Phosphodiesterase (Joyce)
Ligase (Szostak)
3. And combine (for computing elements, at least) them in:
+
Cf. modular design (e.g. Breaker…)
0
1
Logic Gates: YES (Detector or Sensor Gate)
F
F
T A
CG
A T
CG
T A
Active Form A
TA AG
Cleavage
T A
C
rA
T
GT G
IA
C G
GC C C
G C
A T
A G
A GG
A T
AG
GC
A
A T
G
GC
A
CG
G
T
A A*S*IA A
T A
G
TA
A T
GC
GC
AT
C
T
G
G AA TT
A
C
T T A A
+
A
T
G
C
T
A
G
A
C
TA AG
T
G A
C
S A
G
T
T
G
A T
C G
rA
GC C C
G
A T
G C
G
A T
A
A G
A
GC
G
A T
A
G
G
A CG
T
A
A
G
A
IA
T
C
T
C
A
ACA
R
R
A
200000
150000
FU 100000
Inactive Form
Y
I
ES
rA T A T C A C T
OF
250000
50000
A
0
0
F
100 200
t (min)
300
400
I1
0
1
Joyce 1995, Breaker 1999, Tyagi, Kramer 1996
Stojanovic et al., ChemBioChem 2001
Stojanovic et al., J. Am. Chem. Soc. 2002
Switching Primitives (Logic Gates):
I1
I1
I2
0
1
0
0
NOT
I2
0
1
AND
I3
I3
I1
0
I2
I1
0
0
I2
1
0
I1
I3
I3
I2
I2
0
Three-input Gates
0
I3
I2
I1
0
Some demonstrations of molecular computing:
A. Full adder (Lederman et. al, Biochem. 2006)
i1ANDi2ANDi3
T
i1
i2
B. Maya-II (Macdonald et al. Nano Lett. 2006)
i3
1
c3
i1
i2
i3
i1ANDi2
1
2
i1ANDNOTi2ANDNOTi3
F
1
T
2
3
c2
i2ANDNOTi1ANDNOTi3
SUM
2
T
i1ANDi3
1
F
3
3
c1
i3ANDi2
3
i3ANDNOTi2ANDNOTi1
F
3
T
CARRY
2
2
c1
D. AND Hub with Beads (Rudchenko)
C. DNA Calculator (Macdonald)
(Yashin et al. JACS ~2007)
01 × 01 =
01 × 10 = 11 × 01 =
11 × 10 =
11 × 11 =
7AND9
6D7
D10
3AND4A->D5
3 1
1D3
(1×1=1)
(1×2=2)
(3×1=3)
(3×2=6)
(3×3=9)
5
2
5A
4
2D4
7AND9
D10
10A
Implementation of Naughts-and-Crosses Playing Algorithm with
Deoxiribozymes: Molecular Array of YES and ANDANDNOT Gates (MAYA)
Stojanovic, Stefanovic, Nat. Biotech. 2003
MAYA vs. Milan: Losing Game
Mg2+
X
O X
i4
X
7
6
9
9
8
9
9
2
6
1
7
8
7
8
7
6
6
2
9
F
2
3
9
7
6
9
7
1
9
8
4
4
6
9
4
2
9
7
6
8
2
9
9
7
8
i4
7
4
9
i9
i4
6
4
7
8
9
4
6
7
1
1
i9
i4
8
7
F
6
2
9
i9
i4
7
4
4
2
3
6
6
1
7
8
i9
1
2
3
9
4
4
8
9
4
i4
i9
9
4
7
9
1
6
1
8
4
9
i9
i4
i9
6
6
1
7
i9
6
1
6
7
1
9
i9
i4
9
2
9
4
8
7
9
4
9
4
i4
3
9
4
6
6
6
1
2
8
1
i4
i2
4
i9
i4
i2
i9
i4
2
F
i4
9
F
9
9
1
7
7
1
9
i4
8
7
2
4
6
1
6
6
i4
3
6
1
1
4
9
4
9
6
1
7
i4
F
2
6
X O X
O X
O
X
i2
i4
7
1
4
9
1
4
9
i4
1
1
4
7
2
8
i4
F
i4
6
1
1
3
6
1
6
6
9
7
4
F
1
2
6
4
i4
7
1
1
1
7
i4
F
6
2
4
X
X
O X
O
i9
9
4
F
i2
4
4
4
4
3
3
3
3
2
F
2
F
2
1
1
1
0
0
0
-1
1
2 3 4
5 6 7
Wells
8 9
-1
1
2 3 4
5 6 7
Wells
8 9
-1
F
2
9
9
1
1
8
7
i4
9
F
i2
4
i9
i4
i2
i2
i9
i4
i2 i2
i9
2
F
3
6
6
1
1
7
8
7
2
3
4
6
8
9
9
4
i4
i9
9
4
7
4
1
9
4
7
i9
6
1
8
4
9
i4
i2
i9
i4
i9
6
6
1
9
1
9
7
6
9
4
2
1
0
1
2 3 4
5 6 7
Wells
8 9
-1
1
2 3 4
5 6 7
Wells
8 9
The Simplest Moving Primitive:
Zn2+
But, what about multivalent design?
Zn2+
Pei et. al JACS, 2006
AFM Images of Spider at Starting Point
Kyle Lund, Hao Yan, video now: with Nadine Dabby, Erik Winfree
AFM images of Spider on Lanes of Substrates
Kyle Lund, Hao Yan
Video with: Nadine Dabby, Erik Winfree
Center for Molecular Cybernetics Phase II?
START
A
A
D
END
C
B
B
START
END
END
START
Center Members & Friends
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Erik Winfree (CS)
Hao Yan (CHE)
Niles Pierce (ApM)
Paul Krapivsky (Phys)
Sergei Rudchenko (BPh)
Nils Walter (CHE)
Milan Mrksich (CHE)
Darko Stefanovic (CS/EE)
Milan Stojanovic (MEDSci)
Nadrian Seeman (CHE)
C
H
E
•
•
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•
•
•
•
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•
0
5
3
3
0
9
6
Henry Hess (CHE/MATS)
William Shih (CHE)
Srboljub Mijailovich (ME)
Natasha Yonoska (MATH)
Satoshi Murata (CS/ME)
Friedrich Simmel (P-CHE)
Vojislav Stojkovic (CS)
Qiao Lin (ME)
Paul Rothemund (CHE/CS)
Chemical Bonding Center NSF (CHE-0533096)
Acknowledgments:
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Postdocs: Steven Taylor, Renjun Pei, Dmitry Kolpashchikov, Joanne
Macdonald
Tech’s: Stanka Semova, Erik Green, Payal Pallavi, Ma Li
High Shool Program: Harvey Lederman, Yang Lee, Marko Sutovic, Kiran
Pendri, Wengho Lu, Kirill Lebedov, Srikanth Damera, George Lederman,
Kaitlin Kyi.
Tiffany Elizabeth Mitchell
Collaborators:
Sergei Rudchenko (HSS), Ruslan Yashin
Darko Stefanovic (UNM), Mark Olah
Nils Walter (UM, Ann Arbor), Tony Manzo, Chamaree De Silva
Vincent Butler (Columbia)
Milan Mrksich (Chicago), Haim Tsubery
Erik Winfree (Caltech), Georg Seelig, Nadine Dabby
Hao Yan (ASU), Kyle Lund
Current funding NSF (ITR, 3xEMT, and CBC), JDRF, NIH (NCI-R21)
Lymphoma and Leukemia Society Scholarship
Previously: NASA, NSF QuBIC, NSF Biophotonics, NIH (NIBIB), Searle
Potential practical applications:
1. Cell-death by Boolean Calculations:
A.
B.
M1
Cell
Type I
AND Cell
Death
M2
NOT
C.
M1
AND Spare
Cell
Cell
Type II
NOT
M1
AND
Cell
Type III M
2
NOT
M3
2. Glucose-triggered movement of catalytic nanoassemblies:
Negative Feedback
Glucose
+ Insulin
G
G
G
G
Spare
Cell